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. 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. 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. Highlightll will receive $10 million in upfront cash and $10 million in BHVN equity, development and commercial milestone payments of up to $950 million, and tiered royalty payments ranging from mid-single digit to lower teens percentages.  Biohaven and Highlightll will coordinate clinical development across global regions.