Preclinical data highlight numerous pipeline advancements: cytoTIL15™ cells armed with combination-cytokines modulate the tumor microenvironment (TME); spatial profiling of cytoTIL15 cells in PDX models provides greater mechanistic understanding of cell-killing function; and IL12 armored T-cells with precise regulation show anti-tumor activity in solid tumor models.
CAMBRIDGE, Mass., Nov. 7, 2022 /PRNewswire/ -- Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, today announced it will present preclinical data highlighting its recent cytoDRiVE® platform and pipeline advances during the poster sessions at the upcoming SITC Annual Meeting 2022. The abstracts have been posted to the SITC Online Itinerary Planner, will be published in the Journal for ImmunoTherapy of Cancer (JITC) supplement, and are detailed below.
Obsidian will present data from their cytoDRiVE platform for multiple applications, including novel advancements in cytoTIL engineering. New data to be presented highlight developments in cytoTIL15 therapies, in which engineered TIL expressing both membrane-bound IL15 and a combination-cytokine (either IFN-alpha, IL18 or an undisclosed member of the TNF superfamily) demonstrate in vivo persistence, modulation of the TME and anti-tumor activity. Armoring cytoTIL15 therapies with these potent immune mediators may expand the potential reach of cytoTIL therapies to solid tumors marked by an immunosuppressive TME. Additionally, Obsidian will share digital spatial profiling data showing that in an allogeneic melanoma PDX model, cytoTIL15 cells upregulate cell-killing functions while downregulating exhaustion markers. Obsidian will also present advancements to their cytoDRiVE platform to enable enhanced regulation of IL-12 armored T-cells in preclinical solid tumor models.
"Obsidian's research advances highlight the versatility of our cytoDRiVE platform to engineer orthogonal features into cytoTIL15 therapies that will remodel the TME and may expand the potential reach of our IL2-free cytoTIL therapies to solid tumors with immunosuppressive microenvironments where clinical development of TIL therapies has been limited," said Jan ter Meulen, M.D. Ph.D., Chief Scientific Officer of Obsidian Therapeutics. "We are pleased with this rapid progress of our pipeline, further building on our lead cytoTIL15 therapy, OBX-115, which is currently enrolling a Phase I clinical trial."
Details of the presentations are as follows:
Title: Enhancers of innate and adaptive immunity combine with membrane bound IL15 to increase the efficacy of tumor infiltrating lymphocyte (TIL) therapy for tumors with immunosuppressive microenvironments
Category, Presentation Date & Location: Cellular Therapies, Thursday Nov. 10, Poster Hall
Abstract No.: 369
Abstract Summary: Engineered TIL expressing both mbIL15 and a combination cytokine (either IFN-alpha, IL18 or TNFSF-X) showed similar fold expansion, immunophenotype and polyfunctionality in vitro compared to TIL expressing only mbIL15. In the absence of IL2, TIL expressing mbIL15 plus cytokine showed similar in vivo antigen-independent persistence to TIL engineered with IL15 alone. T cells expressing IL15 and either IFN-alpha or IL18 showed improved efficacy and TME remodeling, and combining IL15 with TNFSF-X resulted in growth arrest of syngeneic melanoma tumors in mice.
Title: Digital spatial profiling and antigen-dependent phenotypic analysis of IL15-engineered tumor-infiltrating lymphocytes (cytoTIL15™ therapy) in an allogeneic melanoma PDX model
Category, Presentation Date & Location: Cellular Therapies, Friday Nov. 11, Poster Hall
Abstract No.: 330
Abstract Summary: Digital spatial profiling and single cell sequencing showed that in an allogeneic melanoma PDX model, cytoTIL15™ cells demonstrated enrichment and reactivity for melanoma antigen-specific TCRs, while maintaining TCRβ diversity. cytoTIL15™ cells showed a distinct profile of RNA expression and phenotypic markers, consistent with their increased persistence and anti-tumor efficacy.
Title: Pharmacologically-controlled expression of membrane-bound IL-12 results in T-cell therapy with enhanced potency in preclinical solid tumor models
Category, Presentation Date & Location: Cellular Therapies, Thursday Nov. 10, Poster Hall
Abstract No.: 278
Abstract Summary: T-cells armored with a small molecule-controlled membrane bound IL-12 (mbIL-12) under the cytoDRiVE® platform drives regulation of pharmacodynamic markers and anti-tumor efficacy in xenograft and syngeneic solid tumor models.
About OBX-115
Obsidian's lead cytoTIL15 program, OBX-115, is a novel engineered tumor-infiltrating lymphocyte (TIL) therapy armed with regulated membrane-bound IL15 that is designed to remove the need for concomitant IL2 therapy, a toxic and costly requirement for conventional TILs. OBX-115 preclinical data have demonstrated enhanced TIL persistence, potency and improved tumor control compared to unengineered TILs plus IL2, which is anticipated to improve clinical outcomes in patients suffering from metastatic melanoma and other solid tumors. FDA granted IND clearance for OBX-115 in July 2022. The Phase I FIH clinical trial for OBX-115 is currently recruiting patients. Information regarding the clinical trial is available at clinicaltrials.gov: NCT05470283.
About Obsidian Therapeutics
Obsidian Therapeutics, Inc. is a clinical biotechnology company pioneering engineered cell and gene therapies to deliver transformative outcomes for patients with intractable diseases. Obsidian's proprietary cytoDRiVE® technology provides a way to precisely control the timing and level of protein function by using FDA approved small molecules. Obsidian is headquartered in Cambridge, Mass. The Company has collaborations with Bristol Myers Squibb and Vertex Pharmaceuticals. For more information, please visit www.obsidiantx.com and follow us on LinkedIn and Twitter.
Obsidian Therapeutics Media Contact:
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+1 (914) 310-8172
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