인생이 50줄에 들어서다 보니 과거에 보이지 않던 어떤 인생이 보이기 시작하는 것 같습니다. 특히 일반적으로 배우거나 들은 인생 법칙을 어긋나게 살아온 분들을 만나면 그 분이 얼마나 노력을 했는지에 더 궁금해 지는 것 같기도 합니다.
오늘 나누고 싶은 ‘부러우면 지는거다’의 주인공은 ‘스타강사 김미경’님입니다.
김미경님은 본래 연세대학교 작곡과 학사, 음악 석사인 음대생입니다. 그런데 이 분이 어떤 이유인지 음악이 아닌 소위 아트스피치라는 분야를 개척하고 강사생활을 시작합니다. 처음에는 시간당 2만원의 척박한 강사였지만 방송을 타기 시작하면서 회당 3천만원의 소위 스타강사가 되었죠. 2013년에는 TvN에서 김미경 쇼를 하게 됩니다. 그러던 중 석사논문 표절논란이 일면서 활동을 중단하게 되었죠. 그리고 2020년부터 2022년까지 코로나 팬데믹이 있었고 이 팬데믹이 끝나면서 다시 김미경님이 등장을 하게 됩니다.
유튜브에서요. 코로나 팬데믹 기간 동안 강사를 할 수 없게 되자 생계형으로 Digital Transformation 공부를 하고 책을 발간하면서 이제는 4차산업 시대를 강의하는 사람이 되었습니다. 뿐만 아니라 50대말인 김미경님은 인생 후반전을 가는 중년들을 위해서도 많은 강연에서 용기와 자극을 주고 있습니다. 두가지의 기사를 올립니다. 2013년에 표절과 관련한 김미경님에 대한 기사이고 2023년에 그녀의 귀환에 대한 기사입니다.
이 두 기사를 통해서 김미경님이 지난 10년간 얼마나 처절한 노력을 했을지 생각하면 그것만으로도 큰 격려가 됩니다.
스타 강사가 추락했다. 스타 강사 김미경씨는 성공의 정점에 서 있었다. 스물아홉살에 강사의 세계에 뛰어든 후 20년 사이에 시간당 2만원을 받던 풋내기 강사는 한 번 강의에 3000만원을 받는 베테랑 강사가 됐다. 2009년 첫 책 <가족이 힘을 합하면 무엇이든 이룰 수 있다>를 출간했을 때 그는 이미 국내 최고의 기업교육 전문강사로 알려져 있었다.
기업교육 분야의 스타 강사를 ‘국민강사’로 만든 것은 방송이다. 특히 tvN <스타특강쇼>와 같은 방송 <김미경쇼>가 결정적이었다. 그가 누렸던 대중적 인기를 잘 보여주는 사례는 3월 14일 방영된 <무릎팍도사> ‘김미경’ 편이다. 진행자 강호동씨의 복귀 후 고전을 거듭하던 <무릎팍도사>는 그날 동시간대 시청률 1위를 기록했다.
그러나 며칠 후 인문학 폄하 발언 논란과 논문 표절 의혹 논란이 잇따라 터지면서 김씨는 <김미경쇼>에서 하차했다. 불과 며칠 사이에 정점에서 바닥으로 떨어졌다. 문제는 그의 추락을 언론에 의해 개인적 흠결이 드러난 한 공인의 경력이 치명상을 입은 사건으로만 한정할 수 없다는 점이다.
산업화 초기 자기계발 담론 닮아 ‘퇴행적’
김미경씨를 전국구 스타로 만든 것은 지난해 우리 사회에 휘몰아쳤던, 그리고 지금도 위력을 발휘하고 있는 멘토 열풍과 힐링 열풍이다. 김씨는 ‘독설 멘토’였다. 김난도 교수나 혜민스님 같은 이들이 ‘위로’를 말할 때 김씨는 ‘독설’을 퍼부었다. 다른 이들이 ‘아파도 네 탓이 아니다’ ‘멈추면 비로소 보이는 것이 있다’고 말할 때 그는 “자본주의 사회에서 가장 센 힘이 끝까지 매달려 있는 힘”이라고 말했다.
결핍을 꿈의 재료로 삼아 맹렬하게 앞으로 나아가라고 조언했다. 높은 수위의 표현도 서슴지 않았다. 직설적이고 화끈한 그의 이런 스타일에 대중이 반응했고, 방송이 주목했다. 김미경씨는 애초 tvN <스타특강쇼>의 출연자들 중 한 명이었다. 그러나 김씨의 인기가 고공행진하자 프로그램을 통째로 맡겼다. 올해 1월부터 시작한 <김미경쇼>는 <스타특강쇼>가 이름과 포맷만 일부 바꾼 것이다.
이택광 경희대 교수(문화평론가)는 “김미경 식의 독설은 퇴행”이라고 말했다. 힐링은 산업화의 결과 발생한 개인의 피로를 달래주는 것인데, 김미경 식의 독설은 거꾸로 성공을 강조하는 산업화 초기의 자기계발 담론을 닮았다는 얘기다. 김미경씨는 강연과 책에서 “내가 가장 좋아하는 말이 ‘개천에서 용난다’는 말”이라며 “꿈은 결핍한 사람이 이룬다”고 강조해 왔다.
서동진 계원예술대학교 교수(사회학)는 다른 측면에 주목한다. “독설과 위로는 자기계발 담론의 양면인데, 김미경씨에 대한 열광은 자기계발 담론을 만들어내는 사람에 대한 스타덤이 형성되는 징후로 보인다”고 말했다. 미국에서 형성된 자기계발 담론은 1990년대에 한국에 들어왔다. ‘자기경영’을 내세운 공병호씨나 ‘변화경영’을 내세운 구본형씨는 이 분야에서 독자적인 입지를 확보하고 있는 저술가들이다.
그러나 이들 책의 독자나 강연 참석자들이 김미경씨의 경우처럼 팬덤에 가까운 지지도를 보여주진 않았다. “미국에서는 현대 경영의 구루(스승)로 불리는 톰 피터스나 <성공하는 사람들의 7가지 습관>의 저자 스티븐 코비 같은 사람들을 마돈나 같은 대중연예인과 비슷한 스타로 본다. 이들의 강연은 그 자체로 하나의 퍼포먼스(공연)다. 한국에서도 본격적으로 쇼를 하는 방식이 나타난 것이다. 자기계발 담론을 만드는 사람들이 엔터테이너로 변하고 있다.”
적극적인 몸동작과 강렬한 표현 등 엔터테이너적 요소가 강하다는 점에서 김미경 식 힐링은 김난도 교수나 혜민스님과는 확연히 다르다.
저술과 강연을 통해 우리 사회의 대표적인 힐링전도사가 된 김난도 교수 / 김석구 기자
자기계발은 몇몇 개인이 만들어내는 열풍이 아니다. 그것은 하나의 문화산업이다. 자기계발 문화의 열쇳말은 ‘긍정’이다. 성공학·동기유발·힐링·독설 등 여러 형태로 변주를 거치기는 하지만, 자아를 위로하는 담론이든 성실성을 채찍질하는 담론이든, 자기계발 문화의 근저에 있는 것은 기본적으로 긍정적 사고다.
대표적인 힐링멘토 혜민스님 / 이상훈 기자
달리 말하면, ‘생각이 문제다. 생각만 바꾸면 모든 문제가 해결된다. 그리고 생각은 교정될 수 있다’는 세계관이 자기계발 문화의 저류에 깔려 있다.
2007년 6월 국내에 출간돼 200만부 넘게 팔린 론다 번의 <시크릿>이 대표적이다. <시크릿>의 핵심어는 ‘끌어당김의 법칙’이다. 저자는 원하는 게 있다면 그것을 구체적인 그림으로 그려보는 과정을 반복하라고 말한다. 그러면 온 우주가 그 꿈을 이루게 도와준다는 것이다.
칼뱅주의 반발로 생겨난 ‘긍정적 사고’ 담론
연구자들은 이런 세계관의 뿌리를 미국 개신교의 역사에서 찾는다. 미국 사회에 만연한 자기계발 문화를 비판한 <긍정의 배신> 저자 바버라 에런라이크는 책에서 ‘긍정적 사고’ 문화는 19세기 중반 엄격한 금욕과 고강도 노동을 강조하는 칼뱅주의 신학에 대한 반발로 출현했다고 지적했다. 신대륙 미국에서 칼뱅주의 신학은 즐거움을 죄악시하고 근면한 노동을 통한 자기 절제를 강조했는데, 이러한 금욕문화가 중산층과 여성들 사이에 신경쇠약을 일으켰다.
이에 대한 반발로 분노나 의심 같은 부정적 사고를 금기시하는 긍정적 사고 담론이 생겨났다는 것이다. 이것의 20세기 버전이 국내에도 잘 알려져 있는 노먼 빈센트 필의 <적극적 사고방식>이란 책이다. 빈센트 필은 이렇게 말한다. “성공한 당신의 모습을 그려보고, 그 그림이 지워지지 않도록 마음에 확실히 각인시켜라.” “자신의 힘에 대한 부정적 생각이 떠오를 때마다 그것을 상쇄할 수 있도록 긍정적인 생각을 의식적으로 소리내어 말해보라.” <시크릿>의 메시지와 일치한다.
김진호 제3시대그리스도교연구소 소장은 ‘긍정의 신학’에 주목한다. 김 소장은 <녹색평론> 2013년 3∼4월호 좌담 ‘힐링과 멘토의 시대, 어떻게 볼 것인가’에서 이렇게 말했다. “(미국 대형교회의 치유목회론은) ‘성공을 위한 자기관리’라는 차원과 다른 한편에 ‘실패의 위기를 견디는 자기관리’라는 차원을 갖는다. 전자가 ‘자기계발 신앙’의 차원이라면, 후자는 ‘힐링의 신앙’이라고 할 수 있다.
이런 치유목회론이 한국에 본격적으로 유입된 것은 1990년대의 일이다. 숱한 자기계발 신앙서적과 힐링 서적들이 쏟아져나왔다.” 조선일보는 3월 16일 김미경씨와의 인터뷰에서 “(강연이 진행된) 강당 안 풍경은 종교 부흥회 같았다”라고 썼는데, 김씨는 2010년 국민일보 인터뷰에서 미국 목회자의 설교 동영상을 보다가 영감을 얻었다고 밝혔다.
자기계발 문화는 자아에 편집증적으로 집착한다. 상처받은 개인에게 위로를 건네는 말이든, 정글 같은 세상에서 생존하는 방법을 알려주는 말이든 자기계발 담론에서는 모든 문제해결의 중심에 개인을 둔다. 개인간의 연대나 구조적 모순에 대한 비판을 찾아보기가 어렵다는 것은 자기계발서나 자기계발 강연의 공통된 특징이다.
서동진 교수는 “‘자신을 찾아라’ ‘개성을 발휘하라’ 같은 말에 저항하기는 쉽지 않다. 문제는 자기계발 문화가 개인을 집단으로서의 노동자로 보는 게 아니라 자기 능력에 따라 보상을 받는 노동자로 보는 신자유주의 시스템에서 나타난다는 점이다. 이런 문화에서 개인은 실패를 자신의 탓으로 돌려버린다”고 말했다.
여성커뮤니티 ‘82쿡닷컴’의 한 회원은 3월 17일 이 사이트 게시판에 올라온 김미경씨 관련 글의 댓글에서 이렇게 지적했다. “호불호를 떠나 그 정도 성공했으면 직장에 출근하면서 독하게 애를 떼놓지 못하는 엄마들을 다그치는 건 그만하고 CEO들에게 직장에 유아원을 좀 많이 만들라고 했으면 좋겠어요. 그 정도 위치는 된 것 같은데 언제까지 여자는 강해야 된다고 부르짖을 건지…. 사회구조에는 관심이 없어 보여 조금 씁쓸해요.”
신자유주의 체제가 만들어낸 시대의 불안과 개인들의 좌절이 지금 우리 사회의 자기계발 문화에 동력을 제공하고 있다면, 앞으로는 어떻게 될까. 정윤수 문화평론가는 <녹색평론> 좌담에서 “지금까지는 힐링이라는 미묘한 언어로 미봉해 왔지만, 이것이 솜사탕에 불과하다는 인식이 서서히 확산될 거라고 본다. 물론 종교 출판·미디어 시장은 모양을 바꿔서 또 다른 유행으로 나아가겠지만 변화는 있을 것”이라고 말했다. 다른 견해도 있다.
일자리가 부족한 현재의 경제구조에서 청년층의 열정이 착취당하는 문제를 지적한 <열정은 어떻게 노동이 되는가> 공저자 최태섭 문화평론가는 “사람들이 뭔가 지침으로 삼을 만한 걸 좇다보니 힐링이든 독설이든 ‘저 사람이 뭔가 알고 있는 사람인가보다’라는 느낌을 받는 것 같다. 독설이 지겨워지면 또 다른 트렌드를 찾을 것 같다”고 말했다. 서동진 교수는 “미국에서는 에런라이크 같은 기성세대가 자기계발 문화의 문제점을 비판했다면, 한국에서는 청년층이 염증을 느끼기 시작한 것 같다”고 말했다.
‘호모 아카데미쿠스(homo academicus)’. 인간은 요람에서 무덤까지 평생 공부하는 존재라는 의미다. 특히 요즘처럼 하루가 다르게 새로운 기술이 등장해 세상을 바꿔 놓는 시대엔 호모 아카데미쿠스의 자세를 갖춰야 경쟁에서 살아남을 수 있다. 대한민국 대표 자기계발 멘토 김미경(58)은 ‘평생 하는 공부’의 모범 사례다. 그가 지닌 가장 큰 무기는 좌중을 웃기고 울리는 화려한 입담도, 누구에게나 친근하게 다가가는 친화력도, 지난 30년간 기업과 방송 등 강의 무대에서 쌓아 온 유명세도 아니다. 바로 언제나 현재진행형인 ‘공부’다.
흔들리는 30대 여성들에게 친언니 같은 멘토를 자처하며 현실적인 조언을 담아낸 대표작 『언니의 독설』이 출간된 지 12년이 흘렀다. 그 사이 김미경은 『김미경의 리부트』, 『세븐 테크』, 『웹 3.0 넥스트 이코노미』까지 새로운 기술과 트렌드에 대한 치밀한 공부를 바탕으로 4차 산업혁명 시대 개인의 생존법을 다룬 3부작을 펴냈다. 『언니의 독설』이 인생 경험에서 우러나온 자기계발서라면, 『웹 3.0 넥스트 이코노미』는 거시적인 경제전망서다. 성격이 전혀 다른 책이다. 사람들이 “지난 10년 동안 도대체 무슨 일이 있으셨던 거냐”고 물을 정도다.
“나에게 웹 3.0은 단순히 지적 호기심을 충족하기 위한 공부가 아니다. 처음부터 철저히 생계형 공부였다.” 올해 출간한 『김미경의 마흔 수업』에서 김미경은 이렇게 고백한다. 그 시작은 코로나로 인해 모든 강의가 끊기면서 수입이 ‘0원’이 된 초유의 사태였다. 그는 “강사 생활을 하면서 한 번도 겪어보지 못했던 가장 큰 위기였다”며 “그동안 오프라인 세상에서 아날로그 돈만 벌어왔던 나는 한순간에 길을 잃었다. 도대체 내가 어디서 길을 잃었는지, 어디로 가야 하는지 알려면 답은 공부밖에 없었다”고 회고한다.
그렇게 막막한 마음으로 몇 달을 미친 듯이 공부하다 발견한 단어가 ‘디지털 트랜스포메이션’이었고, 이를 자신의 삶에 적용하기 위해 다시 공부한 끝에 그는 지금 자신의 기존 비즈니스모델을 완벽하게 디지털화한 ‘유튜브 대학’ 형태의 플랫폼 기업 MKYU의 CEO가 됐다. ‘살던 대로 살지 이 나이에 뭘 새로 배워?’라는 말은 그에게는 통하지 않는다. 특히 ‘웹 3.0’처럼 세상에 소개된 지 얼마 되지 않아 젊은 세대도 잘 모르는 개념에는 ‘모두가 1학년이니 먼저 공부하고 선점하는 사람이 주인’이라는 마음가짐으로 접근했다.
“세상의 돈은 언제나 미래로 흐른다”며 항상 반걸음 앞을 내다보는 그의 강의에 사람들이 몰리는 것은 당연지사. 그는 “과거에 대학에서 4년간 전공한 지식으로 20~30년 버티던 ‘올드 러너(old learner)’의 시대는 끝났다”고 단언한다. 앞으로는 좁고 깊은 ‘석박사형 공부’가 아닌 ‘넓게 알고 빨리 연결시키는, 즉시 배워서 즉시 내 일에 적용할 수 있는’ 공부가 생존을 좌우하게 될 것이라는 이야기다. 책 『김미경의 리부트』에서 빠르게 변화하는 시대에 살아남기 위해 그가 매일 실행했던 공부법을 엿볼 수 있는데, 요약하자면 세 가지의 ‘읽기’다.
첫째, 아날로그 신문으로 디지털 세상 읽기. 디지털을 지향하면서 아날로그 신문을 읽으라는 게 역설적으로 느껴질 수 있지만, 알고리즘이 선별한 비슷비슷한 정보와 자극적인 광고로 시선을 빼앗는 디지털 뉴스의 맹점을 보완하기 위해 선택한 방법이다. 김미경은 매일 새벽 6시에 일어나 형광펜과 펜, 수첩을 들고 종이 신문을 읽으며 얻은 키워드나 통찰, 아이디어를 기록했는데, 종이 신문으로 기사를 집중력 있게 읽다 보니 표면적인 현상이 아닌 그 이면의 거대한 진실을 꿰뚫어 보는 ‘촉’이 생기는 것을 경험했다고 한다.
둘째, 트렌드 리포트 읽기. 검색만 할 줄 알면 세계의 저명한 기업연구소, 경제연구소 등이 펴내는 각종 트렌드 리포트를 무료로 구할 수 있는 세상이다. 김미경은 “코로나 이후 제일 중요한 것은 속도다. 하루가 다르게 산업 전반이 변하기 때문에 신속한 정보 업데이트 능력은 필수다”라며 트렌드 리포트가 두꺼운 책과 몇 줄의 뉴스 그 사이를 메꿔 줄 것이라고 조언한다.
셋째, 미래를 현실로 이해하는 독서 습관. 빠르게 고품질의 정보를 얻는 수단으로 책을 빼놓을 수 없다. 김미경은 코로나 이후의 시대에 대비하기 위해 먼저 석학들이 미래 사회를 총체적으로 전망한 책으로 큰 틀을 잡고, 구체적인 디지털 기술에 대한 책들을 찾아 읽었다고 한다. 아마존의 제프 베이조스나 테슬라의 일론 머스크 등 미래를 이끌어가고 있는 회사 CEO들의 생생한 비즈니스 스토리를 다룬 책도 추천했다.
