JBI-802 Phase I: Promise in Treating Immunotherapy-Resistant Tumors and MPN/MDS with Thrombocytosis

Jubilant Therapeutics, a biotech firm, has unveiled early findings from a Phase I clinical trial of their novel CoREST inhibitor, JBI-802. This drug, which targets both LSD1 and HDAC6, has shown promising results in treating advanced cancers and may also be beneficial for patients with Essential Thrombocythemia (ET) and Myeloproliferative Neoplasms (MPN/MDS) with high platelet counts.

The initial data from 11 patients demonstrated that JBI-802's exposure increased proportionally with dosage, and there was a significant link between this exposure and the drug's intended effect of reducing platelets. This suggests that the drug achieved an effective level of LSD1 inhibition. Notably, the only side effect observed was a decrease in platelets, which sets JBI-802 apart from other LSD1 inhibitors that may cause anemia or taste disturbances.

Two patients with non-small cell lung cancer (NSCLC), who had not responded to standard immunotherapy, were treated with a lower dose of JBI-802. Despite the absence of a significant platelet decrease at this dosage, both patients exhibited anti-tumor activity. One patient, with a STK11 mutation that typically reduces the efficacy of immunotherapy, experienced a 39% reduction in lung tumor mass and complete resolution of pancoast syndrome, a condition affecting the brachial plexus nerves. This patient has maintained a durable response after nine treatment cycles.

The second NSCLC patient, who had both lung and liver cancer, responded to JBI-802 with over a 50% reduction in liver metastasis, along with improvements in portal hypertension, edema, and overall quality of life.

Dr. Alexander Starodub, a physician at The Christ Hospital in Cincinnati, highlighted the remarkable anti-tumor activity observed in these patients, particularly considering their poor prognosis due to genetic and metastatic factors. He added that the 10 mg dose of JBI-802 was well-tolerated and showed a favorable therapeutic profile.

Preclinical studies have indicated that combining JBI-802 with immunotherapy could have a synergistic effect against tumors, especially those resistant to immunotherapy with STK11 mutations. This suggests that the combination could offer new treatment options for patients with limited therapeutic choices.

Furthermore, the proportional decrease in platelets with dosage indicates that JBI-802 could be effective in treating hematological malignancies like ET and other MPN/MDS conditions characterized by high platelet counts. A Phase I/II study is planned for the near future to explore JBI-802's potential as a novel treatment for these conditions.

Jubilant Therapeutics is focused on developing precision oral medicines that enhance the therapeutic index for genetically defined patients with unmet medical needs in oncology and autoimmune diseases. Their discovery engine, TIBEO, has been instrumental in developing a pipeline that includes innovative drugs for various indications. The company is based in Bedminster, New Jersey, and is supported by a team of globally recognized scientific advisors.