Robert Hershberg, MD, PhD, Celgene executive vice president and head of business development

On its way to being acquired by Bristol-Myers Squibb (BMS), Celgene has restructured its three-year-old alliance with Jounce Therapeutics by terminating their up-to-$2.6 billion collaboration to develop multiple cancer immunotherapies, with Celgene instead committing potentially $530 million-plus for global licensing rights to a single Jounce preclinical candidate antibody.

The narrower collaboration will see Celgene overseeing all development and commercialization for JTX-8064, Jounce’s first candidate to emerge from its Translational Science Platform efforts focused on tumor-associated macrophages. JTX-8064 consists of a potential first-in-class antibody designed to target the leukocyte immunoglobulin like receptor B2 (LILRB2) receptor on macrophages.

In return, Celgene agreed to pay Jounce $50 million upfront; up to $480 million payments tied to achieving development, regulatory, and commercial milestone; and royalties on potential worldwide sales.

“We look forward to advancing its development toward an IND filing,” Robert Hershberg, MD, PhD, Celgene executive vice president and head of business development, said in a statement.

On April 3 at the 2019 American Association for Cancer Research (AACR) Annual Meeting in Atlanta, Jounce trumpeted positive preclinical data for JTX-8064 in a poster presentation (Abstract 5007) showing the immunotherapeutic properties of the antibody candidate to reprogram immune-suppressive macrophages within the tumor microenvironment.

LILRB2 binds to its ligands—classical MHC I molecules such as HLA-A and HLA-B and non-classical MHC I molecules such as HLA-G—and maintains an immuno-suppressive state in macrophages. JTX-8064 is designed to block ligand binding to LILRB2 and induce an immune-activating state in macrophages that according to Jounce may lead to enhancement of the anti-tumor immune response.

In refocusing the collaboration on JTX-8064, Celgene has allowed Jounce to regain full rights to its lead pipeline drug vopratelimab (formerly JTX-2011) and other candidates the companies had been partnering to develop, including the Phase I fully human IgG4 monoclonal antibody JTX-4014.

Vopratelimab is a monoclonal antibody designed to bind to and activate the Inducible T cell co-stimulator (ICOS), a protein on the surface of certain T cells that is believed to stimulate an immune response against a patient’s cancer. JTX-4014 is designed to block binding to PD-L1 and PD-L2. Jounce said it is developing JTX-4014 for potential use in combination with future product candidates.

No longer needed

In ceding control of vopratelimab and JTX-4014, Celgene has signaled that it doesn’t see a need to develop the two candidates as it prepares to be acquired by BMS—since BMS has its own Phase I/II anti-ICOS agonist, BMS-986226, as well as its own marketed anti-PD-1 antibody, the blockbuster cancer immunotherapy Opdivo® (nivolumab).

JTX-4014 is completing a Phase I open-label, dose escalation study (NCT03790488) in adults with advanced refractory solid tumor malignancies, with the aim of determining a maximum tolerated dose and recommended Phase II dose.

In its announcement today, Jounce said it remains on track to identify a recommended Phase II dose for JTX-4014 by year’s end.

Jounce said it also has full rights to “multiple” discovery-phase stromal and T-regulatory programs with undisclosed targets.

Vopratelimab was assessed in the Phase I/II ICONIC clinical trial (NCT02904226). According to preliminary data, Jounce reported at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO), vopratelimab was associated with durable (6+ month) responses based on Response Evaluation Criteria in Solid Tumors (RECIST) responses and other tumor reductions, with investigators using an ICOS pharmacodynamic biomarker in their assessment.

The Phase I portion of the ICONIC trial established the safety of vopratelimab in combination with two marketed cancer immunotherapies, BMS’ Yervoy® (ipilimumab) and Merck & Co.’s Keytruda® (pembrolizumab), based on dose escalation. where it was found to be safe and well-tolerated, both alone and in combination with BMS’ Opdivo.

However, an abstract published by Jounce before the ASCO conference showed that in gastric cancer, a RECIST partial response with vopratelimab monotherapy was observed in one of seven patients, and two RECIST partial responses and stable-disease responses with vopratelimab plus Opdivo were seen in two of 19 patients. Those results disappointed investors, touching off a selloff that sent the share price falling 35% from $17.67 on May 16 to $11.45 the following day.

Shares have mostly slumped since then, falling to $4.09 at yesterday’s close—but bounced back to $4.63 this morning, up 13%, after spiking as high as 41% in after-hours trading late yesterday soon after the restructuring was announced.

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