(Picture: Alex Zhavoronkov, Ph.D., founder and CEO of Insilico Medicine)
Boston Dr. Lim is here. Alex Zhavoronkov was a computer scientist but became interested in aging and computer science. In order to study aging, he quit his job and went to Johns Hopkins University to get master degree of biotechnology and finally got PhD in biophysics in Moskow University. In 2011, Alex and Charles R. Cantor published a PLOS One paper demonstrating how artificial intelligence could be used for aging research. This paper became the foundation to start “Insilico Medicine” in 2014. Since the founding, Insilico Medicine raised more than $400 million through multiple rounds and delivered novel small molecules against novel therapeutic targets to human clinical trials. The most advanced product is INS017_055 targeting TNIK to treat fibrosis. So far 9 preclinical novel molecules can be nominated every year and goal is to deliver 15 molecules a year. I expect both INS018_055 and other novel generative AI-generative drugs could finish the FDA approval line in the end. Moreover, Alex would like to tackle clinical testing with generative AI. I wonder how Insilico Medicine team could crack the code. Insilico Medicine is global company.
GlaxoSmithKline and Insilico Medicine are partnering to explore how the latter’s artificial intelligence technology can aid in the drug discovery process.
The duo kept mum on the details but said the agreement comes after Baltimore-based Insilico completed a series of pilot challenges. First, Glaxo will “evaluate Insilico’s technology in the identification of novel biological targets and pathways of interest,” according to a statement.
Based at Johns Hopkins University’s Emerging Technology Centers, Insilico uses genomics, big data analysis and deep learning for in silico drug discovery, or drug discovery through computer modeling. The company has its own drug discovery programs in cancer, amyotrophic lateral sclerosis and diabetes, as well as in age-related diseases such as sarcopenia, Parkinson’s disease and Alzheimer’s disease.
“We are delighted to be working with the Insilico team, as they have exhibited curiosity, agility and AI expertise that we value,” said John Baldoni, senior vice president of platform technology and science at GSK, in the statement. “GSK recently established a drug discovery unit to explore how this rapidly developing field might drive drug discovery at a higher velocity, with greater precision and at a reduced cost. The collaboration with Insilico represents one of several approaches we are exploring to take advantage of emerging technology that might make us more effective and efficient, always keeping in mind the patients who need new medicines.”
The collaboration is GSK’s second drug discovery deal of the summer based around AI. In July, the Big Pharma inked a deal with Exscientia—which automates drug discovery with its AI-enabled platform—that could see the Dundee, U.K.-based company rake in up to £33 million ($42.7 million) in research payments. The Exscientia partnership aims to identify small molecules to treat as many as 10 targets chosen by GSK.
“In our opinion, GSK is one of the most innovative science-led healthcare companies, which realized the potential of artificial intelligence early and has demonstrated its ability to partner with innovative startups in the field. We are delighted to collaborate with arguably, some of the world’s best scientists on chronic diseases with unmet need,” Alex Zhavoronkov, Ph.D., founder and CEO of Insilico Medicine, said in the statement.
WuXi AppTec is partnering up with Insilico Medicine through a venture capital investment to boost its artificial intelligence-driven drug and biomarker discovery platforms.
While a smaller, previous research collaboration with WuXi AppTec has been ongoing, the new agreement represents a larger push to validate and optimize Insilico’s pipeline, with plans to formally integrate the Baltimore-based company’s technology with WuXi AppTec’s laboratory infrastructure.
Insilico’s generative adversarial networks employ two, competing neural networks to produce and evaluate candidates and drug targets through a machine learning-based discovery pipeline.The total investment amount was undisclosed.
The transaction was a joint effort between WuXi AppTec’s Research Services Division and Corporate Venture Fund, which led the VC funding round. BOLD Capital Partners and Pavilion Capital, a subsidiary of Temasek Holdings, also participated in the financing—as well as Juvenescence, a longevity therapeutics company that holds a discovery partnership with Insilico.
“WuXi AppTec and Insilico Medicine share a mutual vision that artificial intelligence and machine learning will optimize the drug discovery process by increasing the probability of success at the pre-clinical level,” WuXi AppTec Chairman Ge Li said in a statement.
“Insilico Medicine’s domain expertise in next-generation artificial intelligence, coupled with WuXi AppTec’s capability platform, can potentially improve the efficiency of drug discovery and increase the productivity to serve our partners,” Li added.
Under the agreement, the companies will perform a series of experiments, where novel molecules discovered at Insilico will be tested at WuXi AppTec. A series of milestones apply to preclinical candidates in challenging biological targets, including orphan diseases with no known crystal structure and no known ligands.
“Our collaboration with WuXi AppTec enables us to focus on artificial intelligence without the need to invest in the expensive laboratory infrastructure,” said Alex Zhavoronkov, Insilico’s founder and CEO.
“More than 90% of the molecules discovered the traditional techniques and tested in mice fail in human clinical trials. Our goal at Insilico Medicine is to develop advanced end-to-end AI solutions to discover the optimal preclinical candidates,” Zhavoronkov said.
Insilico plans to use the funding to build upon its work in novel molecule discovery, as well as expand its biomarker initiatives.
“We have been looking to collaborate with artificial intelligence-enabled technologies to enhance the drug discovery and development process,” said Edward Hu, WuXi AppTec’s chief financial officer and chief investment officer.
“What impressed us the most about Insilico Medicine was the breadth of its technological capabilities and applications, ranging from target identification and small molecule generation using next-generation artificial intelligence to expertise in blockchain and aging research.”
AI-based drug designer Insilico Medicine has raised $37 million to help commercialize its technology, on the heels of a landmark paper for the company that showed its computer networks were able to generate, synthesize and preclinically validate a series of promising compounds from scratch in less than 50 days.
Insilico also plans to build out its senior management team. Specifically, it’s angling for industry veterans that could help secure discovery partnerships with biopharmaceutical companies across different therapeutic programs, including in cancer, immunology, fibrosis, nonalcoholic steatohepatitis and central nervous system conditions.
The series B round was led by China-based Qiming Venture Partners, with participation from Eight Roads, F-Prime Capital, Lilly Asia Ventures, Sinovation Ventures, Baidu Ventures, Pavilion Capital, BOLD Capital Partners and others, including longevity-focused company Juvenescence.
“The company is an industry leader in the AI-powered drug discovery vertical,” Qiming Managing Partner Nisa Leung said in a statement. “We look forward to seeing it shortening the time for drug discovery and creating synergies with our portfolio companies.”
Another of the company’s investors—Deep Knowledge Ventures, which has backed Insilico since its 2014 seed round—described its work as one of the fund’s most promising, and a central player among its companies focused on AI-based drug discovery and longevity.
Additionally, the firm is currently launching two new subsidiary funds in those two areas—dubbed AI-Pharma and Longevity.Capital—according to Deep Knowledge Managing Partner Margaretta Colangelo, who described (PDF) them as “hybrid investment funds” combining the features of venture and hedge funds to help derisk projects.
Earlier this month, Insilico had its work published in Nature Biotechnology, demonstrating how machine learning networks could potentially shave years off of traditional hit-to-lead timelines for drug development.
In 21 days, the company was able to conceptualize 30,000 novel small molecules against a target linked to fibrosis. Over 25 more, Insilico and its partners synthesized the six most promising and tested them in both in vitro and live mouse models.
Within 25 more days, they had screened out and synthesized the six most promising compounds, tested them in vitro for selectivity and metabolic stability and had the lead candidate go on to show favorable activity in live mouse models.
The advent of artificial intelligence holds the promise to reset the industry’s expectations of how long it should take to develop a new drug from scratch. And with serious new investments, Insilico Medicine is looking to make it an everyday reality.
The company, with operations straddling the U.S. and Hong Kong, raised $255 million in series C funding led by Warburg Pincus—a big step up from its last round, which topped just $37 million, in 2019—serving as a reflection of what it has achieved in the intervening years.
That year, Insilico showed its AI systems could generate tens of thousands of novel molecules for a particular target, whittle them down to the most promising candidates and demonstrate promising drug activity in mouse studies of the disease, all in less than 50 days.
And this past February, the former Fierce 15 winner reported the completion of in vitro and in vivo preclinical studies—in a span of fewer than 18 months and with a total price tag of about $2 million—for an oral compound with a brand new mechanism of action that aims to improve lung function in patients with pulmonary fibrosis.
Insilico has also commercially launched its PandaOmics AI engine for target discovery, its Chemistry42 system for molecule design and its InClinico service for predicting clinical trial outcomes—while maintaining collaborations with Pfizer, Astellas, Johnson & Johnson, Taisho and other international drugmakers. And outside of human medicine, it’s partnered with agriculture company Syngenta to develop new molecules for more sustainable farming techniques.
Now, with its hefty proceeds, the company plans to move its therapeutic programs forward into human clinical trials as well as launch research programs for additional novel targets.
The series C round included new backing from CPE, OrbiMed, Mirae Asset Capital, B Capital Group, Deerfield Management, Maison Capital, Lake Bleu Capital, President International Development Corporation, Sequoia Capital China and Sage Partners as well as funds from its previous investors Qiming Venture Partners, Pavilion Capital, Eight Roads Ventures, Lilly Asia Ventures, Sinovation Ventures, BOLD Capital Partners, Formic Ventures and Baidu Ventures.
The funding total follows other large venture capital hauls in the AI drug prospecting space, including insitro’s massive $400 million round this past March and Atomwise’s $123 million draw last year.
More recently, SoftBank led a funding round for Exscientia that could net it up to $525 million in financing and equity commitments. Meanwhile, Recursion Pharmaceuticals ramped up its IPO to just over $500 million by the time it closed.
Insilico Medicine, a clinical-stage end-to-end artificial intelligence (AI)-driven drug discovery company, announced today that it has completed a $60 million Series D financing from a syndicate of global investors with expertise in investing in the biopharmaceutical and life sciences sectors.
New investors, including a large, diversified asset management firm on the US West Coast and BHR Partners joined the round, along with current investors, including lead investor of Series C financing round Warburg Pincus, B Capital Group, Qiming Venture Partners, BOLD Capital Partners and Pavilion Capital. Insilico’s founder and CEO, Alex Zhavoronkov, PhD, also invested in the Series D round.
Capital raised in the round will further bolster Insilico’s financial position and fuel the growth of its advancing pipeline, including its lead program which is currently in a Phase I study, and continued development of its Pharma.AI platform. The proceeds will also fund ongoing global expansion and planned strategic initiatives, including a fully automated, AI-driven robotic drug discovery laboratory, and fully robotic biological data factory to complement Insilico’s vast curated data assets.
“Despite unprecedented market conditions in the biotechnology sector, we raised this Series D round from several of the most reputable US-based and global investors,” said Alex Zhavoronkov, PhD, Founder and CEO of Insilico Medicine.“It is a testament to the strength of our end-to-end AI platform, which has been validated by many partners, and produced our first novel antifibrotic program discovered using AI and aging research, and designed using our generative AI chemistry engine. This unique program completed a first-in-human Phase 0 study in healthy volunteers and has entered Phase I clinical trials. We have also nominated seven preclinical candidates across a number of other disease indications since 2021. I am very excited about this progress and have decided to personally invest in this round.”
“The application of artificial intelligence and machine learning for drug discovery has incredible potential to transform the way new therapies are developed,” said Min Fang, Managing Director, Head of China Healthcare at Warburg Pincus. “For Insilico, 2022 is a year of incredible growth and progress. They have demonstrated the value of combining deep scientific expertise with cutting-edge technology capabilities to significantly accelerate drug discovery. We’re delighted to continue to partner with the Insilico team and support a company that is at the forefront of this innovation.”
Since the previous round of financing, Insilico has developed a growing portfolio in frontier areas empowered by its proprietary AI platform. Seven programs in its internal pipeline have progressed to the IND-enabling stage, including a novel 3CL protease inhibitor for COVID-19 treatment, and two synthetic lethality programs targeting MAT2A and USP1 for oncology. It also successfully completed a Phase 0 microdose study and entered a Phase I clinical trial with its first internally developed program targeting fibrosis.
“With the power of cutting-edge AI platforms developed fully in house and validated by many global pharmaceutical companies and our innovative, highly parallel, fully distributed drug discovery model, we nominated seven preclinical candidates since I joined the company in 2021,” said Feng Ren, PhD, Insilico’s Chief Scientific Officer and Head of Global Research and Development. “I have 15 years of experience working in large pharmaceutical companies and CROs and I am impressed by the speed and quality of our discovery programs. We plan to continue expanding the breadth of the pipeline and enhance our AI and robotics capabilities globally. Our rapidly growing team is composed of talented and experienced scientists in drug discovery with diverse backgrounds and relentless passion for novelty and innovation, and fully committed to developing novel drugs with a sense of urgency for the waiting patients.”
Insilico has also expanded its collaborations with the pharmaceutical industry through co-development and software licensing deals with a number of major pharmaceutical companies. Since the launch of its PandaOmics™ and Chemistry42™ in late 2020, nine out of the top 20 pharmaceutical companies have licensed Insilico’s AI platforms. In 2022, Insilico signed a multi-asset partnership deal with Fosun Pharma in January, and a drug discovery co-development deal with EQRx in March. Notably, Insilico achieved its first major milestone and nominated a preclinical candidate for the QPCTL program for cancer immunotherapy in less than 40 days into the strategic collaboration with Fosun Pharma.
About Insilico Medicine
Insilico Medicine, a clinical stage end-to-end artificial intelligence (AI)-driven drug discovery company, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques to discover novel targets and to design novel molecular structures with desired properties. Insilico Medicine is delivering breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases and aging-related diseases.
In Suzhou, a city 30 minutes by train from Shanghai, there’s a nondescript building that looks like it’s covered in Death Star surface tiles. In the middle of the building’s facade is a logo of a square computer chip with an Erlenmeyer flask in the middle. The logo seems to glow the color of green battery-charging lights.
A virtual walkthrough starts at the lab entrance. Like a scene from Mission Impossible, the doors are primed to open with facial recognition followed by touch activation on the airlock-like, floor-to-ceiling door. If the video weren’t on mute, I wouldn’t be surprised to hear hydraulic and whooshing sounds.
“I want to make you feel like you’re in Star Wars,” Alex Zhavoronkov, co-founder and co-CEO of Insilico Medicine, told me while showing real-life footage of his fully automated laboratory from his laptop.
As the camera guided me through the futuristic doors of his real-life sci-fi lab—Zhavoronkov has dubbed it Life Star—it pans into a glass room the size of a tennis court, with mechanical arms swinging and autonomous mobile robots shuttling around. “Here the magic happens,” smiled Zhavoronkov.
The robot works with various types of samples—cells, tissues, or organoids—prepping them for various kinds of imaging and next-generation sequencing techniques, including those for profiling DNA, RNA, and methylation. After the robotic ballet finishes generating data, the data goes back to Insilico’s trademark artificial intelligence (AI) for target selection. If anything interesting shows up, scientists will begin a validation process.
Life Star is functional around the clock. And every one of Insilico Medicine’s programs is now supported in some way by the autonomous, AI-powered robotics laboratory. Construction for his robotic laboratory in China began during the COVID-19 pandemic. “The government allowed us to bubble there, so people lived there!” Zhavoronkhov said, showing me a picture of himself lying on what looked like a gurney in a room covered with plastic. “I slept there for four months.”
The scientist
Zhavoronkov, whose real name is Aleksandrs Zavoronkovs (according to his Twitter), is unabashedly ambitious and brilliant; he’s a borderline mad scientist. He doesn’t fit the sci-fi motif of an evil genius that wants to take over the world (although Insilico Medicine has sites in Suzhou, Shanghai, Hong Kong, Taipei, Abu Dhabi, New York, San Francisco, and Montreal).
Under his leadership, Insilico has raised a total of $401.3M in funding over 10 rounds. Their latest funding was raised on Aug 10, 2022, from a second Series D round led by Prosperity7 Ventures and Aramco Ventures, bringing the total Series D financing to $95 million. New investors, including a large, diversified asset management firm on the U.S. West Coast and BHR Partners joined the round, along with current investors, including lead investor of Series C financing round Warburg Pincus, B Capital Group, Qiming Venture Partners, BOLD Capital Partners, and Pavilion Capital. Zhavoronkov’s fundraising has allowed him to take Insilico global, having opened several R&D centers around the world, and partnered with multiple pharmaceutical, biotechnology, and academic institutions.
Zhavoronkov holds two bachelor’s degrees from Queen’s University, a Master’s degree in biotechnology from John Hopkins University, and a PhD in physics and mathematics from Moscow State University. Since 2012, he has published over 150 peer-reviewed research papers, and two books including “The Ageless Generation: How Biomedical Advances Will Transform the Global Economy.” Zhavoronkov is an adjunct professor of artificial intelligence at the Buck Institute for Research on Aging. In addition to serving on the advisory or editorial boards of various journals and co-chairing the annual Aging Research and Drug Discovery conference, Zhavoronkov writes articles for Forbes in his free time.
The real McCoy
In the past year, Insilico nominated a handful of preclinical candidates, and generated positive topline Phase I data in human clinical trials with an AI-discovered novel target and AI-designed novel molecule for idiopathic pulmonary fibrosis that received Orphan Drug Designation from the FDA and is nearing Phase II clinical trials. Insilico also recently announced that its generative AI-designed drug for COVID-19 and related variants have been approved for clinical trials, as has the company’s USP1 inhibitor for the treatment of patients with solid tumors.
This past year, Insilico Medicine has used its end-to-end AI-backed drug discovery and development pipeline to nominate nine preclinical candidates in small molecules, which Zhavoronkov thinks can be pushed up to fifteen a year.
Of these, Insilico Medicine was able to advance through preclinical trials and into Phase I in about one year. To put that in perspective, recent research from McKinsey shows that, over the past decade, the average time to take a new medication from candidate nomination for preclinical testing to first-in-human trials has been about 26 months. Additionally, for a pharma company seeking to move three to five investigational new drugs into first-in-human studies every year, an acceleration down to a year, applied across the portfolio, could translate into a risk-adjusted net present value exceeding $400 million.
Zhavoronkov, who is very matter-of-fact, has a bone to pick with most people who say they run AI companies for drug discovery and development. “The company should be using deep learning technology to some extent,” said Zhavoronkov. “For me to consider somebody as an AI company, I would really need to see a substantial AI component, like deep learning and generative AI, and the company should at least to some extent contribute to the development of the software field, not just use somebody else’s tools.”
And then there are those who, Zhavoronkov said, claim to be AI companies, but they are just users and those who are doing high-level googling or Excel with advanced algorithms. “I have never seen an incubator company produce a genuine AI product from an AI system,” said Zhavoronkov.
“I’m not going to name them, but usually the founder of these companies was actually not exactly in the field right away.” Successful VC companies like Flagship Pioneering and Foresight Capital were created to access financial markets, he said. “Some of [these companies] missed the opportunity to list because 2021 was the year of abundance. Everybody got enormous amounts of money and huge valuations. Some companies jumped onto the market prematurely, some timed it extremely well, and some did not list. We’re in 2023! Show me a single asset! Lots of hype, but no results. So, the industry has consolidated.”
Zhavoronkov thinks that the resulting environment has been tough on young entrepreneurs who are getting into the field and have good ideas and algorithms, but cannot fundraise because investors have seen their money go up in flames.
