amsokigene autoleucel (OBX-115) / Obsidian, UT MD Anderson Cancer Center - LARVOL DELTA

Trial in progress: Agni-01 phase 2 cohort of OBX-115 tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced (adv) melanoma (ESMO 2026) - P1/2 | "Background OBX-115 TIL are engineered to express membrane-bound IL15 (mbIL15) regulated by the FDA-approved small-molecule drug acetazolamide (ACZ), abrogating the need for IL2 in the treatment regimen. ACZ 500 mg/day is administered starting Day 0 (two ≤7-day periods within 28 days), with ACZ redosing for ≤7 days at Week 5, 11, 17, and 23, and upon progression when new anticancer therapy is not immediately warranted. Nine sites are open and recruiting, with additional sites being activated."

Clinical • IO biomarker • Metastases • P2 data • Tumor-infiltrating lymphocyte • Eye Cancer • Melanoma • Oncology • Solid Tumor • BRAF • IL15 • IL2

Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Melanoma • Oncology • Solid Tumor

Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma (clinicaltrials.gov) - P1 | N=21 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | N=30 ➔ 21 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Melanoma • Oncology • Solid Tumor

Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Melanoma • Oncology • Solid Tumor

Agni-01: Safety and Efficacy of OBX-115 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=32 | Active, not recruiting | Sponsor: Obsidian Therapeutics, Inc.

Checkpoint inhibition • New P1/2 trial • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • BRAF

Agni-01: Safety and Efficacy of OBX-115 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=52 | Recruiting | Sponsor: Obsidian Therapeutics, Inc. | N=32 ➔ 52

Enrollment change • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • BRAF

Agni-01: Safety and Efficacy of OBX-115 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=32 | Recruiting | Sponsor: Obsidian Therapeutics, Inc. | Active, not recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • BRAF

Agni-01: Safety and Efficacy of OBX-115 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=208 | Recruiting | Sponsor: Obsidian Therapeutics, Inc. | Trial completion date: Jun 2028 ➔ Jun 2029 | Trial primary completion date: Jun 2028 ➔ Jun 2029

Trial completion date • Trial primary completion date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • BRAF

Agni-01: Safety and Efficacy of OBX-115 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=208 | Recruiting | Sponsor: Obsidian Therapeutics, Inc. | N=52 ➔ 208

Enrollment change • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • BRAF

Agni-01: Safety and Efficacy of OBX-115 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=52 | Recruiting | Sponsor: Obsidian Therapeutics, Inc. | Trial completion date: Oct 2027 ➔ Jun 2028 | Trial primary completion date: Oct 2025 ➔ Jun 2028

Trial completion date • Trial primary completion date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • BRAF

Obsidian Therapeutics…announced a poster presentation of updated data in patients with immune-checkpoint inhibitor (ICI)-resistant advanced melanoma from the Phase 1 single-center first-in-human (FIH) study and the Phase 1/2 Agni-01 multicenter study of amsokigene autoleucel…at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting (Businesswire) - "The poster presentation will summarize pooled safety data across the FIH study and the Phase 1/2 Agni-01 multicenter study, and an efficacy update from Agni-01 patients treated at the recommended phase 2 dose (n=15). In addition, a trial-in-progress poster describing the phase 2 registration-enabling cohort of Agni-01 evaluating amsoki-cel in patients with ICI-resistant advanced melanoma will be presented."

First-in-human • Retrospective data • Trial status • Melanoma

OBX-115 TIL cell therapy in ICI-resistant advanced melanoma: Pooled safety and updated efficacy with minimally invasive tumor tissue procurement, low-dose lymphodepletion, and IL2-free regimen (SITC 2026) - No abstract available

Clinical • Metastases • Melanoma • Oncology • Solid Tumor • IL2

Trial in progress: Agni-01 phase 2 cohort of OBX-115 tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma (SITC 2026) - No abstract available

Clinical • Metastases • P2 data • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor

Recent Advances in Tumor-Infiltrating Lymphocyte Therapy for Melanoma. (PubMed, Curr Treat Options Oncol) - "We then review current clinical evidence for conventional TIL products, including lifileucel, TM001, LM103, HS-IT101, and GC101, highlighting their efficacy and safety profiles...In addition, advances in genetically engineered TILs, such as OBX-115, KSQ-001EX, and IOV-4001, are reviewed...Challenges and future directions of TIL therapy in melanoma are also discussed. Overall, TIL therapy constitutes a rapidly evolving and clinically potent treatment modality for melanoma."

