Acetazolamide

OBX-115 continues to demonstrate a positively differentiated safety pro to IL2-dependent non-engineered TIL cell therapy: no DLTs, no Grade 4 or higher non-hematologic TEAEs observed. OBX-115 efficacy pro 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. CAMBRIDGE, Mass.--(BUSINESS WIRE)-- 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 Pro 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 pro 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.

TIL therapy uses naturally occurring immune cells that detect and attack cancer cells. Image credit: Shutterstock/Christoph Burgstedt. Obsidian Therapeutics has raised $160.5m in a Series C financing round, with plans for the funds to be injected into the biotech’s tumour-infiltrating lymphocyte (TIL) cell therapy programme. Obsidian, already backed by Bristol Myers Squibb (BMS), added Novo Nordisk Foundation’s investment arm Novo Holdings to its arsenal of investors in this latest round. US investment firm Wellington Management led the oversubscribed Series C. The US biotech previously raised $115m in a Series B round in 2021. Obsidian’s lead asset is OBX-115 , which is part of its TIL programme. OBX-115 is a TIL cell therapy – which expands and enhances the patient’s own immune cells extracted from around and within the tumour itself. Unlike the emerging chimeric antigen receptor (CAR) T cell therapies , TILs already have multiple tumour target recognition. The T cell immunotherapy is in a Phase I clinical trial for the treatment of melanoma and a Phase I/II clinical trial for the treatment of non-small cell lung cancer (NSCLC). In the melanoma trial (NCT05470283), which is being sponsored by the MD Anderson Cancer Centre, OBX-115 is being administered in combination with the diuretic acetazolamide. Data from the study will inform dose levels for a Phase II trial. The company reported an objective response rate of 50% and a complete response rate of 33% in topline data released in December 2023. See Also: Seaport emerges after $100m raise with ex-Karuna team at helm Pluri launches manufacturing division as cell therapy pipeline progresses The NSCLC trial (NCT06060613) is investigating OBX-115 as a monotherapy, with endpoints assessing the drug’s safety and efficacy in treating advanced solid tumours. Obsidian said the Series C proceeds will go towards clinical trial activities and manufacturing scale-up with a view to conducting pivotal trials. Obsidian has engineered OXB-115 such that it produces the membrane-bound interleukin 15 (IL-15). Interleukin-2 (IL-2) co-administration is usually needed with traditional TIL cell therapies to act as an immunostimulatory agent. Obsidian states that the membrane-bound IL-15 could widen patient access by reducing potential toxicities associated with high-dose IL-2. Vertex and BMS have seen the potential in Obsidian’s platform, both signing multi-year partnerships with the biotech to discover and develop new cell therapies. Last month, Iovance Biotherapeutics ’ Amtagvi (lifileucel) became the first TIL cell therapy to get regulatory backing in the US, winning a US Food and Drug Administration (FDA) accelerated approval. Obsidian’s OBX-115 will face competition from Iovance, with Amtagvi indicated for the treatment of metastatic or unresectable melanoma. Iovance has priced its immunotherapy at $515,000 in a market where there are currently no other FDA-approved cell therapies for the treatment of solid tumours. Amtagvi is forecast to generate sales of $846m by 2029, according to GlobalData’s Pharma Intelligence Centre. GlobalData is the parent company of Pharmaceutical Technology. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva. Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. By Cytiva Thematic By downloading this case study, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy