SEMA4A

PALO ALTO, Calif.--( BUSINESS WIRE )--Immune-Onc Therapeutics, Inc. (“Immune-Onc”), a private, clinical-stage biopharmaceutical company dedicated to advancing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors, today announced a Phase 1b/2 clinical trial collaboration with Roche to evaluate Immune-Onc’s IO-108, a first-in-class antibody targeting LILRB2 (also known as ILT4), in combination with Roche’s atezolizumab and bevacizumab for the first-line treatment of patients with locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC). Atezolizumab and bevacizumab is the first cancer immunotherapy combination regimen approved by the U.S. Food and Drug Administration for this setting and is the recommended standard of care by the National Comprehensive Cancer Network. “We are excited to work with Roche to accelerate the development of IO-108,” said Charlene Liao, Ph.D., chief executive officer and board chair of Immune-Onc. “IO-108 has demonstrated clinical activity and an acceptable safety profile across multiple solid tumors as monotherapy and in combination with T cell checkpoint inhibitors. The collaboration marks a significant milestone in establishing IO-108 as the preferred myeloid checkpoint inhibitor for combination with standard of care immunotherapy regimens in solid tumors.” Under the collaboration, Roche will sponsor and conduct the global, randomized Phase 1b/2 trial to evaluate the safety, efficacy and pharmacodynamics of IO-108 in combination with atezolizumab and bevacizumab compared to atezolizumab and bevacizumab, the standard of care treatment regimen for advanced liver cancer. ABOUT THE RANDOMIZED CLINICAL TRIAL The Phase 1b/2 global, randomized HCC study is part of Roche’s Morpheus-Liver program. It will evaluate IO-108 in combination with atezolizumab and bevacizumab (“triplet”) versus atezolizumab and bevacizumab (“doublet”), the standard of care in patients with locally advanced or metastatic and/or unresectable HCC with no prior systemic treatment. Initially, 40 patients will be enrolled across 25 sites worldwide in the IO-108 triplet combination, which will be compared to an active control arm of the atezolizumab and bevacizumab doublet combination. The study’s primary endpoint is objective response rate, and key secondary endpoints include progression-free survival and overall survival. Under the terms of the clinical collaboration agreement, Roche will manage the study operations, and Immune-Onc will supply IO-108 to support the trial while retaining global rights to IO-108. Tecentriq® (atezolizumab) and Avastin® (bevacizumab) are registered trademarks of Genentech, a member of the Roche Group. Learn more about the trial here . ABOUT HEPATOCELLULAR CARCINOMA According to the American Cancer Society 1 , more than 800,000 people are diagnosed with liver cancer each year worldwide. It is also one of the leading causes of cancer deaths worldwide, accounting for more than 700,000 deaths each year. The number of people diagnosed is predicted to rise, with the incidence of liver cancer increasing by 55.0% and the number of deaths increasing by 56.4% between 2020 and 2040 2 . Hepatocellular carcinoma is the most common form of liver cancer in the United States, making up almost 90% of cases 3 . Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD), and cirrhosis resulting from these conditions 4 . 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 dedicated to discovering and 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 antagonist 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). IO-202 has the potential to be the best-in-class antibody therapy for lupus and can extend to other indications in immunology and inflammation. 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 . American Cancer Society. About Liver Cancer. Accessed Dec. 7, 2023 at https://www.cancer.org/content/dam/CRC/PDF/Public/8698.00.pdf The latest global burden of liver cancer: A past and present threat. Clin Mol Hepatol. 2023 Apr; 29(2): 355–357. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7:6. doi.org/10.1038/s41572-020-00240-3 Epidemiology of non-alcoholic fatty liver disease and hepatocellular carcinoma. JHEP Rep. 2021 Aug; 3(4): 100305. doi: 10.1016/j.jhepr.2021.100305

– Phase 1 data show encouraging clinical benefit for IO-108 as a monotherapy and when combined with pembrolizumab, suggesting potential to overcome resistance to T-cell checkpoint inhibitors – – Preclinical data for IO-312, a novel bispecific antibody targeting LILRB4 (ILT3) and CD3 (LILRB4 x CD3) will be presented as a late-breaking poster at AACR 2023 – PALO ALTO, Calif.--(BUSINESS WIRE)-- Immune-Onc Therapeutics Inc. (“Immune-Onc”), a private, clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, today announced encouraging Phase 1 dose escalation data for IO-108, a novel myeloid checkpoint inhibitor targeting Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4). The data will be presented in an oral session at the American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida, April 18. Preclinical data for IO-312, a novel bispecific antibody targeting LILRB4 (ILT3) and CD3 (LILRB4 x CD3) will also be presented on April 18 as a late-breaking poster at AACR 2023. “We are very encouraged to see promising signs of clinical activity across multiple solid tumor types and a favorable safety pro our first-in-class myeloid checkpoint inhibitor, IO-108,” said Charlene Liao, Ph.D., chief executive officer and board chair of Immune-Onc. “Our data demonstrates the utility of IO-108 as a new therapeutic modality to address key unmet needs for patients with solid tumors that do not respond to, develop resistance to, or relapse following, treatment