A checkpoint team-up against solid tumors

More specifically, OSE-172 is a SIRP-alpha antagonist targeting myeloid lineage cells. SIRP-alpha is a receptor expressed by myeloid lineage cells such as dendritic cells (DCs), tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). In targeting SIRP- alpha, OSE-172 reportedly prevents the ligand CD47 from binding to and triggering the cellular inhibitory effects of SIRP-alpha. The therapeutic candidate is currently in late-stage preclinical development and has shown potential in various cancers, with Boehringer Ingelheim and OSE Immunotherapeutics highlighting its potential use for advanced solid tumors.

According to the companies, OSE-172 has the potential to enhance antitumor immunity by improving T cell activity through enhancement of DC antigen presentation functionality, potentiating the phagocytic and inflammatory properties of macrophages in the tumor microenvironment and enabling differentiation of MDSCs to an effector state.

“This partnership with Boehringer Ingelheim is a real recognition of the value of our innovative approach to treating cancer and will create an exciting new alliance to fuel the Phase 1 development of OSE-172,” said Dr. Dominique Costantini, CEO of OSE Immunotherapeutics. “Boehringer Ingelheim’s expertise and insights will be invaluable as we step up the clinical development and work to commercialize this new treatment paradigm.”

“We are excited to partner with OSE Immunotherapeutics to develop this promising, novel cancer immunotherapy,” Dr. Jonathon Sedgwick, global head of the Cancer Immunology & Immune Modulation Research division of Boehringer Ingelheim, remarked in a press release. “A key area of focus is the identification of drugs that target myeloid cell immune regulatory receptors, of which SIRP-alpha is a leading example. We are dedicated to developing groundbreaking, first-in-class therapies that can transform the lives of patients and help win the fight against cancer.”

With this deal, Boehringer Ingelheim acquires the global rights to develop, register and commercialize OSE-172 as part of its continued work in immuno-oncology research and development. Under the terms of the agreement, OSE Immunotherapeutics will receive a €15-million upfront payment from Boehringer Ingelheim and potential additional short-term milestones of up to €15 million upon initiation of a Phase 1 clinical study. All told, though, OSE Immunotherapeutics could earn more than €1.1 billion total upon reaching pre-specified development, commercialization and sales milestones, plus royalties on worldwide net sales.

OSE Immunotherapeutics was created in May 2016 through the merger of OSE Pharma, an immuno-oncology company developing specific immunotherapy activating T lymphocytes, and Effimune, a biotechnology company specializing in immune regulation with clinical applications in autoimmunity, transplantation and immuno-oncology.

Although the news release about the deal did not mention specific cancers to be targeted by OSE-172 initially, Boehringer Ingelheim’s primary focuses in the cancer realm are on lung and gastrointestinal cancers.

In other Boehringer Ingelheim news on the cancer front, the company also announced in mid-March an expansion of it existing collaboration to develop novel anti-cancer compounds with Nashville, Tenn.-based Vanderbilt University. The expanded research partnership will focus on the discovery and development of new chemical therapeutics targeting the pro-survival protein MCL1 as a potential therapy against MCL1 dependent cancers. This is the third collaboration between Boehringer Ingelheim and Vanderbilt University to pursue discoveries made in the laboratory of Dr. Stephen W. Fesik, at the Vanderbilt University School of Medicine.

“MCL1 is one of the top 10 overexpressed genes in human cancer, where it plays a role as a survival factor,” said Dr. Lawrence J. Marnett, the dean of basic sciences in the Vanderbilt University School of Medicine. “It is a great target for therapy but candidate drugs need to disrupt high affinity protein-protein interactions, which is very challenging. The Fesik laboratory has made impressive strides in developing such compounds, and it is exciting to see them advanced toward clinical development through the partnership with Boehringer Ingelheim.”

MCL1, when overexpressed, can prevent cancer cells from undergoing programmed cell death (also known as apoptosis). This necessitates the discovery of a molecule that binds extremely tightly and selectively to MCL1 in order to sufficiently induce on-target, mechanism-based cancer cell death.

“Boehringer Ingelheim has an outstanding oncology drug discovery infrastructure that brings various research and development groups together to tackle challenging cancer targets,” commented Fesik, who is a professor of biochemistry, pharmacology and chemistry at Vanderbilt. “In combination with our multidisciplinary team of structural biologists, medicinal chemists and cell biologists, we will work to search for anti-cancer compounds that inhibit MCL1 in order to tackle this complex area of unmet medical need.”