ACE-2223 is the first clinical-stage small molecule for ALS designed to directly target and disrupt aggregated TDP-43.

Acelot, a biotechnology company developing small molecule therapies for challenging targets in diseases with high unmet need, today announced the initiation of the Phase Ia clinical trial of ACE-2223 to evaluate its safety, tolerability, and pharmacokinetics in healthy adults. The first-in-class, orally bioavailable small molecule, ACE-2223, is designed to specifically bind to and disrupt aggregated TDP-43, a dysfunctional protein present in approximately 97% of sporadic ALS cases, with the goal of restoring normal TDP-43 function.

"We are incredibly honored to move this first in class program representing a potentially disease modifying therapy forward for people with ALS,” said Katie Planey, PhD, MBA, Chief Executive Officer of Acelot. "In ALS, there is an urgent need for targeted therapies that modulate upstream targets and that urgency drives every step of our work at Acelot. With a robust preclinical data package and our first healthy participant now dosed, our focus is clear - move as quickly as we can toward delivering a new option to patients in need."

ALS is a devastating and fatal motor neuron disease which progressively limits muscle control. Patient survival is typically between 20 to 48 months from onset, and the disease affects over 30,000 patients in the United States per year. The majority of ALS cases are sporadic, with no family history of the disease. Despite recent advances, there remains a significant unmet need for therapies that address the underlying cause of the disease.

“Targeting TDP-43 aggregation represents a true paradigm shift in how we approach ALS treatment," said Mark Forman, MD, PhD, Chief Medical Officer and Chief Development Officer of Acelot. "Initiating this Phase Ia trial for ACE-2223 marks our transition into a clinical-stage company and moves us closer to demonstrating how disruption of these toxic protein aggregates can fundamentally alter the progression of ALS."

About ACE-2223
ACE-2223 is an investigational first-in-class, orally bioavailable, small molecule with a novel mechanism of action. Preclinical models show that ACE-2223 targets aggregated TDP-43 and rescues downstream mRNA splicing function demonstrated by reduction of key cryptic exons such as STMN2 and UNC13A. In two ALS mouse models, ACE-2223 demonstrated critical readouts such as target engagement, reduction of neuroinflammation, neurofilament light chain (Nf-L), and a significant extension of survival. To date, there is no approved therapy for sporadic ALS that reduces neurofilament light chain or extends survival.

About Acelot
Acelot is a clinical-stage company dedicated to developing therapies for diseases with high unmet need by pursuing structurally challenging targets. The company leverages its proprietary RESOLUTE computational platform together with rigorous biology and mechanistic validation to identify and advance novel small molecule therapeutics. Acelot's lead program, ACE-2223, is currently being evaluated in a Phase Ia clinical trial. The company is headquartered in South San Francisco. To learn more about Acelot, please visit www.acelot.com.

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