IO-108

– Complete remission (CR) rate of 50% and overall response rate (ORR) of 66.7% in 18 evaluable patients with CMML treated with IO-202 in combination with azacitidine – – CR rate of 83.3% and ORR of 100% in CMML patients with high LILRB4 expression – PALO ALTO, CA, USA I December 09, 2024 I Immune-Onc Therapeutics, Inc. (“Immune-Onc”), a private clinical-stage biopharmaceutical company advancing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors, today presented updated data from its Phase 1b expansion cohort evaluating IO-202, a first-in-class anti-LILRB4 antibody, in combination with azacitidine (AZA) in patients with chronic myelomonocytic leukemia (CMML). These new findings were highlighted in an oral presentation at the 2024 American Society of Hematology (ASH) Annual Meeting in San Diego, California. The updated results from this trial in hypomethylating agent-naïve CMML showed that IO-202, in combination with AZA, achieved a complete remission (CR) rate of 50.0% and an overall response rate (ORR) of 66.7% among the 18 efficacy evaluable patients based on the International Working Group (IWG) 2023 response criteria for higher-risk myelodysplastic syndromes. 1 Further analysis revealed that efficacy favors patients with high LILRB4 expression, who achieved a CR rate of 83.3% (5/6) and an ORR of 100% (6/6). Responses were observed in patients across all subgroups, including those with proliferative disease, elevated blast counts, unfavorable mutations, and high symptom scores. These findings underscore the potential of IO-202 to address an important unmet need in CMML, where the only approved treatment with hypomethylating agents yields modest CR rates of 7-17%. 2 There is a critical need for innovative therapies for CMML, as no new treatments with a novel mechanism of action have been approved in over 30 years. The prognosis for CMML patients remains poor, with a median survival of less than three years. Allogenic hematopoietic cell transplant (HCT) is the only potentially curative option, yet fewer than 15-20% of patients are eligible to undergo HCT. As a novel agent, IO-202 demonstrates promising clinical benefits, addressing a significant unmet need. In this study, treatment with IO-202 in combination with AZA enabled 38.9% of the patients to successfully bridge to HCT. Additionally, four out of six transfusion-dependent patients became transfusion-independent. IO-202 is well-tolerated at the preliminary recommended Phase 2 dose (60 mg/kg followed by 30 mg/kg every two weeks​) among 21 safety-evaluable patients. No dose-limiting toxicities were reported. “These results represent a positive advance in the treatment of CMML, a disease with very limited options and poor outcomes,” said Gabriel N. Mannis, M.D., IO-202 Phase 1 investigator and associate professor of medicine, division of hematology, Stanford Cancer Institute, Stanford University. “The favorable correlation between LILRB4 expression and treatment response underscores the contribution of IO-202 to efficacy consistent with its mechanism of action. Achieving a 50% complete response rate overall—and an 83% complete response rate in patients with high LILRB4 expression—demonstrates the potential of IO-202 as a highly impactful therapy. Additionally, the ability to bridge nearly 40% of patients to transplant and help most transfusion-dependent patients achieve independence offers new hope for improving outcomes in this challenging disease.” “We are encouraged by the promising clinical activity and tolerability of IO-202 in this trial,” said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. “These data support a pivotal study to evaluate IO-202 in combination with azacitidine as a frontline treatment for hypomethylating agent-naïve CMML. We look forward to working closely with regulators to bring this potentially life-changing therapy to patients.” ABOUT CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) CMML is a rare form of blood cancer, with an overall incidence of 0.35 cases per 100,000 population in the United States. 3 CMML is characterized by persistent elevation of peripheral blood monocytes (≥0.5×10 9 /L; monocytes ≥10% of white blood cell count) for over three months, accompanied by dysplastic features in the bone marrow. 4,5 The only FDA-approved therapies currently available for CMML are hypomethylating agents, such as azacitidine, which achieve a complete response rate of just 7-17%. 2 ABOUT LILRB4 (also known as ILT3) LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on monocytes and monocyte-derived cells. LILRB4 is expressed on certain hematologic cancer cells, such as myelomonocytic leukemia blasts, and on certain pathogenic cells involved in autoimmunity and inflammatory processes. ABOUT IO-202 IO-202 is a first-in-class IgG1 antibody with specific, high-affinity binding to LILRB4 and depletes LILRB4 positive cells via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. As such, IO-202 is a targeted therapy with broad potential in blood cancers and autoimmune and inflammatory diseases. IO-202 has completed the dose escalation part of the first-in-human, multicenter, open-label Phase 1 study in the U.S., and the data was presented at the European Hematology Association (EHA) Congress in 2023. This Phase 1 trial has advanced to the dose expansion stage to evaluate IO-202 in combination with azacitidine ( NCT04372433 ) in patients with newly diagnosed chronic myelomonocytic leukemia (CMML) who have not received any hypomethylating agents (HMA). The U.S. Food and Drug Administration granted IO-202 Fast Track Designations for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) and relapsed or refractory CMML, respectively. The FDA has also granted IO-202 Orphan Drug Designations for the treatment of AML and CMML, respectively. ABOUT IMMUNE-ONC THERAPEUTICS, INC. Immune-Onc Therapeutics Inc. (“Immune-Onc”) is a private, clinical-stage biopharmaceutical company developing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors. Immune-Onc has a differentiated pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB). Immune-Onc’s focused platform approach has led to the development of several promising therapeutics across various stages of development. Those include IO-108, an antagonist antibody targeting LILRB2 (also known as ILT4), in Phase 1b/2 clinical development for solid tumors, and IO-202, a first-in-class antibody targeting LILRB4 (also known as ILT3), in Phase 1b clinical development for the treatment of acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Additional assets in Immune-Onc’s pipeline include IO-312 (a novel bispecific antibody targeting LILRB4 and CD3), IO-106 (first-in-class antagonist antibody targeting LAIR1), and undisclosed immunology and oncology programs. Immune-Onc has established agreements with leading biopharmaceutical companies, including BeiGene , Regeneron, and Roche , to support its global product development plans for IO-108 and IO-202. It has received research grants from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) and the California Institute for Regenerative Medicine (CIRM) and investment from The Leukemia & Lymphoma Society Therapy Acceleration Program® (LLS TAP®). Headquartered in Palo Alto, California, Immune-Onc has assembled a diverse team with deep expertise in drug development and proven track records of success at leading biopharmaceutical companies. For more information, please visit www.immune-onc.com and follow us on X and LinkedIn . SOURCE: Immune-Onc Therapeutics