tomaralimab (OPN-305) / Opsona - LARVOL DELTA

UN UPDATE OF A PHASE II EXPLORATORY STUDY OF OPN-305, A TOLL-LIKE RECEPTOR 2 (TLR-2) ANTIBODY, IN PATIENTS WITH LOWER RISK MYELODYSPLASTIC SYNDROMES WITH PRIOR HYPOMETHYLATING AGENT (HMA) THERAPY (EHA 2017) - "...Pts with isolated del(5q) should have received therapy with lenalidomide...If after 16 weeks of therapy, there was no response, azacitidine on a 3 day schedule, could be added to OPN-305...Treatment with OPN-305 in pts with previously treated lower-risk MDS was well tolerated with no significant toxicities and 53% ORR including 20% transfusion independence, and potential association between TLR2 levels and response"

P2 data • Biosimilar • Leukemia • Myelodysplastic Syndrome

TLR2 inhibition for cancer therapy, a novel approach with Tomaralimab a humanised IgG4 antibody (EORTC-NCI-AACR 2018) - P1/2; "...Toll-like receptors (TLRs) are a group of innate sensors that are key in the activation of immune responses...Opsona have developed a fully humanised monoclonal antibody Tomaralimab (OPN-305) against TLR2 that has potential as a novel clinical candidate in a range of cancers...Tomaralimab therapy was also assessed in recurrent paclitaxel-resistant ovarian cancer where it significantly delayed the regrowth of tumours via a decrease in intra-tumoural myeloid-derived suppressor cells (MDSCs)...In summary, Tomaralimabs beneficial effects in a range of animal models of solid organ tumours as well as in a clinical study of MDS suggests a potential broad applicability of this novel treatment through multiple mechanisms. To date, clinical benefit had been seen with Tomaralimab therapy in heavily pre-treated lower risk MDS patients that have failed HMA therapy."

Late-breaking abstract • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Melanoma • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Pancreatic Cancer

TOMARALIMAB, A FULLY-HUMANIZED TOLL-LIKE RECEPTOR 2 (ADPD 2022) - "In PD mouse models, intravenously injected Tomaralimab reached the brain parenchyma and this was sufficient to ameliorate PD pathologies such as aSyn aggregation, gliosis, neuroinflammation, as well as behavioral defects. Conclusions These results strongly support the beneficial effects of Tomaralimab on PD pathologies in various model systems, providing a rationale for the therapeutic development of Tomaralimab for the cure of Parkinson’s disease."

IO biomarker • CNS Disorders • Immunology • Inflammation • Movement Disorders • Parkinson's Disease

TOLL LIKE RECEPTOR 2 (TLR2) SIGNALING PROMOTES APOPTOSIS OF PREMALIGNANT HEMATOPOIETIC STEM AND PROGENITOR CELLS IN A MOUSE MODEL OF MYELODYSPLASTIC SYNDROME (ISEH 2017) - "In fact, an inhibitory TLR2 antibodyis currentlyin clinicaltrial for useinMDS (OPN-305, Opsona Therapeutics). Further supporting this, TLR2 surface expression is often (38% of cases) lost upon transformation. Ongoing experiments are aimed at determining the mechanism by which TLR2 signaling promotes premalignant cell death."

Biosimilar • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Placebo-Controlled Study to Evaluate the Safety and Efficacy of OPN-305 in Preventing Delayed Renal Graft Function (clinicaltrials.gov) - P2; N=351; Active, not recruiting; Sponsor: Opsona Therapeutics Ltd.; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar • Immunology

Loss of Toll-like Receptor 2 Results in Accelerated Leukemogenesis in the NUP98-HOXD13 Mouse Model of MDS (ASH 2017) - "...In fact, an inhibitory TLR2 antibody is currently in clinical trial for use in MDS (OPN-305, Opsona Therapeutics)...An assessment of caspase-1 and caspase-3/7 activities showed a significant reduction in activated caspase-1 in the HSPCs of NHD13;Tlr2-/- mice compared to NHD13;Tlr2+/+ mice (average luminescence units: 7310 vs. 10164), suggesting that TLR2 specifically promotes inflammasome-dependent cell death in the NHD13 mice...Thus, down-regulation of TLR2 may be a later event in the progression of MDS to acute leukemia, and complete inhibition of this pathway may, in fact, facilitate the survival of pre-leukemic HSPCs. Ongoing experiments are aimed at elucidating the mechanism by which TLR2 signaling promotes premalignant cell death in MDS and understanding how TLR2 is down-regulated upon transformation to leukemia."

Biosimilar • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Phase I/II Study of OPN-305 in Second-line Lower Risk Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2; N=96; Completed; Sponsor: Opsona Therapeutics Ltd.; Active, not recruiting ➔ Completed

Trial completion

Follow up Protocol to the Phase I/II Study of OPN-305 in Second-line or Third-line Lower Lower Risk Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2; N=14; Completed; Sponsor: Opsona Therapeutics Ltd.; Active, not recruiting ➔ Completed; N=52 ➔ 14

Clinical • Enrollment change • Trial completion