Five years ago, there was not much happening with cancer immunotherapeutics at a commercial level. Now, almost every company with biological research capacity is working in the area. The tipping point was Bristol-Myers Squibb Co.’s antibody Yervoy (ipilimumab), the first and as yet only therapeutic product marketed as a “checkpoint inhibitor.” Approved by the FDA in March 2011, Yervoyinhibits a protein called CTLA-4, only recently recognized as a mechanism by which tumors can shut down the immune system and thereby protect themselves. Impeding inhibition has turned out to be an exceedingly successful approach in a subset of patients diagnosed with stage IV melanoma. Ordinarily, with a death sentence delayed only months by conventional treatments, some 22% of individuals treated with Yervoy remain alive three years later. The drug fetches $120,000 per four-injection course of treatment, and will generate over $1 billion in revenues for BMS in 2014.

A slew of cancer immunotherapy drug candidates are crowding behind Yervoy. Merck & Co. Inc.'s anti-PD-1 antibody Keytruda (pembrolizumab) was approved on September 4. (SeeAlso see "Safety Profile Of Merck’s Anti-PD-1 Keytruda Shines In FDA Labeling" - Pink Sheet, 5 September, 2014..) In the US, BMS is about eight months behind Merck with its own anti-PD-1 antibody nivolimumab, which gained the world's first approval in Japan in early July. While these Big Pharmas presently lead the surge of clinical development, others, including Roche and AstraZeneca PLC, are gaining momentum along with a growing number of start-ups and “second-stage” biotech companies. Many of today's most promising cancer immunotherapy drug targets, proteins such as CTLA-4, PD-1, PDL-1, TIM-3, LAG-4 and more, were long ago identified in the scientific literature, but – crucially – not in the context of cancer treatment. The groundbreaking insight, credited largely to ipilimumab's discoverer James Allison, PhD, now at the University of Texas MD Anderson Cancer Center, has investors and clinicians alike excited about “freedom to operate” and to develop novel intellectual property.

The backers of Jounce Therapeutics Inc. figure now is a terrific time to build a company capable of making big plays in cancer immunotherapy. The start-up, based in Cambridge, MA, launched in September 2013, with Allison and other pioneers of the field as its founders and advisors. (See[A#2014900116].) That star power, rallied by venture capital firm Third Rock Ventures, has just helped Jounce achieve a major recruiting coup. In early July 2014, Jounce named as its new CEO Richard Murray, PhD, formerly SVP of Merck, responsible for protein therapeutics and vaccines.

Murray's bona fides are beautifully suited to the task at hand: he was integrally involved in advancing Merck's anti-PD-1 program, and in ushering pembrolizumab from the lab through to the acceptance of its Biologics License Application (BLA) filing in just over three years. “That was a Merck that did that,” he notes, adding, “but there is no reason why Jounce can't do as good or better.”

Murray says he made the jump to Jounce “because the founders are absolutely world class, and the depth of knowledge they bring to the table is important. Jounce has been structured to benefit from a continuous flow of their insight.” Jounce aims to leapfrog conventional methods of creating antibodies to new targets, Murray explains, by utilizing a translational R&D approach that begins with cancer tumor specimens gathered by scientific advisor Robert Schreiber, PhD, of the Siteman Comprehensive Cancer Center at Washington University’s School of Medicine. Murray says having access to these clinical samples means that Jounce can “try to make a very early assessment, kind of a blueprint, of which mechanisms might be most relevant to specific types and segments of cancer.”

Like other companies developing immunotherapies against cancer, Jounce envisions creating in addition to inhibitory antibodies like Yervoy, other drugs that act as agonists to directly stimulate the immune system. Theoretically, antibodies against certain new targets could provoke a more specific and effective immune response than interferon and stacks of failed immune stimulators. The idea of mixing and matching agonists and antagonists raises the exciting notion of fighting cancer along different pathways simultaneously – and the disturbing prospect of horribly expensive treatment regimens. But first things first.

For now, Jounce is focusing on identifying single-agent immunotherapies worthy of taking into human testing. The durability of patients' response is a key attraction of immunotherapies that will likely necessitate longer and more expensive clinical trials for everyone in the field, Murray says. But there is a positive counterweight to this challenge, he emphasizes: namely, “the proximity of the first clinical responses.” He notes that Merck and other companies testing anti-PD-1 compounds were able to get a read in just 20 or 30 patients, and then quickly expand the testing cohort around the chosen dose. Antibodies against other new targets should also yield actionable data fast, Murray suggests.

Although some young companies in this blazing-hot field have struck deals with Big Pharmas for preclinical candidates, Jounce has no intention of selling assets so early. “It's not easy to leverage a platform,” Murray observes, “but the big win, the big value, the swing for the fences is the important drug that you create.” With that objective in mind, he says Jounce will pursue development projects that it can take to big inflection points, “to really make a difference for cancer patients.”

Editor’s note: updated post-publication with Keytruda approval.

Jounce's Immunotherapy Recruiting Coup

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