Jounce Therapeutics Regains Global Rights to First-in-Class Macrophage Checkpoint Inhibitor JTX-8064 from BMS

On June 4, Jounce Therapeutics announced that it had regained global development rights to JTX-8064 from BMS.

JTX-8064 is a highly selective antibody against leukocyte immunoglobulin-like receptor B2 (LILRB2) with first-in-class potential. It is the first candidate drug discovered through Jounce Therapeutics’ translational medicine platform to modulate the anti-tumor activity of macrophages. On July 25, 2019, Celgene entered into an agreement with Jounce Therapeutics to acquire exclusive global development rights to JTX-8064, with an upfront payment of $50 million and milestone payments totaling $480 million. However, following its acquisition of Celgene, Bristol Myers Squibb (BMS) evaluated the existing asset portfolio and determined that JTX-8064 overlapped with its existing products, leading to the decision to relinquish the global rights to JTX-8064.

On June 3, BMS notified Jounce Therapeutics that the collaboration agreement regarding JTX-8064 would be terminated. As a result, Jounce Therapeutics has regained all intellectual property rights to JTX-8064 previously licensed to Celgene, and BMS is no longer obligated to make further milestone payments to Jounce Therapeutics.

LILRB proteins are functional inhibitory transmembrane receptors expressed on the surface of myeloid cells. They are classified into five members based on differences in their extracellular immunoglobulin-like domains and intracellular immunoreceptor tyrosine-based activation motifs (ITAMs). The natural endogenous ligands for LILRBs are primarily human leukocyte antigens (HLA-A and HLA-G).

Poster results presented at the AACR 2019 Annual Meeting indicated that the anticancer activity of JTX-8064 may involve two mechanisms. On one hand, tumor-associated macrophages (TAMs) in the tumor microenvironment highly express LILRB2. JTX-8064 blocks the binding of HLA-G on the surface of tumor cells to the LILRB2 receptor on TAMs, thereby reversing the immunosuppressive state of TAMs and promoting their polarization toward the M1 phenotype, which exhibits stronger cytotoxic and pro-inflammatory effects. On the other hand, JTX-8064 can enhance the function of antigen-presenting cells (APCs), thereby boosting the immune efficacy of T cells.

Jounce Therapeutics, founded in 2013, focuses on the development of cancer immunotherapies. In addition to JTX-8064, its most advanced core asset is vopratelimab, an agonist targeting the immune co-stimulatory molecule ICOS (Inducible T-cell CO-Stimulator). Unlike PD-1/PD-L1 inhibitors that relieve T-cell immune suppression, vopratelimab is an immune agonist that activates ICOS on the surface of T cells, promoting T-cell proliferation, regulating T-cell differentiation, and sustaining the effector functions of activated T cells (including memory T cells), thereby enhancing the ability of T cells to kill tumor cells.

In July 2016, Celgene entered into an agreement with Jounce Therapeutics to co-develop vopratelimab and other immunotherapies, paying a $225 million upfront fee and making a $36 million equity investment in Jounce. Celgene was also obligated to pay up to $2.3 billion in subsequent development, regulatory, and commercialization milestones. However, due to unfavorable Phase I clinical data for vopratelimab and the announcement of the acquisition agreement between Bristol Myers Squibb (BMS) and Celgene in January 2019, Celgene announced in July 2019 that it had returned the rights to vopratelimab and the PD-1 antibody JTX-4014 to Jounce Therapeutics. On the same day, Celgene announced that it had acquired global exclusive rights to JTX-8064 from Jounce Therapeutics.

The divestment of licensed-out projects by pharmaceutical giants is typically bad news for small biotech companies. However, Richard Murray, CEO of Jounce Therapeutics, stated, “BMS’s return of the development rights to JTX-8064 presents a valuable opportunity for Jounce. Regaining full rights to this asset will help us further realize our vision of developing novel cancer immunotherapies targeting multiple types of immune cells. We believe that LILRB2 functions as an immune checkpoint on macrophages, and JTX-8064 has the potential to activate the anti-tumor activity of macrophages within the tumor microenvironment. We are eager to advance this program into the clinic as soon as possible.”