Category: Uncategorized

안녕하세요 보스턴 임박사입니다.

BlueRock Therapeutics는 Memorial Sloan Kettering Cancer Center의 Lorence Studer 박사의 MSK-DA01 (Bemdaneprocel, BRT-DA01)의 임상시험 및 상용화를 위해 Versant Ventures와 Bayer가 공동으로 설립한 회사입니다. Bemdaneprocel story에 대해서는 CSO Stefan Irion 박사가 2023 Till & McCulloch Meetings에서 발표한 것을 정리한 아래의 블로그 글을 보면 알 수 있습니다. 정리하면 2000년대 초까지 Parkinson Disease Cell Therapy를 찾기 위한 exploratory clinical trials를 했는데 그 중 “Fetal Cell Approach”만이 효과가 있었고 Fetal Cell의 생산성에 대한 문제로 Pluripotent Stem Cell을 찾기 시작하고

• 2011년에 Nature에 논문을 내고 2014년에는 G-Force PD라는 컨소시엄을 만들었다.
• “Biphasic Wnt Signaling Activation” 방법으로 Clinical-grade doparminergic neuron을 만들어낼 수 있었다.
• 2021년에 Cell Stem Cell에 Bemdaneprocel (BRT-DA01, MSK-DA01)의 preclinical 결과를 냈는데 (1) PCR로 검출가능한 여러 분화 마커를 찾았고 (2) Rat 실험에서 Functional Cure를 확인했다. – 이 결과 BlueRock Therapeutics가 만들어졌다.
• 2021년에 임상1상을 시작해서 12명에 대해 수술적 방법으로 뇌에 구멍을 내어 Bemdaneprocel 을 이식하고 1년간 immunosuppressant를 복용했다. 1.8-5.4 milion cells를 주입한 경우 고용량에서 효과를 보았다.
• PET를 통해서 뉴런세포가 1년간 생존할 뿐만 아니라 주위 뇌세포로 커가는 것을 볼 수 있었다.
• 2024년 상반기에 임상2상을 할 계획이다.

A bench-to-bedside story of BlueRock’s investigational stem cell therapy for Parkinson’s disease – Signals 11/9/2023

BlueRock Therapeutics has generated considerable media buzz with their announcement of positive Phase I clinical trial data on bemdaneprocel (BRT-DA01), an investigational, stem cell-derived, dopaminergic therapy for Parkinson’s disease. The trial is the result of decades of research and investments that yielded this exciting step into clinical translation.

Founded in 2016 by Versant Ventures and Bayer LEAPS, with scientific founders Drs. Lorenz Studer (Sloan Kettering Institute) and Gordon Keller (University Health Network), the mission of BlueRock Therapeutics is to discover and develop novel stem cell-derived therapies to improve treatments for patients. With the recent clinical trial, bemdaneprocel is the company’s most advanced product. Providing insights on the bench-to-bedside journey of bemdaneprocel, Dr. Stefan Irion (Chief Scientific Officer, BlueRock Therapeutics) presented an insider’s view on the investigational cell therapy at the 2023 Till & McCulloch Meetings.

As recapped by Irion, cell therapies for Parkinson’s disease began to emerge in clinical trials in the late 1990s and early 2000s. In these early trials, several different dopamine-expressing cell types were explored, including retinal pigmented epithelial cells, autologous carotid body cells, adrenal medullary cells and fetal cells. With the exception of the latter, trials involving these various cell types were largely unsuccessful.

The fetal cell approach was marked by several limitations, including a limited supply of cells and substantial heterogeneity of the cell population that may have compromised efficacy. As such, research turned to pluripotent stem cells as a potential source of renewable cells that could provide a consistent, scalable, and more refined source for generating dopamine-expressing neurons. In parallel, a global consortium called G-Force PD was formed in 2014 by leaders in the field, including Studer, the eventual scientific cofounder of BlueRock Therapeutics. The purpose of the consortium was to gather consensus and inform the intelligent design of a next wave of clinical trials involving stem cell-derived neurons for Parkinson’s disease treatment.

 In 2011, the lab published a ground-breaking Nature paper detailing the controlled generation of midbrain dopaminergic neurons from human embryonic stem cells. This study provided an important foundation and led to millions in grant funding to develop the cell therapy for clinical trials. To do so, the team needed to adapt the protocol to make it more efficient and scalable, landing on a biphasic Wnt signaling pathway activation strategy for producing clinical-grade dopaminergic neurons that they reported a decade after the seminal Nature paper.

Using the new differentiation protocol, the Studer lab performed extensive preclinical testing of bemdaneprocel, publishing their findings in a Cell Stem Cell paper in 2021. These studies included the identification of a panel of differentiation markers measured by PCR that could be used to validate the phenotype of the cell product and ensure stability after cryopreservation and passing through a delivery device. Using a mouse model, the group performed biodistribution, toxicity, and tumourigenicity studies to demonstrate safety of the treatment.

Studer group showed that rats implanted with bemdaneprocel displayed correction of the rotational bias compared to control rats, providing important evidence for their functional recovery. With these promising preclinical safety and efficacy data, BlueRock Therapeutics initiated plans for clinical trials in humans. Drawing upon previous work in fetal cell clinical trials as well as the rodent studies, the investigators determined estimates for the dose of bemdaneprocel that would be needed for treating human patients with Parkinson’s disease.

Using the body of preclinical data, BlueRock Therapeutics received approvals from Health Canada and the U.S. Food and Drug Administration to conduct a phase I clinical trial. Beginning in 2021, the trial sites included Toronto Western Hospital, University of California Irvine, Weill Cornell Medical College, and Memorial Sloan Kettering Cancer Center. The open-label trial enrolled 12 patients, with the first five patients receiving a low dose of bemdaneprocel (1.8 million cells), and the subsequent patients treated with the high dose (5.4 million cells). A novel surgical technique and device were also developed to precisely implant the cells into the brain via a single burr hole through the skull. The patients will be followed for two years, and Irion presented the one-year interim results that have now been collected for the full cohort. They received immunosuppression for one year after treatment to allow time for the blood-brain barrier to heal from the initial surgery so that it could protect the implanted cells from immune recognition thereafter.

While efficacy data need to be interpreted with caution given that the study is a small open-label trial with risk of placebo effects, clinical scoring systems suggest that patients have improved, particularly those within the high-dose cohort. In addition, positron emission tomography (PET) imaging was performed in patients to measure uptake of a synthetic dopamine analogue and radiotracer to visualize regions of the brain containing dopaminergic neurons. These measurements revealed that the implanted cells survived and persisted at one year follow-up, with engraftment in the expected brain region. In light of this encouraging data, BlueRock Therapeutics has announced plans to begin enrolling patients for a Phase II clinical trial within the first half of 2024. The study will provide new insights on the efficacy of the bemdaneprocel for patients with Parkinson’s disease.

Bemdaneprocel (BRT-DA01, MSK-DA01)의 전임상 연구결과는 Cell Stem Cell 2021년에 보고했습니다.

Preclinical Efficacy and Safety of a Human Embryonic Stem Cell-Derived Midbrain Dopamine Progenitor Product, MSK-DA01. Cell Stem Cell 2021, 28, 217-229. Stefan Irion et al.

Bayer, Versant join forces on $225M Series A for stem cell upstart – Fierce Biotech 12/16/2016

The startup, which is being hailed by the pair as a “next-generation regenerative medicine company” plans to develop best-in-class induced pluripotent stem cell (iPSC) therapies. Its initial focus will be on CNS and CV disease areas.

On the R&D side, it will have ops in Toronto, New York and Boston, with its initial program focused on regenerating heart muscle in patients who have had a heart attack. The program is being worked on in a collab pact with the Toronto-based McEwen Centre for Regenerative Medicine and University Health Network with Dr. Gordon Keller, a leader in stem cell biology, and a scientific co-founder of BlueRock.

BlueRock, Bayer’s stem cell group, details glimpses of efficacy in Parkinson’s disease therapy – Endpoints News 8/28/2023

BlueRock disclosed that one patient temporarily developed seizures a day after the surgery, although the cells themselves did not cause any serious side effects. That 70-year-old man recovered after receiving medication and hasn’t had any seizures since, Ettenberg said.

One year after the surgery, the seven patients who got the high dose of the therapy had a 13-point reduction on a scale that doctors use to measure the motor symptoms of Parkinson’s, and the five patients who got a low dose had a 7.6-point reduction. A 5-point reduction has historically been considered clinically significant. Patients receiving the high dose also cut their time spent with uncontrollable movements — so-called “off time” — each day by about 2 hours.

“We saw an almost around 50% decrease in their off time, which means they’re gaining control of those movement disorders,” Ettenberg said. “If we were writing the script two years ago, this is what we would be hoping for. We’ve gotten everything we need to move this to Phase II.”

Rather than injecting stem cells directly into a patient, the company grows its stem cells into dopaminergic neuronal precursor cells in the lab before a surgeon implants them into each side of a patient’s skull. The goal is to help rebuild the network of dopamine-producing cells in a brain region called the putamen, which is vital for controlling movement but is damaged in Parkinson’s disease. The patients in the study were diagnosed with the condition nine years earlier, on average. And although they were still getting some benefit from levodopa — essentially a dopamine replacement that is the standard of care — all started to lose the full benefit of the treatment over time.

Most of the mild and moderate adverse events were related to immunosuppressant drugs that patients took for one year after the surgery, Ettenberg said. There were no serious adverse events related to the cell therapy, he added, and the seizures one man developed were “somewhat expected for us, and for the field, given that you’re passing a cannula into each side of the brain.”

Since no one got a placebo in the study and there was no control arm, Ettenberg was careful to note that this study was not a true test of the therapy’s effectiveness. “It’s not powered to speak to the clinical benefit here. But of course, we’re all interested in that. And the patients are interested in that. And we need to speak to it,” he said.

The randomized placebo-controlled Phase II trial will seek to more strongly answer questions about the treatment’s efficacy and durability. “We’re still in discussion with the FDA of exactly what that trial design would look like,” Ettenberg said.

These iPSCs partly resemble embryonic stem cells that can be turned into any other cell but with fewer ethical quandaries, and therapies made from iPSCs are only beginning to move from the lab bench and into the clinic. BlueRock’s treatment was made from a cell line that originally came from embryos — fertilized eggs that were never implanted in a patient.

Ettenberg said academic work on those cells started in 2009, three years after iPSCs were made in a petri dish for the first time. Using embryonic stem cells “was the fastest” way forward, he said, adding that there was no fetus involved in making the stem cells, and that the company can perpetually generate new cells from the ones they already have.

“All of the source for this material is already in the freezer. And we will never go back and create another source for that,” he said. “It’s what attracted me to this field in general. You’re making a reproducible, reliable, indefinite source of this material, which can become more drug-like in its characteristics.”

The Parkinson’s treatment is BlueRock’s most advanced program, though the rest of the company’s earlier-stage work focuses on therapies made from iPSCs. BlueRock is getting ready for a Phase I clinical trial with Opsis Therapeutics, a subsidiary of Fujifilm, to make retinal cells for inherited vision diseases. Another program focused on making cardiomyocytes — heart muscle cells — is close behind.

Earlier this month, BlueRock laid off about 50 employees, and Ettenberg said the cuts were expected to help tighten the company’s focus on the next phase of its Parkinson’s program and upcoming retinal disease treatment.

Series A 한 지 3년 후에 Bayer는 $1 Billion Valuation으로 BlueRock Therapeutics를 인수하였습니다.

