Jubilant Therapeutics Inc. has announced the commencement of global clinical trials for two of its pipeline programs, JBI-802 and JBI-778, with the first patients dosed. These trials represent a significant advancement in Jubilant's strategy to develop precision therapeutics for oncology and autoimmune diseases.
JBI-802: Targeting CoREST Complex in Heme-Oncology
JBI-802 is a first-in-class, orally administered dual inhibitor of LSD1 and HDAC6 within the CoREST complex. A Phase I/II clinical trial is now underway to evaluate JBI-802 in heme-oncology indications, specifically Essential Thrombocythemia and Myelodysplastic Syndrome/Myeloproliferative Neoplasms (MDS/MPN) with thrombocytosis.
Previous Phase I studies in advanced solid tumor patients demonstrated a dose-proportional increase in exposure and a strong correlation between exposure and the on-target effect of platelet decrease. Notably, common adverse events associated with LSD1 inhibitors, such as Dysgeusia and Anemia, were not reported. The earlier trial also showed anti-tumor activity in Non-Small Cell Lung Cancer (NSCLC) patients, including a confirmed partial response.
Essential Thrombocythemia, a chronic disease characterized by excessive platelets, affects over 100,000 patients in the United States. Current primary treatment, hydroxyurea, has significant limitations in terms of safety and efficacy, highlighting the unmet need for novel therapies.
JBI-778: A Brain-Penetrant PRMT5 Inhibitor for Solid Tumors
The second clinical trial focuses on JBI-778, an orally available, brain-penetrant inhibitor of PRMT5. This Phase I trial aims to assess the safety and recommended Phase II dose of JBI-778 in patients with 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 drug development has been hindered by safety concerns related to SAM competitive approaches and patient segment limitations of MTAP null tumor-focused inhibition. JBI-778 is designed as a substrate-competitive PRMT5 inhibitor with brain penetration capabilities, showing no adverse effects in preclinical studies and the potential to address both MTAP null and wild-type tumors, including brain tumors and metastases.
Jubilant's Discovery Engine and Future Outlook
Syed Kazmi, CEO of Jubilant Therapeutics 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 focuses on structure-based drug design to generate novel pharmacophores with improved therapeutic indices. Initial clinical data from both trials are expected in 2025.
About JBI-802 and JBI-778
JBI-802 is a selective dual inhibitor of LSD1 and HDAC6, targeting stem cell modulation and immune suppression. Preclinical research has demonstrated synergistic anti-tumor activity and a favorable safety profile. JBI-778 is a potent and brain-penetrant inhibitor of PRMT5, stabilizing SAM binding and exhibiting a superior safety profile in preclinical studies. It has shown significant activity in Tyrokinase-Inhibitor resistant cell lines, brain tumors, and NSCLC models.
