Jubilant Therapeutics Inc. has announced the commencement of global clinical trials for two of its pipeline programs, JBI-802 and JBI-778, marking a significant step forward in the development of novel cancer therapies. The first patients have been dosed in a Phase I/II clinical trial of JBI-802 in heme-oncology and a Phase I clinical trial for JBI-778 in solid tumors. These trials aim to assess the safety and efficacy of these novel drug candidates in genetically defined subsets of patients with select hematological and solid tumor indications with high unmet medical needs.
JBI-802: Dual LSD1/HDAC6 Inhibitor for Heme-Oncology
JBI-802 is a first-in-class, orally administered, small-molecule dual inhibitor of LSD1 (Lysine-specific histone demethylase 1A) and HDAC6 (Histone deacetylase 6) within the CoREST complex. An earlier Phase I study in advanced solid tumor patients showed a dose-proportional increase in exposure across cohorts and a strong correlation between exposure and the on-target effect of platelet decrease. Notably, there were no reports of Dysgeusia and Anemia, typical adverse events seen with LSD1-only inhibitors. The Phase I trial also demonstrated anti-tumor activity in Non-Small Cell Lung Cancer (NSCLC) patients, including a confirmed partial response. These results support the expansion of JBI-802's development into Essential Thrombocythemia and Myelodysplastic Syndrome/Myeloproliferative Neoplasms (MDS/MPN) with thrombocytosis.
Essential Thrombocythemia, a chronic disease characterized by excessive platelets, affects over 100,000 patients in the United States. The primary treatment, hydroxyurea, has limitations in terms of both safety and efficacy, highlighting the need for new therapeutic options.
JBI-778: Brain-Penetrant PRMT5 Inhibitor for Solid Tumors
The second clinical trial focuses on JBI-778, an oral brain-penetrant inhibitor of PRMT5 (Protein arginine N-methyltransferase 5). This trial aims to assess both the safety and the recommended Phase II dose for JBI-778 in mEGFR Tyrosine Kinase Inhibitor (TKI) resistant NSCLC, IDH+ high-grade glioma (HGG), and Adenoid Cystic Carcinoma (ACC).
PRMT5 inhibition has shown promise in multiple cancers but has faced challenges due to safety concerns and patient segment limitations. JBI-778 is a unique substrate competitive brain penetrant PRMT5 inhibitor that has shown no adverse effects in preclinical settings and can address both MTAP null and wild-type tumors, as well as brain tumors, catering to a larger patient segment, including those with brain metastases.
Jubilant's TIBEO Discovery Engine
According to Syed Kazmi, Chief Executive Officer of Jubilant Therapeutics Inc., the two most advanced novel drug candidates at Jubilant Therapeutics Inc. were discovered in-house using their TIBEO (Therapeutic Index and Brain Exposure Optimization) Discovery Engine. This approach utilizes structure-based drug design to generate novel pharmacophores with improved therapeutic index compared to existing agents. Initial clinical data from both JBI-802 and JBI-778 are expected in 2025.
