OR502 / OncoResponse - LARVOL DELTA

Safety and efficacy of OR502, an antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), ± cemiplimab in patients with advanced solid tumors from a phase 1 study. (ASCO 2025) - P1/2 | "All IRRs were grade ≤ 2 and were mitigated by extending infusion duration to 60 minutes, with secondary prophylaxis if necessary (acetaminophen, diphenhydramine)... OR502 has excellent safety and tolerability ± cemiplimab. Based on efficacy, predictable PK and near-complete RO, two mini-expansion cohorts are evaluating OR502 800 mg Q3W ± cemiplimab in patients with cutaneous melanoma or NSCLC who have failed or progressed after ≥ 12 weeks of anti-PD-(L)1. Best objective response (RECIST 1.1), PK and RO."

Clinical • Metastases • P1 data • Colorectal Cancer • Cutaneous Melanoma • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Thymoma • Thymus Cancer • Thyroid Gland Carcinoma

Phase 2 expansions of OR502, an antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2) ± cemiplimab in patients with advanced solid tumors. (ASCO 2025) - P1/2 | "Efficacy is assessed Q6W for 1 year, then Q6 months. Safety follow-up at end of treatment is at 120 days."

Clinical • Metastases • P2 data • Cutaneous Melanoma • Immunology • Infectious Disease • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor

Using adaptive design elements to respond to regulatory changes and emerging data in a phase 1-2 study of OR502 - A best-in-class antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2) (AACR 2025) - P1/2 | "The dose escalation component was completed in ~40 subjects consisting of two arms: A1 (IV OR502 100, 200, 400, 800 and 1600 mg, once every 3 weeks [Q3W]) and A2 (IV OR502 3QW with standard dose cemiplimab). Twenty subjects per cohort provide greater statistical confidence to continue development. In a challenging regulatory environment, this study design using adaptive elements provides the flexibility needed to ensure the rapid progress of drug development."

P1/2 data • Cutaneous Melanoma • Liposarcoma • Lung Cancer • Melanoma • Mucosal Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

Clinical pharmacokinetics and peripheral receptor occupancy of OR502, best-in-class antibody against leukocyte immunoglobulin-like receptor B2 (LILRB2), alone and in combination with cemiplimab (AACR 2025) - P1/2 | "OR502 PK and RO support Q3W dosing, and based on near-complete RO and predictable PK, justify the OR502 dose selected for mono and combo expansion cohorts of 800 mg IV Q3W in PD-(L)1 pretreated cutaneous melanoma and NSCLC, respectively."

Clinical • Combination therapy • Late-breaking abstract • PK/PD data • Cutaneous Melanoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase 1 results of OR502, an antibody against leukocyte immunoglobulin-like receptor B2 (LILRB2), in patients with advanced cancers (SITC 2024) - P1/2 | "OR502 showed preclinical anti-tumor activity alone and in combination with anti-PD-1.1 Study OR502-101 evaluates OR502 safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy alone or combined with cemiplimab. Expansion cohorts are evaluating 800 mg IV Q3W in PD(L)-1 pretreated cutaneous melanoma and NSCLC. Ethics Approval Study OR502-101 has been approved by the Salus non-profit Institutional Review Board in Austin, TX.Download figure Open in new tab Download powerpoint Abstract 1464 Figure 1 OR502 reverses and prevents immunosuppression caused by myeloid cells in the tumor microenvironment"

Clinical • Late-breaking abstract • Metastases • P1 data • Cutaneous Melanoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

OncoResponse Announces Phase 1 Results of the Clinical Trial of OR502, anti-LILRB2 Antibody, in Subjects with Advanced Cancer (PRNewswire) - P1/2 | N=168 | NCT06090266 | Sponsor: OncoResponse, Inc | "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."

P1 data • Trial status • Cutaneous Melanoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Adaptive design elements in a Ph 1–2 study of OR502, a novel antibody against leukocyte immunoglobulin-like receptor B2 (LILRB2), in response to evolving Ph 1 data and changing regulatory environment (SITC 2024) - P1/2 | "By targeting TAMs, OR502 showed preclinical activity as monotherapy and in combination with cemiplimab.1 FDA's draft guidance on dose optimization (Project Optimus2) has made the Phase 1–2 development of novel immunotherapies like OR502 more challenging, requiring demonstration of dose-response, and identifying the minimal effective dose prior to later-phase trials. Conclusions Adaptive elements are an important design feature of the modern Phase 1 trial, permitting flexibility (with oversight) to execute efficient Phase 1–2 development in immune oncology (IO) without undue delays. Consequently, development of OR502, a novel IO agent, has been particularly rapid in a changing regulatory environment, accelerating a potentially effective new drug towards approval."

Cutaneous Melanoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

OncoResponse to Present Phase 1 Results of Clinical Study of OR502, anti-LILRB2 Antibody, as a Late-Breaker Poster Presentation at SITC 2024 (PRNewswire) - "The Phase 1 study results will be presented as a late-breaker poster presentation at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2024)..."