Biomarker • IO biomarker • Journal • Review • Tumor-infiltrating lymphocyte • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • IL2

Top advances of the year in autologous cellular therapy in melanoma and solid tumors. (PubMed, Cancer) - "Lifileucel, the first Food and Drug Administration-approved tumor-infiltrating lymphocyte (TIL) therapy for advanced melanoma, demonstrated durable efficacy in the 5-year analysis of the C-144-01 trial, with an objective response rate (ORR) of 31.4% and prolonged responses in a heavily pretreated population...Preferentially expressed antigen in melanoma (PRAME)-targeted T-cell receptor (TCR) T-cell therapy (anzu-cel, IMA203) showed promising activity in a phase 1 study, with ORR of approximately 50% in checkpoint inhibitor refractory melanoma, durable responses, and manageable toxicity, validating PRAME as a high value target across multiple tumor types...OBX-115, an IL-2 independent TIL platform expressing membrane-bound IL-15 regulated by acetazolamide, demonstrated early clinical activity with ORR of 67% in initial phase 1 data...Finally, afamitresgene autoleucel (afami-cel), a MAGE-A4 directed TCR-T therapy, showed durable efficacy in synovial sarcoma and expanding..."

Journal • Review • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • IL15 • MAGEA4 • PRAME

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients (pts) with immune checkpoint inhibitor (ICI)–resistant advanced melanoma: Phase 1 results of the Agni-01 multicenter study. (ASCO 2025) - P1, P1/2 | "Funded by Obsidian Therapeutics Clinical Trial Registration Number: NCT06060613 Background: OBX-115 TIL are engineered to express mbIL15 regulated by the FDA-approved small-molecule drug acetazolamide (ACZ), abrogating the need for toxic high-dose IL2 after TIL infusion... Early data support clinical benefit (RP2D ORR 67%, DCR 100%) of OBX-115 regulatable engineered TIL cell therapy in the absence of IL2, including with outpatient low-dose LD. The safety profile is highly differentiated, without TRM, ICU transfer, or high-grade CRS. ACZ redosing is well-tolerated and offers an opportunity to deepen responses by inducing re-expression of mbIL15 on engrafted OBX-115 TIL, a unique capability among adoptive cell therapies."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P1 data • Tumor-infiltrating lymphocyte • Heart Failure • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15 • IL6

OBX-115, an interleukin 2 (IL2)-sparing engineered tumor-infiltrating lymphocyte (TIL) cell therapy, in patients (pts) with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma. (ASCO 2024) - P1, P1/2 | "OBX-115 autologous engineered TIL cell therapy does not require co-administration of IL2 due to its regulatable expression of membrane-bound IL15 (mbIL15) using the FDA-approved small-molecule drug acetazolamide (ACZ) to provide cytokine support for TIL expansion and persistence...After lymphodepletion (cyclophosphamide, fludarabine), pts receive OBX-115 followed by ACZ once daily for up to 7 days; ACZ redosing (up to 7 days) is permitted at Wk 6 for non-responders... OBX-115regulatableengineeredTIL cell therapy was well-tolerated and produced consistently deepening and durable responses, indicating that OBX-115 may mediate CRs and durable clinical benefit in ICI-resistant metastatic melanoma without high-dose IL2. OBX-115 investigation continues in this and an ongoing Phase 1/2 multicenter study (NCT06060613)."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • Tumor-infiltrating lymphocyte • Hepatology • Melanoma • Oncology • Pain • Solid Tumor • CD69 • CD8 • ENTPD1 • IL15 • IL2 • PD-1

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients with advanced melanoma that has progressed on/after immune checkpoint inhibitors (ICI): Phase 2 results. (ASCO 2026) - P1/2 | "Clinical Trial Registration Number: NCT06060613 Background: OBX-115 TIL are engineered to express mbIL15 under regulatory control of the small-molecule drug acetazolamide (ACZ); this engineering abrogates the need for toxic high-dose IL2 cytokine support after TIL infusion. OBX-115 TIL cell therapy at RP2D demonstrated encouraging efficacy in 2/3L advanced non-uveal melanoma, an area of unmet medical need. Unique aspects of the OBX-115 regimen, such as low-dose LD, ACZ-inducible mbIL15 expression, and CNB-enabled manufacturing, were associated with manageable side effects and compare favorably with other adoptive TIL approaches. Data support continued investigation of OBX-115 in the ongoing phase 2 portion of Agni-01 and planned registrational study."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P2 data • Tumor-infiltrating lymphocyte • Eye Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

A phase 1/2 study to investigate the safety and efficacy of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced solid tumors. (ASCO 2024) - P1, P1/2 | "OBX-115 TIL are engineered to express membrane-bound IL15 (mbIL15) under dose-dependent regulation using acetazolamide (ACZ), an FDA-approved small-molecule diuretic, avoiding the need for high-dose IL2...Cryopreserved OBX-115 is generated from the pt's own tumor tissue procured by surgical excision or core needle biopsy, and is infused after standard- (5 days) or low-dose (4 days) lymphodepletion (cyclophosphamide and fludarabine), based on clinical status...3. Creelan Nat Med 2021; Schoenfeld SITC 2021."

