• OBX-115 continues to demonstrate a positively differentiated safety profile relative to IL2-dependent non-engineered TIL cell therapy: no DLTs, no Grade 4 or higher non-hematologic TEAEs observed.
• OBX-115 efficacy profile sustained in additional patients, including a 44% ORR with 2 CRs (n=9), and a 50% ORR in patients receiving cell dose >30 × 10⁹ cells.
• Emerging survival and PFS data are promising, with no treatment- or disease-related mortality (OS 100%, median study follow-up of 29.5 weeks) and PFS of 75% at 24 weeks.

Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, today announced updated data from the ongoing Phase 1 first-in-human, dose-escalation study of OBX-115, a novel engineered tumor-derived autologous T-cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15), in patients with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma. These data were presented in an oral presentation delivered by Rodabe Amaria, M.D., professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and principal investigator of the study, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

The oral presentation for the single-center study (NCT05470283) included a 3-month incremental data update (relative to published abstract) on safety (N=10) and efficacy (n=9 per-protocol efficacy analysis set) for patients with advanced or metastatic melanoma.

Summary of OBX-115 Safety and Efficacy Data (April 4, 2024 data cutoff):

OBX-115 Exhibits Positively Differentiated Safety Profile Relative to IL2-Dependent Non-Engineered TIL Cell Therapy:

• All 10 infused patients were alive at data cutoff (median study follow up of 29.5 weeks).
• No patient received care in the intensive care unit.
• No dose-limiting toxicities were observed at any dose level.
• No Grade 4 or higher non-hematologic treatment-emergent adverse events (TEAEs) were reported; 2 patients experienced limited Grade 3 non-hematologic TEAEs.
• No confirmed events of cytokine release syndrome, capillary leak syndrome, or immune effector cell-associated neurotoxicity syndrome were reported.

OBX-115 Sustains Consistent Efficacy Profile, without IL2 Administration, in Patients with Substantially Pre-Treated Resistant/Refractory Disease:

• Patients had disease that was predominantly ICI primary-resistant, with a median of 3.5 (range, 1–6) lines of prior systemic therapy, including a median of 2 (1–3) lines of prior ICI therapy.
• 44% objective response rate (ORR), including 2 complete responses (CRs), using investigator-assessed RECIST 1.1 criteria across all doses (n=9 per-protocol efficacy analysis set).
  • 50% ORR in patients who received OBX-115 dose of >30 × 10⁹ cells (n=6).
• 100% disease control, defined as CR, PR, or ≥12-week duration of stable disease post OBX-115 infusion.
• Progression-free survival (PFS) was 75% at 24 weeks.
• Tumor burden reduction in all 9 patients, including several with tyrosine kinase inhibitor (TKI)-refractory disease and / or prior treated brain metastasis.
• Disease control and responses observed with both fresh and cryopreserved OBX-115 product.

Additional OBX-115 Data Contributing to an Optimized Cell Therapy Product:

• Robust manufacturing process observed for OBX-115, including from tumor tissue obtained using core needle biopsy.
  • Median manufactured OBX-115 dose (N=10): 100 × 10⁹ cells.
• Translational data highlight that the OBX-115 infusion product is optimized for response and persistence: predominantly CD8+ cytotoxic T-cell population, effector memory phenotype, high proportion of CD8+CD39-CD69- (double-negative) “stem-like” progenitor cells and low levels of exhaustion markers.

Dr. Amaria commented, “OBX-115 continues to demonstrate positive safety and efficacy data in additional patients, which is encouraging, given this is a heavily pre-treated patient population with advanced disease. Unfortunately, late-line systemic therapy options offer limited benefit, with ORR of approximately 10% and mPFS of approximately 2–3 months. It is exciting to see a potential new option emerge for these patients with a positively differentiated safety profile and promising early activity achieved without IL2.”

“We believe OBX-115 has the potential to advance the TIL cell therapy field in multiple ways, including enabling non-surgical tumor tissue procurement and abrogating the need for IL2. We are also exploring the ability to re-energize engrafted OBX-115 cells with acetazolamide re-dosing,” commented Parameswaran Hari, M.D., Chief Development Officer of Obsidian. “We look forward to continuing to build on this momentum and apply key learnings from the first-in-human Phase 1 study to our ongoing Phase 1/2 multicenter study, where we are continuing to explore these attributes and optimize the OBX-115 regimen in melanoma and non-small cell lung cancer.”

Obsidian is actively enrolling patients with advanced or metastatic melanoma and non-small cell lung cancer (NSCLC) at multiple sites in its ongoing Phase 1/2 multicenter study. Additional details may be found at clinicaltrials.gov, using identifier: NCT06060613.

About OBX-115

Obsidian’s lead investigational cytoTIL15™ program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. OBX-115 is being investigated in two ongoing clinical trials in advanced or metastatic melanoma and NSCLC (NCT05470283 and NCT06060613).

About Obsidian Therapeutics

Obsidian Therapeutics, Inc. is a clinical-stage biotechnology company pioneering engineered cell and gene therapies to deliver transformative outcomes for patients with intractable diseases. Obsidian’s proprietary cytoDRiVE® technology is designed to precisely regulate the timing and level of protein function by using FDA-approved small-molecule drugs. Obsidian is headquartered in Cambridge, MA. The Company has collaborations with Bristol Myers Squibb and Vertex Pharmaceuticals. For more information, please visit obsidiantx.com and follow us on LinkedIn.

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