(Picture: Juan Jaen and Terry Rosen, source from Chem & Eng News)
안녕하세요 보스턴 임박사입니다.
이번에는 두사람의 과학자의 우정이 낳은 수십년간의 여정에 대해서 좀 나누려고 합니다. 두사람의 이름은 Terry Rosen박사와 Jaun Jaen박사로서 이들의 우정은 학창시절 University of Michigan에서의 만남으로 시작됩니다. 이 두사람은 후에 ,Tularik에서 함께 일하는 기회가 있었습니다. Tularik은 2004년에 Amgen에 합병되었고 이 때 두사람은 잠시 헤어지게 됩니다.
Terry는 10년간 Amgen에 남아서 일을 했고 VP of therapeutic discovery and San Francisco site leader at Amgen이었습니다. 반면에 Juan은 Amgen에 몇년 머문 후 ChemoCentryx에서 CSO and SVP of drug discovery로 일하게 됩니다.
2013년에 Terry Rosen과 Juan Jaen은 다시 의기투합을 해서 Flexus Biosciences를 설립하기로 합니다. 몇가지 중요한 결정을 했는데요. 첫째는 당시 유행하던 Immuno-Oncology 분야보다는 아직 시작되지 않은 Regulatory T cell (Treg)를 modulation하는 small molecule drug discovery로 Business Model을 잡았고 투자자들을 만나기 시작했습니다. 특히 Kleiner Perkins의 VC인 Beth Seidenberg를 만났고 그녀는 Celgene에 이 회사를 소개함으로써 Series A를 완성하게 됩니다. 그리고 이 만남이 결국 BMS로 2년만에 Acquired 되는 결과가 됩니다. Series A & B를 합쳐서 $38 Million을 확보하고 Treg small molecule program을 시작합니다. IDO-1 program이 lead program이었습니다.
If Amgen ($AMGN) and Genentech had a love child that was being raised by Celgene ($CELG) and Kleiner Perkins Caufield & Byers, that would be Flexus Biosciences. Suddenly, after shunning public attention for more than a year, the cancer immunotherapy startup is ready for the limelight now that it is headed toward the clinic, has banked its first two venture rounds totaling $38 million and boasts impressive management, board and advisory rosters.
Flexus was co-founded by CEO Terry Rosen as well as President and head of R&D Juan Jaen. The pair had worked together for almost a decade at Tularik before it was acquired by Amgen for $1.3 billion in 2004, although they had met years earlier as students at the University of Michigan.
Rosen opted to remain with Amgen for nearly a decade, most recently as its VP of therapeutic discovery and San Francisco site leader. For his part, Jaen left Amgen after a few years to be the CSO and SVP of drug discovery at ChemoCentryx ($CCXI). The pair came back together to found Flexus in late 2013.
In early 2013, Rosen left Amgen after some initial conversations with VCs. He spent some time combing through research papers and having open, high-level conversations with leading academics. Rosen and Jaen settled on a strategy of discovering and developing small molecule cancer immunotherapies targeting regulatory T cells with encouragement from Beth Seidenberg of KPCB, who is now the chairperson of Flexus’s board.
She introduced the young company to Celgene. Not surprisingly, the big biotech, which is aggressive in pursuing investment in and partnership with early stage and innovative oncology startups, expressed an interest in investing.
By the time Flexus closed a roughly $13 million Series A in October 2013 from KPCB and Celgene as well as friends and family, the Flexus team, site and technology had already started to coalesce. Kristen Hege, VP of translational development of hematology and oncology at Celgene, is a board observer, and Rosen attributes her with being influential in the company’s evolution as it has moved from discovery toward the clinic.
Before he founded the company, Rosen had long been intrigued by the promise of cancer immunotherapy. He saw the data coming out for Yervoy from Bristol-Myers Squibb ($BMS) as a real proof of concept for the field of cancer immunotherapy. Rather than pursue an immunotherapy segment that was already well attended, such as immune checkpoint inhibitors, Flexus opted to target regulatory T (Treg) cells using small molecules.
He saw the science around Treg cells as thoroughly researched by academics with myriad breakthroughs over the decades, but that the work just hadn’t been translated by an industry that was, at the time, largely afraid of early, ambitious, science-driven startups in the wake of the bursting of overinflated genomics expectations that haunted the sector for years after the rapid 1999-2000 market crash.
Treg cells keep immune response to foreign antigens in check. In cancer, they prevent the immune system from working against the disease. The accumulation of Treg cells typically correlates with a poor prognosis for cancer patients, particularly those with melanoma, lung, ovarian and breast cancers. Flexus is working to modulate these Treg cells that inhibit the patient’s own immune system from attacking the cancer.
