Immunity Pharma Ltd.

Results from phase 2a trial in ALS patients were published in Muscle and Nerve. Statistically significant 58% to 64% slower ALSFRS-R progression rate in IPL344-treated patients compared to the matched PRO-ACT records. NfL was reduced by 27% for patients treated for at least two months. Unadjusted median survival for participants in the IPL344 group was 43.4 months compared with 19.1 months in the historical control group. IPL344 was safe and well-tolerated. JERUSALEM, April 7, 2025 /PRNewswire/ -- The results of a phase-2a clinical trial of IPL344 were published in Muscle and Nerve, the leading American scientific journal specializing in ALS and neuromuscular diseases. Slower ALSFRS-R Progression Following Treatment The nine study participants were treated for varying durations, averaging 11 months per participant, including one individual treated under a compassionate use protocol with comparable dose ranges. Multiple statistical methods were applied to assess the results of this study, primarily through comparison with PRO-ACT, the largest ALS clinical trials dataset available. ALSFRS-R progression rate was reduced by 58% (median, P=0.04) between each participant and their individually matched PRO-ACT control group (116 participants in a group on average). Adjustment for disease stage and rate-indicating covariates indicated a 64% slower ALSFRS-R progression (p = 0.034). All participants except one—who was treated for less than two months—exhibited slower disease progression than their matched controls, with 7 of the 9 progressing at least 40% slower. NfL Reduction and Survival Neurofilaments light chain (NfL), a biomarker for neuronal damage with increasing prominence in the evaluation of ALS studies, was measured before and after treatment. Six participants had blood sampling past the initial 28-day dose-escalating study. In these participants, plasma NfL concentrations were reduced from an average of 79.7 pg/mL at baseline to 58.6 pg/mL following treatment; a mean reduction of 27%. Unadjusted median [95% CI] survival for participants in the IPL344 group, including follow-up beyond treatment period, was 43.4 months [20.5, NA] compared with 19.1 months [17.4, 23] in a historical control group (the placebo group of the ceftriaxone study, selected as control for its particularly long duration). Additional Treatment Benefits IPL344 treated participants gained weight (+0.47 kg/month), while those in the historical PRO-ACT placebo control lost weight (−0.39 kg/month); the difference was statistically significant (p = 0.02) when corrected for covariates. With respect to the respiratory function, measured by slow vital capacity (SVC) adjusted for covariates, IPL344 treated participants had an adjusted mean change of −1.6% per month compared to −2.8% per month in the historical placebo, which is 44% slower. The preliminary data indicate that IPL344 was safe and well-tolerated. "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 do believe there are both scientific rationale and data to support going to a larger, randomized placebo- controlled trial." said Prof. Merit Cudkowicz, Executive Director, Mass General Brigham Neuroscience Institute, Massachusetts Boston. "I am pleased to share this publication with the broader community. 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."" said Prof. Marc Gotkine, Principal Investigator of the study and Head of Neuromuscular and EMG Unit at Hadassah Medical Center, Jerusalem. "Despite the small size of study, we were able to demonstrate clinically meaningful improvements in the 5 endpoints assessed. We are encouraged by the magnitude and the consistency of the results. We thank Prof. Schoenfeld of Harvard medical school, for developing the statistical methods and performing the statistical analysis for this study. We also thank Prof. Shefner, the cofounder of NEALS and Prof, Cudkowicz for supporting our study design and evaluation" said Dr. Ilana Cohen, VP of R&D, Immunity Pharma. "We thank the study participants and their families for their partnership and support. We are encouraged by the potential of IPL344 to be transformative in the fight against ALS, given its initial efficacy across multiple clinical endpoints. This efficacy is driven by its unique mechanism of action that targets key biological processes underlying ALS. We are currently preparing for a large, placebo-controlled clinical trial to further evaluate IPL344 efficacy. If the current results will be reproduced in the larger study, they could offer meaningful benefits to individuals living with ALS." said Eran Ovadia, Immunity Pharma's CEO. Paper details: Marc Gotkine, David A. Schoenfeld, Ilana Cohen, Jeremy M. Shefner, Yossef Lerner, Irun R. Cohen, Colin Klein, Eran Ovadia and Merit E. Cudkowicz, "Akt Activation with IPL344 Treatment for Amyotrophic Lateral Sclerosis: First in Human, Open-Label Study". Muscle and Nerve. 