Biohaven Acquires Exclusive License for Oral, Brain-Penetrant, Dual TYK2/JAK1 Inhibitor for Immune-Mediated Brain Disorders

Biohaven Ltd. announced that it acquired global rights, excluding China regions, for the development of an oral, brain-penetrant, dual inhibitor of Tyrosine Kinase 2 (TYK2) and Janus Kinase 1 (JAK1) for the treatment of brain disorders. BHV-8000 (previously TLL-041) was licensed from Hangzhou Highlightll Pharmaceutical Co. Ltd. (Highlightll) and Biohaven anticipates advancing the agent into a Phase 1 study in 2023.

Dysregulation of the immune system has been implicated in several neurodegenerative and neuroinflammatory disorders including Parkinson’s Disease, Multiple Sclerosis, Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Autoimmune Encephalitis. Over-active immune cells and microglia driving chronic neuroinflammation results in release of cytokines with activation of leukocytes and is thought to contribute to neuronal injury, death, gliosis, and demyelination. The TYK2 and JAK1 signal transduction pathways mediate highly complementary immune and inflammatory signaling events. Targeted, small-molecule therapies that inhibit TYK2 or JAK kinases have separately demonstrated robust efficacy in autoimmune, dermatologic and gastrointestinal disorders. TYK2 is a validated immune target as evidenced by a recent peripheral program that gained FDA approval, and there are multiple additional peripheral non-CNS programs in clinical development. Brain penetrant inhibitors of TYK2/JAK1 have the potential to bring this validated immune target to brain disorders.

There are currently no brain penetrant, selective, dual TYK2/JAK1 inhibitors approved for brain disorders.

Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, “We have gained tremendous insight into the role of the immune system and critical inflammatory signaling pathways with events that drive the onset, propagation and relentless progression of neurodegenerative diseases. BHV-8000, with its blood-brain barrier penetrant activity and dual profile of TYK2/JAK1 inhibition, offers the potential for a unique and highly attractive therapeutic advancement for the treatment of brain disorders. Dual TYK2/JAK1 inhibition is a novel target combination and potentiates complementary activities that permit a graded degree of therapeutic immunomodulation specific to pathogenic neuroimmune pathways. We look forward to advancing BHV-8000 into clinical development and uncovering the potential of neuroimmunomodulation for severe neurological disorders in desperate need of novel treatment options.”

Highlightll was founded by Chris Liang PhD and is focused on the research and development of small molecules for the treatment of autoimmune and inflammatory disorders. Dr. Liang is a Princeton trained chemist and seasoned drug developer who was an inventor of sunitinib and ensartinib. Dr. Liang oversaw the development of the licensed intellectual property, and the compound was designed to be brain penetrant while delivering dual selectivity for TYK2/JAK1 without the toxicity of JAK2/JAK3.

Chris Liang, Ph.D., Chairman and Chief Executive Officer of Highlightll, added, “Biohaven’s proven track record in successfully innovating, developing, and commercializing neuroscience therapies makes them an attractive partner to help maximize the potential of BHV-8000. We have delivered what we believe is a best-in-class dual TYK2/JAK1 molecule and the team at Biohaven has the clinical development expertise to explore its utility in brain disorders. We look forward to working together to expedite development of this compound to improve outcomes for patients in need.”

Dr. Coric added, “The addition of BHV-8000 expands our growing and diverse set of complementary neuro-immunomodulatory therapeutic approaches including selective extracellular degraders (commonly referred to as LYTACs or MoDEs™) against IgG, IgA, and antigen-specific targets in development at Biohaven. We are excited to work with Chris and the team at Highlightll to advance this novel and highly differentiated dual TYK2/JAK1 inhibitor in the treatment of brain disorders.”