- Data demonstrated that ASH41020, a novel CSFR1 tyrosine kinase inhibitor ‘dendranib’, directs macrophage polarization toward the anti-inflammatory M2 phenotype
- ASH41020 treatment lessened disease severity in a preclinical model of multiple sclerosis (MS) to a similar extent to fingolimod, an approved MS treatment
- Study suggests ASH41020 is a potent anti-inflammatory and immunomodulatory agent that warrants further development as a promising treatment for MS patients
REDWOOD CITY, Calif., Aug. 22, 2023 (GLOBE NEWSWIRE) — Ashvattha Therapeutics (“Ashvattha”), a clinical-stage company developing a new class of nanomedicine therapeutics, today presented preclinical data showcasing anti-inflammatory and immunomodulatory effects of ASH41020, its new “dendranib” nanomedicine, in a mouse experimental autoimmune encephalitis (EAE) model of multiple sclerosis (MS). The preclinical data were presented in a poster at the 16th International Society of Neuroimmunology Congress (ISNI) held at the Centre des Congrès Québec in Québec City, Canada, from August 21st – 24th, 2023, and accessible here.
“We are encouraged by these data as they demonstrate our new dendranib candidate, ASH41020, is a potent tyrosine kinase inhibitor and a macrophage switching nanomedicine with the potential to decrease symptom severity after disease onset, warranting further development as a promising treatment for MS,” said Jeff Cleland, Ph.D., CEO and chairman of Ashvattha Therapeutics. “These data build on previous studies that show our precision nanomedicine therapeutics selectively target activated cells in regions of inflammation.”
MS is a chronic inflammatory demyelinating disorder of the central nervous system (CNS). Evidence implicates activation of peripheral macrophages and CNS resident microglia in its pathogenesis. This activation leads to the production of inflammatory molecules, causing axonal damage and cell death. Polarization of these cells toward an M1 phenotype is associated with relapse-independent disease progression, whereas M2-polarized cells are involved in remyelination processes. Reprogramming macrophages and microglia toward an M2 phenotype could be a viable therapeutic option for MS.
ASH41020 was studied in vitro in differentiated human primary monocytes and in a mouse EAE model of MS.
Key details and takeaways from the poster presentation include:
- In differentiated human primary monocytes, ASH41020 decreased M1 and increased M2 macrophage proportion in a dose dependent manner in the M1 polarizing environment. In the M2 polarizing environment, ASH41020 treatment did not affect M1 macrophage proportion but increased M2 macrophage proportion.
- In the EAE model of MS, treatment with ASH41020 after disease onset decreased symptom severity in a dose dependent manner. The magnitude of this effect was similar to fingolimod, a medication used to treat MS.
- ASH41020 administration in the EAE model increased the percentage of M1 and M2 macrophages, showing a trend toward dose dependency for M2 macrophages.
- Collectively, these preclinical data show the anti-inflammatory and immunomodulatory potential of ASH41020.
ASH41020 is a new class of tyrosine kinase inhibitors referred to as “dendranibs,” which are metabolically stable and eliminated intact through the kidneys. ASH41020 selectively inhibits the colony-stimulating-factor-1 receptor (CSFR1) tyrosine kinase only in activated microglia and macrophages. CSFR1 plays a necessary role in the survival and proliferation of CNS microglia, peripheral tissue macrophages and blood myeloid cells. Targeting CSF1R with selective tyrosine kinase inhibitors has shown a decrease in EAE severity and delayed disease onset, making this receptor a viable target for future MS therapeutics.
About Ashvattha Therapeutics
Ashvattha Therapeutics is advancing a new class of clinical-stage nanomedicine therapeutics that traverse tissue barriers to selectively target activated cells only in regions of inflammation. Our targeted nanomedicine approach seeks to redefine precision medicine, empowering a new standard of care across ophthalmology, neurology, and inflammation. For more information, visit: www.avttx.com