“Drug discovery programs are usually like $50 million to scratch the surface; I was shocked,” said Zhavoronkov. “So you raise $400 million and burn half of that in the first year on multiple programs. If you create something great, you can actually generate potential revenue. If you don’t, you’re screwed.”
According to Zhavoronkov, there are only a handful of AI-powered drug discovery and development companies in addition to Insilico Medicine. He cited Recursion and Benevolent AI, although the latter recently announced significant layoffs. If you ask ChatGPT (with data up to 2021) to name two AI-powered drug discovery companies, Insilico Medicine routinely shows up at the top. “I think that we show up there because we publish in this field one or two research papers a month on AI,” he said.
Two are better than one
The reason Insilico Medicine is successful, according to Zhavoronkov, boils down to two reasons. First, they developed a complete end-to-end AI platform in the first few years called PHARMA.AI. This drug discovery engine utilizes millions of data samples and multiple data types to discover signatures of diseases and identify the most promising targets for billions of molecules that already exist or can be generated de novo with preferred sets of parameters. This suite was created to accelerate three areas of drug discovery and development: disease target identification (PandaOmics), generation of novel molecules (Chemistry42), and predicting clinical trial outcomes (inClinico).
Despite the popularity of ChatGPT, Zhavoronkov, not surprisingly, has created something better for anyone asking research questions by text: ChatPandaGPT. This software has integrated advanced AI chat functionality based on recent advances in large language models into its PandaOmics platform. ChatPandaGPT enables researchers to have natural language conversations with the platform and efficiently navigate and analyze large datasets, facilitating the discovery of potential therapeutic targets and biomarkers in a more efficient manner. Insilico Medicine is the first biotech company to implement chat functionality using large language models into its AI drug discovery platform.
Zhavoronkov next shows another video—a sped-up example of using Insilico Medicine’s end-to-end platform. After picking an indication, which Zhavoronkov said is purely based on commercial purposes and can be done with the help of AI, he runs through a use-case of target identification and drug discovery. All it requires is clicking and patience, as it takes hours, even days, to run some of the computations.
Second, Zhavoronkov has a co-CEO, Feng Ren, PhD, whom he said is a real drug hunter. Zhavoronkov met Ren in 2020, while he was at Medicilon, a contract research organization (CRO) providing drug discovery services to biopharmaceutical companies globally. Ren served as Medicilon’s senior vice president and head of the drug R&D service business, with more than 600 chemists and biologists. “He knew how to discover drugs, but he didn’t want to provide services to the others,” said Zhavoronkov. “He wanted to really discover, and he left a lot of money on the table.”
Ren is now using 80% of Insilico Medicine’s resources. “He is utilizing AI to very rapidly accelerate drug discovery and development,” said Zhavoronkov. “That’s the reason why we managed to do nine preclinical candidates last year. We have one proven case where we discovered a new target that generated small molecules and went all the way to Phase I, and Phase II is ready to start in the United States.”
Insilico’s robotics lab has an AI brain, an automated machine body, and the limbs of various complex robots. [Insilico Medicine]
Zhavoronkov wants the best people to work at Insilico Medicine. “We’re super inclusive,” he said. “If you are an alien from a different planet and land in my backyard, come out of this flying saucer and give a hand, I will shake it and say welcome. We don’t care who you are as long as you are really good!”
He first started by hiring people through competitions on AI, such as taking the top three fastest people to outperform the latest release of Google’s DeepMind. With the displacement of people due to the war in Ukraine, at their Abu Dhabi location, Insilico has taken in about 65 “AI refugees” from this region.
Dust in the wind
Part of the legacy that Zhavoronkov wants with Insilico Medicine is that anyone can find drug targets, no matter where they’re from. They could be from countries that have never played a role in drug discovery, or they could be high schoolers. I know the latter case is possible because Zhavoronkov showed me a series of papers that were just published by three high schoolers in collaboration with Insilico Medicine using generative AI to help identify new therapeutic targets for glioblastoma multiforme and aging—his muse.
Like other ambitious biotech entrepreneurs and investors, Zhavoronkov is an aging research aficionado. His interest in aging was his jumping-off point for his entire career. While working a well-paying job in information technology in the early 2000s, he started to keep a pulse on aging research and realized that solving aging would require a computer scientist. So, he quit his job to enroll in the biotechnology program at Johns Hopkins University and then pursued a PhD in biophysics at Russia’s Moscow State University.
Next on Zhavoronkov’s list is to translate all of his work in AI and robotics into a clinical setting. “The patient sample would come in and would be processed in a very similar way, and you would get a prediction for the drugs that were FDA-approved that are good for this patient right there in the hospital,” he said. “If I do this in the next couple of years, I will be able to put a checkmark next to my life.”
While our interview was booked for 30 minutes, Zhavoronkov suddenly paused after an hour of talking. I don’t know why he stopped, although I did spy a notification that said to take a few minutes to himself. I probably couldn’t have stopped him earlier if I had tried. Zhavoronkov is a man on a mission who does not switch off. And I don’t think anyone can stop him.
NEW YORK and HONG KONG, March 13, 2024 /PRNewswire/ — There are thousands of diseases worldwide with no cure or available treatments. Traditional drug discovery and development takes decades and billions of dollars and more than 90% of these drugs fail in clinical trials. The emergence of artificial intelligence (AI) holds promise for streamlining and improving the entire process. However, ushering in a new era of AI-driven drug discovery requires costly and lengthy validation in preclinical cell, tissue, and animal models and human clinical trials.
Now, that preclinical and part of that clinical validation was published in a new study in Nature Biotechnology. In this paper, Insilico Medicine and collaborators present the journey of its lead therapeutic program with an AI-discovered target and novel molecule generated from AI algorithms to Phase II clinical trials. For the first time, the paper discloses the raw experimental data and the preclinical and clinical evaluation of the potentially first-in-class TNIK inhibitor discovered and designed through generative AI. The study underscores the benefits of AI-led drug discovery methodology to provide efficiency and speed to drug discovery and highlights the promising potential of generative AI technologies for transforming the industry.
“When our first paper in the generative AI for generation of novel molecules was published in 2016, followed by many follow-up papers, the drug discovery community was very skeptical. Even after several validation experiments and launch of our AI software platform that is now used by many biopharma companies, many questions remained. Based on the research data, especially those from the live clinical program. To date, I have not seen anything close from any other company in our field,” said Alex Zhavoronkov, PhD, founder and CEO of Insilico Medicine. “From my perspective, the progress of INS018_055 has significant implications for the drug discovery field. It not only serves as a proof-of-concept for Pharma.AI, our end-to-end AI-driven drug discovery platform, but sets a precedent for the potential of generative AI to accelerate drug discovery. Using the publication as a guide, one can extrapolate how generative AI drug discovery tools may streamline early discovery efforts. We anticipate that the expanded application of this platform will address challenges facing industry R&D, including cost and efficiency, and accelerate the delivery of innovative therapies to patients.”
Insilico initiated the research by focusing on fibrosis, a biological process closely associated with aging. The group first trained PandaOmics, the target identification engine of Insilico’s proprietary AI platform Pharma.AI, on the collection of omics and clinical datasets related to tissue fibrosis. Next, PandaOmics proposed a potential target list using deep feature synthesis, causality inference, and de novo pathway reconstruction. After that, the natural language processing (NLP) models of PandaOmics analyzed millions of text files, including patents, publications, grants, and clinical trial databases to further assess the novelty and disease association. TNIK was identified as the most promising anti-fibrosis target. Notably, TNIK had been indirectly linked to multiple fibrosis-driven pathways in previous research but was never pursued as a potential target for IPF. In a separate paper, Insilico scientists demonstrated that TNIK may be implicated in multiple hallmarks of aging.
After selecting TNIK as a primary target, Insilico scientists utilize Chemistry42, the Company’s generative chemistry engine, to generate novel molecular structures with the desired properties using the structure-based drug design (SBDD) workflow. Chemistry42 combines over 40 generative chemistry algorithms and over 500 pre-trained reward models for de novo compound generation, and can optimize both generation and virtual screening based on expert human feedback. Following multiple iterative screens, one promising hit candidate demonstrated activity with nanomolar IC50 values. The group further optimized the compound to increase solubility, promote a good ADME safety profile, and mitigate unwanted toxicity while retaining its remarkable affinity for TNIK, which ultimately produced the lead molecule INS018_055, with less than 80 molecules synthesized and tested.
In subsequent preclinical studies, INS018_055 demonstrated significant efficacy in vitro and in vivo studies for IPF and showed promising results in pharmacokinetic and safety studies across multiple cell lines and multiple species. Furthermore, INS018_055 showed pan-fibrotic inhibitory function, attenuating skin and kidney fibrosis in two additional animal models. Based on these studies, INS018_055 achieved preclinical candidate nomination in February 2021, in less than 18 months following PandaOmics’ proposal of TNIK as a potentially novel target for IPF in 2019.
INS018_055 has exhibited excellent performance in clinical trials to date. In November 2021, 9 months after PCC nomination, the first healthy volunteers were dosed in a first-in-human (FIH) microdose trial of INS018_055 in Australia. This microdose trial exceeded expectations, delivering a favorable pharmacokinetic and safety profile that successfully demonstrated this clinical proof-of-concept and set the stage for the next step of clinical testing. In Phase I trials carried out in New Zealand and China, INS018_055 was tested in 78 and 48 healthy subjects, divided into cohorts focusing on a single ascending dose (SAD) study and multiple ascending dose (MAD) study. The international multi-site Phase I studies yielded consistent results, demonstrating favorable safety, tolerability, and pharmacokinetics (PK) profiles of INS018_055, and supporting the initiation of the Phase II studies.
“Combining AI methods with human intelligence, we have successfully nominated INS018_055, a potentially first-in-class antifibrotic inhibitor, with significant reductions in time and costs”, said Feng Ren, PhD, co-CEO and Chief Scientific Officer of Insilico Medicine. “Encouraged by positive preclinical and available clinical data, we look forward to favorable performance of INS018_055 in Phase 2 clinical trials, which would provide innovative options for patients while bringing more solid evidence for the AI-driven drug discovery industry.”
At the time of this publication, two Phase 2a clinical trials of INS018_055 for the treatment of IPF are being conducted in parallel in the United States and China. The studies are randomized, double-blind, placebo-controlled trials designed to evaluate the safety, tolerability and pharmacokinetics of the lead drug. In addition, the trials will assess the preliminary efficacy of INS018_055 on lung function in IPF patients. As this drug continues to advance, it drives hope for the roughly five million people worldwide suffering from this deadly disease.
Insilico’s drug discovery efforts are driven by its validated and commercially viable AI drug discovery platform, Pharma.AI, which works across biology, chemistry, and clinical medicine, providing the biotechnology and the pharmaceutical industry with advanced generative AI tools to accelerate their internal research and development. Powered by Pharma.AI, Insilico is delivering breakthroughs for healthcare in multiple disease areas, including fibrosis, cancer, immunology and aging-related disease. Since 2021, Insilico has nominated 18 preclinical candidates in its comprehensive portfolio of over 30 assets and has advanced six pipelines to the clinical stage.
Industry Commentary and Additional Information
“There has been much speculation that AI and deep learning methods will have a substantial role in shaping the future course of drug development. This paper presents a very convincing proof of concept.” says Charles Cantor, PhD, Scientific Advisory Board (SAB) at Insilico Medicine, “Driven by AI at nearly every stage from target identification to drug candidate selection, to phase 1 studies, a novel molecule is now ready for phase 2 clinical trials. If this process proves to be general, drug development without AI may well become inconceivable.”
“Healthcare is undergoing an important transformation of digitalization.” says Dr.Kai-Fu Lee Chairman of Sinovation Ventures, CEO of 01.AI. “I believe the use of AI and data science will revolutionize the field of medicine. Insilico Medicine’s TNIK program is a great example, presenting a breakthrough paradigm for discovering medicines from scratch under generative AI in chemistry and biology. The milestones achieved by Insilico, backed by compelling experimental data, will encourage the entire ecosystem that we are marching down the right track to advance life science with state-of-the-art information technology.”
“Although lots of companies are working on AI to improve different steps in drug discovery, Insilico is trying to apply their AI in all early drug discovery and design stages, which is so exciting to me,” says Michael Levitt, PhD, Nobel Laureate in Chemistry, 2013. “Insilico is literally AI from A to Z. They not only identified a novel target, but also accelerated the whole early drug discovery process and they’ve quite successfully validated their AI methods in the TNIK program. Drug discovery is a very wide-ranging project with a lot of uncertainty. AI can cope well with specific techniques for huge amounts of data, and by combining them with clever filtering, we can gain certainty and options from uncertainty.”
“Nowadays, it seems that we read about the virtues of AI, ML, generative design almost daily. There is a feeling that, perhaps, it is overhyped,” says Stevan Djuric, PhD, adjunct professor in medicinal chemistry at the University of Kansas and former head of the global medicinal chemistry leadership team at AbbVie. “However, in this paper, the Insilico Medicine team convincingly demonstrates the power of their proprietary platform which features target identification and validation, medicinal chemistry design and clinical trial components using the aforementioned tools. For experienced medicinal chemists, improving potency of compounds is often not the major challenge, but rather fine tuning of PK (CLu etc) and safety (off-target effects). The Insilico engine, in the case presented, successfully tackled all components of these difficult problems in a particularly timely manner. We will eagerly await news on the further progress of this agent and further clinical candidates discovered using generative AI paradigms.”
“Many people say they are doing AI for drug discovery,” says Alán Aspuru-Guzik, PhD, professor of Chemistry and Computer Science at the University of Toronto and director of the Acceleration Consortium. “A handful are delivering. Insilico’s team has shown both, the identification of a target followed by the development of a therapeutic agent all driven by AI. This, to my knowledge, is the first AI-generated drug in stage II clinical trials. A true milestone for the community and for Insilico. The lessons learned here can be further expanded to accelerate the discovery and development process.”
“When we started the preclinical profiling of INS018_055 for fibrotic diseases, everybody was seeing its target TNIK as a candidate for oncology indications,” saysKlaus Witte, MD, German Medical Board certified Pharmacologist & Toxicologist, Preclinical Consultant to Insilico Medicine. “Although I was skeptical in the beginning, all data that we generated clearly supported Insilico’s prediction of anti-fibrotic efficacy. Looking at the broad set of preclinical and clinical data that is meanwhile available, I’m confident that INS018_055 could become a very valuable treatment option in pulmonary fibrosis and other fibrosis indications. Having helped to bring the compound to its present stage is something I’m really proud of.”
“As a clinician, I see firsthand the need for novel, effective treatments. This landmark work highlights the central role that AI can play in accelerating the path from discovery to treatment, reshaping our strategy against diseases that currently have limited therapeutic options,” says Prof. Christoph Kuppe, PhD, physician scientist at the RWTH Aachen.
“I was struck by the incredible progress Alex and Insilico have made in a single decade,” says Bud Mishra, PhD, professor of computer science at New York University. “The paper focuses on idiopathic pulmonary fibrosis, a disease with complex genetics involving multiple genetic mutations. They broke this complex problem down into two parts: selecting a target (namely, TNIK), and then guiding the drug discovery process by designing small molecules that would bind to that target and make it ineffective. The first part uses heuristics that are based on the scientific experiences accumulated in the past (the target must be novel, easy to understand in terms of interactions with known pathways, and follow the approaches used by others in guiding drug discovery and clinical trials in the past) and hence ideal for NLP using LLMs. The second part uses randomized heuristics to search and optimize over complex combinatorial spaces using DNNs, capable of dealing with naturally occurring ‘easy instances of hard problems.’ Speculatively, the first part will become more difficult over time (hallucination vs. true novelty) and the second part, simpler, as Moore’s law will continue to improve the computational power exponentially.”
Reference Ren, F., et al. A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models. Nat Biotechnol (2024).https://doi.org/10.1038/s41587-024-02143-0
“For the first time in human history, individuals can expect to outlive organizations. This creates a totally new challenge: What to do with the second half of one’s life?” – Peter Drucker, “Managing Oneself,” Harvard Business Review, March-April 1999 and Management Challenges for the 21st Century (HarperBusiness, 1999)
Exactly 25 years ago, Peter Drucker first published these prescient words, six years before his death at 95. His message has only grown in importance.
How to navigate the second half of life, with all the uncertainties about when this half starts, and how long it lasts, is now being approached in a serious way by the Drucker School of Management, part of Claremont Graduate University, in Claremont, California. It has created a new certificate program, SOAR, which stands for Seek, Observe, Act, and Renew. Applications are still open, and it is set to begin this spring, with additional cohorts later this year and in 2025.
I’ve been a member of the SOAR advisory committee for the past year, and have found it to be a fascinating experience. The committee is led by Steve Tarr, a Fellow of the Drucker School, who was interviewed about the program in January by Richard Eisenberg for the MarketWatch article “Retirement-reinvention programs can cost a fortune. These options slash the cost 90%.”
SOAR will have face-to-face components in Claremont plus some related digital activities. It is partially built around the interdisciplinary (or what CGU calls transdisciplinary) values that were so much a part of Drucker’s life and career: self-exploration and exploration with others about meaning and purpose in life, and where that fits into what Drucker called “a functioning society,” drawing on lessons from the visual arts, literature, and the art of conversation.
In its explanatory material, the school outlines that SOAR has been heavily influenced by Drucker’s own roots in how he found new beginnings in Claremont in his early sixties, having moved there in 1971 after 20 years teaching at New York University.
Though he was already well known worldwide at that point, the transition was the beginning of a prolific 34 years, during which he wrote many groundbreaking books and articles. It also marked the transformation of CGU’s management school into the Drucker School of Management in 1987, as well as his pioneering efforts for the school’s Executive MBA program.
Drucker was his own best advertisement for midlife renewal and productive longevity, themes I explore in my recent article for Leader to Leader, “Frances Hesselbein And Peter Drucker: Masterclasses In Productive Longevity.” It appears in the Fall 2023 special commemorative issue for Frances Hesselbein, Drucker’s longtime collaborator, who passed away in December 2022 at the age of 107.
In keeping with the interdisciplinary/transdisciplinary nature of SOAR, the faculty represents a variety of academic specializations and disciplines:
Drucker School of Management
David Sprott Henry Y. Hwang Dean, and Professor of Marketing
Anyone interested in these topics, and the possibility of pursuing them within SOAR or other programs, would do well to refer to questions Drucker recommended to college and graduate students in his May 1966 Harper’s Magazine essay, “The Romantic Generation,” later included in the 1971 collection Men, Ideas & Politics (now titled Peter F. Drucker on Business and Society). He wondered how, in a “society of big organizations,” an individual could “maintain his integrity and privacy.”
He proposed three questions, which he maintained were old inquiries that perhaps needed to be examined in different ways: “Who Am I?;” “What am I?;” and “What should I be?”
He wrote about a variation on this theme, for a wider audience of readers, in the 1969 book The Age of Discontinuity. The questions individuals must ask of themselves in this version also start with “Who Am I?” However, the next two are: “What do I want to be?” and “What do I want to put into life and what do I want to get out of it?” These are timeless questions, and indeed some of the people who may be interested in SOAR were not yet born when Drucker first wrote them. The search for answers may lead to a fulfilling second half of life.