Bayer acquires BlueRock Therapeutics to build leading position in cell therapy – PR Newswire 8/8/2019

Following a 2016 joint venture with Versant Ventures to establish BlueRock Therapeutics, Bayer will acquire the remaining stake for approximately USD 240 million in cash to be paid upfront at closing and an additional USD 360 million payable upon achievement of pre-defined development milestones. With Bayer currently holding 40.8 percent stake, the investment corresponds to a total company value of BlueRock Therapeutics of approximately USD 1 billion. The closing of the transaction is expected during the third quarter of 2019.

2023년 중순에는 Bayer 실적 악화로 12%의 인력감축이 있었습니다.

Bayer-bought BlueRock cuts 12% of workforce across 3 sites as pipeline contracts – Fierce Biotech 8/17/2023

The Bayer-bought cell therapy biotech is taking a pipeline of nine assets and focusing on four, according to a statement from a BlueRock spokesperson. The priority is the company’s cell therapy to treat Parkinson’s that’s gearing up for a phase 2 trial set to begin in the first half of 2024. Ophthalmology asset OpCT-001 will soon join it in human trials, with a formal ask to regulators expected sometime in the next year. BlueRock will also continue work on a second Parkinson’s cell therapy and a stem-cell-derived treatment for heart failure.

The 12% reduction represents layoffs to about 50 employees, the spokesperson added. The cuts will be across sites in Cambridge, New York and Toronto. 

Bayer opens California plant to make cell therapies – Biopharmadive 10/10/2023

Bayer has been investing hundreds of millions of dollars into its Berkeley location, recently launching a Cell Culture Technology Center and cell therapy labs.

지금의 속도로 간다면 임상2상을 마치는 시점에서 FDA Accelerated Approval을 시도할 것 같습니다. 최초의 Parkinson Disease iPSC-derived neurologic Stem Cell Therapy가 되어 환자들에게 희망을 줄지 기대됩니다.

(Picture from Duke Today)

안녕하세요 보스턴 임박사입니다.

RNA Therapeutics 중에서 가장 오래된 기술 중의 하나이면서도 발전이 Antisense, siRNA, mRNA 등에 비해서 상대적으로 임상적인 적용이 더디게 진행된 분야가 RNA Aptamer 분야가 아닌가 하고 생각합니다.

이것은 1998년에 FDA에서 승인된 Macugen (Pegaptanib sodium injection)의 상업적 실패와 연관이 있고 Archemix, SomaLogic과 같은 Aptamer 회사들이 문을 닫거나 Research 회사로 Business model이 변화되는 계기가 되었습니다.

다행히도 최근 Iveric Bio/Astellas Pharma의 Izervay (avacincaptad pegol)이 Geographic atrophy 치료제로 FDA 승인이 되면서 RNA Aptamer의 새로운 중흥기가 올 수 있을지 주목되고 있습니다.

Iveric drug approved for type of vision loss as rival’s safety draws scrutiny – Biopharmadive 8/5/2023

The monthly eye injection, which will be sold as Izervay, is meant to slow progression of the condition, which Iveric and its new owner, Japanese drugmaker Astellas Pharma, estimate affects 1.5 million people in the U.S.

Iveric Bio (former Ophthotech Corporation)의 스토리는 Retina Today 2021년에 잘 소개가 되었습니다.

The Open Secret Behind Iveric Bio’s Continued Success – Retina Today 9/1/2021

Baskings Biosciences에 대해 소개를 하려고 합니다.

Bruce Sullivan 박사는 25년 이상 RNA Aptamer 분야에서 일한 베테랑 교수인데 2007년에 Oligonucleotides 논문에 von Willebrand Factor를 표적으로 하는 Aptamer 연구결과를 발표한 이후에 이 약물의 성질 변형을 위해 오랜 기간 노력을 해 왔습니다.

Antidote-Controlled Platelet Inhibition Targeting von Willebrand Factor with Aptamers. Oligonucleotides 2007, 17, 265-274. Bruce A. Sullivan et al.

10여년의 연구 끝에 2018년에 Bruce Sullivan 교수는 Nature Biotechnology에 Aptamer와 Oligonucleotide reversal agent combination으로 심장호흡기계의 혈액응고를 방지할 수 있다는 결과를 발표했습니다. RNA Aptamer (11F7t)와 small-molecule FXa inhibitor (apixaban) combination으로 anticoagulation이 잘 되는 것을 발표한 것입니다.

Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass. Nat. Biotechnol. 2018, 36, 606–613. Bruce A. Sullivan et al.

RNA Aptamer의 Renal clearance 문제를 해결하기 위해 주로 PEG conjuagation을 하는데 anti-PEG antibody로 인한 문제가 있었습니다. 그런데 우연인지 거의 같은 시기에 Duke University의 Ashutosh Chilkoti 교수 연구실에서 POEGMA라는 새로운 polymer를 발표합니다.

A brush-polymer/exendin-4 conjugate reduces blood glucose levels for up to five days and eliminates poly(ethylene glycol) antigenicity. Nat. Biomed. Eng. 2016, 1, 0002. Ashutosh Chilkoti et al.

Bruce Sullivan 교수와 Ashutosh Chilkoti 교수는 공동연구를 통해서 POEGMA를 Bruce 교수의 RNA Aptamer에 결합시킨 Aptamer-POEGMA conjuagate의 결과를 발표합니다.

PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response. Adv. Mater. 2022, 34, 2107852. Bruce A. Sullivan, Ashutosh Chilkoti et al.

Preclinical Development of a vWF Aptamer to Limit Thrombosis and Engender Arterial Recanalization of Occluded Vessels. Mol. Ther. 2019, 27, 1228-1241. Shahid M. Nimjee, Bruce A. Sullivan et al.

T10으로 부터 T59까지 Truncation optimization을 한 이후에 Antidote를 위해 5개의 Uridine을 넣어서 35-nt Aptamer를 만들었습니다. 이렇게 얻어진 BB-031 (DTRI-031) preclinical development result를 얻었습니다.

이러한 연구결과를 바탕으로 Bruce A. Sullivan교수와 Shahid M. Nimjee교수는 2019년에 Baskings Biosciences를 창업하였고 1년후에 3개 VC로 부터 $5.4 Million Seed Financing을 받아서 BB-031 (DTRI-031) IND-enabling studies와 phase 1을 지원하게 됩니다.

Basking Biosciences, Inc. Completes $5.4M Seed Financing – Smart Business Dealmakers 12/7/2020

Basking Biosciences, Inc., a privately-held biopharmaceutical company developing a next generation treatment for acute ischemic stroke (AIS), announced an initial closing of a $5.4M Seed Series financing. The investor syndicate includes Rev1 Ventures, Broadview Ventures and Viva BioInnovator. Concurrent with the financing, Ryan Helon of Rev1, Thomas Needham of Broadview and Dr. Dan Meyers have joined Basking’s Board of Directors.

Basking is developing the first reversible thrombolytic therapy for acute ischemic stroke (AIS). The Company’s development candidate, DTRI-031, is an RNA aptamer that inhibits von Willebrand Factor (vWF). Basking is co-developing a matched oligonucleotide reversal agent, DTRI-025, for as-needed, rapid reversal of DTRI-031. Basking’s paired therapy has the potential to significantly expand the population of patients that receives acute thrombolytic therapy by extending the treatment window to 24 hours post stroke onset and aligns well with the urgent need in medicine for precision-based therapeutics in cardiovascular disease. The program is expected to enter into human clinical trials in Q2 2021.

BB-031의 임상 1상 결과는 긍정적으로 나왔습니다. 0.1 mg/kg – 4 mg/kg 용량을 IV 주사제에 대한 28-day SAD 시험 중에서 최대용량까지 큰 부작용이 없었고 18분-61분의 약물 반감기를 보여주었습니다.

Basking Biosciences reveals positive data from trial of thrombolytic agent – Clinical Trials Arena 2/10/2023

Healthy volunteers in the Phase I trial were given BB-031 or a placebo in a 6:2 ratio by intravenous bolus at single ascending doses ranging from 0.1mg/kg to 4mg/kg. It was found that the agent was well tolerated and safe throughout the study period of 28 days, and no significant or treatment-emergent adverse events were reported. Additionally, BB-031 demonstrated an apparent mean terminal half-life ranging from 18 minutes at 0.1 mg/kg to 61 minutes at 4mg/kg.

이러한 고무적인 결과를 바탕으로 최근 Arch Venture Partners 주도 하에 $55 Million Series A를 함으로써 임상2상으로 진입할 수 있게 되었습니다. Arch의 Steven Gillis 박사가 Chair of BOD를 맡고 BB-031의 임상2상 PoC와 reveral oligonucleotide BB-025의 임상1상을 위해 노력하게 됩니다.

Triangle-based Basking Biosciences raises $27.5 million – Business North Carolina 11/15/2023

Basking Biosciences Announces Close of $55 Million Financing to Accelerate Clinical Development for First Reversible Thrombolytic for Ischemic Stroke – Duke Today 1/30/2024

Basking will initiate a Phase 2 proof-of-concept trial, the RAISE trial, in patients with acute ischemic stroke (AIS) in 2024. In addition to the RAISE trial, Basking will use the funds to advance BB-025, a complementary rapid-acting reversal oligonucleotide capable of quickly neutralizing the pharmacological activity of BB-031, through a Phase 1 clinical program.  

BB-031의 임상2상 결과가 어떻게 나올지 궁금합니다. BB-025 Oligonucleotide의 임상진행도 순조롭게 되기를 기대해 봅니다. 현재 Basking Biosciences의 Pipeline은 아래와 같습니다

Antidote BB-025에 대한 디자인은 2002년에 Nature에 보고한 바가 있습니다.

RNA aptamers as reversible antagonists of coagulation factor IXa. Nature  2002, 419, 90–94. Bruce A. Sullivan et al.

출처: StatNews

안녕하세요 보스턴 임박사입니다.

Tome Biosciences는 보스턴 MIT의 Omar Abudayyeh 교수와 Jonathan Gootenberg 교수 연구실의 PGI

(Programmable Genomic Integration) 기술 플랫폼을 바탕으로 설립되었습니다.

Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases. Omar O. Abudayyeh, Jonathan S. Gootenberg et al. Nat. Biotech. 2023, 41, 500-512.

PASTE는 Programmable Addition via Site-specific Targeting Elements의 초성을 딴 이름으로 PASTE Platform을 이용해서 Liver Rare Disease와 Autoimmune Disease의 세포치료제 개발에 사용할 계획입니다.

PASTE Expands CRISPR Toolbox by Inserting Large Pieces of DNA – GEN Edge 11/28/2022

Now, a team from MIT describes a new tool called PASTE (programmable addition via site-specific targeting elements) which delivered genes as long as 36,000 DNA base pairs to several types of human cells (as well as to liver cells in mice). PASTE uses a CRISPR–Cas9 nickase fused to two enzymes—a reverse transcriptase and a serine integrase—for targeted genomic recruitment and integration of DNA.

In this study, the researchers showed that they could use PASTE to insert genes into several types of human cells, including liver cells, T cells, and lymphoblasts. They tested the delivery system with 13 different payload genes, including some that could be therapeutically useful, and were able to insert them into nine different locations in the genome.

The researchers are now further exploring the possibility of using this tool as a possible way to replace the defective cystic fibrosis gene. This technique could also be useful for treating blood diseases caused by faulty genes, such as hemophilia and G6PD deficiency, or Huntington’s disease, a neurological disorder caused by a defective gene that has too many gene repeats.

1년여의 Stealth mode 기간을 거쳐서 2023년 12월에 $213 Million Series A/B를 했습니다.

