Jubilant Therapeutics Initiates Global Clinical Trials for JBI-802 and JBI-778
Key Insights
Jubilant Therapeutics (search) has dosed the first patients in Phase I/II trials for JBI-802 in heme-oncology, targeting LSD1 (search) and HDAC6.
JBI-802 previously showed anti-tumor activity in NSCLC (search) patients and is now being developed for essential thrombocythemia (search) and MDS (search)/MPN (search).
A Phase I trial has begun for JBI-778, an oral brain-penetrant PRMT5 inhibitor, in mEGFR TKI-resistant NSCLC (search), IDH+ high-grade glioma (search), and adenoid cystic carcinoma (search).
Jubilant Therapeutics (search) Inc. has announced the commencement of global clinical trials for two of its pipeline programs, JBI-802 and JBI-778, marking a significant step in the company's mission to develop precision oral medicines. The Phase I/II clinical trial of JBI-802 will focus on heme-oncology, while the Phase I clinical trial will evaluate JBI-778 in solid tumors.
JBI-802: Dual Inhibitor for Heme-Oncology
JBI-802 is a first-in-class, orally administered, small-molecule dual inhibitor of LSD1 (search) (Lysine-specific histone demethylase 1A) and HDAC6 (Histone deacetylase 6) within the CoREST complex. Previous Phase I studies in advanced solid tumor patients demonstrated a dose-proportional increase in exposure across cohorts and a strong correlation between exposure and the on-target effect of platelet decrease. Notably, the earlier trial did not report dysgeusia and anemia, adverse events commonly associated with LSD1-only inhibitors. The Phase I trial also showed anti-tumor activity in non-small cell lung cancer (search) (NSCLC (search)) patients, including a confirmed partial response.
These results have provided human proof-of-principle for expanding the development of JBI-802 in essential thrombocythemia (search) and myelodysplastic syndrome (search)/myeloproliferative neoplasms (search) (MDS (search)/MPN (search)) 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 aims to assess the safety and recommended Phase II dose for JBI-778, an oral brain-penetrant inhibitor of PRMT5 (Protein arginine N-methyltransferase 5). This trial will focus on patients with mEGFR tyrosine kinase inhibitor (TKI) resistant NSCLC (search), IDH+ high-grade glioma (search) (HGG (search)), and adenoid cystic carcinoma (search) (ACC (search)).
PRMT5 has been identified as a promising pathway for multiple cancers, but drug development has faced challenges due to safety concerns related to the SAM competitive approach to PRMT5 inhibition and patient segment limitations of MTAP null tumor-focused approach PRMT5 inhibition. 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
Syed Kazmi, chief executive officer of Jubilant Therapeutics (search) Inc., stated that both JBI-802 and JBI-778 were discovered in-house using the company's 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. The company anticipates initial clinical data readouts for both JBI-802 and JBI-778 in 2025, focusing on genetically-defined subsets of patients with select hematological and solid tumor indications with high unmet medical needs.