Clinical • IO biomarker • Metastases • P1/2 data • Tumor-infiltrating lymphocyte • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

Obsidian Therapeutics Announces First Patient Enrolled in the Registration-enabling Cohort of Phase 1/2 Agni-01 Study Evaluating Amsoki-cel (OBX-115) in Advanced Melanoma (Businesswire) - "...'We anticipate reporting topline data from the registration-enabling cohort by year-end 2027'....The single-arm registration-enabling cohort is part of the ongoing Agni-01 study (NCT06060613), which is a multicenter Phase 1/2 study, and designed to further evaluate the safety and efficacy of amsoki-cel at the recommended phase 2 dose (RP2D) in patients with ICI-resistant advanced melanoma....Enrollment is anticipated to be completed by end of Q1 2027....NSCLC Phase 1 data are expected in the first half of 2027."

Enrollment status • P1/2 data • Melanoma • Non Small Cell Lung Cancer

Obsidian Therapeutics to Present Phase 2 Clinical Data for OBX-115 in Advanced Melanoma in Oral Presentation at 2026 ASCO Annual Meeting (Yahoo Finance) - "73% of patients had progression after anti–PD-1 + anti–CTLA-4 doublet therapy. 67% ORR including 2 confirmed complete responses (CR) and 8 confirmed partial responses (PR). Durable clinical benefit, including 8 of 10 responses ongoing as of the median 4.3 month study follow-up. We have been in discussions with the FDA, and after reaching alignment on key design elements including eligibility criteria, clinical trial endpoints and drug product potency assay, plan to pursue a single-arm accelerated approval pathway. We look forward to continuing to advance OBX-115 through the clinic and plan to begin treating patients in the registration-enabling cohort of our multicenter study in mid-2026. Obsidian is also investigating OBX-115 in patients with non-small cell lung cancer (NSCLC) in the Agni-01 trial. NSCLC Phase 1 data are expected in the first half of 2027."

P1 data • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer

OBX-115 membrane-bound IL15 (mbIL15)-expressing engineered tumor-infiltrating lymphocytes (TIL) overcome target cell immune evasion related to major histocompatibility complex (MHC) silencing through both direct killing and transactivation of NK cells in patient-derived autologous non-small cell lung cancer (NSCLC) models (AACR 2026) - "OBX-115 engineered TIL express mbIL15 under pharmacologic regulation using the FDA-approved small-molecule drug acetazolamide (ACZ). Our data demonstrate that, similar to previously reported MHC-I-independent tumoricidal effect observed in melanoma CD8+ T cells, OBX-115 engineered mbIL15-expressing NSCLC TIL partially retain cytotoxicity and reactivity toward autologous tumor cells in MHC-loss models. Further, transactivation of autologous NK cells via mbIL15 uniquely enhances activity."

Clinical • Late-breaking abstract • Tumor-infiltrating lymphocyte • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • B2M • CD8 • IFNG • IL15 • STAT5

Obsidian Therapeutics, Inc…announced an oral presentation of Phase 2 results in patients with advanced melanoma from the Phase 1/2 Agni-01 multicenter study of OBX-115, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago, IL, May 29–June 2, 2026. (National Law Review)

P2 data • Melanoma

Obsidian Therapeutics and Galera Therapeutics Announce Merger Agreement and $350 Million Concurrent Private Placement (Businesswire) - "In support of the transaction, Galera and Obsidian have secured commitments for an oversubscribed private placement financing that is expected to result in total gross proceeds of $350 million..The combined company’s cash and cash equivalents balance at closing, including the funds from the private placement financing, is anticipated to fund the combined company’s operations into the second half of 2028 and provides runway through key clinical milestones for Obsidian’s lead product candidate, OBX-115. These include Phase 1 data from the ongoing NSCLC trial expected in the first half of 2027, and by year-end 2027, topline data from their melanoma registration-enabling trial. The combined company will also continue to support Galera’s pipeline."

M&A • P1 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

Tumor-infiltrating lymphocytes (TIL) engineered with membrane-bound IL15 (cytoTIL15 cells) exhibit pharmacologically regulatable signal transduction in cis and trans (AACR 2024) - P1 | "The mbIL15 expressed by cytoTIL15 cells is regulated via a carbonic anhydrase 2 (CA2) drug-responsive domain, which allows expression to be induced upon delivery of the FDA-approved small molecule ligand acetazolamide (ACZ) and was designed to engage the IL2Rβ and IL2Rγ receptors in both cis and in trans. cytoTIL15 cells demonstrate functional engagement of cytokine receptors via mbIL15 in both cis and in trans, including phosphorylation of STAT5 and S6. Taken together, these data highlight the potential for robust activity of cytoTIL15 cells through potentiation of ACZ-dependent mbIL15 activity in both cis and trans."

Late-breaking abstract • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • CD8 • IL15 • STAT5