Tome Biosciences Raises $213M to Commercialize MIT Developed Genome Editing Tech – GEN Edge 12/14/2023

Earlier this week, Tome raised $213 million in Series A and B funding from investors including Andreessen Horowitz (a16z) Bio + Health, ARCH Venture Partners, GV, Longwood Fund, Polaris Partners, Bruker Corporation, FUJIFILM Corporation, and Alexandria Venture Investments. The funds will support Tome’s efforts to develop and commercialize programmable genomic integration (PGI) technology that was in-licensed from the Massachusetts Institute of Technology (MIT).

Tome’s portfolio includes integrase-mediated PGI (I-PGI), which utilizes proprietary integrases to precisely insert large sequences into the genome. I-PGI tech is based on the programmable addition via site-specific targeting elements (PASTE) approach to genome editing, first discovered at MIT by Tome’s co-founders Omar Abudayyeh, PhD, and Jonathan Gootenberg, PhD. 

펀딩을 한지 1달도 채 되지 않아서 Shakked Halperin 박사의 Replace Therapeutics를 인수했습니다. Tome Biosciences는 DNA Writing을 하는데 Reverse Transcriptase를 쓰는 반면 Replace는 DNA Ligase를 사용하기 때문에 두 기술을 접목함으로써 PASTE platform 기술의 영역을 확장할 수 있는 장점이 있습니다.

Exclusive: Weeks after $213M launch, Tome acquires a Berkeley gene editing startup for DNA ligase technology – Endpoints News 1/2/2024

Less than a month after launching with $213 million in funding, gene editing company Tome Biosciences has acquired a tiny Californian startup called Replace Therapeutics to expand its repertoire of DNA-altering tools. Tome will pay Replace $65 million in upfront and near-term milestone payments and up to $185 million total in stock and cash, the company told Endpoints News.

Replace was founded by Shakked Halperin, a former scientist at the Innovative Genomics Institute at UC Berkeley. Halperin’s first startup, Rewrite Therapeutics, was acquired for $45 million upfront by the CRISPR company Intellia Therapeutics in 2022 for its so-called DNA writing technologies, which use Cas enzymes to direct polymerases to make corrections, deletions and insertions to the genome.

At his newer startup, Replace, Halperin made a tool that uses Cas9 to make a nick in the genome’s double helix and uses an enzyme called a DNA ligase to stitch in a new piece of code tens to hundreds of letters long.

Kakkar said it’s too early for Tome to have established a drug program around the ligase technology, but he cited Huntington’s disease and a liver disorder called hemochromatosis as examples of conditions that could be potentially addressed with the approach.

He also thinks the tool could improve Tome’s original goal of inserting larger pieces of DNA with integrases. Tome currently relies on a reverse transcriptase to write a genetic landing pad, telling the integrase where to insert the therapeutic gene. The ligase approach provides an “alternative method of placing a beacon,” Kakkar said.

이제 막 시작하는 Tome Biosciences의 PASTE platform 기술은 아직 Animal PoC 정도밖에 되어 있지 않은 것으로 보이는데 NHP study를 지나서 Human clinical trials을 할 수 있을지 기대가 됩니다.

안녕하세요 보스턴 임박사입니다.

Janux Therapeutics는 Tumor Activated T-Cell Engager (TRACTr) platform을 기반으로 Precision Oncology회사입니다.

Janux Therapeutics는 2017년에 CEO David Campbell 박사가 Founder로서 San Diego에 있는 Early-stage VC Avalon BioVentures의 Incubator인 “COI Pharmaceuticals” 안에서 설립되었습니다. 2018년 5월에 CSO Tommy DiRaimondo 박사가 조인한 후 18개월동안 Stealth-mode로 Tumor Activated T-Cell Engager (TRACTr) platform을 Build-up 한 이후에 Merck와 $1 Billion 규모의 딜을 성사시켰습니다.

Janux pairs up with Merck for $1B-plus T-cell engager deal – Fierce Biotech 12/18/2020

In early preclinical work, its candidates have shown “comparable anti-tumor efficacy relative to standard T cell engagers but lack the associated liabilities related to cytokine release, healthy tissue toxicities, or systemic immune activation.” The proof, however, will need to be shown in clinical trials.

그리고 3개월이 지난 후 $56 Million Series A를 해서 TROP2-TRACTr, PSMA-TRACTr 프로그램 중 하나를 2022년 상반기에 임상시험으로 진입시킨다는 계획이었습니다.

Janux Therapeutics Announces $56 Million Series A to Advance Novel Cancer Drug Candidates Using T Cell Engager (TRACTr) Technology – Business Wire 3/3/2021

Janux’s proprietary Tumor Activated T Cell Engager (TRACTr) technology is designed to overcome specific limitations of current T cell immuno-oncology therapies. The financing will be used to advance Janux’s preclinical pipeline, including a TROP2-TRACTr and PSMA-TRACTr, with expected advancement of the Company’s first candidate into the clinic in the first half of next year.

Series A $56M 한지 한달후에 $125 Million Series B를 바로 했습니다. 1달만에 EGFR-TRACTr 파이프라인이 새로 들어갔습니다.

Janux Therapeutics Closes $125 Million Series B Financing to Advance Next Generation T Cell Engager Immunotherapies into Clinical Trials – Business Wire 4/20/2021

The proceeds of the financing will help support the advancement of Janux’s pipeline of next generation T cell engager immunotherapies, including a PSMA-TRACTr, EGFR-TRACTr, and TROP2-TRACTr, into initial proof of concept clinical trials.

Series B를 한지 한달 후에 Nasdaq IPO $100 Million를 발표하고 6월에 계획의 거의 두배인 $194 Million IPO를 했습니다.

Cancer Biotech Janux Therapeutics Files for $100 Million IPO – Biospace 5/21/2021

Janux plans to use the funds raised from the IPO to submit four Investigational New Drug (IND) applications to the U.S. Food and Drug Administration (FDA) in the first half of 2022.  The lead program is PSMA-TRACTr for metastatic Castration-Resistant Prostate Cancer (mCRPC). The next two are EGFR-TRACTr for colorectal cancer and head and neck cancer and TROP2-TRACTR for triple-negative breast cancer, urothelial cancer and non-small cell lung cancer. The least advanced program is Costim bispecific, targeting PC-L1xCD28 in solid tumors.

IPO 이후 2023년 중순까지의 스토리는 아래 기사에 잘 정리가 되어 있습니다. PSMA-CD3 TRACTr인 JANX007과 EGFR-CD3 TRACTr인 JANX008의 임상1상이 진행 중이었고 그 결과를 2024년초에 발표할 계획이었습니다.

Janux Therapeutics Aiming to Develop Safer T-Cell Engagers With Enduring Efficacy – Precision Medicine Online 7/27/2023

Janux is building two lines of products using this technology.

The tumor-activated T-cell engager (TRACTr) platform produces T-cell engagers with a tumor antigen-binding domain and a CD3 T-cell binding domain.

In contrast, the tumor-activated immunomodulator (TRACIr) platform produces bispecifics with a tumor antigen-binding domain and a costimulatory CD28 binding domain.

Based on these preclinical insights, the company is conducting a Phase Ia trial in which metastatic castration-resistant prostate cancer (mCRPC) patients will receive JANX007 by intravenous infusion once a week in 21-day cycles. Investigators will increase the dose until a maximum-tolerated dose is identified, and then in the expansion stage, patients will receive doses at previously identified tolerable levels. Investigators are monitoring prostate-specific antigen (PSA) levels and PSMA expression in relation to patient response.

Janux’s second clinical stage program is an EGFR/CD3-directed T-cell engager, JANX008. Based on this, the firm began a Phase I trial of the drug in April in patients with advanced or metastatic solid tumors, focusing on colorectal cancer, squamous cell carcinoma of the head and neck, non-small cell lung cancer, and renal cell carcinoma. Campbell said the company chose those four tumor types because EGFR is overexpressed in anywhere from 50 percent to 95 percent of patients.

그리고 최근 발표한 임상1상 결과는 매우 고무적이어서 하루만에 주가가 3배로 뛰었습니다.

Janux shares triple on early cancer immunotherapy data – Biopharmadive 2/27/2024

Yet Janux’s results, while early and from only a small number of people, suggest its drug could have fewer serious safety risks. None of the 23 treated participants with metastatic castration-resistant prostate cancer experienced severe cases of an immune side effect known as cytokine release syndrome, or CRS, for instance.

Efficacy results, meanwhile, showed treatment led to substantial decreases in a prostate cancer marker that’s indicative of benefit. At higher doses Janux tested, all six treated participants had a 30% or higher decrease in this marker, known as prostate-specific antigen. Five had a 50% or higher decline, and one had a greater than 90% decline.

임상1상 자료는 아래의 회사 Presentation에 잘 나와 있습니다.

JANX007, JANX008의 임상시험이 소규모이고 초기단계이지만 Therapeutic Window를 크게 넓힐 수 있다는 점에서 많은 기대가 됩니다.

안녕하세요 보스턴 임박사입니다.

보스턴에 있는 Atlas Ventures는 약 2년 정도의 Stealth-mode incubating을 통해 회사를 만드는 Early-Stage Venture Capital Firm입니다. 회사를 만드는 시점의 Business Model과 시간이 지남에 따라 Business Model이 변하는 경우가 많이 있는데요 Atlas Ventures는 이런 변화를 통해서 회사를 성장시키는 강점을 가지고 있다고 생각합니다.

Ikena Oncology는 본래 2017년에 University of Texas 교수인 George Georgiou의 “Kynase Program을 포함한 3개의 프로그램을 바탕으로 “Kyn Therapeutics”라는 이름으로 설립된 회사입니다.

AskAt Inc. Announces Global Immuno-Oncology Licensing Agreement with Arrys Therapeutics Inc. – AskAt Press Release 12/14/2017

일본 AskAt Inc로 부터 $1.2 Billion 규모의 딜을 통해 Atlas Ventures 와 OrbiMed가 세운 Arrys Therapeutics가 Prostaglandin E2 receptor 4 (EP4) antagonists인 AAT-007과 AAT-008을 인수했고요. 이 중 AAT-007을 ARY-007로 명명해서 이 약물은 Kyn Therapeutics에서 개발하기로 합니다.

Kyn Therapeutics Banks $49M to Advance Cancer Immunometabolism Therapies – Biospace 12/14/2017

Atlas-backed I-O specialist Kyn comes out of stealth mode – Fierce Biotech 12/14/2017

Kyn Therapeutics가 Series A $49 Million을 할 때 3개의 프로그램이 있었습니다.

• ARY-007: Prostaglandin E2 receptor4 antagonist
• Kynase or Kynurenine degradating enzyme program
• AHR (Aryl Hydrocarbon Receptor) inhibitor

2019년 초에 Celgene과 Kynase, AHR program에 대해 $80 Million upfront와 $15 Million 지분투자를 하게 됩니다.

BMS Buyout Not Stopping Celgene from Launching Cancer Collaborations with Kyn, Obsidian – 1/18/2019

그리고 같은 해에 회사의 프로그램이 Kynurenine보다 더 확장되어서 Ikena Oncology로 회사명을 변경하게 됩니다. 이에 대한 얘기는 Ikena Oncology CEO인 Mark Manfredi의 블로그 글이 있습니다.

Kyn to Ikena: The Art and Science of Rebranding – LifeSci VC 12/17/2019

그리고 2년후에 Series B $120 Million을 하게 됩니다.

Ikena bags $120M to advance growing pipeline of cancer drugs – Fierce Biotech 1/5/2021

IK-175 (AHR) and IK-412 (Kynurenine) 두 프로그램이 BMS/Celgene과의 계약된 프로그램이었고요. IK-175 개발 스토리는 아래 논문에 실렸습니다.