with T cell checkpoint inhibitors.” The Phase 1 dose escalation study of IO-108 is intended to evaluate primary objectives of safety and tolerability, and secondary and exploratory objectives of pharmacokinetics, immunogenicity, pharmacodynamic (PD) biomarker effects, and antitumor activity of IO-108 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors. The trial enrolled 25 advanced cancer patients with relapsed/refractory solid tumors. Patients received escalating doses of IO-108 (60 mg -1800 mg) intravenously once every three weeks (Q3W). Treatment with IO-108 was well-tolerated to the maximum administered dose (1800 mg Q3W); the maximum tolerated dose was not reached. Among 23 evaluable patients (11 monotherapy, 12 combination therapy plus 1 crossover), results showed 1 complete response and 4 stable disease patients in the monotherapy cohorts and 3 partial responses and 4 stable disease patients in the combination cohorts. The 4 responding patients remain on study with an ongoing treatment duration of 8 to 12+ months as of abstract submission. Clinical benefit correlated with baseline characteristics and post-treatment changes in PD biomarkers including reprogramming of myeloid cells and activation of T cells. “Treating patients who are refractory to treatment with T-cell immune checkpoint inhibitors remains an ongoing challenge across many tumor types,” said IO-108 Phase 1 investigator, Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon. “I am very encouraged by these results, particularly the complete response to IO-108 monotherapy treatment in the Merkel cell carcinoma patient who had progressed on prior anti-PD-1 treatments. These findings suggest that LILRB2 is a critically important immunotherapy target.” The initial data from dose escalation supports further development of IO-108. The preliminary recommended Phase 2 dose (RP2D) is 1200 mg Q3W which is projected to achieve full receptor occupancy in at least 90% of patients. The ongoing IO-108 Phase 1 study is actively enrolling several biomarker-driven dose expansion cohorts, using IO-108 at RP2D as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab), both in the U.S. and China. Immune-Onc oral and poster presentation details are as follows: Abstract Number: 9498 Title: A first-in-human phase 1 trial of IO-108, an antagonist antibody targeting LILRB2 (ILT4), as monotherapy and in combination with pembrolizumab in adult patients with advanced relapsed or refractory solid tumors: Dose escalation study Presenter: Matthew H. Taylor, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon Session Title: Novel Immunotherapy Combination Clinical Trials Session Date and Time: Tuesday, April 18, 2:30 p.m. - 4:30 p.m. ET Presentation Number: CT040 Abstract Number: LB217 Title: A novel bispecific LILRB4/CD3 antibody with potent killing of monocytic acute myeloid leukemia cells Presenter: Charlene Liao, Ph.D., chief executive officer of Immune-Onc Therapeutics, Inc. Session Title: Late-Breaking Research: Immunology 2 Session Date and Time: Tuesday, April 18, 9:00 a.m. - 12:30 p.m. ET Location: Poster Section 36, Poster Board #10 Abstracts and full session details can be accessed through the AACR Online Program Planner ABOUT IO-108 IO-108 is a fully human IgG4 monoclonal antibody with high affinity and specificity towards LILRB2 (also known as ILT4). It blocks the interaction of LILRB2 with multiple ligands that are involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A and CD1d. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer annual meeting and the 2022 American Association for Cancer Research annual meeting demonstrate that IO-108 functions as a myeloid checkpoint inhibitor and promotes innate and adaptive anti-cancer immunity. The ongoing Phase 1 study of IO-108 in adult cancer patients has completed dose escalation in the U.S. (NCT05054348) and is actively enrolling several expansion cohorts, as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab, cemiplimab or tislelizumab), both in the U.S. and China. To date, IO-108 has been well tolerated with demonstrated clinical activity in multiple tumor types, both as a monotherapy and in combination with pembrolizumab. ABOUT IMMUNE-ONC THERAPEUTICS, INC. Immune-Onc Therapeutics Inc. (“Immune-Onc”) is a private, clinical-stage cancer immunotherapy company dedicated to the discovery and development of novel myeloid checkpoint inhibitors for cancer patients. The company aims to translate unique scientific insights in myeloid cell biology and immune inhibitory receptors to discover and develop first-in-class biotherapeutics that reverse immune suppression in the tumor microenvironment. Immune-Onc has a differentiated pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB) of myeloid checkpoints. Immune-Onc’s focused platform approach has led to the development of several promising therapeutics across various stages of development. Those include IO-108, a first-in-class antagonist antibody targeting LILRB2 (also known as ILT4), in Phase 1 clinical development for solid tumors and IO-202, a first-in-class antagonist antibody targeting LILRB4 (also known as ILT3), in Phase 1 clinical development for the treatment of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and solid tumors. Additional assets in Immune-Onc’s pipeline include IO-106, a first-in-class antagonist antibody targeting LAIR1, IO-312, a novel bispecific antibody targeting LILRB4 and CD3 (LILRB4 x CD3), and multiple undisclosed programs. Immune-Onc has established agreements with leading biopharmaceutical companies, including BeiGene and Regeneron, 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 and follow us on Twitter and LinkedIn.