There’s not much in the way of a guide to figuring out what comes next after retiring from a full-time job. There are, however, terrific reinvention programs from institutions like Harvard, Stanford, Notre Dame, the University of Chicago and the University of Texas — if you can afford their price tags of $60,000 or more.
Many people can’t.
That’s why I was intrigued to hear about SOAR, a new four-month, virtual and in-person hybrid program from Claremont Graduate University. It starts in April 2024 and costs $3,995, plus housing. That’s still hardly chump change, I realize, but after speaking with Steve Tarr, a fellow at CGU’s Drucker School of Management who runs SOAR, I thought the details were worth sharing.
What’s different?
“Some of the other midlife programs have what you might call a capstone project, and you put together a business plan or figure out what a nonprofit you’re going to start is going to look like. That’s not us,” Tarr said. “If you come up with one of those ideas at SOAR, that’s great, but really it’s more about finding out who you are.”
SOAR stands for Seek, Observe, Act and Renew. The website says the program — run by CGU and the Drucker School of Management — is designed to empower the 25 to 30 SOAR fellows to “make creative decisions about the next steps in their lives.”
A month later, the participants will spend three days on the CGU campus, situated 35 miles east of Los Angeles. “The immersive experience with your cohort in Claremont is what’s going to build this,” Tarr said.
In May and again in June, the fellows will meet up online to talk with professors and discuss ways of integrating the lessons into their daily lives.
This isn’t how SOAR was first envisioned, though. Originally, it was going to be a longer and costlier on-campus program.
But since the program is partly run by the management school named for Peter Drucker — the late Claremont professor and founder of modern management — its development has itself been a market-research project.
Focus groups considered three alternative SOAR formats: a nine-month residential program, a four-month program with multiple three-day weekends on campus, and the hybrid model that was ultimately chosen.
They favored the latter due to “accessibility and their own time management,” Tarr said.
The SOAR curriculum, aimed at meeting the needs of “successful leaders transitioning in their careers,” has five parts.
Museum of Me looks at how museums tell stories in order to help fellows to tell their own stories.
Transitions deals with the emotions and challenges of change, teaching the tools and mindsets to navigate transitions effectively and move into the next phase of life.
Great Conversations assigns books and poems to help answer essential questions like: What is joy? What is a life well lived?
Purpose and Impact, taking a cue from Drucker’s priorities, helps fellows find the intersection between what they care about, what they’re good at and what the world needs so they can better define their next contribution. I’d call it finding your ikigai, the Japanese concept I’ve written about for MarketWatch.
Design Your Life uses design-thinking tools to generate ideas for your next chapter.
CGU plans to offer a second hybrid session of SOAR in fall 2024 and then, in early 2025, a third session that might feature an international trip or include immersive time at a Hollywood studio. CGU intends to run each session every year.
There will be a separate charge for each of the three sessions (the cost for sessions 2 and 3 has not yet been determined). Participants in Session 1 will get a discount on the subsequent sessions.
SOAR has similarities to a few other relatively inexpensive midlife programs from the Nexel Collaborative, a global alliance of colleges offering such programs.
The University of Colorado, Denver, offers the four-month, hybrid Change Makers program ($3,400 in fall 2024).
Union Theological Seminary runs the small, virtual, four-month Encore Transition Program twice a year ($2,500 in 2023).
The Encore Connecticut program for people who want to transition into nonprofit work is held over a series of Fridays and Saturdays on the Hartford campus of the University of Connecticut ($2,950 in 2023).
The Kokomo Experience and You Academy at Indiana University-Kokomo is typically four to six in-person sessions over a month or two (the February 2024 series on preparing for the April 2024 solar eclipse costs $140).
What’s coming
The University of Minnesota Advanced Careers Initiative, which paused in fall 2020, is expected to relaunch in late 2024 as a streamlined intergenerational version. It will likely have two options: fully online or a hybrid program like SOAR’s. The cost has not been determined.
Yale’s School of Management is working on an intergenerational encore program that’s expected to take place on campus and online; Marc Freedman, co-CEO of CoGenerate, formerly known as Encore.org, is the program’s co-designer and co-faculty director. Details, including the cost, curriculum and dates, will be announced in 2024.
The CGU folks are hopeful that SOAR will soar but note that the program may well change in future sessions, depending on what the 2024 fellows have to say about it.
“If the market says adapt, we will adapt,” Tarr said.
Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, today announced that Bristol Myers Squibb (NYSE:BMY) has opted to extend the term of the parties’ multi-year strategic collaboration for the discovery and development of novel, regulated cell therapies that utilize Obsidian’s cytoDRiVE® technology for the controlled expression of the immune enhancer CD40L. Today’s announcement builds on the existing relationship between Obsidian and Bristol Myers Squibb, initiated in 2019, and follows the first opt-in decision by Bristol Myers Squibb in 2020.
“We are delighted to extend our productive strategic partnership with Bristol Myers Squibb, an industry leader in the field, to advance next-generation cell therapies to patients with solid tumors and other malignancies,” said Paul K. Wotton, Ph.D., Chief Executive Officer of Obsidian Therapeutics. “This announcement comes at an exciting time for Obsidian as our own lead program using cytoDRiVE technology enters the clinic.”
This multi-year collaboration extension provides Bristol Myers Squibb with the exclusive option to in-license worldwide rights for cell therapy candidates incorporating Obsidian’s cytoDRiVE technology to control the expression of CD40L for the treatment of cancer. Under the terms of the agreement, Obsidian is eligible to receive potential future milestone and royalty payments.
Obsidian Therapeutics has reported positive top-line data from a Phase I clinical trial of its cell therapy candidate, OBX-115, to treat metastatic melanoma.
The first-in-human trial that is underway is designed to analyse the efficacy and safety of OBX-115 in patients with melanoma that has relapsed and/or is refractory to previous treatment with an immune checkpoint inhibitor (ICI).
An objective response rate (ORR) of 50%, with 33% complete responses, was reported at a median follow-up period of 18 weeks.
Disease control rate in the trial was 100%, with responses intensifying over time.
No dose-limiting toxicities were reported in the trial, and the treatment-emergent adverse event profile was in line with that of lymphodepletion.
A tumour-infiltrating lymphocyte (TIL) cell therapy with pharmacologically regulatable membrane-bound IL15, OBX-115 has the potential to become a therapeutic option for melanoma and other solid tumours.
Obsidian Therapeutics chief development officer Parameswaran Hari said: “The OBX-115 data show its potential to be a meaningful advancement in the treatment of metastatic melanoma and TIL cell therapy.
“These initial topline results support the promise for OBX-115 to drive responses in this heavily pre-treated patient population and facilitate the expansion of TIL cell therapy in melanoma to a broad group of patients, without the need for IL2 [interleukin-2].”
In another development, the company enrolled the first subject in a multicentre Phase I/II clinical trial of OBX-115 in patients with advanced or metastatic melanoma who are resistant to ICI therapy.
Obsidian Therapeutics CEO Madan Jagasia said: “These positive results underscore the potential for OBX-115 TIL cell therapy to offer patients with metastatic melanoma a differentiated TIL therapy, without the need for IL2.
“Furthermore, the emerging profile of OBX-115 indicates it will allow expansion of TIL cell therapy into a broad patient population, including those who may not be able to tolerate IL2 or choose not to receive it.”
Obsidian Therapeutics announced Wednesday that it raised $160.5 million to push its tumor-infiltrating lymphocyte (TIL) program further in clinical trials.
The Series C raise comes after Obsidian reported initial data from six patients with advanced melanoma who received its tumor-infiltrating lymphocyte cell therapy. With the new $160.5 million, Obsidian plans to push its TIL therapy, OBX-115, forward in multicenter studies in both melanoma and non-small cell lung cancer.
“On the back of that press-released data, we launched into the journey of the Series C financing,” Obsidian CEO Madan Jagasia told Endpoints News in an interview. In December, Obsidian shared that three of six melanoma patients responded to its TIL therapy at a median follow-up of about four months, with two of those patients going into complete remission.
The Series C was led by Wellington Management and included Foresite Capital, Atlas Venture, Bristol Myers Squibb, Novo Holdings, RTW Investments and RA Capital Management, among many others.
In February, Iovance Biotherapeutics won the first FDA approval for a TIL therapy, Amtagvi, also in melanoma. In Amtagvi, the cells are not engineered before they are expanded and are reliant on interleukin-2, which is used both during the manufacturing process and administered to patients after they receive the cell therapy. Obsidian believes that its engineered TIL therapy can do away with that reliance on IL-2.
“You are limiting your patient access because only a subset of patients are fit enough to tolerate high-dose IL-2 in the TIL regimens,” Jagasia said. “The approach that we took is — and it’s been known for a while — IL-15 can replace IL-2 in manufacturing.
“What it allows us to do fundamentally is deliver TIL cell therapy without exposing the patient to a high-dose IL-2 and expand the market opportunity,” Jagasia added. The idea is that Obsidian’s drug can be an outpatient cell therapy treatment.
Obsidian plans to complete its mid-stage studies in 2025, as well as complete key manufacturing milestones required by the FDA with its Series C funding, which would set the stage for registrational studies of OBX-115 down the line.
“Clinical data backed up by good translational science should be able to cut through the noise of the market and then get rewarded,” Jagasia said. “I’m optimistic that if the data remains consistent, and the macro economics remain stable, there would be an opportunity to take this to an IPO at the right time in the clinical development journey.”
Obsidian closed its $115 million Series B raise in September 2021 and a Series A round worth $49.5 million in December 2017.
I feel privileged to have all of you as my circle. We have been together for many decades and will be more decades to come with love and trust. Sometimes I have been thinking who I am and why I became blessed. But I couldn’t find any answer inside of me. My talent, intelligence or background are far from perfect but less than mediocre. However, everything we have received from God and our society is so much abundant and overfilled.
As you know, I have been promoted late last year with 6 years of waiting period. It was happened just one day when I totally have given up any hope to get promoted further under my current boss. Unexpectedly, my boss announced to my promotion with full smile. It was slightly weird but happy moment in my life. I don’t think I reserve this much long tenure of work and achievement without your supports. Especially, the devastating time of covid-19 pandemic circumstances which made me less sleep more work without any boundaries between work and life. There was many times I would feel miserable although blessed. Your supports and love always were always with me and I could get over my hardships and back to work with new energy every single day.
Now we have been current blessed family ever.
Michelle and John got married last year as well. During all the time from your first date to the marriage, you have been faithful and such a loving couple. I have been felt so blessed to have you a new couple and such a beautiful partners. Most of your journey of career and moving from DC area to Boston to get closer to us were so nice to me. Especially, for Kathy.
Many more – your new house and new pets and so on and so forth.
With all those blessings, there is another happiness was waiting for us. That is Kathy’s college application!
Personally, this was one of big milestones for me. From the day one of Kathy’s birth at Yale Hospital, I prayed to God for your life and his being with you all the time regardless of my presence or absence. God was faithful as always and is present with you and us all the time. Immanuel!!
What I truly see most of current situation is the fact that Kathy, you became to know and trust in God with strong commitment ever. That’s my true conviction and receiving my old prayers through the Lord’s hands. This is such a blessing!!
Still I could not understand and recognize what I have done to have these blessings. None!!
We will be together as always and come and go as a strong family and trusted company from here and there. We will start our journey to find your best fit of Kathy’s college this weekend and next weekend. I hope we could end up with almost united huddle with great joy to cheer Kathy’s new destination!!
I love you all and wish you and I have such a wonderful journey as a great family until the end.
Gritstone Bio has unique technology platform consisting of chimpanzee adenovirus vector (chAd) and self-amplifying messenger RNA (samRNA) to develop vaccines and personalized cancer vaccine.
Gritstone bio is the latest drug developer to be tapped for the Biomedical Advanced Research and Development Authority’s (BARDA’s) Project NextGen, with the biotech in line for more than $400 million to conduct a 10,000-person phase 2 study of its COVID-19 vaccine.
BARDA has contracted the company to conduct a U.S.-based randomized phase 2b trial assessing Gritstone’s self-amplifying mRNA (samRNA) vaccine candidate against an approved vaccine. Preparations for the study, which will be fully funded by the government, are already underway, and the trial is due to kick off in the first quarter of 2024, the biotech said in the Sept. 27 release.
Gritstone’s candidate, which the company has dubbed the CORAL program, is designed to drive both B-cell and T-cell immunity against the virus that causes COVID-19 by using a combination of samRNA and immunogens containing both spike and additional viral targets.
“First-generation COVID-19 vaccines provided great utility during the height of the pandemic but are limited in breadth and durability of clinical protection,” CEO Andrew Allen, M.D., Ph.D., said. “CORAL was designed to address these limitations by inducing durable neutralizing antibody and T cell-based immunity against current and future SARS-CoV-2 variants.”
The contract, worth up to $433 million, is part of the U.S. Department of Health and Human Services’ Project NextGen, which is focused on accelerating the development of new vaccines and therapeutics that can provide broader and stronger protection against COVID-19.
Recent months have seen a flurry of NextGen contracts go out, including $326 million pledged to Regeneron to push ahead with its next-generation monoclonal antibody against COVID-19.
Gritstone is best known for its work in cancer vaccines, with its lead program, dubbed GRANITE, in phase 2/3 trials for metastatic, microsatellite-stable colorectal cancer.
Evercore analyst Jonathan Miller said the BARDA announcement “does give some validation for Gritstone’s approach, and is certainly a nice signal of continued government support for COVID research.”
However, the GRANITE trial, which is expected to read out in the first quarter of 2024, is “by far the most important event” for the company from investors’ point of view, Miller added in a Sept 27 note.
Since then, this Californian company has been going through tough rides with a series of setbacks.
After Gritstone bio nabbed $433 million in federal funds to test its next-generation COVID-19 vaccine candidate, the planned phase 2b trial will get a late start thanks to a manufacturing-related delay. On the flip side, the company believes the delay should add to the trial’s regulatory value.
The study was originally slated to kick off during this year’s first quarter, but it will now launch during the fall in order to “allow use of fully GMP-grade raw materials,” the company disclosed in a press release. GMP is the acronym for good manufacturing practice, which are a group of regulations that govern drug production standards.
“The change likely increases the regulatory value of this large study, is expected to improve study interpretability, and may enable us to contemporaneously address the latest seasonal variant,” Gritstone co-founder and CEO Andrew Allen, M.D., Ph.D., said in the release.
The move was made after “recent communication” with the FDA and input from the Biomedical Advanced Research and Development Authority (BARDA), Allen added.
BARDA contracted the 10,000-participant study in September as a part of its Project NextGen, which looks to speed up the development of new vaccines and therapies that can provide broader and stronger protection against COVID. Regeneron, among others, was also tapped for the project with a $326 million investment.
Gritstone’s candidate, called CORAL, differs from traditional mRNA vaccines because of its self-amplifying technology.
The approach was designed to address the limitations of traditional first-generation mRNA COVID vaccines by “inducing durable neutralizing antibody and T cell-based immunity against current and future SARS-CoV-2 variants,” Allen said in a prior release. With its upcoming study, Gritstone will test its candidate against an approved COVID vaccine.
Elsewhere, Gritstone bio is best known for its cancer vaccines. Its lead program, dubbed GRANITE, is in phase 2/3 testing for metastatic, microsatellite-stable colorectal cancer, with a readout expected soon.
Gritstone Bio is laying off 40% of employees after delaying the start of a phase 2 trial testing its COVID-19 vaccine, which in turn pushed back the receipt of federal funds.
The layoffs announced after-market on Thursday are the latest consequence of a manufacturing delay that was revealed earlier in February. The phase 2b CORAL trial, originally slated to launch in the first quarter, was pushed to the fall to “allow use of fully GMP-grade raw materials.” But Gritstone now says that delaying the trial resulted in some external funding falling through.
“The lack of near-term funding necessitated this difficult step to fortify our balance sheet and cash position, which unfortunately means an impact to our workforce,” CEO Andrew Allen, M.D., Ph.D., said in a release. The funding referenced is the first tranche of funds from the federal government announced late last year.
The company did not say how much was expected in this first tranche of payments from the Biomedical Advanced Research and Development Authority. But the contract is worth up to $433 million through Project NextGen, which is funding a number of companies’ efforts to create new strategies to fight COVID-19. Gritstone is conducting a 10,000-person U.S.-based phase 2 study for its self-amplifying mRNA (samRNA) vaccine candidate. The study was expected to get off the ground in the first quarter.
Gritstone’s other priorities, including the phase 2 portion of a phase 2/3 study of a personalized cancer vaccine, remain unchanged, according to the release. Data are expected from that program later this quarter, Allen said.
Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, today announced the pricing of an approximately $32.5 million underwritten public offering of its common stock (or pre-funded warrants to purchase common stock in lieu thereof) and accompanying common warrants to purchase common stock (or pre-funded warrants to purchase common stock in lieu thereof), before deducting underwriting discounts and commissions and offering expenses.
The offering consists of (i) 8,333,333 shares of common stock and accompanying common warrants to purchase up to 8,333,333 shares of common stock at a per share exercise price of $1.65 (provided, however, that the purchaser may elect to exercise the common warrants for pre-funded warrants in lieu of shares of common stock at an exercise price of $1.65 minus $0.0001, the exercise price of each pre-funded warrant), at a combined public offering price of $1.50 per share and accompanying common warrant and (ii) to a certain investor in lieu of common stock, pre-funded warrants to purchase up to 13,334,222 shares of common stock at a per share exercise price of $0.0001 and accompanying common warrants to purchase up to 13,334,222 shares of common stock at a per share exercise price of $1.65 (provided, however, that the purchaser may elect to exercise the common warrants for pre-funded warrants in lieu of shares of common stock at an exercise price of $1.65 minus $0.0001, the exercise price of each pre-funded warrant) at a combined public offering price of $1.4999 per pre-funded warrant and accompanying common warrant, which represents the per share combined purchase price for the common stock and accompanying common warrants less the $0.0001 per share exercise price for each such pre-funded warrant. The accompanying common warrants will be immediately exercisable for shares of common stock or pre-funded warrants in lieu thereof, and will expire on the twelve-month anniversary of the date of issuance. All of the shares of common stock, accompanying common warrants and pre-funded warrants are being offered by Gritstone bio. The offering is expected to close on or about April 4, 2024, subject to the satisfaction of customary closing conditions. TD Cowen and Evercore ISI are acting as the joint book-running managers for the offering.
Gritstone bio’s gamble on a novel endpoint has backfired. The cancer vaccine failed to trigger hoped-for changes in circulating tumor DNA (ctDNA), causing the phase 2 trial to miss its primary endpoint and leaving the biotech clinging to immature survival data.
Investigators randomized 104 patients with metastatic microsatellite stable colorectal cancer to take one of two front-line therapies. All patients received induction and maintenance chemotherapy. Around half of the subjects also received Gritstone’s personalized neoantigen cancer vaccine, Bristol Myers Squibb’s Yervoy and Roche’s Tecentriq during the maintenance phase.