TEAD inhibitor IK-930이 IND -enabling study를 하는 상황이었죠.

KRAS program은 Lead Optimization하는 상황이었습니다.

2021년에 IPO $143.8 Million을 했는데 아래는 당시의 파이프라인 리스트입니다.

Ikena Oncology Announces Closing Of $143.8 Million Initial Public Offering And Exercise In Full Of The Underwriters’ Option To Purchase Additional Shares – Goodwin 4/5/2021

Ikena Oncology to lay off 35% of staff – Biopharmadive 1/19/2024

Jilted by Bristol Myers, Ikena cuts headcount by 35% in retreat from drug discovery – Fierce Biotech 1/19/2024

BMS의 딜이 종료되면서 올해 초에 35% 인력감축을 하게 되었고 모든 Discovery Program은 중단하고 IK-930 (TEAD)와 IK-595 (MEK-RAF) 두개의 임상에만 치중하기로 방침을 정한 상태입니다.

향후 IK-930의 임상 성공 여부가 상당히 중요해 질 것 같습니다

안녕하세요 보스턴 임박사입니다.

MASH (Metabolic-Associated SteatoHepatitis) 질환은 NASH (Non-Alcoholic SteatoHepatitis)라고 불리던 병의 새로운 이름인데 수십조원대의 시장규모가 예상되는 질환입니다. 다만 Biology에 대한 이해가 여전히 진행 중이기 때문에 여러가지 다른 Mode of Actions에 대한 치료제들이 개발되고 있는 상황입니다. Madrigal의 Resmetirom과 Cymabay의 Seladelpar에 대해서는 글을 의견을 남긴 적이 있습니다.

BIOTECH (10) – Madrigal Pharmaceuticals의 NASH 치료제 MGL-3196 (Resmetirom) 임상 3상 결과

BIOTECH (89) Cymabay Therapeutics: Seladelpar, an oral, selective peroxisome proliferator-activated receptor delta (PPARδ) agonist

Inventiva Pharma는 2011년에 Abbott Laboratories의 Spin off 회사로 설립이 되었습니다. 이 연구소는 2009년에 Abbott Laboratories가 Solvay Pharma로 부터 인수했는데 인수한지 2년 후 문을 닫기로 결정하게 됩니다. 이에 당시 General Manager였던 Frédéric Cren과 Research Director였던 Pierre Broqua박사가 Abbott과 협상을 통해서 70여명의 직원과 20만개 이상의 파이프라인, 그리고 연구소와 연구팀을 인수하고 Inventiva Pharma를 설립하기로 하게 됩니다. Abbott은 Inventiva를 재정적으로 지원하면서 2개의 프로그램 공동계약을 맺게 됩니다.

Frédéric Cren는 Inventiva의 Cofounder이자 CEO이고 Pierre Broqua 박사는 Cofounder이자 CSO로 창업초기부터 지금까지 이어지고 있습니다.

Abbott Completes Acquisition of Solvay Pharmaceuticals – PR Newswire 2/16/2010

Abbott (NYSE: ABT) today announced that it has completed its EUR 4.5 billion ($6.2 billion) acquisition of Belgium-based Solvay Pharmaceuticals, providing Abbott with a large and complementary portfolio of pharmaceutical products and expanding Abbott’s presence in key global emerging markets.

Launch of Inventiva, a New French Biotech Company Specializing in Research Partnerships in Therapeutic Innovation 30 August 2012 – Biospace 8/30/2012

Co-founded by Frédéric Cren, formerly General Manager of Research at Laboratoires Fournier, and Dr Pierre Broqua, formerly Research Director at Laboratoires Fournier at Daix, Inventiva has a staff of more than 70 experienced people, including around 20 researchers and more than 40 specialized technicians.

In order to achieve its objectives, Inventiva has at its disposal a library of around 200,000 compounds, a 12,000m2 laboratory, state-of-the-art facilities and drug discovery teams grouped into three departments – biology and pharmacology, chemistry and ADME/PK – as well as cross-disciplinary research capabilities (compound management, pre-formulation, toxicology, etc).

In order to promote the start-up and sustainability of Inventiva, Abbott is providing the new company significant financial support. Inventiva is already working on two research programs for Abbott in the field of auto-immune diseases and the treatment of diabetic nephropathy.

Frédéric Cren, Co-Founder and CEO of Inventiva, said: “The launch of Inventiva is the culmination of an ambitious project to create a French leader among biotech firms by drawing on the recognized research capabilities of the Daix site. Inventiva will capitalize on the rapidly growing outsourced pharmaceutical research market to implement significant partnerships with large pharmaceutical groups in its areas of specialization: Parkinson’s disease, oncology, auto-immune diseases and fibrosis. With experienced research teams, already identified research programs and significant development potential, Inventiva has all the necessary assets to become a leading regional and national player in pharmaceutical research.”

Inventiva Pharma는 2017년에 Paris Euronext에 IPO를 합니다.

Inventiva raises 48 mln euros in IPO on Euronext Paris – Euronext – Reuters 2/15/2017

Lanifibranor (IVA337)의 임상2b상 결과를 바탕으로 임상3상을 준비하고 MPS VI or Maroteaux-Lamy syndrome 치료제인 Odiparcil (IVA336) 임상시험을 위해 Nasdaq 상장을 하게 됩니다. 2018년 JMC Paper에 Lanifibranor (IVA337) 개발 스토리를 게재했는데 이 약물이 20만개 이상의 Compound library의 HTS (HIgh-Throughput Screening)결과로 얻어진 Lead compound를 Optimization한 것으로 그 과정을 소개했습니다.

Inventiva aims for $90M Nasdaq IPO after positive phase 2 – Fierce Biotech 6/22/2020

Riding the wave of a phase 2 win, Inventiva is gearing up for its U.S. IPO. The French biotech filed to raise up to $90 million in its Nasdaq debut, which will push its lead program into a phase 3 NASH study and advance a treatment for a rare lysosomal storage disorder.

2021년에 Lanifibranor의 임상2b 결과는 NEJM에 발표되었습니다. 800mg과 1200mg에 대해 임상2b를 진행했는데 Primary end point와 Secondary end point는 모두 충족하는 결과로 나왔습니다.

그리고 안전성의 경우에도 800mg의 환자 cohort에서는 Placebo와 유사한 데 1200mg cohort에서는 조금 독성이 있는 것으로 보였습니다.

그런데 임상3상 중에 환자 한명이 Aminotransferase라는 liver enzyme의 레벨이 상승함에 따라 임상이 일시 중단되었다고 발표했습니다.

Inventiva pauses phase 3 MASH study over patient’s raised liver enzymes – Fierce Biotech 2/16/2024

The event marks the first serious adverse reaction reported in any clinical trial of lanifibranor to date, Inventiva pointed out. The trial’s data monitoring committee has reviewed the adverse reaction report “in conjunction with other milder cases of elevation of aminotransferases among trial participants,” the company said.

하지만 Clinical Hold는 아닙니다. DMC는 임상 환자들이 6주마다 간수치 검사를 받고 신규 환자가 autoimmune liver or thyroid disease가 없어야 한다는 조항을 들어 임상진행을 계속할 수 있다고 했기 때문입니다.

The committee recommended that the study can continue if patients receive liver monitoring every six weeks and if new patients diagnosed with or with a predisposition to autoimmune liver or thyroid disease are excluded from the trial. As a result, the biotech has moved to temporarily suspend screening and randomizing any new patients into the study while the criteria are put in place.

CEO인 Frédéric Cren은 임상시험이 1달 반 정도 지나면 다시 시작할 수 있다고 말했습니다.

“All our teams are working diligently, and we are confident that recruitment will resume in around four to six weeks’ time,” CEO Frédéric Cren said in the release. Inventiva had been on schedule to complete patient screening in the trial by the end of March but said the pause means the first visit of the final patient enrolled may occur later in the first half of the year.

2023년 1월에 FDA 권고에 따라 NATIV 임상3상 프로토콜의 수정을 한 상태인데 이 수정을 통해서 임상3상의 시간이 크게 단축될 수 있게 되었습니다.

Inventiva announces changes to the clinical development of lanifibranor, including plans for a new Phase III trial in patients with NASH and compensated cirrhosis – Press Release 1/4/2023

“following a consultation with the U.S. Food and Drug Administration (“FDA”), Inventiva has decided to modify the clinical development plan of lanifibranor for the treatment of NASH. Inventiva’s request for a consultation with the FDA followed a public communication by the FDA suggesting that an alternative approach to seek full approval in patients with NASH could be considered upon submission of positive results of a Phase III trial using a histology surrogate endpoint in patients with NASH and a Phase III clinical outcome trial in patients with NASH and compensated cirrhosis. The Company’s proposed changes to the NATiV3 trial are designed to align with the alternative regulatory approach and are expected to be beneficial to the overall lanifibranor clinical program by

1) reducing the number of biopsies a patient undergoes during the trial from three to two,

2) reducing the trial duration a patient has to consent to from 7 years to 72 weeks,

3) offering all patients in the trial access to a lanifibranor treatment for at least 48 weeks by allowing them to enter into a new active treatment extension study, and

4) potentially expanding the addressable patient population to include patients with NASH and compensated cirrhosis.”

현재 Inventiva Pharma의 ipeline은 아래와 같습니다. 현재 2개의 약물이 임상시험 중이고 Lanifibranor (IVA337)이 임상3상으로 가장 앞선 상태이고, Odiparcil (IVA336)은 임상2상이 진행 중입니다.

곧 Lanifibranor (IVA337)의 임상3상이 재개되고 승인까지 되어서 MASH 환자들에게 좋은 치료제가 제공되면 좋겠다는 생각입니다.

안녕하세요 보스턴 임박사입니다.

저는 Biotech 과학자로 일하면서 짬짬이 예술과 문학, 운동을 취미로 하는 삶을 추구하고 있습니다. 그동안 몇분의 과학자이면서 미술과 관련한 분들에 대한 생각을 올린 적이 있는데요.

부러우면 지는거다 (23) – Daniel Jay at Tufts University – Art+Science

부러우면 지는거다 (25) – Victor Gonzalez: Chemist with Art Pigments Analysis

제가 근무하는 Cambridge까지 집에서 출퇴근을 하려면 편도 1시간 이상을 달리게 되는데요 이 시간동안 저는 WCRB Radio에서 나오는 Classic Music을 줄곧 들으면서 다닙니다. 제 차가 다행히 빵빵한 사운드를 자랑하다 보니 Rush Hour의 출퇴근길에 도로가 정체되더라도 저로서는 음악을 더 많이 들을 수 있으니까 가장 행복한 시간이 되었죠. 종전에는 주로 Popsong을 들었는데 Popsong은 노래가 너무 짧고 중간 중간에 나오는 DJ의 추임새를 저는 별로 선호하는 편이 아니어서 차츰 WCRB를 듣게 되었습니다.

CRB – Classical 99.5: Classical Radio Boston

저는 아직 클래식 음악에는 문외한에 가까워서 공부하는 중인데요. WCRB의 음악을 듣다보면 저는 교향곡이나 협주곡을 좋아하는 것 같더라구요. 저의 귀에 마음이 드는 음악을 만나면 다시 집에 와서 Youtube로 찾아서 다시 들어봅니다. 그리고 그 노래에 대한 역사적 배경이라든가 작곡가에 대한 것, 연주한 Orchestra와 지휘자 등에 대해 찾아보게 되는데요.

