Jubilant Therapeutics Inc. reports isoform-selective PAD4 inhibitors demonstrating high In Vitro selectivity and potency and In Vivo oral bioavailability and anti-tumor activity
PAD4 inhibition a novel pathway to inhibit tumor metastasis and tumor growth
Data presented at the American Association of Cancer Research Annual Meeting 2022
BEDMINSTER, New Jersey – April 11, 2022 – Jubilant Therapeutics Inc. a biopharmaceutical company advancing small molecule precision therapeutics to address unmet medical needs in oncology and autoimmune diseases, today announced data to be presented at the American Association of Cancer Research (AACR) Annual Meeting 2022. The data reports on the pharmacokinetic and anti-cancer properties of isoform-selective peptidyl arginine deiminase 4 (PAD4) inhibitors as potential therapeutics to treat cancer. The poster will be presented during the Novel Targets and Pathways session at 9 a.m. CDT on April 12, 2022. The abstract is available here.
PAD4 activity in tumor cells may play a significant role in cancer metastasis. The first-in-class mechanism of PAD4 inhibition reduces neutrophil extra-cellular traps (NETs) which stimulates cancer cell adhesion, migration and invasion. Therefore, inhibition of PAD4 could be a novel strategy to inhibit cancer progression and metastasis. Jubilant Therapeutics Inc’s drug discovery platform created a number of lead molecules with b in vitro potency and high selectivity to PAD4 compared to PAD1, PAD2 or PAD3. Oral dosing with a mouse breast cancer model resulted in approximately 50% tumor growth inhibition versus approximately 35% with anti-PD1 antibody and was well tolerated. Molecular correlates of PAD4 inhibition were associated with tumor growth inhibition. These results were observed with additional breast and lung cancer animal models and with other lead PAD4 inhibitors developed by the Company.
“These results highlight the potential of PAD4 inhibition as a treatment for cancer,” said Luca Rastelli, Ph.D., Chief Scientific Officer, Jubilant Therapeutics Inc. and co-author of the poster. “We are characterizing lead candidates from distinct chemical scaffolds, that are orally available, highly selective for PAD4 to address unmet needs in both oncology and autoimmune disorders.”
About PAD4
Peptidyl arginine deiminase 4 (PAD4) is an enzyme that converts protein arginine or mono-methylarginine to citrulline. The PAD4-mediated hypercitrullination reaction in neutrophils causes the release of nuclear chromatin to form a chromatin network termed Neutrophil Extracellular Traps (NETs). NETs have been shown to be associated with several pathological processes including, fibrosis, ischemic stroke, preeclampsia, thrombosis, cancers and other autoimmune diseases. Jubliant Therapeutics Inc. is targeting PAD4 inhibition as a novel strategy to treat inflammatory diseases, cancer progression and metastasis.
About Jubilant Therapeutics Inc.
Jubilant Therapeutics Inc. is a patient-centric biopharmaceutical company advancing potent and selective small molecule modulators to address unmet medical needs in oncology and autoimmune diseases. Its advanced discovery engine integrates structure-based design and computational algorithms to discover and develop novel, precision therapeutics against both first-in-class and validated but intractable targets in genetically defined patient populations. The Company is progressing its most advanced program - first in class dual inhibitor of LSD1/HDAC6 to Phase I/IIa in 1H 2022, followed by additional INDs with novel brain-penetrant modulators of PRMT5 and PDL1, as well as PAD4 inhibitors in oncology and inflammatory indications. Jubilant Therapeutics Inc. is headquartered in Bedminster, NJ and guided by globally renowned key opinion leaders and scientific advisory board members. For more information, please visit www.jubilanttx.com or follow us on Twitter @JubilantTx and LinkedIn.