The primary endpoint looked at changes in ctDNA. On that measure, Gritstone’s drug combination was numerically worse than chemotherapy alone, with the molecular responses in the vaccine and control arms coming in at 30% and 41.7%, respectively. Gritstone attributed the result to its misunderstanding of how ctDNA would change after treatment.
“With regard to defining molecular response, we simply got it wrong,” Gritstone CEO Andrew Allen, M.D., Ph.D., said in a statement. “CtDNA levels in both arms decreased on chemotherapy for longer than we anticipated, generating similar short-term molecular response rates across arms and rendering our protocol measure of ctDNA change uninformative.”
While the study missed its primary endpoint, Allen latched on to progression-free survival (PFS) data to contend that the results are “highly encouraging.” The PFS rate was higher in the vaccine group than in the control arm after six months and nine months. However, the lines crossed around the 12-month mark, creating a short period in which PFS probability was higher in the control arm.
The hazard ratio favored the vaccine regimen, clocking in at 0.82 in the overall population, but the wide confidence intervals make it impossible to draw firm conclusions. Gritstone reported a hazard ratio of 0.52 in a subgroup of high-risk patients. PFS data are more mature in the subgroup, leading Allen to call the result “a striking signal,” but, again, the confidence intervals are wide enough that the vaccine may be less effective than the control. Allen had discussed what would be a good PFS result at an event in March.
“The separation [of the curves], of course, is likely and important, but the lifting of the tail is what we really care about,” Allen said at the time. The CEO cited Bayer’s Stivarga as an example of a drug that “shifted PFS by about two months [and is] not widely used because survival is basically no different.”
Gritstone picked ctDNA, rather than the widely used and accepted PFS, as its primary endpoint because of concerns about “pseudo progression.” The term describes people whose tumors appear to grow after treatment but then shrink. That happens when T cells enter tumors and proliferate. Initially, this causes lesions to grow, but they then collapse as the immune cells wipe out the tumor.
Evidence of pseudo progression made Gritstone “a little bit leery” about PFS, Allen said, and led it to make ctDNA the primary endpoint. The hope was that ctDNA would provide a clear signal that the therapy is working and make the case for pushing ahead to an overall survival (OS) readout that will provide the truest test of efficacy.
Instead, the study missed the ctDNA endpoint, leaving Gritstone looking to immature PFS results that, at best, show trends favoring the vaccine to make the case for its therapy. The biotech expects to have mature PFS data in the third quarter of 2024, with OS data set to follow in the first half of next year.
The timing of the readouts is important, because Gritstone’s cash is running low. The biotech ended last year with $79.2 million, a sum it told investors would fund operations into the third quarter of 2024. Gritstone proposed a public offering in the immediate aftermath of the phase 2 data Monday and later priced a $32.5 million sale at $1.65 a share.
Gritstone’s share price has bounced between a low of $1.14 and high of $3.33 over the past year. The stock fell almost 33% in the wake of the updates Monday, falling to $1.58 in after-hours trading.
The following corporate presentation is about GRANITE phase 2 results.
Productive Longevity에 대해 관심을 가지고 글을 쓰고 있는데 우리말로 번역하면 “생산적으로 오래삶”이라고 할 수 있을 것 같습니다. 즉, 노화라는 의미보다는 오래산다는 것에 방점을 찍는 용어라고 할 수 있죠. 노년학 (Gerontology)에서 노화에 대한 다양한 정의가 있는데 이것을 하나로 잘 정의해 주신 김수형님의 글이 있어서 아래에 나누고자 합니다.
나이 들어간다는 것은 우리에게 어떤 의미일까? 나이 들어간다는 것은 한편으로 늙어간다는 것이고, 신체적으로나 정신적으로나 성숙해져간다는 의미를 담고 있을 것이다. 이러한 나이 들어감, 한편으로 늙어간다는 것은 누구에게나 일어나는 필연적이고, 보편적인 현상이며, 어떻게 생각하면 가차 없이 발생하는 현상일 것이다. 이런 나이 들어가는 것과 늙어가는 것을 영어로는 ‘Aging’이라는 단어로 쓰인다. 한글로 번역하면 ‘고령화’, ‘노화’, ‘나이 먹음’을 의미한다. ‘노화’를 바라보는 시각은 비유적으로 컵 안에 반 정도 있는 물을 어떻게 바라보는지와 유사할 것이다.
긍정적인 시각으로 컵 안에 있는 물을 바라본다면 ‘아직도 물이 반이나 남았네!’라고 볼 것이고, 부정적인 시각으로 바라본다면, ‘물이 반 밖에 안 남았네!’라고 볼 것이다. ‘늙어감’을 바라보는 시각도 이와 비슷하지 않을까 묻고 싶다. 늙는 것을 긍정적인 시각으로 바라본다면, 나이 들어가는 것은 새로운 성장의 단계로 볼 수 있을 것이다. 여러 가지 단어가 떠올려진다. 낙관주의, 도전, 기회, 친밀감, 건강함, 목적, 열정 등 활동적이며 인생을 적극적으로 생활하는 액티브한 노년의 모습이 보인다. 하지만 그 반대로 생각하면 비관주의, 약함, 슬픔, 외로움, 두려움, 후회 등 부정적인 단어가 떠올려진다. 누구에게나 찾아오는 늙음을 여러분은 어떻게 바라보고 싶은가? 물론 개인적인 차가 있겠지만 단순히 나이로 생각하기 보다는 노화를 받아들이는 태도에 따라 노년의 모습도 달라지지 않을까 한다.
그럼 잘 늙어가는 모습은 어떤 것이 있을까? 우리 주변에서 찾을 수 있는 멋진 노년의 모습은 어떤 것이 있을까? 이에 대한 정답은 우리가 어떻게 노년의 모습을 정의하는지에 따라 다양하게 나타날 수 있다. 여기서는 8가지 늙어감의 모습을 제시하고 싶다.
첫째로 성공적 노화이다. 영어로 표현하면 ‘Successful aging‘이다. 성공적 노화는 ’질병과 장애가 없고, 인지적 기능과 신체적 기능을 유지하며, 적극적으로 인생참여를 지속하는 것‘으로 미국의 노년학자인 Rowe와 Kahn이 1987년에 발표한 논문에서 정의하고 있다. 신체적으로 건강하고, 인지와 정신적 기능을 유지하며, 사람과 사회 속에서의 관계를 잘 유지하는 것을 중시하고 있다.
둘째로는 활동적 노화이다. 보통 액티브 에이징(Active aging)이라는 영어 표현으로도 쓰인다. 활동적인 노년의 모습을 유지하기 위해서는 건강한 삶, 지속적인 사회참여, 경제적인 안정 등 3가지 조건이 충족될 필요가 있다.
세 번째로 긍정적으로 노년을 바라보는 모습이다. 영어로 ’Positive aging‘이라고 표현한다. 해외 유명인사들 중에 늙음을 긍정적으로 바라본 글귀가 여럿 있다.
미국의 작가이자 사회운동가였던 배티 프리던은 나이 들어가는 것은 ’잃어버린 젊음‘이 아니라, 새로운 기회와 힘의 단계라고 하였다. 미국의 유명 건축가였던 프랭크 로이드 라이트는 늙어가는 것을 “내가 더 오래 살수록, 더욱더 멋진 인생이 될 것”이라고 했고, 영화배우 아누크 에이미는 나이 들어가는 사람의 모습에서 진정한 아름다움을 찾을 수 있다고 했다.
네번째로 창의적인 노년의 모습이 있다. 창의적인 노화, 즉 Creative aging은 두 가지 측면에서 생각해 볼 수 있다. 하나는 사회참여와 기술습득에 초점을 맞춘 예술 프로그램에 적극적으로 참여하는 형태이고, 다른 하나는 지역사회 내에서 지속적으로 성장하고, 배우고, 공헌한다는 적극적인 사회 참여의 형태로 생각해 볼 수 있다.
다섯 번째로 젊게 살아가는 노년의 모습도 생각해 볼 수 있다. ’노노족‘이라는 말이 유행한 적이 있다. ’N0+老“, 즉 ‘노(NO)’와 ‘노(老)’를 합성해 만든 신조어이다. 건강 챙기기에 관심이 높고, 여행과 취미 활동에도 적극적이며, 외모에서도 실제 나이보다 훨씬 젊게 보이는 부류를 일컫는 말이다. 우리 주변에서도 젊은이 못지않은 왕성한 활동력을 보이고, 특히 젊은 층의 문화를 수용하려고 노력하는 젊은 노객을 본 적이 있을 것이다.
여섯 번째로 스마트(Smart)하게 노년을 살아가려는 모습이 나타나고 있다. 단순히 똑똑하게 나이 든다는 것이라고 해석하기 보다는 적극적인 배움을 통해 스스로 직접 노년을 디자인하는 모습을 스마트 에이징이라고 표현하고자 한다.
일곱 번째로, 현대 사회에 기술적 진보에 따라 디지털을 활용하는 노년의 모습이 나타나고 있다. 흔히, 디지털 에이징(Digital aging)이라고 표현한다. 정보통신기술(ICT)을 활용해 건강하고 활동적으로 나이 든다는 것을 의미한다. 디지털 기기에 친숙하지 않은 노년층을 위해 스마트폰을 사용하는 법을 알려주는 교육이나 노년층 대상 컴퓨터 강좌가 최근 성황리에 운영되는 이유이기도 하다.
마지막으로 생산적 노화의 모습이다. 영어로 표현하면 Productive aging이다. 긍정적인 노년의 모습을 통해 개인이 자신의 삶과 지역사회에서 중요한 공헌을 할 수 있다는 부분을 강조한 접근방식으로 해석된다. 일의 맥락에서 생산적 노화를 살펴보면, 근로자가 나이가 들어서도 그 기능을 유지하고 발휘될 수 있도록 모든 사람에게 안전하고 건강한 근로 환경을 제공하는 것을 포함한다는 것을 의미한다.
지금까지 여덟 가지로 해석된 다양한 늙어감의 모습을 살펴보았다. 각각의 노화의 모습이 의미를 담고 있는지 설명한 내용이었다. 어떤 면으론 늙어감의 모습이 진화된다고 해석할 수 있다.
우리 주변에 있는 고령자를 볼 때 어떤 노년의 모습으로 대입될 지 찾아보는 것도 흥미로운 일일 것이다. 아마 위에 포함된 노년의 모습을 많이 발견할 때….점차 노년이 행복한 사회로 되지 않을까?
Once considered an undruggable target, KRAS now has two FDA-approved therapies vying for a blockbuster cancer market.
Mirati Therapeutics’ Krazati, also known as adagrasib, will take on Amgen’s first-to-market Lumakras thanks to an FDA accelerated approval in previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Krazati marks Mirati’s first commercial product, and the biotech will focus on efficacy in its marketing pitch, CEO David Meek told Fierce Pharma in an interview ahead of the approval. J.P. Morgan analyst Eric Joseph, Ph.D., has in late November put Krazati’s risk-weighted peak sales estimate across multiple indications at $1.7 billion but then lowered the number to $1.3 billion a few days ago, as blockbuster hopes for the drug have dwindled since a Keytruda combination readout.
Mirati is charging Krazati at a list price of $19,750 for a 30-day supply, a company spokesperson told Fierce Pharma. Krazati is given in 600-mg capsules twice daily. By comparison, Lumakras costs slightly less with a list price of $17,900 per month
In the phase 2 registrational portion of the KRYSTAL-1 trial, Krazati shrank tumors in 43% of patients when used in patients with previously treated NSCLC bearing KRAS G12C mutations. By comparison, Lumakras, given 960 mg once daily, showed a 36% tumor response rate in its own phase 2 trial. And the number dropped to 28% in a larger phase 3 trial.
Similar to Lumakras’ situation, the FDA has required Mirati to run a postmarketing study to test a lower 400-mg twice daily regimen of Krazati. The FDA’s oncology department has recently put an emphasis on dose optimization under Project Optimus. The agency has criticized drugmakers for pushing for the highest tolerable dose in early clinical testing without carefully examining the benefit-risk balance.
About 25% to 50% of NSCLC cases develop brain metastases during the course of the disease. In another key component of Mirati’s commercial campaign, Krazati has shown a brain tumor response rate of 33% versus 25% for Lumakras in patients with baseline brain metastases in its own study. A label with that brain metastases information would be a “nice-to-have” that can differentiate Krazati from the competition, but the data are not included, J.P. Morgan’s Joseph pointed out in a Tuesday note.
In a pooled analysis of the phase 1/2 KRYSTAL-1 trial, patients on Krazati lived a median 14.1 months. By comparison, Lumakras takers survived a median 12.5 months in its phase 2 trial and 10.6 months in the phase 3 study. Krazati’s own phase 3 confirmatory trial, KRYSTAL-12, which compares Krazati with the chemotherapy docetaxel, is underway.
Cross-trial comparisons come with intrinsic problems such as patient characteristics differences. But Meek stressed that Krazati’s response data are best-in-class so far.
In what Meek calls a “halo” effect, Mirati also hopes doctors will notice the company’s recent early results for Krazati’s combination with Merck’s PD-1 inhibitor Keytruda. The early-stage KRYSTAL-7 trial showed what Barclays analysts called “good safety but modest activity” in newly diagnosed NSCLC. In contrast, Merck’s Keytruda combo reported lackluster efficacy data while raising a serious liver safety concern.
“I think we’re the KRAS leader,” Meek said in the interview. “We will set the direction where this KRAS agent goes.”
But while Mirati’s KRAS-Keytruda combo data looked better than Amgen’s, Krazati’s commercial potential is under question as well. The company’s stock price has been about halved after the KRYSTAL-7 combo study, reflecting investors’ concern that the companies’ planned phase 3 trials might not succeed.
Although Krazati is Mirati’s first commercial launch, it’s not the first for the Mirati people. The company has built a sales force with average 19 years of experience in oncology, and the staffers were hired based on their experience in lung cancer, Meek noted.
Mirati has talked to nearly all of the top payer plans and received positive feedback, Chief Commercial Officer Ben Hickey told investors during the company’s third-quarter earnings call last month. Mirati expects to have broad coverage within the first few months of launch, he said.
Krazati’s launch comes as Lumakras experienced a sequential sales decline in the third quarter to $75 million. Amgen attributed the slowdown to a price adjustment as part of reimbursement deal in Germany.
Next up, Mirati plans to launch two phase 3 trials of Krazati—at the 400-mg twice daily dose—in combination with Keytruda in front-line NSCLC this year. The company is discussing a potential accelerated approval pathway for Krazati in third-line colorectal cancer and will have more to share in early 2023, Meek said. The confirmatory KRYSTAL-10 trial for a cocktail of Krazati and Eli Lilly’s Erbitux in second-line colorectal cancer is also expected to read out later next year. In addition, the company has a candidate for KRAS G12D mutations that’s slated to enter clinical testing next year.
With all the pipeline advancement, Mirati has recently reportedly attracted buyout interest from Big Pharma. Mirati has tapped an adviser, and larger pharmas are considering the “merits of a transaction,” Bloomberg reported late November.
“We’re real busy,” Meek said in his interview with Fierce Pharma. “We’re really focused on executing our clinical plans and our launch plans.”
However, any potential acquirer might have pulled out by now, BMO Research analyst Evan David Seigerman said in an investor note after the KRYSTAL-7 combo readout. The phase 3 combo trials Mirati plans to run will take a long time to read out, and existing early-stage data don’t bode well, he said.
Bristol-Myers Squibb (BMY.N), opens new tab on Sunday said it will acquire cancer drugmaker Mirati Therapeutics (MRTX.O), opens new tab for up to $5.8 billion, diversifying its oncology business and adding drugs it hopes can help offset expected lost revenue from patent expirations later this decade.
Bristol will pick up Mirati’s portfolio drugs that target the genetic drivers of specific cancers including its lung cancer drug, Krazati, which was approved in December.
A second compound – MRTX1719 – which could be used in some types of lung cancer was also attractive to the company, Bristol executives said in an interview.
“We think this really helps strategically complement our oncology portfolio but also, from a financial standpoint, it helps out commercially in the back half of the decade,” said Adam Lenkowsky, Bristol’s Chief Commercialization Officer.
The company said that it will buy Mirati for $58 per share in cash, or around $4.8 billion. Mirati has around $1.1 billion in cash on hand, so “we’re paying essentially $3.7 billion enterprise value…we think with that we’ve gotten a very attractive deal,” Lenkowsky said.
Mirati stockholders will also receive one non-tradeable contingent value right for each Mirati share held, potentially worth $12.00 per share in cash, representing an additional $1 billion of value opportunity, the company said
Bristol will finance the transaction with a combination of cash and debt, the company said in a statement.
The U.S. Food and Drug Administration in December approved the drug to treat adults with advanced lung cancer.
“With multiple targeted oncology assets including Krazati, Mirati is another important step forward in our efforts to grow our diversified oncology portfolio and further strengthen Bristol Myers Squibb’s pipeline for the latter half of the decade and beyond,” said Chris Boerner, Bristol’s incoming CEO and current chief operating officer, in a statement.
The New York-based company has been pressured by declining demand for two of its top drugs, the blood cancer treatment Revlimid and blood thinner Eliquis, which face generic competition.
Bristol is buying Mirati at a time when the shares are considerably cheaper than they were. Mirati’s shares touched a 52-week high of $101.3 apiece on Nov. 28 and are now trading at $60.2.
The transaction is expected to be dilutive to Bristol’s non-GAAP earnings per share by approximately 35 cents per share in the first 12 months after the transaction closes, the statement added.
In April, Bristol said CEO Giovanni Caforio would step down in November and be succeeded by Boerner.
Last year, Bristol acquired drug developer Turning Point Therapeutics for $4.1 billion in cash to help bolster its arsenal of cancer drugs.
Bristol Myers Squibb looks on track to overtake Amgen as the KRAS leader in lung cancer after following up its rival’s FDA setback with a positive confirmatory trial readout.
BMS’ Krazati significantly reduced the risk of tumor progression or death compared with chemotherapy in patients with pretreated KRAS G12C-mutated non-small cell lung cancer (NSCLC), the company said Thursday. The KRAS inhibitor came to the New Jersey pharma as part of its recent acquisition of Mirati Therapeutics.
The assessment was made by a blinded central review committee of the pivotal phase 3 KRYSTAL-12 study, which serves as the confirmatory trial for Krazati’s accelerated approval as a second-line therapy. BMS said it’s finishing a full evaluation of the data and will share results with regulators.
Besides declaring that the trial met its primary endpoint of progression-free survival, the independent data reviewers noted that Krazati was better than chemo at shrinking tumors, which was one of the trial’s secondary endpoints. The improvements on both endpoints were statistically significant and clinically meaningful, according to BMS.
The trial remains ongoing to evaluate whether Krazati can extend patients’ lives. BMS didn’t specify which direction Krazati’s survival outcomes are trending right now. Progression-free survival has typically been an approval-worthy endpoint in second-line NSCLC, unless there’s a negative trend in overall survival.
