Bristol Myers Squibb Exercises Global Option for Obsidian's cytoDRiVE™-Powered CD40L Cell Therapy Candidate

Compiled by Keke

On September 15, Obsidian Therapeutics, a biotechnology company pioneering controllable cell and gene therapies, announced that Bristol-Myers Squibb (BMS) had exercised a global exclusive license option to obtain a cell therapy candidate featuring controlled expression of the immunomodulatory factor CD40L, based on the cytoDRiVE™ technology. This marks the first time BMS has exercised an option since collaborating with Obsidian to develop novel cell therapies. Under the terms of the agreement, Obsidian is eligible for potential future milestone payments and royalties related to this candidate drug.

In early January 2019, Bristol-Myers Squibb (BMS) announced its decision to acquire Celgene for $74 billion. Later that month, Celgene announced a strategic collaboration and development agreement with Obsidian Therapeutics, with undisclosed financial terms. Following the successful acquisition of Celgene by BMS, this partnership was transferred to BMS. It is reported that if the selected cell therapy proves as effective as hoped, Obsidian Therapeutics will provide a level of control surpassing that of current cell and gene therapies.

Obsidian Therapeutics’ Key R&D Technologies (Image source: Company website)

Introduction to ObsidianInfusional cell therapy using chimeric antigen receptor (CAR)-modified T cells (CAR-T) has demonstrated significant clinical efficacy in the treatment of certain B-cell malignancies, particularly in multiple myeloma. However, CAR-T therapy has remained largely unsuccessful in the treatment of solid tumors due to multiple barriers, including insufficient CAR-T cell expansion, an immunosuppressive tumor microenvironment, and tumor escape mediated by loss of target antigens.

Engineered CAR-T cells that produce immunomodulatory factors, such as interleukin-12 (IL-12) and cluster of differentiation 40 ligand (CD40L), have been shown to enhance functional activity by driving T-cell expansion, conferring resistance to immunosuppression, improving antigen presentation, and inducing antigen spreading. However, the clinical application of IL-12 and CD40 signaling pathway activators is limited by systemic toxicities associated with their potent pharmacological activity.

Obsidian’s selection of CD40L as an early test target for its cytoDRiVE™ technology reflects the role of tumor necrosis factor superfamily members in promoting dendritic cell activation. CD40L, a member of the tumor necrosis factor superfamily, is transiently expressed on activated CD4+ T cells and facilitates the licensing and activation of dendritic cells (DCs) through interaction with the CD40 receptor. Even though native CD40L is downregulated, co-expression of engineered CD40L in CAR-T cells has the potential to reduce escape by antigen-negative tumors, thereby enhancing anti-tumor efficacy.

The cytokine program associated with CD40L-mediated dendritic cell (DC) activation can also enhance T-cell proliferation and activity. However, activation of the CD40 pathway using agonist antibodies leads to systemic immune activation associated with adverse clinical events, thereby limiting therapeutic applications. Therefore, it is hypothesized that precise and titratable modulation of CD40L will enable its safe incorporation into CAR-T cell therapies, thus paving the way for next-generation, potent cellular immunotherapies.

Reference Sources:

1. Obsidian Therapeutics Official Website

2. Bristol Myers exercises option on Obsidian's CD40L cell therapy

3. Obsidian Therapeutics Announces Bristol Myers Squibb Opt-In of cytoDRiVE™ Cell Therapy Candidate