클래식음악의 장점은 같은 곡이라도 지휘자의 해석과 연주자의 연주에 따라 천차만별로 다른 것 같아요. 전 그런 다양함이 좋더라구요. 그리고 클래식 음악은 가사가 없기 때문에 상상이 풍부해지기도 하고요.

Classic Music과 과학자를 접목시킨 분에 대해서는 오늘 처음으로 올리게 된 것 같습니다. 소개할 분은 오재원 한양대학교 소아청소년과 교수입니다. 오재원 교수님은 한양대학교 의과대학을 졸업하고 모교에서 교수직을 맡으시고 있는데요.

오재원 교수, 음악의 숲속에서 학문의 결실을 맺다 – 한양뉴스포럼 5/18/2022

오재원 의학과 교수는 한양대병원 개원 50주년을 기념해 저서 <필하모니아의 사계> 1,200여 권을 기증했다. <필하모니아의 사계>는 총 4권으로 10여 년에 걸쳐 완간됐다.

오 교수는 의과대학 소아청소년과 교수이자 한양대학구리병원 소아과 과장이다. 또한, 미국 The University of Tennessee 알레르기 면역학 연구 전임의, Johns Hopkins University 소아 알레르기학 연구 전임의, 미국 Stanford University School of Medicine 소아 임상 면역학 교환교수를 맡고 있다. 본업인 의사부터 취미 생활인 음악인, 작가까지 세 마리의 토끼를 모두 잡은 오 교수를 만나 그의 삶을 들어봤다.

오 교수는 음악인과 작가로서도 활동하고 있다. 그는 2003년부터 코로나19 유행 전까지 병원에서 환자들을 위한 ‘음악산책’이라는 콘서트를 매달 마지막 주에 진행해왔다. 콘서트에서는 직접 바이올린을 연주하며 환자들의 쾌유를 빌었다. 이를 바탕으로 2005년 한양대 의료원 매거진 <사랑을 실천하는 병원>에서 ‘클래식 스토리’ 연재를 제안받은 그는 매달 클래식 음악에 대한 글을 쓰기 시작했다.

클래식 스토리’는 해를 거듭하며 흥행했다. 이후 2008년 의학전문지 <의사신문>으로부터 클래식 음악에 대한 칼럼을 제안받아 <클래식 이야기>를 매주 연재했다. 이에 대해 오 교수는 “어느덧 글을 쓴 지 15년이 됐다”며 “그간 작성해온 글을 정리해 <필하모니의 사계 I, II, III, IV>를 집필하게 됐다”고 말했다.

오 교수는 “특히나 클래식 음악에는 철학이 가미돼 있다”며 “시대를 뛰어넘는 고전을 읽듯 좋은 작품을 들을수록 마치 칡뿌리 씹듯 처음엔 쓰다가도 점점 그 단맛을 느낄 수 있다”고 클래식 음악을 설명했다. 또한, 그는 “음악은 우리의 무기력함에 무거워진 육체를 드높여 완벽한 아름다움으로 도약하게 하는 생명력이 있다”고 덧붙였다.

그리고 의협신문에서 최근에 오재원 교수님을 인터뷰한 기사가 있어서 여기에 올립니다.

평생을 음악과 함께한 의사, 오재원 교수 이야기 – 의협신문 6/20/2023

취재를 위해 오 교수의 연구실 문을 두드리고 안에 발걸음을 내려놓자 진풍경이 펼쳐진다. 벽면 한 쪽은 밀스타인과 호로비츠를 비롯해 역사를 장식한 음악가들의 명 음반들이 천장 바로 밑 손이 닿지 않는 선반까지 빼곡하게 채우고 있다. 사무 책상과 가장 가까운, 손이 바로 뻗치는 칸에는 LP판들이 바람 샐 틈 없이 메워져 있다. 제작된 지 수십 년은 되었을 터지만 옛 모습을 그대로 간직하고 있다. 맞은편에는 턴테이블이 고풍스러운 자태를 뽐내고 있다. 누가 봐도 예술을 깊이 사랑하는 이의 공간임을 단번에 알아챌 수 있다. 그가 수많은 LP판 중 하나를 꺼내 턴테이블 위에 올려놓자, 이윽고 바늘 끝이 빙글빙글 돌아가는 LP판을 찬찬히 훑으면서 베토벤 교향곡 3번이 흘러나온다. 커다란 스피커 두 대를 마주 보고 안락의자에 앉아 눈을 감으니, 예술의전당 R석을 방불케 하는 서라운드에 잠시 취재를 잊고 음악에 잠기게 된다. 

“클래식 음악을 스트리밍으로 듣는 것은 마치 최고의 요리사가 정갈하게 만든 음식을 통조림 껍데기에 넣어 먹는 것과 같아요. 디지털 신호로 변환된 음악은 본래의 예술적 혼을 담을 수는 없습니다. 그래서 조금 손이 더 가더라도 LP판으로 음악을 듣거나, 직접 공연을 보러 가는 것을 선호합니다.“

그의 연구실에 들어온 지 10분이 채 되지 않아 음악에 대한 그의 비범한 애정에 금세 매료되고 말았다. 무언가에 온전히 몰두할 수 있는 축복에 감사한다고 오 교수는 말한다.

“음악이 좋아서 사실 음대에 진학하고 싶었던 생각도 있었죠. 초등학생 때 처음 바이올린을 시작했는데, 그때는 공부보다도 바이올린 연습을 더 많이 했던 것 같습니다. 하지만 전공을 하려면 더 어린 나이부터 체계적으로 배워야 하는데, 제가 시작한 나이는 현실적으로 너무 늦은 나이였습니다. 어쩔 수 없이 음대의 꿈은 포기했지만, 그게 의대에 진학하고서도 약간 미련이 남았는지 음대생 친구들과 많이 어울렸어요. 예과 때는 4중주나 3중주를 결성해 라이브 카페에서 공연하면서 용돈 벌이도 했습니다. 우리 모교(한양대학교의과대학)의 오케스트라에서도 악장 자리를 맡아서 활동했는데, 지금 오케스트라 공식 명칭인 ‘키론 오케스트라’는 40년 전 제가 본과 1학년 시절에 지은 이름입니다.”

“책 <필하모니아의 사계>도 처음부터 책으로 내려고 생각한 건 아니었고, 원래는 작은 칼럼으로 시작했습니다. 여기 병원(한양대학교구리병원) 원보에 지금까지도 제가 매달 클래식 음악을 소개하는 글을 써내고 있는데, 우연히 <의사신문> 기자가 그걸 본 거죠. 어느날 연락이 와서 <의사신문> 한 면을 줄 테니 연재를 해줄 수 있겠느냐고 부탁하더군요. 그렇게 <클래식 이야기>라는 이름으로 2008년부터 매주 정식 연재를 시작하게 됐습니다. 시간이 지나면서 점점 좋아해 주시는 분들이 많아지고, 많은 분이 찾아 주셨습니다. 그렇게 총 12년 동안 총 500곡의 글을 투고했고, 이 글들을 모아서 책으로 만든 것이 바로 <필하모니아의 사계>입니다.” 

“라디오도 정말 우연한 계기로 시작했습니다. 처음 라디오에 출연한 건 KBS의 이충헌 의학 기자가 진행하던 ‘라디오 주치의’에서였는데, 제가 소아과 알레르기 전문의 패널로 거기에 몇 번 나가서 의학적인 이야기로 인터뷰를 했습니다. 그러다가 어느 날 이충헌 기자가 제가 클래식 음악을 좋아하는 것을 알고, “프로그램 끝나는 시간에 10분 정도 시간을 줄 테니 거기에 음악을 한 곡씩 틀어주고 끝냈으면 좋겠다”고 제안을 하더군요. 그렇게 ‘힐링 뮤직’이라는 이름으로 음악 코너를 시작하게 되었습니다. 주로 슈만의 트로이메라이라든지, 베토벤의 비창 소나타 2악장처럼 라이트한 클래식들, 많은 사람이 한 번쯤은 ‘이 곡 좋은데?’라고 생각할 수 있는 곡들을 위주로 했습니다.”

“뭐든지 열심히 하는 게 중요한 것도 있지만, 결국 자기가 좋아하는 일이어야만 끝까지 할 수 있습니다. 저 같은 경우는 글 쓰는 게 즐거웠고, 어디 가서 누구한테 이런 음악 얘기해 주는 게 되게 즐거웠습니다.”

“어느 날 회진을 도는데 한 10살쯤 된 아이가 “선생님 사진 보니까 바이올린 하던데” 하며 대뜸 자기가 선생님 앞에서 연주를 해보고 싶다고 하더군요. 며칠 후에 진짜로 다인 병실 앞에서 그 아이가 연주 했습니다. 연주를 끝까지 하고는 저에게 3/4사이즈의 그 조그만 악기를 내밀면서 연주해달라고 그러더군요. 그래서 저도 답가를 해줬더니 환아들도 되게 좋아하고 옆에 있던 보호자들도 굉장히 좋아했습니다. 제가 회진 끝나고 나갈 때쯤, 보호자 한 분이 “환자를 위한 콘서트를 한 번 제대로 해보는 건 어떠냐”고 말씀하셨는데, ‘환자와 보호자도 원한다면 정말 뜻깊겠다’는 생각이 들더군요. 그렇게 연주회를 처음 시작하게 됐습니다. 

그래서 제가 직접 피아노도 구매해서 로비에 놓고, 주변에 계신 첼리스트 그리고 피아니스트 전공자들의 도움을 얻어 삼중주를 결성했습니다. 음악회 이름을 ‘음악 산책’이라고 붙였는데, 환자들이 편한 때에, 언제든 늦게 와도 되고 그냥 몸이 힘들면 일찍 올라가도 되고, 편한 마음으로 들르시라는 취지에서 그렇게 했습니다. 휠체어나 침대 같은 것도 들어올 수 있게 장소도 병원 강당 말고 로비로 정했습니다. 저녁 6시 이후가 되면 회진도 끝나고 식사도 끝나고 환자들이 무료하게 TV만 쳐다보고 있는 경우가 많아요. 그래서 7시에 하면 환자들이 많이 내려와서 봅니다. 한 70, 80명씩 내려와서 볼 때도 있고 그랬어요. 그리고 음악도 너무 어려운 것보단, 영화 음악이나 팝송, 어떨 때는 조용필·최백호 분들의 가요까지도 삼중주로 편곡해서 많이 했습니다. 그럼 할아버지 할머니들도 참 좋아했습니다. 사실 환자들하고 의사들의 관계를 보면, 의사는 딱딱하게 의학적인 얘기만 하게 될 때가 많고, 특히 소아청소년과는 어린아이들도 많다보니 의사를 어렵게 생각하는 환자들이 많습니다. 이렇게 환자를 위한 음악회를 여니까 환자들이 관심을 둔다고 느끼고 더 가깝게 느끼는 것 같아 뿌듯하죠.”

“여러 가지 행복 중 최고의 것은 내가 가진 것을 나누어주는 일입니다. 인생은 결국 빈손으로 나서 빈손으로 간다는 말이 있죠. 그러니 살아있는 동안 내가 가진 것들을 최대한 많은 사람에게 나누어주는 것이 가장 좋은 일입니다. 지금까지 학술 서적과 교양서적도 많이 썼고, 거기에 논문도 쓰고 음악 활동도 하려다보면 사실 저녁 10시까지도 집에 못 가는 일이 부지기수였죠. 하지만 그게 저한테는 행복입니다. 개인적인 목표로 나중에는 의료봉사를 해보고 싶네요. 우리나라 지방 소도시나 외국으로 나가서 의술을 베풀고 싶습니다.”