- Oral presentation highlights interim clinical data from Phase 1 dose escalation study of IO-108, a novel myeloid checkpoint inhibitor targeting LILRB2 (ILT4) as a monotherapy and in combination with pembrolizumab in patients with solid tumors - - Company announces late-breaking abstract from new preclinical program, IO-312, a novel LILRB4 x CD3 bispecific antibody for acute myeloid leukemia - PALO ALTO, Calif.--(BUSINESS WIRE)-- Immune-Onc Therapeutics, Inc. (“Immune-Onc”), a private, clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting myeloid checkpoints, today announced that Phase 1 dose escalation data for IO-108, a novel myeloid checkpoint inhibitor targeting Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4) is selected for oral presentation at the American Association for Cancer Research (AACR) Annual Meeting being held April 14 - 19, 2023 in Orlando, Florida. In addition, preclinical data for IO-312, a novel bispecific antibody targeting LILRB4 (ILT3) and CD3 (LILRB4 x CD3) will be presented as a late-breaking poster at AACR 2023. “We are very excited that our interim clinical data of IO-108 is selected for oral presentation at AACR 2023. This reflects the clinical significance and broad market potential of IO-108 as monotherapy and in combination with an anti-PD-1 for treatment in a variety of solid tumors. Such a distinguished recognition, together with the acceptance of our IO-312 late breaking abstract for poster presentation at the meeting, signifies the strength and breadth of our pioneering myeloid checkpoint inhibitor programs across multiple cancer types,” said Charlene Liao, Ph.D., founder, chief executive officer and board chair of Immune-Onc. “Immune-Onc has built a strong oncology pipeline guided by our deep expertise in myeloid biology and drug development, and we are proud that our first-in-class myeloid checkpoint inhibitors are demonstrating clinical benefits in Phase 1 studies for patients with some of the hardest-to-treat cancers.” Details of Immune-Onc’s AACR 2023 presentations are as follows: Abstract Number: 9498 Title: A first-in-human phase 1 trial of IO-108, an antagonist antibody targeting LILRB2 (ILT4), as monotherapy and in combination with pembrolizumab in adult patients with advanced relapsed or refractory solid tumors: Dose escalation study Presenter: Matthew H. Taylor, M.D., assistant member, Developmental Cancer Therapeutics Laboratory and co-medical director, Providence Melanoma Program, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon. Session Title: Novel Immunotherapy Combination Clinical Trials Session Date and Time: Tuesday, April 18, 2:30 p.m. - 4:30 p.m. ET Presentation Number: CT040 Abstract Number: LB217 Title: A novel bispecific LILRB4/CD3 antibody with potent killing of monocytic acute myeloid leukemia cells Presenter: Charlene Liao, Ph.D., chief executive officer of Immune-Onc Therapeutics, Inc Session Title: Late-Breaking Research: Immunology 2 Session Date and Time: Tuesday, April 18, 9:00 a.m. - 12:30 p.m. ET Location: Poster Section 36, Poster Board #10 Abstracts and full session details can be accessed through the AACR Online Program Planner ABOUT IO-108 IO-108 is a fully human IgG4 monoclonal antibody with high affinity and specificity towards LILRB2 (also known as ILT4). It blocks the interaction of LILRB2 with multiple ligands that are involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A and CD1d. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer annual meeting and the 2022 American Association for Cancer Research annual meeting demonstrate that IO-108 functions as a myeloid checkpoint inhibitor and promotes innate and adaptive anti-cancer immunity. The ongoing Phase 1 study of IO-108 in adult cancer patients in the U.S. (NCT05054348) has completed dose escalation and is actively enrolling several expansion cohorts, as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab or cemiplimab). To date, IO-108 has been well tolerated with demonstrated clinical activity in multiple tumor types, both as a monotherapy and in combination with pembrolizumab. The company is also actively enrolling a Phase 1 clinical trial in China to evaluate IO-108 in solid tumors, as a monotherapy and in combination with anti-PD-1 antibodies (pembrolizumab or tislelizumab). ABOUT IMMUNE-ONC THERAPEUTICS, INC. Immune-Onc Therapeutics Inc. (“Immune-Onc”) is a private, clinical-stage cancer immunotherapy company dedicated to the discovery and development of novel myeloid checkpoint inhibitors for cancer patients. The company aims to translate unique scientific insights in myeloid cell biology and immune inhibitory receptors to discover and develop first-in-class biotherapeutics that reverse immune suppression in the tumor microenvironment. Immune-Onc has a differentiated pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB) of myeloid checkpoints. 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 1 clinical development for solid tumors and IO-202, a first-in-class antagonist antibody targeting LILRB4 (also known as ILT3), in Phase 1 clinical development for the treatment of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and solid tumors. Additional assets in Immune-Onc’s pipeline include IO-106 (first-in-class antagonist antibody targeting LAIR1), IO-312 (a novel bispecific antibody targeting LILRB4 and CD3 (LILRB4 x CD3), and multiple undisclosed programs for solid tumors and hematologic malignancies. Immune-Onc has established agreements with leading biopharmaceutical companies, including BeiGene and Regeneron, 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 and follow us on Twitter and LinkedIn.