As for Amgen, the California drugmaker recently applied for full approval of its first-to-market KRAS inhibitor, Lumakras, based on progression-free survival data from the phase 3 CodeBreaK 200 trial. The study would have served its purpose had it been done properly. But the FDA figured its results couldn’t be reliably interpreted, and a group of external advisers agreed.
The agency and its advisory committee experts voiced concerns about disproportionate patient dropout rates between the two trial arms in Lumakras’ CodeBreaK 200 study as well as a bias for investigators to be more likely to call tumor progression early for patients on chemo so that they could cross over to receive Lumakras.
Both problems were chalked up to the enthusiasm around Lumakras as the first FDA-approved KRAS inhibitor.
By comparison, Krazati’s KRYSTAL-12 requires confirmation from a blinded central review to determine tumor progression before crossover.
Despite the compromised trial results, the FDA has let Lumakras stay on the market while Amgen runs another confirmatory trial to be completed no later than February 2028. The recently launched phase 3 CodeBreaK 202 trial is comparing Lumakras against Merck’s Keytruda in their respective combinations with chemotherapy for patients with newly diagnosed, advanced, PD-L1-negative, KRAS G12C-positive nonsquamous NSCLC.
Lumakras’ setback gives Krazati an opportunity to catch up. Before the BMS buyout, Krazati in the third quarter posted $16.4 million in sales, coming in below analysts’ expectations. Lumakras generated $52 million sales during the same period.
BMS’ Krazati also appears to hold more potential in the first-line setting. While Amgen was forced to combine Lumakras with chemo alone, a better liver toxicity profile has allowed BMS to pair Krazati with drugs in the PD-1 inhibitor class. A phase 3 trial is testing the Krazati-Keytruda combo in first-line KRAS G12C-mutated PD-L1-high NSCLC. And the company expects phase 2 results this year to guide its development path in PD-L1-low disease.
Both BMS and Amgen are also gunning for approvals in colorectal cancer, which is a smaller market than NSCLC. Amgen recently reported that Lumakras, at its currently approved 960-mg dose and used in combination with Vectibix, extended the median progression-free survival to 5.6 months versus 2.2 months for standard treatments in patients with chemo-refractory KRAS G12C colorectal cancer. The result came from the phase 3 CodeBreaK 300 trial.
A regulatory submission based on the study was planned in the first half of 2024, Amgen said during its fourth-quarter report. The company recently also launched a phase 3 trial for Lumakras in combination with Vectibix and chemo in first-line colorectal cancer.
For its part, BMS has the phase 3 KRYSTAL-10 study for Krazati and Eli Lilly’s Erbitux in second-line colorectal cancer, with a readout expected this year.
Themis Bioscience, a Vienna, Austria-based biotechnology start-up developing vaccines to prevent infectious diseases, has completed a €5m Series A financing round.
The round was co-led by Ventech and Crédit Agricole Private Equity.
The company intends to use the funds to advance the pre-‐clinical and clinical development activities for its lead product candidates, a Dengue and a Chikungunya Fever vaccine, which are both based on a novel vaccine vector technology (Themaxyn™) that was initially developed at the Institut Pasteur in Paris.
Founded in 2009 and led by CEO Erich Tauber, Themis Bioscience received seed financing by the academic business incubator INiTS, the austria wirtschaftsservice (aws) and The Austrian Research Promotion Agency (FFG).
VIENNA, Austria I March 02, 2015 I Themis Bioscience (‘Themis’), a biotechnology company developing innovative prophylactic vaccines for emerging tropical infections, and the Institut Pasteur, an international biomedical research center based in Paris (France) today announced the publication of the phase I study results for a recombinant measles-virus-based chikungunya vaccine (MV-CHIK) in The Lancet Infectious Diseases. The study was performed in collaboration with the Department of Clinical Pharmacology at the Medical University of Vienna and the Viral Diseases Branch of the Walter Reed Army Institute of Research (WRAIR) in the USA.
The peer-reviewed article is entitled “Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial“.
Chikungunya fever is a mosquito-borne viral disease causing symptoms including fever, headache, joint and muscle pain and bleeding of the nose and gums. Importantly, a large number of infected patients suffer from chronic sequela months and years after the acute infection. The chikungunya virus originated in Asia and western and central Africa and rising levels of travel and global warming led to increasing incidences of the disease in temperate zones, thus becoming a global health threat. Since late 2013, more than one million cases have been reported in the Americas and the Caribbean alone, resulting in a significant public health and economic burden.
Themis’ recombinant measles-chikungunya vaccine phase I study was conducted between November 2013 and June 2014 with a total of 42 healthy male and female individuals from age 18-45 being randomised into 4 cohorts for this dose escalation study. Subjects were administered one injection with either a low, medium or high dose of the chikungunya vaccine or the active comparator Priorix (standard measles vaccine). The study investigated the immunogenicity, safety and tolerability of the vaccine. In addition, randomized participants received a booster injection on either day 28 or day 90 after the first vaccination.
The candidate vaccine raised concentrations of neutralising antibodies to chikungunya in all dose cohorts after one immunisation, with seroconversion* rates of participants producing anti-chikungunya antibodies of 44% in the low, 92% in the medium, and 90% in the high-dose group. The immunogenicity of the candidate vaccine was not affected by pre-existing anti-measles immunity. The second vaccination resulted in a 100% seroconversion for all participants in the candidate vaccine groups. The candidate vaccine had an overall good safety profile, and while the rate of adverse events increased with vaccine dose and volume, no vaccination-related serious adverse events were recorded.
Dr. Frederic Tangy, head of the Viral Genomics and Vaccination Unit at the Institut Pasteur (Institut Pasteur, CNRS UMR-3569), who developed this vaccine technology, explained: “The measles vaccine has already proven its high efficacy and safety on more than a billion vaccinated individuals during the last 30-40 years. Therefore, this platform offers an excellent safety profile and the clear advantage of a validated and easy manufacturing process. The present result demonstrates that a measles vector can be used in the presence of pre-existing immunity to measles, likely because it is a replicating vector. This gives another great advantage to this vaccine strategy.”
“Recent outbreaks have raised awareness of chikungunya virus worldwide and whilst further work is needed to show safety, tolerability, and ability of the vaccine to protect against live chikungunya virus, our trial data suggest that this novel vaccine is an excellent candidate to help address this urgent medical need”, explains Dr. Erich Tauber, CEO of Themis. “With these promising results we are advancing the chikungunya vaccine programme and aim to move rapidly into phase II studies.”
* seroconversion rate: percentage of participants/patients that produce antibodies
About Themis:
Themis Bioscience GmbH develops prophylactic vaccines with a focus on emerging tropical infectious diseases and has initial vaccine candidates currently in development for chikungunya and dengue fever. The company has exclusive, worldwide licenses for chikungunya- and dengue vaccines, based on the innovative and fully patent-protected measles virus vaccine vector platform from the Institut Pasteur in Paris. This platform underpins Themis’ growing pipeline of vaccines. Themis and Institut Pasteur are actively collaborating on additional targets. Themis was founded by experienced vaccine experts in September 2009 and is based in Vienna. For more information, visit the website: http://www.themisbio.com
Themis Bioscience (‘Themis’), a biotechnology company developing innovative prophylactic vaccines for emerging tropical infections, announced today the first closing of EUR 7 Million in a Series B financing of up to EUR 10 Million, led by new investor Wellington Partners. Existing investors Ventech and Omnes Capital (formerly Crédit Agricole Private Equity) also participated in the round. Dr Regina Hodits, General Partner at Wellington Partners will join Themis’ Board.
With their Chikungunya fever vaccine candidate demonstrating good immunogenicity, safety and tolerability in a Phase 1 clinical trial (Results published in The Lancet Infectious Diseases, March 2015), Themis plans to progress this lead product candidate into clinical phase II trials. In parallel the company will advance its other promising development pipeline in collaboration with the Institut Pasteur in Paris, originators of the measles vector platform licensed to Themis.
Themis also announced the new structure of its Board with Dr Gerd Zettlmeissl being named Chairman of the Board. Dr Zettlmeissl spent more than 20 years in executive positions in the international pharmaceutical and vaccine biotech industry. From 2005 until May 2011 he served as CEO of Intercell AG. Experienced biotech and vaccine industry expert Dr Jean-Paul Prieels will join as a new member the expanded board. He served as Senior Vice President of R&D at GlaxoSmithKline Biologicals until January 2011, led GSK’s global vaccine R&D development activities and was Head of Research for GSK Vaccines.
Dr Erich Tauber, CEO of Themis stated: “With the new funds, we are planning to move our Chikungunya vaccine candidate quickly into a Phase 2 clinical trial and also achieve important milestones for the other vaccine candidates in our preclinical development pipeline. We are very pleased to have Wellington Partners leading this financing round and I would like to welcome Dr Regina Hodits and Dr Jean-Paul Prieels to the Board. I am sure that Themis will profit from their scientific and industrial expertise in supporting our goals to establish new partnerships within the pharmaceutical industry and to drive our product pipeline towards commercialisation.”
Dr Regina Hodits, General Partner at Wellington Partners, commented: “With global warming and increased travel activities, tropical diseases like Chikungunya, Dengue fever, and other viral diseases are becoming a serious threat to global health. Based on a proven measles vaccine platform, Themis’ portfolio of vaccine candidates represent an attractive investment opportunity for Wellington, and they have the potential to address urgent unmet medical needs.”
In 2011, Themis raised EUR 5 Million in a series A financing following a seed financing round from Austria Wirtschaftsservice (AWS) in 2009, and other substantial financial contributions from Austrian national funding agencies like FFG and Inits.
About a year after a €10 million series B, Austrian vaccine company Themis has secured a series C in the same amount led by new investor Global Health Investment Fund (GHIF).
The money will again be used to advance a chikungunya vaccine, which is being tested in three phase 2 trials in central Europe, Puerto Rico and U.S. mainland, a Zika candidate that entered human testing last April, as well as other preclinical assets against RSV and norovirus. These vaccines are based on Themis’ proprietary Themaxyn platform developed at Institut Pasteur, which uses a measles vaccine as a vector to carry antigen-encoding genes.
Themis recently reported positive interim results from the European trial on its chikungunya vaccine, the most advanced program in its pipeline. The vaccine induced neutralizing antibodies in all treatment groups 56 days after first immunization, and the seroconversion rate reached 95% after two doses.
The European trial will have final readouts midyear, but CEO Erich Tauber, Ph.D., told FierceVaccines that the U.S. and Puerto Rico trials were delayed by hurricanes Harvey and Maria. The program also received £3 million worth of funding from the U.K.’s National Institute for Biological Standards and Control to develop a monkey challenge model and to conduct a small phase 1 in the country.
New investor GHIF led the round because it sees “tremendous potential in Themis’ technology platform” and is “impressed with Themis’ ability to navigate complex clinical, regulatory and manufacturing issues,” commented GHIF partner Glenn Rockman, who has joined Themis’ board.
While at J.P. Morgan’s investment banking division, Rockman worked with the Bill & Melinda Gates Foundation to build GHIF. The fund is focused on late-stage projects in drugs, vaccines and diagnostics for diseases that burden low-income populations. It has supported projects in malaria, tuberculosis, HIV/AIDS, cholera and preventable causes of maternal and infant mortality.
No vaccine is available for either chikungunya or Zika, both mosquito-borne viruses. In chikungunya, Themis is notably vying against PaxVax, which in-licensed its candidate from the NIH, and India’s Bharat Biotech and secretive Moderna are working on their phase 1 programs. More candidates are competing in Zika, including one from Inovio, a U.S. Army-developed shot Sanofi recently walked away from, and one from a Valneva-Emergent BioSolutions partnership, among others.
The Coalition for Epidemic Preparedness Innovations (CEPI), the high-profile public-private vaccine initiative launched in 2017, has signed its first company agreement, granting Themis an investment of up to $37.5 million to develop new vaccines against Lassa fever and MERS.
The grant spans a five-year period and will support Themis through phase 2 testing, providing safety and immunological data plus the manufacturing of investigational supplies for efficacy trials or emergency deployment during outbreaks.
Discoveries made by Institut Pasteur and the Paul Ehrlich Institut are set to become the basis for Themis’ Lassa and MERS candidates, respectively. Those two research institutions have identified antigens for inclusion in vaccine compositions and have demonstrated proof of concept in animal studies, Themis CEO Erich Tauber told FierceVaccines.
Themis will apply its measles vector platform—which it exclusively licensed from Institut Pasteur—to design the vaccines. The platform has been used in the company’s lead program for Chikungunya, which is in phase 2 trials in 600 patients in the U.S. and Europe. Its Zika candidate also uses the platform and has entered human testing, while other assets against norovirus, RSV and CMV are in preclinical stages.
“The fact that Themis has developed a versatile technology platform for the discovery, development and production of vaccine approaches is very attractive,” CEPI spokeswoman Rachel Grant told FierceVaccines. “This means as well as focusing on MERS and Lassa we hope this technology will have value beyond those specific diseases. ”
No additional financial details were disclosed, but given CEPI’s founding principle of equitable access, Grant said the agreement contains provisions that support providing vaccines at affordable costs to people in need.
CEPI focuses on epidemic vaccine development, especially where there’s unfavorable market incentives but potentially big public health benefits. The idea is to fund promising vaccine candidates so that they’re available immediately when an outbreak begins.
Officially launched in 2017 by governments and nonprofits such as the Bill & Melinda Gates Foundation and Wellcome Trust, the group has also attracted major vaccine makers including GlaxoSmithKline, Merck, Johnson & Johnson, Pfizer, Sanofi and Takeda. It has so far collected $630 million of its $1 billion target funding. The European Commission has also promised a contribution of €250 million that will support relevant projects through its own mechanisms.
To start, CEPI selected Lassa, MERS and Nipah as initial diseases to target, none of which have approved vaccines. The coalition actually aims to develop two promising vaccine candidates against each of these diseases, and Grant said CEPI is going through intensive technical and legal due diligence with a number of companies to finalize additional agreements over the coming months.
For a second project that will identify platforms for rapid vaccine development against unknown pathogens, Grant said a call for proposal has received 35 high-caliber applications. They’re currently being shortlisted through an external peer review process, and CEPI’s scientific advisory committee will reach a conclusion by the end of June.
The grant comes as Nigeria suffers an unprecedented Lassa fever outbreak. The overall fatality rate is 1%, but for this year, it has reached 22% among confirmed and probable cases in the current Nigerian outbreak, the WHO reported.
MERS, first identified in 2012, causes severe respiratory illness, and it resulted in 186 cases and 36 deaths during an outbreak in South Korea in 2015.
A partnership between Inovio and South Korea’s GeneOne, with help from the Walter Reed Army Institute of Research, currently has the most advanced MERS vaccine program in phase 1 testing.
As for Lassa, according to a comprehensive summary by CEPI, no vaccine has progressed out of preclinical stages. Inovio, for one, is working on a candidate with the U.S. Army Medical Research Institute for Infectious Diseases.
Under Themis’ second partnering agreement with the Coalition for Epidemic Preparedness Innovations (CEPI), the Vienna-based company is eglible to receive up to $21m to push Phase III testing of its Chikungunya vaccine candidate, MV-CHIK. CEPI’s Chikungunya-vaccine development mandate was launched in 2019 with support from the European Commission’s Horizon 2020 programme.
In Phase II trails, Themis’ live-attenuated, measles-vectored chikungunya vaccine (MV-CHIK), which has FDA fast track and EMA PRIME status, showed good safety and tolerability as well as immunogenicity. Themis announced that the non-dilutive funding will provide a significant portion of the capital required for Themis’ Phase III clinical trial of MV-CHIK expected to start this year. The pivotal multi-center Phase III trial will be launched in Europe, US and the Americas and will also test a single-shot regimen.
The World Health Organization (WHO) has highlighted Chikungunya, which causes arthritis-like symptoms, as a major public health risk. The disease was first identified in Tanzania in 1952, with sporadic outbreaks of the disease reported subsequently across Africa and Asia.In 2004 the disease began to spread quickly, causing large-scale outbreaks around the world. Climate change is set to further amplify the threat posed by Chikungunya. As the climate warms, more areas across the world will become habitable for the mosquito vectors that transmit the virus, thereby increasing the size of the human population at risk of infection. In 2007, for example, an outbreak of Chikungunya virus infections was declared for the first time in Europe, with more than 200 human cases reported in Italy.
Since the re-emergence of the virus, the total number of cases has been estimated at over 3.4 million in 43 countries.Chikungunya is spread by the bites of infected female Aedes mosquitoes and causes fever, severe joint pain, muscle pain, headache, nausea, fatigue and rash. Joint pain is often debilitating and can persist for weeks to years.
Themis’ first partnership with CEPI, announced in March 2018, provided up to $37m in funding to support vaccine development and manufacturing for Lassa fever and MERS.
Merck & Co. will partner with Themis Bioscience to develop vaccine candidates based on Themis’ measles virus vector-based platform, through the Austrian biotech’s first-ever collaboration with a major biopharma.
Themis says the platform, which it licenses from the Institut Pasteur in Paris, can incorporate large recombinant genes coding for selected antigens into its genome. Vaccines developed through the platform are designed to deliver multiple selected antigens—such as full-length proteins or virus-like particles—directly to macrophages and dendritic cells, thus triggering a specific immune response to the selected antigens.
The companies have committed to developing vaccine candidates against an undisclosed disease target. Speaking with GEN, Themis CEO Erich Tauber, MD, would not disclose what indications the companies are focusing on.
“What I can say is the measles virus vector technology allows to exploit infectious diseases and cancer indications, and when it comes to infectious diseases, we use the measles virus to bring our specific antigens into the body. Those might be difficult to express in normal cell systems,” Tauber said.
“Another advantage is we can use exactly the same manufacturing process for each new vaccine target. And when it comes to cancer, the measles virus itself has strong oncolytic activity,” Tauber said, such as mediating tumor cell lysis, T cell activation, and specific tumor cell targeting. “The measles virus can kill cancer cells. And we enhance this activity by putting in specific therapy enhancing proteins like immune modulators.”
Merck has agreed to make an unspecified equity investment in Vienna-based Themis under the companies’ collaboration and exclusive license agreement, which Themis said could generate for it more than $200 million.
In addition to the equity investment, Merck agreed to provide Themis an unspecified amount of research funding, as well as up to approximately $200 million in payments tied to achieving development and sales milestones, plus royalties on approved products from the collaboration.
“We continue to evaluate technologies with the potential to deliver novel vaccine candidates,” Daria Hazuda, PhD, CSO, Exploratory Science Center and vp of infectious diseases and vaccine discovery at Merck, said in a statement. “We look forward to collaborating with the scientists at Themis.”
Surging vaccines sales
Merck credits human vaccines, along with cancer treatments led by the blockbuster immunotherapy Keytruda® (pembrolizumab), with its most recent positive quarterly results.
During the second quarter, Merck said, overall company sales rose 12% year-over-year to $11.760 billion—or 15% excluding the effect of foreign exchange rates. The biopharma giant finished Q2 with $2.670 in GAAP net income, up 56% from $1.707 billion in the second quarter of 2018.
