Myrobalan raises $24M to advance trio of CNS programmes
11 Jan 2024
Phase 2
Myrobalan Therapeutics announced a $24 million raise Wednesday to fuel its pipeline of brain-penetrant, oral small molecules against targets involved in demyelination and neuroinflammation.
The series A was led by Co-win Ventures, with participation from new and existing investors including Guan Zi Equity Investment (Li Shui) Partnership (Limited Partnership), 3E Bioventures Capital, and AB Magnitude Ventures Group.
The company’s website lists multiple sclerosis (MS), Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) as potential indications for the former candidate, which is intended to deplete maladaptive microglia that cause neuroinflammation, remyelination blockade and axon degeneration, while allowing for the repopulation of new microglia.
The latter compound could be used to treat neuromyelitis optica (NMO), Parkinson’s disease (PD) and stroke, in addition to ALS, MS, and AD. GPR17 acts as an intrinsic brake to the differentiation and maturation of oligodendrocytes, which are myelinating cells. By blocking GPR17, remyelination is promoted in a diseased or injured nervous system to restore neuronal health.
Myrobalan co-founder Zhigang He discovered the potential of CSF1R and GPR17 inhibition to treat CNS diseases by studying the regrowth of axons in mice. While his team had successfully found a way to trigger axon regeneration after crushing mice’s optic nerves, the nerve fibres weren’t myelinated – which is necessary for speedy transmission between neurons, and the lack of which is a hallmark of several neurodegenerative diseases. After screening a panel of small molecules to measure their impact on oligodendrocyte precursor cell differentiation into myelination-competent oligodendrocytes, He and his team found that dual CSF1R/GPR17 inhibition after injury resulted in the myelination of about 60% of the mice's regenerated axons.
The results were featured in a 2020 issue of Neuron, a journal published by Cell Press.
The company’s third disclosed candidate is an allosteric TYK2 inhibitorTYK2 inhibitor Myrobalan is exploring to treat MS, AD and PD, thanks to its anti-neuroinflammation effects.
“To restore brain functions, we focus on two important drivers of neurodegenerative diseases, demyelination and neuroinflammation,” Wang said. “Therapies targeting these novel mechanisms will be critical tools for neurologists in the future, as monotherapy or in combination with standard of care. It will be fantastic if in 10 to 15 years, we could combine a neuroprotective agent with anti-neuroinflammation and remyelinating drugs to maximise the chance for our patient to recover brain functions.”
While no clinical compound has been successful targeting neuroinflammation to treat a CNS disease, TYK2’s potential to do just that has steadily been gaining attention. Last month, Sudo Biosciences debuted with $116 million and a TYK2 inhibitorTYK2 inhibitor it plans to bring into the clinic this year for MS. Biohaven is also planning a 2024 start for a Phase II trial of its dual TYK2/JAK1 inhibitor BHV-8000 to treat PD. For more, see Spotlight On: Biohaven's next act – testing if JAKs can ply another trade.
According to its website, Myrobalan also has a discovery-stage programme in schizophrenia, but has not disclosed its mechanism of action.
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