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.Terry Rosen
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.Beth Seidenberg
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.
"All these immune checkpoint inhibitors boost the immune system in one way or another. The piece that was getting less attention is--how is the tumor evading the immune system in the first place?" Rosen said in an interview with FierceBiotech.
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.
Flexus has taken its time accumulating a top-tier group of executives and board members. Dr. David Goeddel, the first scientist hired by Genentech whose work was the basis for 5 marketed therapeutics there, is also on the Flexus board. Goeddel is a managing partner at The Column Group, which participated in the Flexus Series B round that closed at the end of July at over $25 million.
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."
Among the Flexus executives are COO Yujiro Hata, who was VP of corporate development and strategy at Onyx Pharmaceuticals, which Amgen acquired for $10.4 billion in October 2013; and CSO Jordan Fridman, who was executive director of pharmacology at Incyte ($INCY).
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."