However, human health vaccines sales zoomed 33% year-over-year, to $2.0 billion, or 36% when excluding currency impacts. Two vaccines led Merck’s sales surge: PROQUAD (Measles, Mumps, Rubella and Varicella Virus Vaccine Live) and VARIVAX (Varicella Virus Vaccine Live), a vaccine to help prevent chickenpox, saw their combined sales jump 58% in Q2, to $675 million from $426 million in the year-ago quarter. Merck cited higher demand, including from private-sector buyers, and U.S. pricing, as well as government tenders in Latin America and higher demand in Europe.
Merck also reported a 46% quarterly sales jump (50% excluding currency impacts)—to $886 million from $608 million in Q2 2018—for the tandem of GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] and GARDASIL 9, vaccines indicated to treat some cancers and other diseases caused by HPV. Merck cited primarily public sector buying patterns, U.S. demand and pricing, and the ongoing commercial launch in China, as well as higher demand in Europe, driven primarily by increased vaccination rates for both boys and girls.
Expanding pipeline range
Merck’s collaboration with Themis is likely to expand the range of indications for vaccine candidates in the pipeline of Themis, which has focused most in developing vaccines against infectious diseases, but also has several preclinical immuno-oncology programs.
In October 2018, Themis signed an exclusive worldwide license agreement of undisclosed value with Max-Planck-Innovation GmbH, the technology transfer agency of the Max Planck Society, to develop, manufacture, and commercialize therapies based on an oncolytic measles virus platform jointly developed by the Eberhard-Karls-University Tübingen and the Max Planck Institute for Biochemistry.
Themis’ most advanced pipeline program is an unpartnered chikungunya vaccine candidate MV-CHIK, which Tauber said remains on track for a Phase III trial set to begin later this year. The pivotal multi-center trial will test a single-shot regimen, with patients to be dosed at centers in Europe, the U.S., and the Americas.
In June, Themis was awarded up to $21 million in non-dilutive capital toward development of the chikungunya vaccine by the Coalition for Epidemic Preparedness Innovations (CEPI), part of CEPI’s third call for proposals with support from the European Union’s (EU’s) Horizon 2020 research funding program under grant agreement No. 857934. The award is intended to accelerate regulatory approval of the chikungunya vaccine and ensure that at-risk populations have access to the vaccine by funding a “significant” portion of the capital needed for the Phase III trial, Themis said at the time.
Themis once planned to fund the Phase III trial through an up-to-€55.3 million ($61.3 million) initial public offering on Euronext Amsterdam, but postponed the IPO in November 2018, citing adverse market conditions.
The chikungunya candidate is also under study in a Phase II trial (NCT03807843) designed to assess the vaccine’s safety and immunogenicity in adults with a history of chikungunya infection; and another Phase II trial (NCT03635086) designed to investigate the immunogenicity, safety, and tolerability of MV-CHIK as well as the long-term durability of anti-chikungunya antibody response after administration of different dose levels of the vaccine in three different formulations.
Last year, CEPI awarded Themis up to $37.5 million toward developing vaccines for Lassa fever and Middle East respiratory syndrome (MERS).
Merck has struck a deal to buy Themis to accelerate the development of a COVID-19 vaccine. The takeover will see Merck, a latecomer to the response to SARS-CoV-2, apply its vaccine capabilities to a candidate based on Themis’ measles vector platform that is set to enter the clinic this year.
Themis is developing a pipeline of vaccines based on a measles virus vector platform it licensed from Institut Pasteur. By engineering the virus to express different antigens, Themis aims to use the same vector and manufacturing system to develop vaccines that induce protection against a wide range of infectious diseases, including COVID-19.
“Together with Institut Pasteur, we have worked on very closely related viruses like SARS and MERS [and] demonstrated the platform is very useful in eliciting an immune response,” Themis CEO Erich Tauber said. “We started [SARS-CoV-2] vector design in February. We have started in vivo models … and are now preparing for clinical trials.”
Merck is now set to apply its vaccine capabilities to the program. The Big Pharma has a major human vaccine operation, which generated sales of $8.4 billion last year, but it stayed on the sidelines in the early days of the pandemic as peers such as AstraZeneca, Pfizer and Sanofi placed bets on COVID-19 vaccine candidates.
News of a change in strategy came late in April when Merck said it was talking to “multiple groups” about three viral vector platforms. The talks manifested in an agreement to buy Themis, a privately owned Austrian biotech, for an undisclosed sum. In selecting Themis as a key plank of its COVID-19 strategy, Merck has indicated it thinks the biotech’s vaccine can clear a high bar.
“The task before us is one that requires a vaccine that will be quite stimulatory and that will yield neutralizing antibodies ideally with a single immunization. Of course, it must first be safe because you’re talking about a vaccine that would in principle be given to much of the world’s population,” Roger Perlmutter, president of Merck Research Laboratories, told investors last month.
Themis, as part of a consortium featuring Institut Pasteur, partnered with the Coalition for Epidemic Preparedness Innovations (CEPI) to develop a COVID-19 vaccine in mid-March. Earlier this month, Themis disclosed a deal with service provider ABL Europe covering the production of the vaccine in France.
Merck, which plans to start testing the vaccine in humans this year, has previously said it is trying to identify internal resources and contract manufacturers that can enable it to produce 1 billion doses of a COVID-19 vaccine and plans to make Themis’ shot at sites in the U.S. and Europe. The ability of Merck to bring such scale to bear factored into Themis’ decision to sell up.
“The limiting step for everybody will be manufacturability and manufacturing capacity. Merck brings an enormous skill level, expertise and capacity in terms of manufacturing technology. They’re using very similar technology already. They have been manufacturing measles vaccines for 60 years or so,” Tauber said.
Merck bought into the concept behind Themis’ platform last summer when it tasked the biotech with developing vaccines against an undisclosed target and invested in its series C round. Now, Merck has decided to acquire its partner outright.
The takeover will give Merck ownership of the platform, which Themis thinks has immuno-oncology applications, and a pipeline led by a phase 3-ready chikungunya vaccine candidate. Merck also sees the acquisition as a way to “ build a pandemic preparedness capability” against future threats.
For now though, COVID-19 is the focus. Merck and CEPI have entered into a memorandum of understanding about the need to make the vaccine “accessible to those who need it, including low-income, middle-income and high-income countries, based on the medical need.” Tauber raised Merck’s approach to vaccine access in explaining why it is the right partner, citing the Big Pharma’s work on Ebola as evidence that it is “very enthusiastic about global supply of vaccines.”
After Merck & Co. got off to a late start in the COVID-19 vaccine race and made an early exit, the drug giant is in talks to aid the global vaccine manufacturing effort.
The drugmaker is “actively involved” in discussions with governments, health agencies and other pharmaceutical companies to “identify the areas of pandemic response where we can play a role, including potential support for production of authorized vaccines,” a spokesman said via email.
News of the talks comes about two weeks after Merck abandoned both its coronavirus vaccine candidates—one it acquired through its Themis buyout and the other it was studying in partnership with IAVI. Merck said the two shots had produced immune responses weaker than those prompted by natural infections as well as by other COVID-19 vaccines.
Still, the company believes it has an “important responsibility to contribute to the pandemic response,” the spokesman said, and remains “at the ready to do so.”
While Merck hasn’t indicated which companies it could help with production, there has been industry talk about a potential tie-up with Novavax. After the vaccine biotech last month presented positive phase 3 data on its candidate, Evercore ISI analyst Josh Schimmer said he suspected Merck might “step up” as Novavax’s manufacturing partner.
Novavax CEO Stan Erck then told CNBC’s Meg Tirrell that Merck “could be a good partner for us as they don’t have a competing product.” He also named GSK as a company with those capabilities. At the time, Merck told Tirrell it was focused on therapeutics.
Meanwhile, Merck has two coronavirus therapeutics in development—MK-4482 and MK-7710—and the company believes it can make a “meaningful contribution” to the fight against the pandemic by focusing its resources on those candidates, its spokesman said.
Last summer, as COVID-19 vaccine programs raced forward, Merck CEO Ken Frazier said the hype about vaccines launching in late 2020 was doing a “grave disservice” to the pandemic fight. Vaccines previously took years to develop, he pointed out, and Merck itself was responsible for many of them.
He wasn’t alone. Merck and other major vaccine players were taking a slower, time-tested approach, experts said, but their vaccines could end up reaching more people worldwide than more revolutionary shots would. Things didn’t turn out that way. Pfizer, Moderna, AstraZeneca and other programs are now either rolling out or nearing rollouts, while several leading vaccine giants have either exited the field or faced R&D setbacks.
If Merck does strike a manufacturing deal with a COVID-19 vaccine player, it won’t be the first company to do so. After an R&D setback on its GSK-partnered vaccine, Sanofi last month said it would produce 100 million doses of the Pfizer-BioNTech mRNA vaccine for Europe.
The Pfizer-BioNTech team has also enlisted Swiss drugmaker Novartis in its global push to produce billions of doses. In a deal unveiled in late January, Novartis said it would allow BioNTech access to its site in Stein, Switzerland. Manufacturing there will start next quarter, and doses will be ready from the site by the third quarter.
Also this week, Teva said it was in talks to help with COVID-19 vaccine production. The company has sites in Israel, Europe and the U.S. that could be used in the global effort, CEO Kåre Schultz said, according to The Wall Street Journal.
(Picture: Rudolf Jaenisch & Richard A. Young, Whitehead Institute)
안녕하세요 보스턴 임박사입니다.
Omega Therapeutics는 2015년에 Whitehead Institute의 Rudolf Jaenisch 교수와 Richard A. Young 교수에 의해 Cell Stem Cell에 발표한 Insulated Genomic Domains (IGDs)를 이용해서 Epigenomic Programming을 할 수 있다는 아이디어로 2017년에 Flagship Pioneering의 David Barry 박사에 의해 설립되었습니다.
CAMBRIDGE, Mass. (December 10, 2015) –Whitehead Institute researchers have created a map of the DNA loops that comprise the three dimensional (3D) structure of the human genome and regulate gene expression in human embryonic stem (ES) cells and adult cells. The location of genes and regulatory elements within this chromosomal framework could help scientists better navigate their genomic research, establishing relationships between mutations and disease development.
“This is transformational,” says Whitehead Member Richard Young. “This map allows us to predict how genes are regulated in normal cells, and how they are misregulated in disease, with far greater accuracy than before.”
In order to regulate gene expression, a regulatory element needs to contact its target gene. Through looping, element/gene partners that are distant from each other in linear DNA can be brought together. Most disease mutations occur in regulatory elements, but if the partnership between a seemingly far-flung gene and the regulatory element is not known, the mutation data is of limited use. This draft map, which can help scientists predict the relationships between mutated elements and their target genes, is described online this week in the journal Cell Stem Cell.
“When thinking about disease, we need to think about the structure of the genome in 3D space because that is how we now understand that genes are regulated,” says Xiong Ji, a postdoctoral researcher in the Young lab and a co-author of the Cell Stem Cell paper.
One of Ji’s co-authors, graduate student Daniel Dadon, agrees. “This three-dimensional information helps us to interpret regulatory and mutational data with unprecedented accuracy. It’s not just a bag of genes and regulatory elements in the nucleus—this is a highly organized structure that confers function.”
Previous research in mouse ES cells by Young’s lab and others determined that a chromosome’s DNA is formed into loops that are anchored at their bases by proteins called CTCFs. The benefits of the loops are two-fold. First, the loops help organize and package two meters of DNA to fit into a nucleus that is approximately 5 micrometers in diameter. Second, each loop creates an insulated neighborhood that restricts the action of a regulatory element to genes that resides in the same loop. As graduate student and co-author Diego Borges-Rivera states, “The genome’s 3D shape is a key mechanism underlying gene regulation.”
By studying human ES cells, scientists in the Young lab and the lab of Whitehead Founding Member Rudolf Jaenisch created an initial genome map consisting of 13,000 loops established by CTCF anchors and determined that the average insulated neighborhood is 200 kb in length and contains a single gene. The team found that most of the the mapped CTCF anchor sites in the human ES cells genome are maintained in other human cell types and furthermore, that these loop anchor sequences are highly conserved in primate genomes. Such a surprising degree of conservation indicates that these neighborhoods create a foundational framework for gene regulation that is maintained throughout development and across species.
In a further finding that underscores the importance of the genome’s 3D structure in human health, the Whitehead team found that the CTCF anchor regions are mutated in a broad spectrum of cancer cells. The team predicts that these new maps of the human genome will provide the foundation for improved understanding of the genetic alterations that cause many additional diseases.
This work was supported by the National Institutes of Health (NIH grants HG002668 and HD 045022), National Cancer Institute (NCI), the Erwin Schroedinger Fellowship (J3490) from the Austrian Science Fund, and the Simons Foundation (SFLIFE 286977). Jaenisch is a founder of Fate Therapeutics and Young is a founder of Syros Pharmaceuticals.
2017년 7월부터 2019년 6월까지 우선주 투자방식으로 $28 Million Series A를 받았습니다.
Series A Preferred Stock Financing. From August 2017 to June 2019, we issued and sold to investors in private placements an aggregate of 56,775,232 shares of our Series A preferred stock at a purchase price of $0.50 per share, for aggregate consideration of approximately $28.4 million.
그리고 2019년 9월에 처음으로 회사의 존재를 세상에 알렸습니다. 2년여의 Stealth mode를 거친 후 발표를 한 것이죠. 이 당시에는 모든 프로그램이 전임상 단계였습니다.
Flagship Pioneering launched Omega Therapeutics, a company aiming to take genomic medicine “to the next level.” Founded on the work of two MIT professors, the company is working on treatments that adjust gene expression up or down without making permanent changes to the genome.
Richard Young, Ph.D., and Rudolf Jaenisch, M.D., first described how 3D closed loops of DNA control genomic activity in 2015. Long strands of DNA make these loops because they have to fit into the cell’s nucleus—the loops help “organize and package two meters of DNA” to fit into a space that is about 5 micrometers, or five millionths of a meter, across, the researchers said in a statement at the time. Each loop is an “insulated neighborhood” of one or more genes and their regulatory elements.
Omega is targeting these neighborhoods, called Insulated Genomic Domains (IGDs), with a platform that could be applied to a variety of ailments.
“If you think about it, other than some viral and other infections, pretty much all human disease is due to the dysregulation of genomic expression,” Omega CEO Mahesh Karande, a Novartis alum and former CEO of Macrolide, told FierceBiotech. “Disease mostly occurs because of dysregulation of the genome, by genes not being expressed at the right level. They’re over- or under-expressed. We are able to tune that expression to the native level it’s supposed to be at.”
The Cambridge, Massachusetts-based biotech is mapping IGDs to different diseases and figuring out which of these neighborhoods plays a role in different diseases. From there, it will create treatments it calls Omega Controllers that adjust gene expression to healthy levels.
This adjustment happens without making permanent changes to the genome by switching genes on or off, cutting disease-causing genes out or putting in a healthy version of a faulty gene.
“In nature, generally things are not all the way on or all the way off, but rather turned to a very specific range in a healthy setting,” said Omega Chief Scientific Officer Thomas McCauley, Ph.D., the former CSO of Macrolide and Translate Bio. “Our Omega Controllers are able to target IGDs using the map that Mahesh mentioned and target the right place on that IGD to restore gene function at the right level.”
Because the approach could work for so many disease areas, Omega plans to ink some partnerships as well as work on its own pipeline, said David Berry, M.D., Ph.D., a general partner at Flagship, in a statement. Omega’s treatments could be used to boost the efficacy of in vivo and ex vivo therapies, he said.
In the in vivo space, checkpoint inhibitors are a potential candidate.
“Many of them are not as effective as you’d like them to be. Sometimes immuno-oncology agents act only on 30% of the patient population,” Karande said.
Omega could identify specific genes in patients that affect how they respond to these treatments. For example, if a gene is expressed in patients who don’t respond to a certain immuno-oncology drug, Omega might knock down the expression of that gene to make that drug more effective. On the ex vivo side, Karande envisions Omega’s technology being used when cell therapies are being engineered outside the body.
이듬해인 2020년에 $85 Million Series B를 하면서 임상진입을 시도한다고 발표를 했습니다.
Less than a year after launch, Omega Therapeutics is getting an $85 million cash boost. It will push a pipeline of treatments toward the clinic as well as bankroll the identification of new targets for genomic medicines.
“We had founded Omega with a long-term vision to create a controllable epigenomic programming platform,” Omega CEO Mahesh Karande told Fierce Biotech. Rather than switching genes on and off, cutting out disease-causing genes or replacing them with healthy versions, Omega’s platform is designed to adjust gene expression to healthy levels.
The company’s work is based on “neighborhoods” of genes and their regulatory elements found in loops of DNA called Insulated Genomic Domains (IGDs). These loops occur because long strands of DNA need to fit into the cell’s nucleus.
“In nature, generally things are not all the way on or all the way off, but rather turned to a very specific range in a healthy setting,” Omega Chief Scientific Officer Thomas McCauley, Ph.D., said in a previous interview. Omega’s “epigenomic controllers” are designed to target the right place on specific IGDs to restore gene function at the right level, he said.
Since launch, Omega has been working to figure out which neighborhoods play a role in different diseases.
“We could have gone in various directions,” Karande said. But Omega landed on a handful of areas. It’s advancing five programs spanning oncology and inflammation as well as autoimmune, metabolic and rare genetic diseases, the first of which should hit the clinic in 2021.
In addition to tweaking gene expression without making permanent changes to the genome, Omega’s approach offers advantages over a small-molecule approach to epigenetics.
“There are a number of companies developing small-molecule therapies for epigenetic targets, almost exclusively in cancer,” McCauley.
“The issue is really specificity, in having those molecules go everywhere in the body as opposed to having them go to specific cell types and specific locations in the genome,” McCauley continued, adding that the benefits of such treatments might outweigh the risks in oncology but that this risk-benefit profile may be unacceptable in other diseases.
In its first efforts, Omega is going after targets with links to specific diseases that are well understood, McCauley said. Moving forward, it will take advantage of the lessons it learns to look for new targets.
“We’re looking for the ability to expand laterally,” he added.
One of those lateral expansions could be into COVID-19. Since inflammation plays a big role in COVID-19 infection, Omega could leverage the work it’s already done in that space to quickly move into drug development against the new coronavirus.
Right now, it’s all systems go with its five—potentially six—programs. Karande said the company would be “remiss” if it did not ink partnerships.
“We are absolutely open to partnering with people. We have a robust discovery platform that has many, many more targets in the pipeline, so yes, partnering is definitely in the cards for us,” he said.
그리고 2021년에는 $126 Million 펀딩을 통해서 OTX-2002 (HCC) 약물의 임상진입과 다른 전임상 약물의 개발을 발표했습니다.
Omega Therapeutics is taking it up a notch. The “genome-tuning” biotech raised $126 million to get its lead program, a treatment for liver cancer, into the clinic as well as to advance a clutch of other preclinical prospects including a treatment for acute respiratory distress syndrome (ARDS), a life-threatening lung injury that can result from COVID-19 infection.