오재원 교수님의 이야기를 듣고 보니 Classical Music을 공부하기로 한 건 잘한 것 같은데 Streaming service로 듣는 것보다 LP를 사서 들어야하나? 이런 생각도 드네요. 아직은 초보니까 Youtube도 감지덕지한 상황입니다. 바쁘시지만 부러운 삶입니다.

안녕하세요 보스턴 임박사입니다.

George A. Scangos 박사 (75세) 는 현재 Infectious Disease Biotech인 Vir Biotechnology의 이사로 계시는 분입니다. 40년의 Biotech career 동안 동부와 서부를 넘나들면서 CEO로 Biotech들을 일군 분이시죠. 작년 1월에 CEO에서는 완전히 은퇴하신다고 선언하셨습니다. 74세때입니다.

미국에는 Greece 출신 이민자들 중에서 성공한 Pharma/Biotech CEO들이 꽤 있습니다. 예를 들면 Merck CEO였더 Roy Vagelos 박사님이 계시죠.

부러우면 지는거다 (8) – Dr. Roy Vagelos

George Scangos 박사님도 Greece 출신 이민자 3세이십니다. 할아버지가 이민자로 오시고 아버지는 보스턴에서 Exxon의 회계업무를 하셨다고 합니다.

Exclusive: Greek-American Scientist Heads Global Campaign for Coronavirus Treatment – Greek Reporter 3/9/2020

Scangos, who grew up in Lynn, Massachusetts before moving to Connecticut, is of direct Greek descent on his father’s side, as his grandparents came to the United States from Greece.

Apart from a successful career in several of the top biotech companies in the US, Dr. Scangos has also served as a Professor of Biology at Johns Hopkins University. He is currently serving on the Board of Trustees of Cornell University and the Board of Overseers of the University of California at San Francisco.

The Greek-American scientist received his B.A. in Biology from Cornell University and a Ph.D. in Microbiology from the University of Massachusetts.

Harvard Business School에 있는 Scangos 박사의 소개를 올립니다.

박사학위 취득후 Yale University에서 Postdoc을 하시고 1987년까지 7년간 Johns Hopkins University 교수가 되셨습니다. Johns Hopkins University 겸임교수로 여전히 후학을 가르치고 계십니다.

George Scangos, Ph.D. – Adjunct Professor, Department of Biology, Johns Hopkins University

Johns Hopkins University에서 Connecticut에 있는 Bayer으로 옮기셔서 10년간 계시면서 1993-1996년에는 President로 계셨죠.

그리고 San Francisco로 넘어가서 Exelixis의 CEO로 1996년부터 2010년까지 CEO로서 14년간 Exelixis의 성장을 이끌었고요 보스턴으로 오셔서 Biogen Idec으로 옮기셔서 2010년부터 2016년까지 회사의 Business Model을 Oncology에서 Neurology로 바꾸셨습니다. Exelixis의 성공을 이끈 George Scangos박사님의 중요성은 Forbes에서 취재한 일이 있습니다. Exelixis의 기반기술보다 George Scangos의 역할이 더 중요하다는 언급이 인상깊습니다.

A Formula For Biotech Success – Forbes 9/26/2000

How does Formela pick them? “I’m looking at four big components: What they’re doing, why they’re doing it, how they’re doing it, and who’s doing it.“

Sometimes “the who” can be incredibly important. For example, Formela says that if Craig Venter Craig Venter , the founder of Celera Genomics , were to walk into his office wanting to start a new company, he might jump at the chance before Venter even explained what he was going to do. But for mere mortals, Formela feels that to start a hot biotech firm, one has to find a way to match top scientists who have a cutting edge technique with an important use for the new technology.

That was the case when he first met with CEO George Scangos George Scangos of San Francisco’s Exelixis, which was originally just going to use fruit flies to look at a few particular proteins. “The what and the why did not impress me that much,” Formela says. “But the who were the brightest in the world.”

2017년에 보스턴 VC인 Arch Venture Partners와 세운 Vir Biotechnology에서 2023년까지 Scangos 박사님이 보여주신 Leadership은 정말 대단했습니다. Scangos박사님의 Biotech Network의 결정체라 할 수 있을까요?

Vir Grows with $500M in Financing, Humabs Acquisition, Two Up-to-$1B Collaborations – GEN Edge 10/18/2017

Less than a year after its launch, Vir Biotechnology today disclosed it has secured more than $500 million in financing toward an acquisition and a series of collaborations launched with two companies—each of which could generate over $1 billion—and four top-tier academic research institutions.

The collaborations, acquisition, and financing are aimed at building the company’s pipeline, technology, and global footprint, all with the goal of developing treatments for infectious diseases, Vir said.

Vir has pinpointed three areas of initial focus: chronic infectious diseases including hepatitis B (HBV), tuberculosis (TB), and human immunodeficiency virus (HIV); respiratory diseases that include influenza, respiratory syncytial virus (RSV), and metapneumovirus (MPV); and health-care acquired infections.

“We expect to move several compounds into clinical development in the next 18 months and we have an option to acquire a portion of a Phase 2 compound targeting flu. We also continue to evaluate several near-term opportunities to acquire additional mid- and late-stage clinical compounds, as well as expand our technology base even further,” Vir CEO George A. Scangos, Ph.D., said in a statement.

Dr. Scangos previously served as Biogen CEO before joining executives with research and industry experience to launch Vir in January with a $150 million commitment from ARCH Venture Partners alone, and additional funds from another prominent lead investor, the Bill & Melinda Gates Foundation.

“I am pleased that in our first year we have been able to align leading ideas, technology, and expertise focused on transforming the care of people with serious infectious diseases and providing a return to our investors,” Dr. Scangos added.

Vir has acquired Humabs BioMed, a Swiss discoverer and developer of fully human monoclonal antibodies to treat serious infections, for an undisclosed price. Humabs’ technology is designed to enable rapid isolation and development of antibodies that have passed natural selection by the human immune system in response to viral and bacterial diseases.

In acquiring Humabs, Vir has added to its portfolio more than 15 antibody development candidates—including preclinical antibodies designed to treat HBV, RSV/MPV, Zika, and dengue—as well as a proprietary antibody discovery platform and antibody engineering capabilities. Vir said Humabs and its employees will continue to operate the acquired company’s facilities in Bellinzona, Switzerland, and maintain its research collaboration with the Institute for Research in Biomedicine.

Vir also agreed to partner with Visterra on developing up to six antibodies to treat infectious diseases  and with Alnylam on up to five RNA interference (RNAi) therapeutics programs for the treatment of infectious diseases.

Visterra could gain from Vir more than $1 billion in payments tied to achieving development, regulatory, and sales milestones, plus royalties from future product sales, under an exclusive research collaboration, license, and option agreement signed by the companies.

Vir and Visterra also agreed to advance three infectious disease antibodies developed with Visterra’s novel Hierotope^TM technology, including antibodies against influenza, RSV, and fungal infections. Vir has the right to launch two additional research programs to develop antibodies against pathogens of its choosing.

With Alnylam, Vir has signed an exclusive license and collaboration agreement covering up to five RNAi therapeutics programs to treat infectious diseases. The companies have agreed to advance ALN-HBV02 for the treatment of HBV jointly, with Alnylam retaining an option to participate in commercialization of the product.

Vir also announced agreements of undisclosed value with four academic research institutions:

• Stanford University—Vir has licensed artificial intelligence technology designed to mine gene expression data for early diagnostic predictions and target discovery.
• Harvard University—Under a five-year strategic research alliance, Vir agreed to foster scientific collaboration with Harvard and provide financial support for innovative research projects in infectious diseases, to which Vir will have exclusive access to negotiate licenses.
• Oregon Health & Science University—Vir expanded an existing relationship with OHSU to include additional sponsored research. OHSU remains a key partner, Vir said, in the development of its cytomegalovirus (CMV) vaccine platform.
• Fred Hutchinson Cancer Research Center—Vir and Fred Hutch have inked a sponsored research agreement focused on cell therapy.

2년만에 Scangos 박사님은 Vir Biotechnology를 Nasdaq에 IPO합니다. 이 결정이 정말 신의 한수인 게 COVID-19이 2019년 11월경부터 알려졌는데 바로 직전에 IPO를 한 것입니다.

Scangos’ Vir heading to Wall Street with $100M IPO – Fierce Biotech 9/4/2019

Exelixis의 CEO로 1996년부터 2010년까지 CEO로서 14년간 Exelixis의 성장을 이끌었고 이후에도 이사회 멤버로 일하시다가 COVID-19 pandemic에 대응하기 위한 BIO에서의 역할을 맡으시기 위해 2020년 3월에 이사회직을 사퇴하셨습니다. 아래는 Scangos 박사님의 이사회 퇴직에 대한 창업자인 Stelios Papadopoulos 박사의 변과 Scangos 박사님의 말씀입니다.

Exelixis Announces George A. Scangos, Ph.D. to Retire From Its Board of Directors – Exelixis Press Release 3/2/2020

“George’s relationship with Exelixis reaches back to the earliest days of the company,” said Stelios Papadopoulos, Ph.D., co-founder of Exelixis and chairman of the Exelixis Board of Directors. “He was instrumental in getting Exelixis off the ground and establishing the scientific, technological, and business foundations that helped to pave the way for Exelixis to mature into the successful commercial oncology company it is today. Our Board of Directors is deeply grateful for his long-term service to Exelixis.”

Dr. Scangos cited his multiple professional and philanthropic commitments as principal reasons for his decision to retire from the Exelixis Board. Since January 2017, he has served as chief executive officer and board member of Vir Biotechnology, Inc., a clinical-stage immunology company focused on treating and preventing serious infectious diseases, including COVID-19.

“I consider myself extremely fortunate to have had the opportunity to serve Exelixis for more than two decades, first as CEO and then in an advisory role as a member of the company’s Board,” said Dr. Scangos. “Since stepping down as CEO almost 10 years ago, it has been tremendously exciting to see Exelixis persevere and prosper. With four marketed products, an expansive clinical development program for cabozantinib, and a reenergized discovery organization, Exelixis’ future is indeed very bright.”

그리고 때를 만난 Vir Biotechnology는 COVID-19 pandemic 동안 중요한 획을 긋게 됩니다.

Former Biogen CEO Scangos to be BIO’S COVID-19 czar: report – Fierce Biotech 3/1/2020

The chief executive of infectious disease biotech Vir, George Scangos, has been handed the reins to lead the biotech industry’s battle against the novel coronavirus COVID-19.

U.S. Vice President Mike Pence is heading up the government’s response to the coronavirus, but Scangos has been tapped by BIO to help lead its efforts to research therapeutics and diagnostics to stave off the spread of the virus.

“The role is still evolving, but it is clear someone needs to pick up the reins. It is only natural for us here at Vir to take on a leadership role,” Scangos said in an interview with Reuters.

This comes as the first deaths from the disease were registered in the U.S. over the weekend. The country is now stepping up its response to the disease with wider testing, which had been fairly limited over the past two months.

BIO의 수장으로서 뿐만 아니라 Vir Biotechnology의 CEO로서도 COVID-19 pandemic을 종식시키기 위해 애쓰셨고 Vir Biotechnology의 Antibody “Sotrovimab“는 GSK와의 협력으로 FDA 승인을 받게 됩니다.

GSK and Vir Biotechnology announce United States government agreement to purchase additional supply of sotrovimab, authorised for the early treatment of COVID-19 – GSK Press Release 1/11/2022

GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) today announced that the US Government will purchase an additional 600,000 doses of sotrovimab, an investigational monoclonal antibody for the early treatment of COVID-19, enabling further nationwide access to sotrovimab for patients. The additional 600,000 doses will be delivered throughout the first quarter of 2022. This agreement is an amendment to earlier commitments announced with the US Government in November 2021

Including the commitments announced today, GSK and Vir have received binding agreements for the sale of approximately 1.7 million doses of sotrovimab worldwide. In addition, today’s agreement also includes the option for the US government to purchase further additional doses in the second quarter of 2022.