Late-breaking abstract • P1 data • Solid Tumor

ImmunoPrecise Antibodies Advances Therapeutic Innovation with Groundbreaking Rabbit Antibody Developments (Businesswire) - "ImmunoPrecise Antibodie...today proudly announces the clinical progress achieved with rabbit monoclonal antibodies designed and developed using IPA’s proprietary B Cell Select platform for the clinical-stage company, OncoResponse Inc...In a live presentation at the recent PEGS 2024 conference, OncoResponse shared exciting updates on two novel antibodies, OR502 and OR641...OR502, a novel, humanized anti-leukocyte immunoglobulin like receptor B2 (LILRB2) antibody, has successfully entered Phase I/II clinical trials, showing excellent safety profile, and is being evaluated for efficacy in treating advanced solid tumors....OR641, a novel, humanized dual antagonist antibody targeting both LILRB1 and LILRB2, has completed Cell Line Development and is undergoing IND-enabling studies. Preclinical models have demonstrated its superior ability to reverse immunosuppression caused by myeloid and lymphoid cells compared to other anti-LILRB1/2 antibodies."

Preclinical • Trial status • Oncology • Solid Tumor

OncoResponse Announces Initiation of Phase 1/2 Clinical Trial of OR502, anti-LILRB2 Antibody, in Subjects with Advanced Cancer (PRNewswire) - "OncoResponse...announced the dosing of the first participant in the Phase 1/2 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. This Phase 1/2 study is 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."

Trial status • Solid Tumor

A Study of OR502, a Monoclonal Antibody Targeting LILRB2, Alone and in Combination With Anticancer Agents (clinicaltrials.gov) - P1/2 | N=168 | Recruiting | Sponsor: OncoResponse, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Melanoma • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

OR502, a best-in-class anti-LILRB2 antibody that enhances both innate and adaptive anti-tumor immune responses (SITC 2023) - "Furthermore, OR502 restored the ability of exhausted T cells to secrete IFN-γ in the presence of M2c macrophages and significantly enhanced the activity of pembrolizumab in combination studies. These data demonstrate that OR502 has superior activity in relieving LILRB2-mediated immune suppression and enhancing both innate and adaptive anti-tumor immunity. Conclusions OR502 is an anti-LILRB2 antibody with best-in-class activity to restore both innate and adaptive immune responses by modulating immunosuppressive phenotype of myeloid cells."

Oncology • CD8 • HLA-B • HLA-G • IFNG • IL10 • LILRB2

A Study of OR502, a Monoclonal Antibody Targeting LILRB2, Alone and in Combination With Anticancer Agents (clinicaltrials.gov) - P1/2 | N=168 | Not yet recruiting | Sponsor: OncoResponse, Inc.

Combination therapy • Metastases • New P1/2 trial • Melanoma • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Taking Clues from Patients to Target TAMS (PEGS 2023) - "OR2805 is a first-in-class clinical antibody directed against CD163 that reverses immunosuppression caused by TAMs and restores T cell function, both in vitro and in vivo. OR502 is a preclinical anti- LILRB2/IL4 antibody that rescues T cells from macrophage-mediated suppression and induces anti-tumor responses."

Clinical • Oncology • CD163 • IL4

OncoResponse Awarded $13 Million in Funding from CPRIT and Raises $14 Million in Added Funds from Investors to Advance Cancer Immunotherapy (PRNewswire) - "OncoResponse...announced it has been awarded a $13 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT). The Company concurrently raised $14 million in new funding from existing investors, led by RiverVest Venture Partners and including ARCH Venture Partners, Canaan Partners, 3B Future Health Fund, Bering Capital, Takeda Ventures, InterVest and others. The CPRIT award and investment will support the advancement of OR502, a best-in-class anti-LILRB2 antibody poised to move to IND and clinical studies. Funds from the existing syndicate will also support continued advancement of the Company's lead immunotherapy candidate OR2805, a fully human monoclonal antibody identified from an Elite Responder using OncoResponse's proprietary B-cell discovery platform. OR2805 is currently being evaluated in a Phase 1 clinical trial."

Financing • Breast Cancer • Head and Neck Cancer • Leiomyosarcoma • Liposarcoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer

Preclinical characterization of OR502, an anti-LILRB2 antibody that rescues innate and adaptive immune responses from LILRB2 mediated immune suppression (SITC 2022) - "Furthermore, OR502 restored the ability of exhausted T cells to secrete IFN-γ in the presence of M2c macrophages and significantly enhanced the activity of pembrolizumab in combination studies. Conclusions We have identified a novel humanized anti-LILRB2 antibody, OR502, that restores innate and adaptive immune responses by modulating immunosuppressive myeloid cells. These data provide a strong rationale for further development of OR502 for cancer treatment."

IO biomarker • Preclinical • Oncology • CD8 • IFNG