LILRB2

– 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

- Data demonstrates potential for IO-108 to enhance immune activation and overcome resistance in advanced solid tumors as a monotherapy and in combination with pembrolizumab - PALO ALTO, CA, November 21, 2024 -- 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 announced the publication of Phase 1 dose-escalation study results of IO-108, its first-in-class antibody targeting LILRB2 (also known as ILT4), in the Journal for ImmunoTherapy of Cancer (JITC), the peer-reviewed, online journal of the Society for Immunotherapy of Cancer (SITC). The paper, entitled “Phase 1 Dose Escalation Study of IO-108, an Anti-LILRB2 Antibody, in Patients with Advanced Solid Tumors,” details the safety, tolerability, preliminary efficacy, pharmacokinetics, immunogenicity, and pharmacodynamic biomarker results from 25 patients with advanced solid tumors enrolled in a first-in-human study of IO-108 as a monotherapy and in combination with pembrolizumab, an anti-PD-1 antibody. In the IO-108 monotherapy cohort, the overall response rate was 9%, with one patient achieving a durable complete response (CR) for over two years. The CR was observed in a patient with treatment-refractory Merkel cell carcinoma whose prior treatment included two lines of immunotherapy (pembrolizumab, followed by a combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4)). Among 13 efficacy-evaluable patients treated with the combination of IO-108 plus pembrolizumab, 3 patients (2 cholangiocarcinoma and 1 colon cancer, all microsatellite-stable cancer types that typically do not respond to T-cell checkpoint inhibitors) had a partial response (23%). Biomarker analysis revealed pharmacodynamic changes consistent with increased T-cell infiltration in tumors, indicating an activated tumor microenvironment in patients with clinical benefit in both monotherapy and combination therapy. Results also demonstrated that IO-108 was well-tolerated at all dose levels, with no dose-limiting toxicities observed. “The durable responses observed in this heavily pretreated patient population underscore the therapeutic potential of IO-108 as both a monotherapy and in combination with T-cell immune checkpoint inhibitors,” said IO-108 Phase 1 investigator and first author of the paper, Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon. “These findings provide compelling evidence that targeting myeloid-cell immune checkpoint LILRB2 offers a novel and promising approach to cancer treatment.” “We are very proud of our positive data published in the Journal for ImmunoTherapy of Cancer (JITC),” said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. “Our data suggest that IO-108 could play a pivotal role as a monotherapy and combination therapy with T-cell immune checkpoint inhibitors and support the broader clinical exploration of IO-108 as a versatile therapeutic option for patients with advanced solid tumors.” Immune-Onc is advancing the development of IO-108 in a Phase 1b/2 global, randomized study that is part of Roche’s Morpheus-Liver program. The study will evaluate IO-108 in combination with atezolizumab and bevacizumab versus atezolizumab and bevacizumab, the standard of care in patients with locally advanced, metastatic and/or unresectable liver cancer with no prior systemic treatment. The study’s primary endpoint is objective response rate, and key secondary endpoints include progression-free survival and overall survival. ABOUT IO-108 IO-108 is a fully human IgG4 monoclonal antibody with high affinity and specificity towards the myeloid checkpoint, LILRB2 (also known as ILT4). It blocks the interaction of LILRB2 with multiple ligands involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A and CD1d. Clinical data from the U.S. Phase 1 dose escalation study of IO-108 (NCT05054348) was presented at the 2023 American Association for Cancer Research annual meeting and demonstrated a favorable safety profile and encouraging clinical benefit utilizing IO-108 as a monotherapy and in combination with anti-PD-1 across multiple tumor types. IO-108 is being studied in several expansion cohorts in adult cancer patients as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab). A global, randomized Phase 1b/2 study is underway to evaluate IO-108 in combination with atezolizumab and bevacizumab as a potential first-line therapy for hepatocellular carcinoma (HCC). 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. MEDIA CONTACT Tara Cooper The Grace Group tara@gracegroup.us media@immuneonc.com 650-303-7306

