Jounce plunges after ASCO abstract reveal

cancer
A trial paired JTX-2011 with Opdivo. (Pixabay)

Shares in Jounce Therapeutics plummeted upon the publication of an abstract for a phase 1/2 trial of its first-in-class ICOS inhibitor JTX-2011, although the company says the drug showed evidence of efficacy.

Jounce was down around 30% premarket as investors digested the preliminary data from the ICONIC trial, which is comparing JTX-2011 on its own and in combination with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) in ICOS-positive tumors, including gastric cancer, triple negative breast cancer (TNBC), head and neck squamous cell cancer (HNSCC) and nonsmall cell lung cancer (NSCLC).

According to the abstract data—which was current as of January 27 so may be different when presented at ASCO on June 2—there was one partial response out of seven gastric cancer patients when JTX-2011 was given as a monotherapy, while two out of five patients with TNBC had stable disease. When paired with Opdivo, there were two partial responses and two patients with stable disease out of 19 patients, and just one partial response out of 15 TNBC patients.

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While Jounce’s chief medical officer Elizabeth Trehu, M.D., says the data “demonstrated evidence of biologic activity and tumor reductions in heavily pre-treated patients who have failed all available therapies,” investors were nevertheless clearly spooked by the data.

The scale of the reaction no doubt reflects the importance of JTX-2011 to the Cambridge, Massachusetts-based biotech’s $2.6 billion immuno-oncology alliance with Celgene, heading for its second anniversary next month.

JTX-2011 is a monoclonal antibody that specifically targets ICOS, a T-cell surface protein that is thought to ramp up the response of T effector cells while damping down the activity of T regulatory cells—a bit like simultaneously pressing the accelerator and releasing the brake on the immune system.

The drug was well-tolerated in the study, according to the abstract, and Jounce is also encouraged by data showing that T cell subgroups expressing ICOS can be detected. That could be a biomarker for response in future trials.

Ahead of the publication of the abstract, Jounce said that the objectives of the trial were to show “an acceptable safety profile, both monotherapy and combo … demonstration that the drug has activity and [a] relationship to a biomarker.”

It said it has hit enrollment targets in the other portions of the study, including the HNSCC and NSCLC cohorts, and is on track to start an arm combining JTX-2011 with a CTLA-4 inhibitor later this year. Clinical and preclinical data suggest that ICOS mediates anti-CTLA4-driven antitumor responses.

It is also expecting to file for approval to start phase 1 trials of PD-1 inhibitor JTX-4014 before the end of 2018.