Immunity Pharma has published promising results from its Phase 2a clinical trial of IPL344 for amyotrophic lateral sclerosis (ALS) in the journal Muscle and Nerve, demonstrating significant slowing of disease progression across multiple endpoints.
The open-label study involved nine participants with rapidly progressing ALS who received once-daily intravenous IPL344 treatment for an average of 11 months. Results showed a statistically significant reduction in disease progression as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
"The ALSFRS-R progression rate was reduced by 58% when comparing each participant to their individually matched control group from the PRO-ACT database," said Dr. Ilana Cohen, VP of R&D at Immunity Pharma. "After adjusting for disease stage and rate-indicating covariates, we observed a 64% slower progression rate, which was statistically significant with a p-value of 0.034."
Biomarker Evidence and Survival Data
Beyond functional measures, the trial demonstrated encouraging biomarker evidence. Neurofilament light chain (NfL), an established marker of neuronal damage, decreased by 27% from baseline in the six participants who continued treatment beyond the initial 28-day dose-escalation period.
Perhaps most striking were the preliminary survival data. Unadjusted median survival for IPL344-treated participants, including follow-up beyond the treatment period, was 43.4 months compared to 19.1 months in a historical control group from the ceftriaxone study.
Prof. Merit Cudkowicz, Executive Director of the Mass General Brigham Neuroscience Institute, commented on the findings: "There is a pressing need for therapies that can slow the progression of ALS beyond current options. The results observed in this open-label, small trial with IPL344 are good pilot data to inform design of next clinical trial. I believe there are both scientific rationale and data to support going to a larger, randomized placebo-controlled trial."
Multiple Endpoints Show Benefit
The study evaluated several secondary endpoints that further support IPL344's potential efficacy. While historical controls from the PRO-ACT database typically lost weight at a rate of 0.39 kg/month, IPL344-treated participants gained an average of 0.47 kg/month, a difference that reached statistical significance (p=0.02) when corrected for covariates.
Respiratory function, measured by slow vital capacity (SVC), declined 44% more slowly in the treatment group compared to historical placebo data. IPL344-treated participants showed an adjusted mean change of -1.6% per month versus -2.8% per month in the historical placebo group.
The drug was reported to be safe and well-tolerated throughout the treatment period.
Mechanism of Action
IPL344 is a small biologically active peptide that stimulates therapeutic cell-signaling processes, including activation of the Akt pathway, which is down-regulated in neurodegenerative diseases. This mechanism aims to induce survival-supporting processes and mitigate stress conditions in affected neurons.
The drug was discovered at the Weizmann Institute of Science in Israel in Prof. Irun Cohen's laboratory and has received orphan drug designation from both the FDA and EMA, granting market exclusivity for at least seven years if approved.
Study Design and Limitations
Prof. Marc Gotkine, Principal Investigator and Head of the Neuromuscular and EMG Unit at Hadassah Medical Center in Jerusalem, noted: "The study participants were specifically selected for their rapid disease progression, and these initial results are encouraging. I am looking forward to seeing this drug evaluated in a larger clinical trial."
The Phase 1/2a trial was designed as an open-label, dose-ranging study with once-daily IPL344 IV treatment administered at home for up to three years. It included a 28-day Phase 1 portion followed by the Phase 2a extension.
While the results are promising, the small sample size and open-label design are important limitations. Eight of the nine participants showed slower disease progression than their matched controls, with seven progressing at least 40% slower.
Future Directions
Eran Ovadia, Immunity Pharma's CEO, expressed optimism about the drug's potential: "We are encouraged by the potential of IPL344 to be transformative in the fight against ALS, given its initial efficacy across multiple clinical endpoints. We are currently preparing for a large, placebo-controlled clinical trial to further evaluate IPL344 efficacy."
The company believes that if the current results are reproduced in a larger study, IPL344 could offer meaningful benefits to individuals living with ALS, a devastating neurodegenerative disease that affects approximately 30,000 people in the United States alone, with about 5,000 new cases diagnosed each year.
David A. Schoenfeld of Harvard Medical School developed the statistical methods and performed the analysis for the study, with additional support from Prof. Jeremy Shefner, co-founder of the Northeast ALS Consortium (NEALS).
The full study, titled "Akt Activation with IPL344 Treatment for Amyotrophic Lateral Sclerosis: First in Human, Open-Label Study," was published in Muscle and Nerve on March 19, 2025.
