OncoResponse Reports Phase 1 Results for OR502 Anti-LILRB2 Antibody in Advanced Cancer Patients

A significant development in cancer immunotherapy was announced by OncoResponse, a clinical-stage biotech company. The firm unveiled the optimistic results of its Phase 1 trial for OR502, a humanized anti-leukocyte immunoglobulin-like receptor B2 (LILRB2) antibody. OR502 is designed to revive both innate and adaptive immune responses which are suppressed by LILRB2. This study aimed to evaluate the safety, tolerability, and initial anti-tumor activity of OR502, both as a standalone treatment and in combination with anti-PD-1 therapy in patients with advanced solid tumors.

The trial results were encouraging, showing that OR502 was well-tolerated with no dose-limiting toxicities (DLTs), serious adverse events (SAEs), or Grade 3 or higher treatment-related adverse events. The findings revealed promising efficacy signals, with a disease control rate of 65%. The monotherapy regimen resulted in two partial responses (PR) and nine cases of stable disease (SD) out of 17 participants.

Chief Executive Officer Clifford Stocks expressed enthusiasm about the results, noting that the completion of this Phase 1 study marks a significant step in their mission to develop impactful cancer treatments. The next phase of clinical tests is set to include patients with cutaneous melanoma and non-small cell lung cancer (NSCLC).

Chief Scientific Officer Kamal Puri highlighted that OR502's unique binding to LILRB2 reverses immunosuppression in cancer, offering a new treatment avenue for patients struggling with the effectiveness of checkpoint inhibitor (CPI) therapies. OncoResponse has been working on strategies to block or reprogram tumor-associated macrophages (TAMs) to enhance anti-tumor activity, with OR502 showing superior preclinical and early clinical results compared to other anti-LILRB2 antibodies.

The Phase 1 trial was an open-label, multicenter, first-in-human study involving dose escalation and expansion phases. The primary objectives were to determine the maximum-tolerated dose (MTD) and optimal dose for OR502 as both monotherapy and in combination with anti-PD-1 therapy, cemiplimab. The study comprised two parts: Part A focused on dose escalation to identify the MTD or optimal dose, while Part B involved an expansion phase in patients with advanced solid tumors to establish the recommended Phase 2 dose (RP2D) and assess preliminary anti-tumor activity. The trial also examined potential biomarkers throughout the study, with a more detailed evaluation in a separate biology cohort.

OR502 targets LILRB2, an immunoinhibitory receptor found on TAMs within the tumor microenvironment (TME). TAMs typically inhibit the effectiveness of CPI therapies and prevent T cells from attacking tumors. By blocking TAMs’ inhibitory activity and promoting the activity of tumor-killing T cells, OR502 aims to enhance CPI therapy responses. This action blocks LILRB2's interaction with HLA-G on tumor cells, preventing the suppression of myeloid cells. Higher LILRB2 expression is associated with reduced patient survival across various tumor types. OR502, a humanized monoclonal antibody, aims to reverse CPI therapy inhibition by targeting LILRB2 and boosting the activity of tumor-killing T cells.

OncoResponse is a clinical-stage biotech company specializing in immuno-oncology. It focuses on developing cancer immunotherapies based on insights from the immune systems of Elite Cancer Responders. Through a strategic alliance with MD Anderson Cancer Center, OncoResponse employs a proprietary B-cell discovery platform to identify and develop novel antibodies targeting immune cells within the TME. Their leading clinical candidate, OR502, is an anti-LILRB2 antibody designed to counter LILRB2-mediated immune suppression and enhance both innate and adaptive immune responses.