Expanding the reach of TIL therapy
We are a biotechnology company pioneering engineered tumor infiltrating lymphocyte (“TIL”) therapies to deliver transformative outcomes for patients suffering from solid tumor malignancies.
We engineer cytoTIL™ therapies using our proprietary cytoDRiVE® platform technology to express regulated therapeutic proteins to enhance anti-tumor activity.
OUR LEAD PROGRAM
Conventional TIL therapy has led to durable clinical responses in some patients with metastatic melanoma and non-small cell lung cancer, however the widespread clinical benefit has been limited due to efficacy challenges and toxicity concerns associated with required IL2 regimens.
We are advancing a pipeline of novel, engineered cytoTIL therapies to overcome many of these challenges and deliver safer, more effective TIL therapies for more patients.
Our lead program, cytoTIL15 (OBX-115), is an engineered TIL product armed with membrane-bound IL15 (mbIL15) to drive improved efficacy, including magnitude and duration of response. By replacing IL2 with mbIL15, cytoTIL15 also eliminates the need for concomitant IL2 therapy, a toxic and costly requirement for conventional TILs.
Benefits of TIL-endogenous mbIL15 vs. systemic IL2
TIL expansion & persistence
Drive adjacent NK cell
expansion & activity
Drive phenotype towards
CD8+ and memory T-cells
Unlike IL2, suppresses activation-induced cell death, doesn’t affect
Tregs or cause capillary leak syndrome-associated toxicity
Elimination of IL2 from the TIL treatment regimen is a significant advantage, driving the opportunity to displace conventional TIL therapy requiring systemic IL2. Eliminating IL2 is projected to expand patient eligibility by capturing patients who cannot tolerate or access IL2 administration. We believe Obsidian is the only company pursuing this unique approach as all other TIL approaches in development incorporate some form of systemic IL2.
cytoTIL15 expands the reach of TIL therapy, reaching previously ineligible patients:
- Patients ineligible for conventional TIL due to IL2 toxicity (older, frail, organ dysfunction, etc.)
- Patients without access to a TIL center equipped to administer IL2
Our preclinical data across numerous in vitro and in vivo assays demonstrate enhanced potency, persistence, and anti-tumor efficacy of cytoTIL15 (without IL2) compared to conventional TIL + IL2.
Our first cytoTIL15 candidate, OBX-115 for patients with metastatic melanoma, is anticipated to enter clinical development in 2022.
OBX-115 Additional Solid Tumors
Gene Editing Undisclosed
*Early research ongoing to explore OBX-115 + PD-1 combination in melanoma
Our proprietary cytoDRiVE® platform leverages drug responsive domains (DRDs) to control protein function using an FDA-approved small molecule.
For a particular protein of interest, Obsidian engineers a gene cassette with a DRD tag, which is then packaged and inserted into the cell. The cell produces fusion protein consisting of the protein to be regulated, fused to a DRD, which is stabilized in the presence of a small molecule ligand. The stabilized fusion protein can be expressed intracellularly, membrane-bound or secreted. In the absence of the small molecule ligand, the DRD assumes a disordered conformation that is recognized by the quality control mechanisms of the cell, resulting in degradation of the fusion protein by the proteasome.
Obsidian has a growing library of internally discovered DRDs of varying sizes and purposes, and Obsidian’s cytoDRiVE® Discovery Platform enables rapid optimization of tunable and functional proteins. We have developed an extensive synthetic biology engineering toolkit to optimize protein functionality in any cell type, including but not limited to, type I/II membrane proteins, membrane-tethered cytokines, intracellular proteins, secreted proteins and genome editing proteins.
In addition to our wholly owned TIL programs, we have two existing partnerships with Bristol Myers Squibb (BMS) and Vertex Pharmaceuticals leveraging our cytoDRiVE® platform technology. Our platform technology is highly versatile, and we believe there are numerous applications for our core DRD technology across therapeutic areas and modalities. We are open to continuing to explore opportunistic partnerships for our platform technology. For more information, please contact email@example.com.
Bristol Myers Squibb
Obsidian is proud to collaborate with BMS (via acquisition of Celgene) in the discovery and development of novel, regulated cell therapies that utilize Obsidian’s cytoDRiVE technology. Our collaboration is focused on two specific immunomodulatory factors, IL12 and CD40L, which require precise control to optimize their therapeutic benefit. This multi-year collaboration provides BMS with the exclusive option to in-license worldwide rights for cell therapy candidates that incorporate regulated IL12 or CD40L for the treatment of cancer.
In September 2020, Obsidian announced that BMS has exercised its option to an exclusive worldwide license to a cell therapy candidate based on Obsidian’s cytoDRiVE technology for the controlled expression of the immunomodulatory factor CD40L.
In April 2021, Obsidian and Vertex Pharmaceuticals entered into a strategic research collaboration and licensing agreement focused on the discovery of novel therapies that regulate gene editing for the treatment of serious diseases. The collaboration leverages Obsidian’s cytoDRiVE platform technology to discover gene-editing medicines whose therapeutic activity can be precisely controlled using small molecules and Vertex’s established scientific and clinical capabilities in small molecule, cell and genetic therapies to more rapidly bring these approaches to patients.