Transforming ALS Treatment: Dunad Nominates DUN’040 as Development Candidate

Dunad Therapeutics is pleased to announce the formal nomination of Development Candidate, DUN’040 for the treatment of both sporadic and familial ALS. DUN’040 is a first-in-class covalent, brain-penetrant small molecule inhibitor of the lipid kinase PIKfyve that mitigates the TDP-43 proteinopathy found in 97% of all ALS patients. Modulating TDP-43 by PIKfyve inhibition represents a disease modifying therapy and a critical proximal disease target in ALS, and potentially other TDP-43  associated CNS disorders.  

The covalent mechanism unique to DUN’040 creates a  differentiated CNS  therapy which results in a selective and sustained tissue inhibition of PIKfyve. In vivo models show that DUN’040 achieves high CNS exposure and target occupancy with a 1:1 brain:plasma ratio. DUN’040 has also demonstrated survival benefit and restoration of cryptic splicing in preclinical studies with ALS patient-derived stem-cell derived motor neurons.. Early toxicology studies have revealed a strong correlation between exposure and target occupancy across animal species providing a wide therapeutic index which will facilitate clinical translation and proof-of-concept in ALS.  

DUN’040 has the potential to be a transformational medicine for ALS, a disease of high unmet need that lacks impactful disease-modifying treatments.  Dunad will be initiating IND-enabling studies to support a Phase I study that will assess safety and pharmacokinetics,  in addition to the ability to measure target engagement and occupancy afforded by the covalent properties of DUN’040.  

“By mapping the fundamental properties of our covalent molecules with the use of chemoproteomics and other  biochemical and biophysical tools, Dunad was able to deliver a very high quality molecule and achieve this development milestone  in a short interval”, said CEO and President, Pearl S. Huang,   “ We look forward to further characterization of our molecule and testing a truly innovative novel treatment strategy for ALS”