Sotrovimab, which was granted Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA) in May 2021, is an investigational single-dose intravenous (IV) infusion SARS-CoV-2 monoclonal antibody. Under the EUA, sotrovimab can be used for the treatment of mild-to-moderate COVID-19 in adults and paediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalisation or death.

GSK and Vir expect to manufacture approximately 2 million doses globally in the first half of 2022 and additional doses in the second half of the year.

George Scangos, PhD, chief executive officer of Vir, said: “As the Omicron variant continues its rapid spread alongside the still prevalent Delta variant, we are pleased to once again work with the US government to provide more access to sotrovimab for people in the US at high risk of progression to severe COVID-19. Data from multiple pseudo-virus and live virus preclinical studies, generated by industry and academia, continue to demonstrate that sotrovimab retains activity against all tested variants of concern and interest. We are proud of our ongoing contributions to the fight against the COVID-19 pandemic here in the US and around the world.”

안타깝게도 이후에 변종에 대한 약효 미달로 인해 승인은 취소되었지만 그래도 이 노력은 높이 사야한다고 생각합니다.

FDA pulls authorization for GSK-Vir’s COVID therapy as BA.2 cases rise – Reuters 4/5/2022

Biogen에서 Scangos 박사님의 CEO로서의 업적은 Medical Marketing and Media에서 잘 정리가 되었습니다.

Former Biogen CEO George Scangos retires after 40-year pharma career – Medical Marketing and Media 1/25/2023

Scangos, a biotech lifer, is perhaps best known for previously serving as CEO at Biogen for six years starting in 2010, where he helped steer the company in a new direction. Under Scango’s leadership, Biogen dropped programs in cancer and instead focused its efforts on neuroscience – including the ALS drug Spinraza.

Scangos also bet $2.5 million on the now controversial Alzheimer’s treatment, Aduhelm, which was approved by the Food and Drug Administration in 2021 under the accelerated approval pathway.

Scangos left Biogen in 2016 and joined Vir in 2017, where he guided the company through the tumultuous years of the COVID-19 pandemic. A crowning achievement was Vir’s COVID-19 monoclonal antibody, sotrovimab, which was granted emergency use authorization by the FDA in 2021.

“George led the company through a period of significant transformation, accelerated its growth and established a broad pipeline and strategy that we believe will support our long-term success,” Vicki Sato, chairman of the board at Vir, said in a statement. Before his stint at Biogen, Scangos also served as president and CEO of Exelixis for 14 years, as well as chair of lobbying group PhRMA in 2016.

“[Vir] is operating from a position of strength with significant cash, an impressive pipeline and critical near-term catalysts that have the potential to support multiple important therapies,” Scangos said in a statement. “[W]e have laid out a vision for the company that gives me great confidence in Vir’s ability to transform the infectious disease landscape.”

이제 CEO 역할에서는 은퇴를 공식적으로 하신 상태이지만 일을 완전히 그만두신 건 아닙니다. 현재 George Scangos 박사님은 Arch Venture Partners의 Venture Partner로 계십니다.

George Scangos, Venture Partner at Arch Venture Partners

He is a former Chair of PhRMA, and the California Healthcare Institute. He was also a member of the Board of Directors of the Global Alliance for TB Drug Development.

Dr. Scangos currently serves on the boards of Agilent Technologies, Inc., Voyager Therapeutics, Inc., Octave Bioscience, Rezo Therapeutics and Life Sciences Cares. Dr. Scangos is currently a venture partner at ARCH Venture Partners.

Goerge Scangos, Director at Vir Biotechnology

George Scangos 박사님이 지금도 새로운 Biotech Platform을 만드는데 중요한 역할을 하시고 Global Biotech, Pharma, Academia 등과의 Networking을 통해서 이 분야의 발전에 조력하시는 모습은 저에게 큰 귀감이 되어서 이렇게 글을 남깁니다.

안녕하세요 보스턴 임박사입니다.

나이가 들어감에 따라 부부가 친구처럼 지낼 수 있다면 금상첨화라고 생각하는데요 그렇게 사시는 선배 부부가 있어서 여기에 소개를 하려고 합니다. 위 사진 어떤가요?

너무 귀엽지 않나요? 이 부부는 딸의 권유로 Instagram에 자신들의 사진을 올리기 시작했습니다.

Bon Pon 부부의 Instagram – BonPon511

이 분들은 이미 2017년 경부터 전세계적으로 유명세를 탔습니다. 몇가지 기사를 나눕니다.

이들을 보니 ‘늙고 싶다’… 60대 부부의 패션 인스타그램 – 국민일보 4/6/2017

60대 일본인 부부가 남다른 패션 감각을 자랑하는 커플룩으로 소셜미디어 스타 반열에 올랐다. 개설 4개월이 조금 넘은 이 부부의 인스타그램은 5일 현재 42만여명이 소식을 받아보고 있다. 올리는 사진마다 수만 개의 ‘하트’가 쏟아진다.

주인공은 남편 본(Bon·61)과 아내 폰(Pon·60)씨다. 모두 인스타그램에서 쓰는 애칭이다. 일본 매체에 인터뷰가 제법 실렸지만, 부부가 사는 곳과 실제 이름은 알려지지 않았다.

학창시절 만나 20대 초반 부부의 연을 맺은 뒤 37년간 결혼생활을 했다. 그 시절을 살아온 다른 부부의 인생과 다를 바 없다. 그러나 이 부부가 인스타그램(www.instagram.com/bonpon511)에서 보여준 커플룩 센스와 다정한 모습은 우리의 머릿속에 있는 노부부와 완연히 달랐다.

결혼생활이 37년이라고 해도 실제 함께한 시간은 그 세월의 3분의 1 정도밖에 안 된다. 최근 은퇴해 이제 겨우 천천히 둘만의 시간을 가질 수 있게 돼 기쁘다. 남은 인생을 사이좋게 살고 싶다“는 아내 폰의 마마스타 인터뷰 대답이, 노부부의 ‘졸혼’을 떠올리는 요즘 세태에 깊은 울림을 줬다.

폰과 본의 인스타그램 계정 ‘bonpon511’의 511은 두 사람의 결혼기념일이다.

‘귀염뽀짝’ 커플룩·달콤 애칭…“이 부부처럼 늙어가고 싶어” – 경향신문 2/25/2019

일본의 노부부들이 나이가 들어도 ‘멋’을 포기하지 않는 법을 알려주고, 저렇게 늙어갈 수 있다면 나이 먹을 만하겠다 싶은 용기를 준다. 일본은 우리에게 ‘졸혼’이란 신세계를 알려준 나라이지만, 앞서 고령화를 경험한 사회답게 부부가 행복하게 늙어갈 수 있는 노하우를 알려줄 인생 선배들도 많다.

<아직 즐거울 날이 잔뜩 남았습니다>(웅진지식하우스)는 인스타그램에서 어느새 80만명의 글로벌 팬을 거느리고 있는 일본의 은퇴한 60대 부부의 이야기다. 책은 이들이 원래 살던 단독주택에서 체력적으로 관리가 가능한 작은 아파트로 이사하는 것에서부터 시작한다. 가지고 있던 가구와 식기 등 모든 살림살이의 양을 10분의 1로 줄이고 낡은 아파트를 직접 수리하면서 삶의 ‘마지막 터전’을 준비하는 모습은 역설적이게도 첫 보금자리를 꾸미는 신혼부부처럼 설렘 가득하다.

그러나 무엇보다 이 부부를 사회관계망서비스(SNS) 스타로 만든 것은 ‘커플룩’ 패션이다. 요새는 젊은 연인들도 손발 오그라든다며 잘 입지 않는 커플룩이지만, 서로를 ‘본’(bon·남편)과 ‘폰’(pon·아내)이란 애칭으로 부르는 은발의 부부가 맞춰입은 커플룩은 의외로 신선하고 귀엽다. 딸의 권유로 시작한 커플룩 덕분에 오히려 젊은 시절보다 나이가 든 지금 패션의 즐거움에 눈을 뜨게 됐다. 폰이 체크무늬 티셔츠를 입으면, 본은 같은 패턴에 색깔만 다른 셔츠를 입거나 머플러를 두르는 식이다. 연금으로 생활하고 있으니 값비싼 옷은 사기 어렵다. 이들은 젊은이들처럼 인터넷 옥션을 통해 모던한 분위기의 저렴한 옷들을 구입한다. 이들의 커플룩 사진이 올라오는 인스타그램은 그때마다 수많은 ‘좋아요’ 세례를 받는다.

노부부의 일상과 패션을 다룬 일본의 책들이 연이어 한국에 소개되고 있는 것은 일본이 우리보다 앞서 고령화 사회를 경험한 나라임과 무관하지 않다. 일본 서점가에는 노인들이 읽으면 좋은 책, 노인들이 가면 좋은 음식점 등 노년생활을 즐기며 살 수 있는 세부적인 조언의 책들이 많이 출간된다.

<아직 즐거울 날이 잔뜩 남았습니다>를 낸 웅진지식하우스 측은 “발매 일주일도 되지 않아 2쇄가 결정되는 등 한국에서의 반응도 뜨겁다”면서 “인스타그램 팔로어나 독자 반응을 살펴보면, ‘이 부부처럼 살고 싶다!’ ‘따라하고 싶다!’라는 반응들이 많다”고 말했다.

‘세계 80만 팔로워’ 日 백발 패셔니스타 부부…중저가 브랜드·중고 의류로 멋내 – 세계일보 2/14/2019

일본의 60대 부부인 본(63·Bon)씨와  그의 아내 폰(61·Pon) 여사가 화제다. 백발 패셔니스타로 불리는 이 부부는 단정하면서도 센스 있는 커플 패션을 담은 사진을 인스타그램에 올려 유명인사가 됐다. 

본·폰 부부는 2016년 12월부터 인스타그램으로 SNS(사회관계망서비스) 활동을 시작했다. 

본·폰 부부는 퇴직 후 일상 생활을 사진으로 찍게 됐는데, 이를 인스타그램에 공유한 게 큰 인기를 끌었다.  

네티즌들은 이 부부에게 수만개의 ‘좋아요’를 선사하면서 각국 언어로 “이렇게 살고 싶다”, “정말 멋진 부부다”, “이 부부처럼 늙고 싶다” 등의 댓글을 다는 등 이들의 포스트에 열광했다. 

본·폰 부부는 지난 13일 인스타그램을 통해 조선일보와 가진 인터뷰에서 “호기심을 잃지 않고 긍정적 사고를 하는 것이 젊게 사는 비결“이라고 라이프 스타일을 설명했다.

두 사람이 지난 8일 출간한 에세이집 ‘아직 즐거운 날이 잔뜩 남았습니다'(웅진지식하우스·표지 사진)에 의하면 이 부부는 1970년대 도쿄의 미술전문학교에서 만나 80년 5월11일 결혼했다. 

그래픽 디자이너로 일하던 본씨가 퇴직하자 부부는 30년간 거주하던 아키타의 2층짜리 단독 주택을 떠나 센다이 소재 방 2개짜리 저렴한 아파트에 정착한 뒤 제2의 신혼생활을 만끽하고 있다. 연금 생활자인 만큼 자동차는 없애고 살림살이도 10분의 1로 줄였다. 옷을 구입할 땐 한벌에 5000엔(약 5만원) 이하의 중·저가 브랜드에서 골랐고, 야후 옥션에서 중고 의류도 사 입었다.