From an initial list of 10 to 15 potential targets, Flexus narrowed down its priorities to three initial targets that it could hit with small molecule candidates. It hopes to get into the clinic with a selective IDO-1 inhibitor candidate by the end of 2015, with the potential in the first quarter of 2016 for a combination study with another drug such as an immune checkpoint inhibitor or even a more traditional anticancer agent. In addition to the potential for in-licensing, Rosen said he expects the company to internally generate one IND filing annually.
Alexander Rudensky, the chairman of the Immunology Program and director of the Ludwig Center at Memorial Sloan Kettering Cancer Center, chairs the startup’s clinical and scientific advisory board. A National Academy of Sciences member, Rosen noted that Rudensky “is probably the biggest name in Treg biology in the context of oncology.”
On the mission of the company, Rosen summed up, “We are focused on altering the tumor microenvironment by interfering with the biology of immunosuppressive Treg cells. This will enable effector T and natural killer cells, the soldiers of the immune system, to attack and eradicate those tumors. Our goal is to turn cancer into a chronic disease that is managed with drugs that are safe and easy to administer.”
BMS acquires biotechnology firm Flexus Biosciences for $1.25bn. – Pharmaceutical Technology 4/9/2015
Bristol-Myers Squibb (BMS) has completed the acquisition of biotechnology firm Flexus Biosciences for around $1.25bn. Under the deal, Flexus has received an upfront payment of $800m, in addition to the development milestone payments that could total up to $450m.
As part of the deal, BMS received full rights to F001287, Flexus’s lead preclinical, small-molecule IDO1-inhibitor targeted for IND filing in the second half of this year.
The deal also includes the acquisition of Flexus’s IDO/TDO discovery programme that includes its IDO-selective, IDO/TDO dual and TDO-selective compound libraries.
All non-IDO/TDO assets of Flexus, from and after the closing, will be retained by the newly formed entity created by the current shareholders. The new entity also retains assets related to Flexus’s Phase I FLT3 and CDK4/6 inhibitor, its earlier stage small-molecule Treg cancer immunotherapy programmes and current personnel and facilities.
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 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.
“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.”
Bristol-Myers Squibb drops phase 3 trials of $800M IDO drug. – Fierce Biotech 5/1/2018
Bristol-Myers Squibb has pulled two phase 3 clinical trials of the IDO1 inhibitor it acquired through an $800 million takeover of Flexus. The studies are the latest dominoes to fall following the failure of Incyte’s rival IDO drug to move the needle in a pivotal trial.
Enrollment in the phase 3 trials of Bristol-Myers’ IDO1 drug BMS-986205 and cornerstone checkpoint inhibitor Opdivo in patients with non-small cell lung cancer or head and neck cancer was just getting started when news of Incyte’s setback hit less than four weeks ago. The Incyte data triggered a rapid re-evaluation of the IDO field, causing first NewLink and now Bristol-Myers to reconsider their strategies. The rethink led Bristol-Myers to halt the trials after recruiting just one of the 1,750 subjects it initially planned to enroll across the two studies. Bristol-Myers listed “business objectives have changed” as the reason for canning the trials.
Bristol-Myers has also effectively killed a phase 3 trial of the IDO1-PD-1 combination as a first-line treatment of patients with metastatic or unresectable melanoma, the same indication targeted in the Incyte study. The trial is active but has stopped enrollment well short of its target. Bristol-Myers had planned to enroll 700 patients, but recruitment stopped with 72 subjects on board.
The actions wipe out Bristol-Myers’ near-term chances of establishing BMS-986205 as an essential add-on to Opdivo in some critical indications for its immuno-oncology franchise. But they fall short of completely killing off the asset.
With that in mind, Bristol-Myers is still enrolling patients in seven phase 1 and 2 trials featuring BMS-986205, including a study of the IDO1 drug in combination with Opdivo—and, in some cases, Yervoy—in 907 patients with advanced tumors. Four other trials featuring BMS-986205 are enrolling 200 to 500 patients. These studies also feature LAG-3 candidate relatlimab and a clutch of Bristol-Myers’ established oncology products.
BMS-986205는 Incyte Pharmaceuticals의 Epacadostat (INCB2436205)의 임상실패의 영향으로 BMS가 임상3상을 중단하는 결과를 맞게 됩니다. 비록 IDO1 inhibitors의 class action으로 임상이 중단되었지만 BMS-986205가 Phase 3까지 잘 진행되고 있었다는 것을 보았을 때 Flexus의 Drug Development는 잘 진행되었던 것을 알 수 있습니다.
BMS-986205의 HCC에 대한 Phase 1/2결과는 2024년 Investigational New Drug에 보고되었습니다.
IDO1 Inhibitors의 개발에 대한 좋은 리뷰를 남깁니다.
Flexus Biosciences가 BMS에 인수될 때, BMS는 IDO/TDO programs에만 관심이 있어서 나머지 프로그램을 가지고 Terry와 Juan은 새로운 회사인 Arcus Biosciences를 설립합니다. Arcus Biosciences에 대해서는 다음에 얘기하겠습니다.
BOSTON DR LIM 