GUILFORD,CT, April 5,2023 — AI Therapeutics, Inc., a clinical-stage biopharmaceutical company developing novel therapeutics for rare diseases, announced today positive results from a Phase 2a clinical trial of AIT-101 (LAM-002A) inpatients with C9ORF72 amyotrophic lateral sclerosis (ALS). In the study, participants taking AIT-101 demonstrated increased expression of the target engagement biomarker (sGPNMB) and a 73% reduction in the toxic protein aggregate (poly(GP)) over 12weeks. The study also met its primary endpoints of safety and tolerability, and confirmation of delivery of drug and three active metabolites into the brain.
“This is exciting progress toward a new treatment for ALS,” said Dr. Murat Gunel, Chair of the Department of Neurosurgery and Professor of Genetics and of Neuroscience at Yale University and Chair of the Scientific Advisory Board and member of AI Therapeutics’ Board of Directors. “This study provides early clinical evidence of AIT-101’s ability to clear the toxic protein aggregates that may contribute to the adverse pathology of ALS and provides a strong rationale for further clinical studies.”
“The positive results of this trial are encouraging for further development of AIT-101 in ALS. AIT-101 belongs to a new class of experimental therapeutics that directly target the clearance of toxic protein aggregates in motor neurons, which is a hallmark of ALS. This data may have broad implications for all ALS individuals, not only for C9ORF72 ALS individuals tested in this trial,” said Suma Babu, MBBS,MPH, Principal Investigator of the trial, a physician scientist at the Healey Center for ALS at Massachusetts General Hospital and Assistant Professor of Neurology at Harvard Medical School. “This patient-centric, biomarker-driven, Phase 2a ALS clinical trial was able to efficiently inform us about the biological efficacy and CNS drug delivery of AIT-101 in C9ORF72 ALS individuals, using a relatively small sample size, short placebo exposure duration and short trial duration overall, while also providing trial completers with the option of long term expanded access to AIT-101.”
Brigette Roberts MD, Chief Executive Officer of AI Therapeutics, said, “AI Therapeutics is acutely aware of the urgent need for new disease-altering agents for underserved patient populations such as ALS. We are encouraged by the results of this initial study of AIT-101, our first-in-class PIKfyve kinase inhibitor. In particular, we are impressed with the speed and magnitude of reduction of toxic protein aggregates as measured by poly(GP). We thank all the patients and investigators who participated in this study; the dedication of so many towards this and other clinical studies offers inspiration and hope for patients suffering from this devastating disease.”
In addition to today’s Phase 2a clinical data announcement, AI Therapeutics is disclosing for the first time that AIT-101 has demonstrated efficacy in a TDP-43 animal model of ALS. This new data, together with activity demonstrated in in vitro studies of patient derived motor neurons with both familial and sporadic ALS, suggests that the drug could have broad applicability across multiple forms of ALS.
Detailed results from the Phase 2a trial and theTDP-43 animal model will be submitted for peer-reviewed publication and presentation at a future medical congress.
The 24-week study in 15 participants with C9ORF72 ALS consisted of a 12-week, randomized, placebo-controlled portion in which participants were assigned to AIT-101 or placebo in a ratio of 2:1, followed by a 12-week open-label extension and, subsequently, a long-term extension study (ongoing) for study participants. The primary, secondary, and exploratory endpoints included safety, tolerability, cerebrospinal fluid levels of drug and active metabolites, the effect of AIT-101 on biomarkers of target engagement, toxic protein aggregates and neurodegeneration. The Phase 2a clinical trial was conducted with the current formulation ofAIT-101, also known as LAM-002A. Additional information is available atwww.clinicaltrials.gov (NCT05163886).
AIT-101 is a first-in-class, potent and highly selective inhibitor of the lipid kinase PIKfyve. Inhibition of PIKfyve leads to activation of the transcription factor TFEB which drives the increased clearance of toxic protein aggregates via the autophagy lysosomal pathway. AIT-101 has now been demonstrated to reduce aggregates in human subjects, to improve the survival of motor neurons in in vitro models of familial and sporadic ALS, and to ameliorate functional deficits in a mutant TDP-43 animal model of ALS. AIT-101 is the most clinically advanced PIKfyve inhibitor in development.
About AI Therapeutics
AI Therapeutics was founded by Dr. Jonathan Rothberg, serial entrepreneur and Recipient of the National Medal of Technology and Innovation for inventing highspeed “Next-Gen” DNA sequencing, with the goal of utilizing artificial intelligence to accelerate the clinical development of drugs for rare diseases. The company is building out an expansive rare disease pipeline with the help of its Guardian AngelTM Platform, a suite of artificial intelligence tools that use deep learning to understand complex disease biology and the action of potential new therapeutics. To learn more, visit: AI Therapeutics.com.
 LAM-002A is the formulation of AIT-101 used in the current Phase 2 study
 Clinicaltrials.gov identifier: NCT05163886