On 07 November 2019, BioNova Pharmaceuticals Ltd. and Kadmon Holdings (NYSE: KDMN) entered into a strategic partnership to develop and commercialize BN101(KD025) for graft-versus-host disease (GVHD) in China. BioNova plans to initiate clinical trial in the 4th quarter of 2020.
BN101 is an orally available, selective small molecule inhibitor of ROCK2 (Rho-associated coiled-coil kinase 2), a molecular target involved in multiple autoimmune, fibrotic and neurodegenerative diseases. This is the only ROCK2 inhibitor being investigated in clinic for multiple indications, including chronic GVHD (cGVHD), IPF, and autoimmune diseases. BN101 was granted Breakthrough Therapy Designation by the US FDA in October 2018 for the treatment of cGVHD.
A pivotal registration study (KD025-213) is ongoing in the US, evaluating BN101 in post hematopoietic stem cell transplant patients with cGVHD and having received at least two prior lines of systemic therapy. In May 2020, Kadmon announced KD025-213 topline results of the primary analyses that were even more robust than its interim data. Kadmon is submitting its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) under the Real-Time Oncology Review (RTOR) pilot program, an initiative of the FDA's Oncology Center of Excellence. Kadmon is on track to complete its NDA submission in the 4th quarter of 2020.
On 16 March 2020, BioNova Pharmaceuticals Ltd. and Carna Biosciences Inc. (JASDAQ: 4572) entered into a license agreement to develop and commercialize BN102(AS-1763), a novel next-generation non-covalent Bruton's tyrosine kinase (BTK) inhibitor for the Greater China territory.
BTK is a validated target in B-cell receptor pathway that plays a critical role in B-cell malignancies. The current approved covalent BTK inhibitors (i.e., ibrutinib, acalabrutinib, and zanubrutinib) have changed the treatment paradigm of B-cell malignancies, including CLL/SLL, MCL, MZL, and WM. However, patients treated with covalent BTK inhibitors eventually develop acquired resistance that leads to disease progression. More and more evidence shows that BTK C481S mutation is the predominant resistance mechanism to the covalent BTK inhibitors. With the wide usage of covalent BTK inhibitors, there is an emerging significant unmet medical need in relapsed or refractory diseases resulted from acquired resistance of BTK C481S mutation for which the next generation BTK inhibitors can overcome.
BN102 is a next generation, highly potent, selective, and non-covalent BTK inhibitor developed not only to specifically target patients with C481S mutation, but also to have potentially superior efficacy and safety to the earlier generations of BTK inhibitors. BN102 is currently undergoing IND enabling studies and is expected to enter clinic in early 2021. BN102 has demonstrated high potency against both wild type and C481S mutant BTK in cell-based assays as well as in mouse xenograft models. BN102 is also highly selective against BTK with limited activities against other TEC family kinases and other kinases with cysteine binding sites, including EGFR, BLK, ERBB2/4, and JAK3, therefore is expected to show less off-target toxicities in human.
BN103 and BN104 are two small molecule compounds currently in discovery stage. They are designed to target two oncogenic pathways which are believed to be dominant drivers of specific hematologic malignancies. By leveraging BioNova’s deep knowledge and understanding of the molecular targets and current unmet medical needs, in combination with the state-of-the art discovery platform at our partners, we believe these two wholly owned compounds may have best-in-class potential and fast development and regulatory pathway.