– Late-Breaker Poster Presentation to occur at the 39 th Annual Society for Immunotherapy of Cancer (SITC) conference on November 9 th , 2024 – – Ongoing study to evaluate OR502 as monotherapy and in combination with anti-PD-1 therapy – HOUSTON, TX, USA I November 7, 2024 I OncoResponse, a clinical-stage biotech company advancing immunotherapies derived from the immune systems of Elite Cancer Responders, today announced the results of the Phase 1 trial of OR502, a novel, humanized anti-leukocyte immunoglobulin like receptor B2 (LILRB2) antibody that rescues innate and adaptive immune responses from LILRB2 mediated immune suppression. The Phase 1 study was designed to determine the safety, tolerability, and preliminary anti-tumor activity of OR502 administered as a monotherapy and in combination with anti-PD-1 in subjects with advanced solid tumors. “We are pleased that OR502 has demonstrated an excellent safety profile and compelling early efficacy signals. OR502 was well tolerated up to the highest dose level with no DLTs, SAEs or Grade ≥ 3 treatment-related AEs. The study showed promising early efficacy signals in monotherapy, including 2 PR and 9 SD (N=17) for a disease control rate of 65%. We are excited to conduct the next phase of clinical studies, which will evaluate OR502 in two mini-cohorts of patients, including cutaneous melanoma and NSCLC. Completing this Phase 1 study reflects our ongoing commitment to develop impactful treatments to improve outcomes for cancer patients,” said Clifford Stocks, Chief Executive Officer of OncoResponse. “OR502 binds to LILRB2 in a unique way to reverse immunosuppression in cancer and offers a potential treatment option to patients who have otherwise struggled with CPI therapy effectiveness,” said Kamal Puri, PhD, Chief Scientific Officer of OncoResponse. “OncoResponse has spent years devising strategies to block or reprogram tumor associated macrophages to drive anti-tumor activity. We are excited by the vast promise of OR502 with preclinical and initial clinical data showing superiority over other anti-LILRB2 antibodies.” About the Phase 1 Trial This Phase 1 study was an open-label, multicenter, first-in-human dose-escalation and expansion study designed to determine the safety, tolerability, and preliminary anti-tumor activity of OR502, a fully human IgG1 antibody that binds specifically to LILRB2. OR502 will be administered as a monotherapy and in combination with anti-PD-1, cemiplimab, in subjects with advanced solid tumors. The study consists of two parts. Part A of the study was a dose-escalation phase to determine the maximum-tolerated dose (MTD) or optimal dose of OR502 for further evaluation as monotherapy and in combination. Part B is an expansion phase in subjects with advanced solid tumors treated with OR502 at two separate doses, to help determine the recommended Phase 2 dose (RP2D) for further development and determine preliminary anti-tumor activity. The role of potential biomarkers will be evaluated throughout the study, and more intensively in a separate biology cohort. Additional details are available on ClinicalTrials.gov , identifier: NCT06090266. About OR502 LILRB2 is an immunoinhibitory receptor expressed on tumor-associated macrophages (TAMs) found in the tumor microenvironment (TME). TAMs inhibit the activity of checkpoint inhibitor (CPI) therapy and prevent T cells from killing tumors. Blocking the inhibitory activity of TAMs and promoting the activity of tumor-killing T cells reverses inhibition of CPI therapy, potentially leading to more and deeper responses to CPIs in patients. This is the mechanism of OR502, which modulates LILRB2 by blocking its engagement of HLA-G on tumor cells and prevents the suppression of the myeloid cells. Elevated expression of LILRB2 correlates with reduced patient survival in various tumor types. Our humanized monoclonal antibody, OR502, targets LILRB2 and blocks the inhibitory activity of TAMs and promotes the activity of tumor-killing T cells, reversing inhibition of CPI therapy. About OncoResponse OncoResponse is a clinical-stage, immuno-oncology biotech company developing cancer immunotherapies using clues from the immune systems of Elite Cancer Responders. In a broad strategic alliance with MD Anderson Cancer Center, OncoResponse deploys a proprietary B-cell discovery platform to identify and develop novel antibodies targeting immune cells in the tumor microenvironment. The company’s lead clinical candidate, OR502 is a best-in-class anti-LILRB2 antibody that rescues innate and adaptive immune responses from LILRB2-mediated immune suppression and entered clinical study in 2023. For more information please visit www.oncoresponse.com and follow us on LinkedIn and X . SOURCE: OncoResponse