CAMBRIDGE and BOSTON, Mass.—Following the recent news of a $74 billion acquisition of Celgene by Bristol-Myers Squibb (BMS), Celgene has apparently been busy seeking collaborations in the oncology sector. While it’s not known how much of a role (if any) BMS played in these alliances, they do fit BMS’s stated goal of expanding a cancer portfolio.
The first strategic alliance Celgene struck was with Obsidian Therapeutics, for the discovery and development of novel, regulated cell therapies that utilize Obsidian’s Destabilizing Domain (DD) technology. The collaboration is based on Obsidian’s DD technology for the controlled expression of two immunomodulatory factors, IL12 and CD40L, that have the potential to augment the power of adoptive cell therapies but require precise control to optimize their therapeutic benefit.
Destabilizing Domains (DDs) are small, human protein domains that confer conditional stability to a fused payload protein that is engineered into a cell or gene therapy product. In the absence of a specific small-molecule ligand, the fusion protein is rapidly degraded, whereas in the presence of the ligand the fusion protein becomes stable and functional. Obsidian reportedly uses this approach to equip engineered cell therapies with controllable functions that can be precisely and dynamically tuned by the administration of small-molecule medicines that are currently approved, readily available and can be dispensed by a treating physician.
“Obsidian’s technology has the potential to unlock the activity of cell therapy in a number of new settings, particularly against solid tumor malignancies, and this is a prime example of the new technologies that we see enabling broader applications for CAR-T and cell therapies for the treatment of cancer. We value the innovation that the Obsidian team can bring and we look forward to working together to bring powerful new immunotherapies to patients,” said Robert Hershberg, MD, PhD, Executive Vice President, Business Development & Global Alliances for Celgene Corporation.
The multi-year collaboration provides Celgene with the exclusive option to in-license worldwide rights for cell therapy candidates that incorporate DD-regulated IL12 or CD40L for the treatment of cancer. The collaboration includes an upfront payment and equity investment by Celgene, and potential future milestone and royalty payments.
“This collaboration focuses the Obsidian team on product development, accelerates the advance of our innovative technology toward clinical applications, and positions us to expand our own platform and portfolio,” noted Michael Gilman, PhD, CEO of Obsidian. “We are thrilled to be partnering with Celgene and will benefit from their capabilities in the development and commercialization of cancer medicines. We share an ambitious vision of the potential for cell therapy to benefit patients with cancer and look forward to working together with the Celgene team to realize it.”
Celgene’s second strategic collaboration is with Kyn Therapeutics. The goal of the collaboration is to develop novel immuno-oncology therapies through uniting Kyn’s immuno-oncology expertise and pipeline with Celgene’s capabilities for developing and commercializing medicines in areas of high unmet medical need. The alliance begins with an upfront payment and an equity investment by Celgene, which receives exclusive options to license Kyn’s aryl hydrocarbon receptor (AHR) antagonist program and its kynurenine-degrading enzyme (“Kynase”) program.
AHR and kynurenine are associated with immunosuppression in a range of tumor types, through multiple cellular metabolic mechanisms that modulate both innate and adaptive immunity. These attributes make them compelling targets for investigative therapies, particularly in patients who do not fully benefit from current treatments like checkpoint inhibitors.
“At Kyn, our team has built a diverse portfolio informed by the most compelling biology in the field of immunometabolism to establish a leadership position in this area of innovative cancer therapy development,” mentioned Mark Manfredi, Ph.D., president and chief executive officer of Kyn Therapeutics. “Celgene’s R&D capabilities and focus on groundbreaking biology are a strong strategic fit for Kyn’s programs. As a fast-growing immuno-oncology therapeutics developer, we also welcome Celgene on board as an equity investor and supporter of our R&D strategy and leadership.”
Under the terms of the agreement, Kyn will receive an upfront cash payment of $80 million and an equity investment from Celgene for exclusive options to globally license the Kynase and AHR antagonist programs. For each program, Kyn is responsible for R&D activities through Phase 1b, at which time Celgene can opt in to lead and fund global development and commercialization of the licensed programs. If successful, Kyn is eligible for substantial clinical, regulatory and commercial milestone payments. Kyn will also receive tiered royalties on worldwide net sales on products resulting from development of the licensed programs.
“This collaboration signals our continued commitment to work with partners to develop innovative treatments for patients with unmet medical need,” added Hershberg.
