On April 10, 2021 Jubilant Therapeutics Inc., a biopharmaceutical company advancing oral, small molecule modulators to address unmet medical needs in oncology and autoimmune diseases, reported that preclinical data from two programs evaluating the company’s PRMT5 inhibitor and PD-L1 inhibitor as anti-cancer agents, will be presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting taking place virtually from April 10-15, 2021 (Press release, Jubilant Therapeutics, APR 10, 2021, View Source [SID1234577872]).

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"We are excited to announce these important data from our PRMT5 and our PD-L1 programs that show efficacy and tolerability in preclinical models," said Syed Kazmi, President and Chief Executive Officer of Jubilant Therapeutics Inc. "Our oral PRMT5 inhibitor has good plasma and sustained brain exposure which results in strong target inhibition, tumor growth delay and survival advantage in both xenografts and orthotopic brain models. Our oral anti-PDL1 immunotherapeutics, with a shorter half-life, are an attractive alternative to current intravenous antibody therapies especially in the maintenance settings with potential to limit immune-mediated toxicities and side effects via innovative dosing approaches, while maintaining the class-based wide anti-tumor efficacy. We look forward to continuing our work on these programs as we see great potential for treating multiple cancers."

A link to the e-posters, listed below, is available through the AACR (Free AACR Whitepaper) website.

Title: Novel, small molecule PRMT5 inhibitors for treatment of cancer
Poster Number: 1128
Date and Time: April 10, 2021 at 8:30 a.m. Eastern Daylight Time (EDT)
Session Title: Epigenetic Targets
Presenter: Dhanalakshmi Sivanandhan, et al.

Title: Novel, small molecule inhibitors of PD-L1/PD-1 interaction
Poster Number: 1630
Date and Time: April 10, 2021 at 8:30 a.m. Eastern Daylight Time (EDT)
Session Title: Immune Checkpoints
Presenter: Dhanalakshmi Sivanandhan, et al.

PRMT5 over-expression, shown in several cancers including lymphoid, lung, breast, glioblastoma, gastric etc., is thought to be an important factor in its tumorigenicity due to its repressive function on tumor suppressor gene expression. Key highlights from an evaluation which examined the tumor growth inhibition of PRMT5 inhibitor JBI-778 in multiple cancer cell lines as well as glioblastoma, include the following:

JBI-778 is a potent PRMT5 inhibitor that is selective against other PRMTs;
JBI-778 shows potent anti-proliferative activity against a number of cancers;
This oral small molecule demonstrated anti-tumor efficacy in a Mantle Cell lymphoma model with an ED50 of < 10 mg/Kg and a complete tumor growth inhibition (97%) at a dose of 50mg/kg; and
JBI-778 exhibited sustained brain exposure and significant tumor growth inhibition in an orthotopic glioblastoma model, translating into substantial survival advantage.
JBI-778 is currently being evaluated for the treatment of multiple cancers and IND-enabling studies have commenced.

PD-L1 expression is an immune evasion mechanism exploited by many cancers, such as melanoma, non-small cell lung cancer and breast cancer, which permits cancer progression and metastasis. Key highlights from the PD-L1/PD-1 study which examined the ability of JBI-1527 to inhibit PD-L1 and restore T-cell proliferation and function, include the following:

JBI-1527 is a potent, selective inhibitor of PD-L1 which induces dimerization of the protein thereby alleviating PD-L1-induced suppression of T cell activation;
The inhibitor shows similar modulation of cytokines as Pembrolizumab in BioMAP assay and competes with anti-PD-L1 blocking antibody suggesting similar binding site on PD-L1; and
In CT-26 and MC38-hPD-L1 syngeneic models, the small molecule showed strong tumor growth inhibition comparable to anti-PD-L1 mAb/Atezolizumab, and was well tolerated.
Studies to further assess JBI-1527 and additional compounds are underway.

Jubilant Therapeutics Inc. is developing a pipeline of novel, differentiated therapeutic assets; for partnership opportunity inquiries please contact [email protected].