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.
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 (BTD) by the US FDA in October 2018 for the treatment of cGVHD.
In May 2020, Kadmon announced pivotal trial ROCKStar (KD025-213) reached endpoint with topline results demonstrated clinical meaningful efficacy. Kadmon submitted belumosudil New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) under the Real-Time Oncology Review (RTOR) pilot program in November 2020, and received full approval in July 2021.
Upon receiving BTD by NMPA, BioNova initiated BN101 Phase 1 and Phase 2 trial in China in December 2020 and April 2021, respectively. BN101/belumosudil China NDA was submitted in November 2021.
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.
Carna Biosciences Inc. initiated Phase I healthy volunteers ’clinical trial in Europe in 2021. Subject recruitment and study drug dosing are completed while data analysis and clinical study report are ongoing. BioNova submitted an investigational new drug (IND) application for BN102 for the treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and B-cell Non-Hodgkin Lymphoma (NHL) to the China National Medical Products Administration (NMPA) in January 2022, and received IND clearance on March 15, 2022. A multi-center Phase I clinical trial for CLL and B-NHL patients is underway with target date of first patient enrollment in mid-2022.
On 12 October 2021, BioNova Pharmaceuticals Ltd. and Sutro Biopharma, Inc. (NASDAQ: STRO) entered into collaboration to develop and commercialize BN301(STRO-001), for patients with hematologic cancers in Greater China.
BN301 is a CD74-targeting ADC, based on Sutro’s integrated cell-free protein synthesis and site-specific conjugation platform, XpressCF+™, currently being investigated in a Phase 1 clinical trial in US. Sutro is currently enrolling patients with multiple myeloma and non-Hodgkin’s lymphoma in a dose-escalation trial and the maximum tolerated dose has not yet been reached. BN301 was granted Orphan Drug Designation by the FDA for multiple myeloma in October 2018.
BN104 is a novel, potent and highly selective small molecule menin inhibitor for potential treatment of acute leukemias with rearranged mixed lineage leukemia (MLLr) gene. It showed optimized drug-like properties and excellent efficacy in MV4-11 xenograft mouse model. Furthermore, BN104 has low risk in corrected QT interval (QTc) prolongation given the fact that it is an extremely weak human ether-a-go-go related gene (hERG) inhibitor with IC50 of greater than 100 uM. To date, BN104 has demonstrated favorable toxicity profile in preliminary preclinical studies.