두 사람은 에세이집에서 소박한 삶에서 느끼는 잔잔한 행복과 세월의 연륜에서 묻어나는 생활 지혜, 철학을 소개하고 있다. 또 화제를 모은 옷차림과 패션 센스를 공유하게 된 사연도 공개했다. 

결혼생활 40년차 노부부가 전한 삶의 철학과 금슬좋은 부부관계의 팁은 그리 대단하지는 않다. 소박하면서도 남다른 일상을 보내다 보면 행복한 노년을 맞을 수 있다고 부부는 입을 모은다.

보스턴 임박사 생각

너무 보기 좋지 않나요? 나이가 든다고 낡아질 것이 아니라 호기심을 가지고 매사에 열심히 사랑하다 보면 이렇게 예스럽게 나이들어갈 수 있을 것 같아요. 부럽습니다.

안녕하세요 보스턴 임박사입니다.

RAPT Therapeutics는 2015년에 Bristol-Myers Squibb (BMS)가 Flexus Biosciences를 $1.25 Billion에 인수한 이후 BMS가 관심이 없는 “FLX925, a dual inhibitor of FLT3 and CDK4/6″을 가지고 Spin off해서 FLX Bio라는 이름으로 설립되었습니다.

Flexus Biosciences Chemists Spin Off New Company After Bristol-Myers Squibb $1.25 Billion Buyout – Biospace 4/8/2015

After San Carlos, Calif.-based Flexus Biosciences was bought by New York’s Bristol-Myers Squibb Company for $1.25 billion in February 2015, company execs Terry Rosen and Juan Jaen turned around and started a new company.

Less than two months later, two of the Flexus’s executives and founders, Terry Rosen, Flexus chief executive officer, and Juan Jaen, head of Flexus research and development, have joined to form a new company. They plan to crank out a new immuno-oncology drug candidate once a year.

The Bristol-Myers Squibb deal bought the company and the ID01 and TD02 compounds, but the rest of the assets are being spun into the new company. Although details are still pending, Rosen and Jaen expect funding will come from investors who invested in Flexus.

The most likely candidate for the new company is FLX925, a dual inhibitor of FLT3 and CDK4/6, which were licensed from Thousand Oaks, Calif.-based Amgen in 2004. They first met while students at the University of Michigan. Rosen stayed with Amgen in May 2014.

The two men worked together at South San Francisco, Calif.-based Tularik before that company was acquired by Amgen . Rosen stayed with Amgen, but Jaen left to be the chief science officer and senior vice president of drug discovery at ChemoCentryx, Inc. , then joined together in 2013 to form Flexus.

“We’ve done some good initial work,” says Rosen in a statement, “and we feel good about it, but our goal is to build something that is long term and sustainable.”

FLX Bio는 Celgene 주도하에 $29 Million Series A를 한 후 $50 Million Series B를 했습니다.

Backed by Celgene, Bay Area Startup FLX Bio Bags $50 Million to Push Lead Drug into Clinic – Biospace 4/28/2016

FLX’s FLX925 is a selective inhibitor of FLT3 and CDK4/6 and is being studied in a proof-of-concept study in patients with acute myeloid leukemia. The drug is moving into a Phase I clinical trial. FLX925’s dual-inhibitor action may be more effective in treating FLT3-mutated AML than other FLT3 inhibitors, resulting in greater clinical benefit. Furthermore, FLX925 has the potential to treat a wider array of cancers beyond AML, the company said on its website. In addition to FLX925, FLX also has two pre-clinical immuno-oncology programs in early development.

The $50 million raised in the latest round will go nicely with $29 million in Series A funding privately-held FLX previously raised. That makes $79 million in less than one year since FLX Bio was founded. The Series B financing was supported by multiple venture capital and biotech groups, including The Column Group (TCG), Topspin Partners, Kleiner Perkins Caufield & Byers (KPCB) and Celgene .

그리고 1년만에 다시 $60 Million Series C를 했습니다. 이 때에는 Google Ventures (GV)가 투자를 했습니다. 2017년에 CCR4 Inhibitor Tivumecirnon (FLX475)의 임상1상이 시작했습니다. BMS/Flexus Biosciences에서 가져온 FLX925는 파이프라인에서 제외되었습니다.

Celgene, GV-backed FLX gets off $60M round, kick-starts I-O trials – Fierce Biotech 12/21/2017

South San Francisco, California-based FLX emerged from Bristol-Myers Squibb’s $800 million takeover of Flexus Biosciences, with a pipeline of prospects the Big Pharma decided it could live without.

It now has the cash and the early data to push on with phase 1 tests, just started, for its oral CCR4 inhibitor FLX475. This drug focuses on a key pathway by which tumors recruit regulatory T cells to suppress tumor immunity. By blocking this pathway with a CCR4 antagonist, the biotech is betting that it can prevent regulatory T cell recruitment to the tumor site, reduce the number of regulatory T cells in the tumor and importantly, enable immune activation and tumor killing. The biotech also sees FLX475 as having the potential to boost cell-based immunotherapies, such as CAR-T and cancer vaccines, which could lead to combos in the future.

The company adds that it’s also now looking to pick out another clinical candidate next year, this time targeting ubiquitin specific protease 7 (USP7), as well as working on its GCN2 program. USP7 plays a key role in two cancer pathways: it promotes the formation and function of regulatory T cells by deubiquitinating and stabilizing FOXP3; and it maintains low levels of p53, a prevalent tumor suppressor protein (and the focus of several other early-stage biotechs), thereby allowing the tumor to grow unchecked.

GCN2, meanwhile, is a myeloid-derived suppressor cell target that works downstream of IDO and arginase. GCN2 inhibition has the potential for superior efficacy, as it can reverse immune suppression caused by depletion of both tryptophan and arginine.

FLX475 hits the clinic on the strength of preclinical data presented by FLX earlier this year. Those results showed that FLX’s CCR4 antagonists block the migration of regulatory T cells—in the tumor but not in peripheral tissues—and aid the expansion of activated effector T cells. Adding the CCR4 antagonist to anti-PD-L1 and anti-CD137 antibodies dialed up the tumor-killing effects of these drugs.

FLX lists the CCR4 antagonist program as the most advanced in its pipeline, despite having started life with a FLT3 and CDK4/6 inhibitor that was already in phase 1. Flexus moved that drug, FLX925, into the clinic just before being bought by Bristol-Myers. FLX925 has since disappeared from FLX’s pipeline, although a phase 1/1b dose-escalation trial is listed as ongoing on ClinicalTrials.gov.

2년 후 FLX Bio는 Immuno-Oncology에 주력하던 Business Model을 Allergy와 Inflammator Diseases로 확대하면서 사명을 RAPT Therapeutics로 바꿉니다. 그리고 오늘 얘기할 Zelnecirnon (RPT193)의 임상시험 계획을 발표했습니다.

FLX Bio keeps it capital in RAPT Therapeutics rebrand – Fierce Biotech 5/24/2019

Now, the biotech is renaming itself RAPT Therapeutics to reflect its expansion into allergy and inflammatory diseases.

“Since our founding, we have internally discovered and advanced two unique drug candidates that target CCR4, with FLX475 in development for the treatment of multiple cancers and RPT193 expected to enter clinical studies in the second half of 2019,” Wong said.

Unlike FLX475, which focuses on Tregs, the inflammation candidate RPT193 takes aim at helper T cells. Tregs suppress other immune cells to shut down the immune response—for example, to prevent autoimmune disease—while helper T cells activate other immune cells. RPT193 is designed to block the movement of type 2 helper T cells into inflamed tissues and reduce inflammation in diseases such as asthma, rhinosinusitis and atopic dermatitis. RAPT plans to file an IND for the drug by the end of the year.

사명 변경을 한 지 한달 후 $37 Million Series C Extension을 했고요.

Bringing Novel Investigational Treatments for Eczema, Asthma and Cancer One Step Closer to Approval. RAPT Therapeutics completes $37 Million Series C Extension – Press Release 6/18/2019

4개월만에 IPO를 했습니다.

Rapt Therapeutics revives IPO, files to raise $75M – Fierce Biotech 10/23/2019

2019년 12월에는 한국의 한미약품이 Tivumecirnon (FLX475) 의 한국 및 중국판권을 $10 Million upfront 포함 $118 Million 규모의 계약을 맺었습니다.

Rapt edges into Asia with Hanmi I-O deal worth up to $118M – Fierce Biotech 12/3/2019

IPO 후 4개월만에 다시 $75 Million 유상증자를 했습니다.

RAPT Therapeutics Announces Pricing of $75 Million Public Offering – CNN Business 2/7/2020

다시 1년 후에 $144 Million 유상증자를 했습니다.

RAPT Therapeutics announces closing of public offering of common stock and full exercise of underwriter’s option to purchase additional shares – Press Release 6/18/2021

다시 1년반만에 $75 Million 유상증자를 했습니다.

RAPT Therapeutics $75 million follow-on offering – Davis Polk 11/22/2022

유상증자로 충분한 자금확보를 하고 Zelnecirnon (RPT193)과 Tivumecirnon (FLX475) 의 임상이 잘 진행되던 중 Zelnecirnon의 임상시험을 받던 아토피 피부염 환자의 간기능이 나빠지면서 임상시험이 중단되었습니다. Tivumecirnon (FLX475)의 임상시험은 계속 진행됩니다.

RAPT faces ‘unfortunate and unexpected’ clinical hold after liver failure in atopic dermatitis trial – Fierce Biotech 2/20/2024

Rapt Therapeutics is reeling from an “unfortunate and unexpected” clinical hold after a patient in a phase 2 immunology trial experienced liver failure that may be related to the study drug. 

The serious adverse event occurred in a phase 2b atopic dermatitis trial. The cause remains unknown but Rapt said the event may be “potentially related to zelnecirnon.”

The FDA notified Rapt of the clinical hold on both the phase 2b atopic dermatitis trial and a phase 2a study in asthma. 

Rapt noted that roughly 350 patients have been treated with the drug across three trials and no signs of liver toxicity had been reported before now and there has been no evidence of potential liver toxicity in clinical trials. At the end of November, Rapt published phase 1 data of zelnecirnon which found that the drug was “generally well-tolerated” with no serious adverse events and that all reported side effects were mild-to-moderate. 

The South San Francisco biotech says that the person had a drug allergy to Dupixent, an autoimmune disease requiring thyroid hormone replacement therapy, contracted COVID-19 during the trial and used “an herbal supplement known to be associated with liver failure.” 

That meant little to investors, with the company’s share price nosediving after the markets opened Tuesday, down 64% from $25.97 to $9.25.

With the inflammation program on hold for now, all attention turns to Rapt’s phase 2 oncology med, tivumecirnon, which is being tested alone and in a combo with Merck & Co.’s Keytruda.

Rapt reported $184.8 million in cash on hand at the end of September, enough to last into the middle of 2025. 

아토피 피부염 임상2b를 진행하는 중이었는데 QD 50mg, 200mg, 400mg의 3개의 cohort로 진행 중이었고 환자는 268명이 참가한 상태입니다.

Zelnecirnon (RPT193)의 메카니즘은 아래와 같습니다. helper T cell을 조절합니다.

현재 RAPT의 파이프라인은 아래와 같습니다.

2024년 1월에 발표한 회사 Presentation은 아래에 링크합니다.

Clinical Hold를 풀기 위해서 많은 노력을 하리라 생각하는데 당분간 증자는 어려워 보이네요. 건투를 빕니다.