The company is working on a new class of treatments called “epigenomic controllers,” which are designed to adjust the expression of target genes. Unlike gene therapies and gene editing approaches that switch genes on and off, cut out disease-causing genes or replace faulty genes with their healthy versions, Omega’s treatments tune gene expression up or down without making permanent changes to DNA.
Its work is based on “neighborhoods” of genes and their regulatory elements found in loops of DNA called Insulated Genomic Domains (IGDs). These loops occur because long strands of DNA need to fit into the cell’s nucleus. Omega’s “epigenomic controllers” are designed to restore gene function to healthy levels by targeting the right place on specific IGDs.
The series C financing follows an $85 million B round in July 2020, which went toward identifying new targets and driving several programs across multiple disease areas through preclinical development.
“When we started, we needed to explore the depth of the platform—we didn’t want to pigeonhole ourselves,” said CEO Mahesh Karande. “That’s how we delineated eight programs at five different targets.”
Omega has started IND-enabling studies for its lead program, OTX-2002, an epigenetic controller programmed to control expression of c-myc, an elusive cancer-driving gene. It is developing the treatment for hepatocellular carcinoma, the most common form of liver cancer.
Unlike Gilead’s antiviral Veklury (remdesivir) and anti-SARS-CoV-2 antibodies from Eli Lilly and Regeneron, Omega’s COVID-19 treatment focuses on ARDS, which is caused by an inflammatory response in the lungs.
“We treat diseases created by functional or structural changes in IGDs and ARDS creates a functional change in a multigenic IGD where cytokines get supercharged and expressed,” Karande said. With its epigenomic controller, Omega aims to reduce the expression of those cytokines.
The company hopes the treatment will fill a gap in COVID-19 treatment.
“The standard of care [for ARDS] is quite insubstantial and largely palliative, involving mechanical ventilation and where possible, steroids,” said Omega Chief Scientific Officer Thomas McCauley, Ph.D.
Besides liver cancer and ARDS linked to COVID-19, Omega is focusing on regenerative medicine, inflammatory diseases, alopecia, non-small cell lung cancer and a group of skin conditions called neutrophilic dermatoses.
The financing will also bankroll a manufacturing scale-up as well as the expansion of Omega’s technology. As it develops drug candidates, it will continue to improve its platform, “taking the guesswork out of it” and making sure it can keep generating new drugs in a reliable and replicable way, Karande said.
As it continues its quest toward the clinic, Omega will build up its workforce, particularly its clinical organization and manufacturing unit.
Omega Therapeutics, Inc. (Nasdaq: OMGA) (“Omega”), a development-stage biotechnology company leveraging its OMEGA Epigenomic Programming™ platform to harness the power of epigenetics to develop a new class of DNA-sequence-targeting, mRNA-encoded programmable epigenetic medicines, today announced the pricing of its initial public offering of 7,400,000 shares of its common stock at a price to the public of $17.00 per share. All of the shares of common stock are being offered by Omega. The gross proceeds from the offering, before deducting underwriting discounts and commissions and estimated offering expenses payable by Omega, are expected to be approximately $125.8 million, excluding any exercise of the underwriters’ option to purchase additional shares. Omega’s common stock is expected to begin trading on the Nasdaq Global Select Market under the ticker symbol “OMGA” on July 30, 2021. The offering is expected to close on August 3, 2021, subject to satisfaction of customary closing conditions. In addition, Omega has granted the underwriters a 30-day option to purchase up to an additional 1,110,000 shares of common stock at the initial public offering price less underwriting discounts and commissions.
Goldman Sachs & Co. LLC, Jefferies LLC and Piper Sandler are acting as joint book-running managers of the offering. Wedbush PacGrow is acting as lead manager.
2023년에 OTX-2002의 8명의 환자에 대한 Preliminary clinical trials 결과를 발표했는데 Genetic selectivity와 MYC 가 dose-range에 맞게 감소하는 것을 보고함으로써 플랫폼의 기술이 임상에서도 작용을 한다는 것을 일단 소규모 임상에서 증명을 했습니다.
The investigational mRNA therapeutic OTX-2002 demonstrated encouraging safety, tolerability, and pharmacokinetics in a small population of patients with hepatocellular carcinoma (HCC) and other solid tumors related to the c-MYC (MYC) oncogene, according to a press release on findings from the phase 1/2 MYCHELANGELO I trial (NCT05497453).1
Investigators reported highly specific on-target engagement and epigenetic changes among all 8 patients receiving 0.02 mg/kg (n = 4) or 0.05 mg/kg of OTX-2002 (n = 4) every 2 weeks. The agent’s modulation of MYC rapidly and durably downregulated MYC oncogene expression in all 8 patients; investigators highlighted a mean reduction of 55% at 7 days following treatment.
Treatment with OTX-2002 also produced consistent pharmacokinetic data at both dosing levels, as investigators observed little variability and quick clearance within patients. Additionally, there was no accumulation after additional doses of OTX-2002, and the agent produced low and transient levels of immune response with no adverse effects (AEs) impacting pharmacokinetics. Investigators reported that both initial dose levels of the agent demonstrated anti-tumor activity below the predicted threshold established by preclinical models.
OTX-2002 was well tolerated among patients, and investigators observed no dose-limiting toxicities. Patients mostly experienced grade 1 or 2 AEs, the most common of which included infusion-related reactions (26%) such as fever and chills. These toxicities appeared to be comparable with the known profiles of other FDA-approved agents administered via lipid nanoparticles.
“We are thrilled to see that all 8 patients evaluated at these initial low doses demonstrated clear evidence of on-target epigenetic changes and correlated rapid, robust and durable decreases in MYC mRNA expression levels,” Thomas McCauley, PhD, chief scientific officer at Omega Therapeutics, said in the press release. “These early clinical data are consistent with our preclinical experiments, giving us confidence that our approach has the potential to translate to anti-tumor activity and clinical benefit. Coupled with encouraging safety and predictable pharmacokinetics, we believe that OTX-2002 holds transformative potential for patients living with HCC.”
In the ongoing open-label MYCHELANGELO I trial, investigators are assessing the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of OTX-2002 on its own in part 1 and with standard-of-care treatments in part 2 among those with relapsed/refractory HCC and other solid tumor types associated with MYC oncogene expression. Investigators are conducting the trial at clinical sites in the United States and Asia. As of the data cutoff point of September 18, 2023, a single patient with HCC remained on treatment in the 0.05 mg/kg cohort.
The trial’s primary end points are dose-limiting toxicities, treatment-emergent AEs, overall response rate, and duration of response.
Patients 18 years and older with metastatic, advanced, or recurrent solid tumors that have progressed following standard-of-care therapy and intermediate or advanced stage, Child-Pugh A HCC not amenable to locoregional therapy or curative treatment approaches are able to enroll on the study. Having an ECOG performance status of 0 or 1 is another requirement for enrollment.
“We look forward to continuing to work with clinical investigators, patients, and the FDA as we advance our MYCHELANGELO clinical program and evaluate the potential of OTX-2002 to bring a new treatment option to the community [of patients with liver cancer],” Mahesh Karande, president and chief executive officer at Omega Therapeutics, said in a press release at the time of the orphan drug designation.2
References
Omega Therapeutics announces promising preliminary clinical data for OTX-2002 from ongoing MYCHELANGELO™ I trial. News release. Omega Therapeutics. September 26, 2023. Accessed September 26, 2023. https://shorturl.at/hmqNZ
Omega Therapeutics receives orphan drug designation for OTX-2002 for the treatment of hepatocellular carcinoma. News release. Omega Therapeutics. November 2, 2022. Accessed September 26, 2023. http://bit.ly/3fqiafd
금년 새해 첫날에 Flagship Pioneering과 Novo Nordisk의 계약에 의해서 Omega Therapeutics의 IGD Platform을 이용해서 Obesity 치료제를 개발하는 공동계약을 맺었고 계약 규모는 $532 Million입니다.
As part of a pact with Flagship Pioneering, Novo Nordisk has inked separate cardiometabolic disease research deals with two Flagship-founded biotechs that are worth up to $532 million each.
The freshly formed agreements are with Omega Therapeutics and Cellarity, two Massachusetts biotechs that fall under Flagship’s umbrella. The partnerships are part of a broader ecosystem collaboration Flagship and Novo Nordisk’s Bio Innovation Hub struck up in mid-2022 that aims to quickly build a portfolio of breakthrough medicines for cardiometabolic and rare diseases.
Using Novo’s disease expertise and technology from Flagship’s bioplatform companies, the goal is to generate three to five research programs within the first three years of the partnership, Novo Nordisk’s head of the Bio Innovation Hub Uli Stilz, Ph.D., told Fierce Biotech in an interview.
For these first two deals, each company, Novo Nordisk and Flagship’s Pioneering Medicines—an initiative that develops treatments by using and expanding Flagship innovations—will work together to advance their respective programs through preclinical development. Novo will then have the chance to take the programs into the clinic.
The Big Pharma will reimburse R&D costs and give each company and Pioneering Medicines the chance to make up to $532 million dollars in upfront and milestone payments, plus tiered royalties.
With Omega, Novo will look to expand upon its blockbuster obesity franchise (does the drug Ozempic ring a bell?) with the biotech’s platform, which is made to design programmable epigenomic mRNA medicines that precisely target and modulate gene expression at the pre-transcriptional level.
“We have been pioneers over a 20-year journey in obesity and we want to continue to be a pioneer,” Stilz said, adding that being a pioneer means entering uncharted scientific territory, which is where Omega comes in.
The biotech will use its platform technology to develop an epigenomic controller as part of a new obesity management approach. While many existing therapeutics for weight management focus on appetite regulation, Omega wants to target thermogenesis, a natural metabolic function that regulates overall energy balance.
“What is so exciting for us is that it’s a very different approach than what we have been doing so far,” Stilz said. “I haven’t seen something similar anywhere else. So, we’re really pushing the boundary of science and innovation through this co-creation and collaboration.”
Omega already has some proof-of-concept to support its mission to design programmable mRNA medicines by replicating how nature’s control system works, Omega President and CEO Mahesh Karande told Fierce Biotech. The company’s platform is applicable across almost every disease process, Karande said, and Omega is currently evaluating one of its assets in a phase 1/2 trial for patients with hepatocellular carcinoma.
Now, the company will put its platform to work to control metabolic activity and potentially develop a more durable approach to obesity management.
“Epigenomic control and epigenomic controllers have not existed before. We have literally created this field,” Karande said. “And now we have signed our first major agreement with a company that is an expert in obesity, metabolics and cardiovascular. So, for us, this is hugely validating.”
Meanwhile, Cellarity will plug away at creating a small molecule therapy to treat metabolic dysfunction-associated steatohepatitis (MASH)—the new term for nonalcoholic steatohepatitis (NASH)—a chronic and progressive liver disease for which there is no currently approved treatment. The indication has a high unmet patient need, with only four investigational treatments ever making it into phase 3 development for MASH, led by Madrigal Pharmaceutical’s resmetirom, which is awaiting an FDA decision this spring.
Cellarity and Novo hope to develop a small molecule therapy for the indication by using the biotech’s platform that is designed to provide new insight into cellular dysfunction and allow for drug creation that has been historically inaccessible using traditional drug discovery methods.
Cellarity combines biology, chemistry and AI machine learning to understand cell behavior, Novo’s Stilz explained. Novo Nordisk has previously connected with Cellarity, asking the biotech in September 2022 to identify novel cell behaviors involved in MASH disease progression, work that will now be expanded upon under the new research collaboration.
그리고 얼마전에 Omega Therapeutics는 현재 임상 중인 OTX-2002와 전임상 중인 몇개의 약물에 집중한다는 전략적 우선순위 결정을 하면서 35%의 인원 감축을 하는 구조조정안을 발표한 상황입니다. 일단 플랫폼의 초기 임상이 성공하는 것이 중요하기 때문에 올바른 결정을 한 것으로 보입니다. 좋은 결과가 있기를 바랍니다.
Omega Therapeutics, Inc. (Nasdaq: OMGA) (“Omega”), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, today announced financial results for the fourth quarter and full year ended December 31, 2023, and a strategic prioritization initiative to focus resources on near-term milestones to support long-term shareholder value.
“2023 was an important year for Omega where we executed to plan and demonstrated clinical validation of an epigenomic controller to regulate c-MYC in humans for the first time. These proof-of-platform clinical data, coupled with our research collaboration with Novo Nordisk in obesity, support the ability of the OMEGA platform to potentially address epigenomic regulation of almost all human genes across broad therapeutic areas including cancer, cardiometabolic conditions and liver regeneration,” said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. “Initial clinical data from our ongoing Phase 1/2 MYCHELANGELO I trial of OTX-2002 demonstrated controlled modulation of MYC expression levels, one of the most challenging gene targets in oncology, and an encouraging disease control rate and stable disease in heavily pre-treated, late-stage HCC patients. We are within what we believe is a clinically meaningful dose range and, as we continue to see a promising safety profile for OTX-2002, have recently opened enrollment of Cohort 5. We look forward to sharing additional updates from this program throughout 2024.”
“Today we also announced a strategic prioritization, implemented to ensure we have sufficient resources to advance our lead program and maximize near- and long-term value creation from our platform. As part of this initiative, we are taking difficult but necessary actions to streamline our team and optimize our R&D efforts and cost structure to extend our cash runway into the first quarter of 2025. These changes will unfortunately affect a number of our colleagues, and we are grateful for their dedication and contributions to our mission,” continued Mr. Karande. “As we sharpen our focus, we look forward to the opportunities ahead to generate meaningful clinical data for OTX-2002, continue to demonstrate the broad potential of our platform, and establish additional partnerships. We remain steadfast in our mission to pioneer a new class of programmable epigenomic mRNA medicines to transform the treatment of a broad range of diseases.”
Recent Highlights and Key Anticipated Milestones
Development Pipeline and Platform
Advanced the Phase 1/2 MYCHELANGELO™ I clinical trial evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC):
OTX-2002 continues to advance in monotherapy dose escalation.
As of March 24, 2024, data from the first three cohorts (0.02 mg/kg – 0.06 mg/kg) showed:
OTX-2002 continued to be generally well tolerated, with no dose-limiting toxicities observed.
Consistent dose-dependent pharmacokinetics with no drug accumulation observed following repeat doses.
All patients demonstrated controlled modulation and downregulation of MYC mRNA expression, an important oncogene regulating cell function and cell death.
The interim disease control rate (DCR) for the target population of HCC patients was 80%, reflecting 4 out of 5 efficacy-evaluable patients having a best overall response of stable disease. These patients had an average of three or more previous therapies and entered the trial with a life expectancy of less than 12 weeks. The DCR for patients with non-HCC solid tumors in the trial (n=5) was 40%, indicating the potential specificity of OTX-2002 for HCC.
The Company continues to evaluate patients with HCC in Cohort 4 at the 0.12 mg/kg dose level, which recently cleared the 28-day dose limiting toxicity (DLT) window. Based on preclinical experience and modeling, Omega believes this dose level is within the expected active dose range. In March 2024, the Company opened enrollment for Cohort 5 at a dose level of 0.3 mg/kg.
Omega expects to report additional updated clinical data from monotherapy dose escalation in mid-2024.
The Company plans for expansion into monotherapy and combination settings in mid-2024.
Announced research collaboration with Novo Nordisk to develop a novel therapeutic for obesity management:
The collaboration will leverage Novo Nordisk’s expertise in research and development within cardiometabolic diseases and Omega’s proprietary platform technology to develop an epigenomic controller designed to enhance metabolic activity.
Unlike traditional approaches focused on appetite suppression, the program aims to leverage precision epigenomic control to enhance thermogenesis, a naturally occurring metabolic process that burns calories.
Under the terms of the agreement, Novo Nordisk will reimburse all R&D costs and has the right to select one target to advance for clinical development. Omega and Flagship’s Pioneering Medicines are eligible to receive up to $532 million in upfront, development and commercial milestone payments, as well as tiered royalties on annual net sales of a licensed product, which will be split equally between the parties.
Continued to advance and expand OMEGA platform capabilities:
Presented new preclinical data supporting the breadth of Omega’s platform capabilities, including bidirectional and multiplexed epigenomic control of gene expression in liver inflammation and fibrosis at the American Association for the Study of Liver Diseases’ (AASLD) The Liver Meeting® 2023.
A HNF4A-targeting epigenomic controller led to a durable increase in HNF4α expression, preferential upregulation of HNF4α P1 promoter isoforms, and reduced key measures of fibrosis both in vitro and in vivo, supporting this development candidate’s potential for the treatment of fibrotic liver disease.
In preclinical models, liver-specific multiplexed targeting of CXCL9, CXCL10 and CXCL11 via an epigenomic controller led to a significant reduction in T-cell migration, a critical driver of inflammation-induced liver injury, supporting the potential of this approach as a novel treatment for inflammatory liver diseases.
Corporate
Announced cost reduction and strategic prioritization initiative to maximize near- and long-term value creation opportunities:
Following a strategic review, the Company has focused its pipeline and reduced overall headcount by approximately 35%. These fiscally disciplined actions are expected to extend the Company’s cash runway into Q1 2025.
Positions the Company to achieve key clinical data readouts from the monotherapy dose escalation and dose expansion stages of the MYCHELANGELO I clinical trial.
The Company will prioritize certain preclinical programs and platform efforts:
Prioritized preclinical programs include OTX-2101 for non-small cell lung cancer (NSCLC), the HNF4A program in liver regeneration, and development of an epigenomic controller for obesity in collaboration with Novo Nordisk.
Core work on platform biology, epigenomic controllers, and characterization of LNP delivery to the lung and other tissues will continue.
An updated corporate presentation is available on the Investors section of the Company’s website at https://ir.omegatherapeutics.com/.
Fourth Quarter and Full Year 2023 Financial Results
As of December 31, 2023, the Company had cash, cash equivalents and marketable securities totaling $73.4 million, which is expected to fund operations into Q1 2025.
Research and development (R&D) expenses for the fourth quarter of 2023 were $15.5 million, compared to $26.0 million for the fourth quarter of 2022. R&D expenses for 2023 were $77.2 million compared to $81.2 million in 2022. The $4.0 million decrease in R&D expenses in 2023 compared to 2022 was primarily due to lower external research and manufacturing costs, consulting and professional fees, and lab expenses, partially offset by an increase in personnel-related expenses, including stock-based compensation to support business growth, and facilities and other costs.
General and administrative (G&A) expenses for the fourth quarter of 2023 were $6.2 million, compared to $5.7 million for the fourth quarter of 2022. G&A expenses for 2023 were $26.2 million, compared to $23.7 million in 2022. The $2.5 million increase in G&A expenses in 2023 compared to 2022 was primarily due to higher professional and consulting fees, and facilities and other administrative costs.
Net loss for the fourth quarter of 2023 was $20.2 million, compared to $30.8 million for the fourth quarter of 2022. Net loss for the year ended December 31, 2023, was $97.4 million, compared to a net loss of $102.7 million for the year ended December 31, 2022. The decrease in net loss for 2023 compared to 2022 was primarily due to decreases in R&D expenses.
BOSTON DR LIM 