19 March 2025. About the Phase 1/2a ALS Clinical Trial The Phase 1/2a trial is an open-label, dose-ranging study with once-daily IPL344 IV treatment (at home) for up to 3 years. The study includes a 28-day Phase 1 portion, followed by the Phase 2a portion of the study. The study was conducted at the Hadassah Medical Center, Jerusalem. All participants were rapidly progressing ALS patients. About IPL344 IPL344 is Immunity Pharma's lead drug candidate. IPL344 was discovered in the Weizmann institute of Science, Israel, at Prof. Irun Cohen's Laboratory. IPL344 is being developed as an intravenous injection for the treatment of ALS. IPL344 received orphan drug designation from FDA and EMA which grants exclusivity for at least seven years. About Immunity Pharma Immunity Pharma Ltd. (IPL) is a privately-held clinical-stage neurology-focused biopharmaceutical company that develops therapies for neurodegenerative diseases, with an initial focus on ALS. IPL's drugs are small biologically active peptides that stimulate therapeutic cell-signalling processes including activation of the Akt pathway which is down-regulated in neurodegenerative diseases. These drugs mitigate progression of neurodegenerative diseases by inducing survival-supporting processes and mitigating stress conditions. IPL's drugs are being developed as treatment for ALS, Parkinson's disease and other neurodegenerative diseases. For more information, please visit Contact: Eran Ovadia, [email protected] WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Treatment with IPL344 was well tolerated Changes in the slope of decline in ALSFRS-R demonstrated 48% slower disease progression (p=0.028); and 64% slower progression when adjusted for disease stage and rate (p=0.034) Study suggests benefits in weight gain, respiration, and survival Plasma neurofilament (NfL) reduction observed following IPL344 treatment JERUSALEM, Jan. 17, 2024 /PRNewswire/ -- Immunity Pharma, a clinical-stage neurology-focused biopharmaceutical company, today announced positive top line results from the Phase 2a trial with IPL344 in amyotrophic lateral sclerosis (ALS) patients. The study demonstrated statistically significant efficacy as measured by change in the slope decline of ALSFRS-R. The drug was well tolerated, and the study suggests benefits in weight gain, respiration, and survival. Neurofilament (NfL) reduction was observed following IPL344 treatment. In this study, once-daily treatment with IPL344 for up to 36 months was well tolerated, with no major drug related serious adverse events (SAE). No participants discontinued treatment due to drug-related AEs. IPL344 treated patients showed a mean slope of decline in ALSFRS-R of -0.53, equating 48% slower disease progression (p=0.028). Adjustment for disease stage and rate-indicating covariates, indicated a 64% slower ALSFRS-R progression (p=0.034). In addition, a statistically significant increase rather than decrease was observed in body weight of IPL344 treated patients (p=0.02; compared to the PRO-ACT database of patients treated with placebo). Median survival of patients in this study was 29 months vs. 19 months of placebo treated patients in the ceftriaxone study (post-treatment follow-up is still ongoing), indicating a trend toward reduced risk of death in favor of IPL344 (p=0.13). There was a non-significant trend for preserved respiration capacity (44% slower reduction in average %SVC loss per month vs. historical placebo; p=0.15). Biomarker data for plasma neurofilament light (NfL) levels were obtained for eight subjects. NfL concentrations were reduced during IPL344 treatment in all but one participant. In the six subjects that had blood sampling past the initial dose-escalating phase, plasma NfL concentrations were reduced by a mean of 20%, suggesting decrease of neuronal injury following IPL344 treatment. "We are excited that treatment with IPL344 was well tolerated in people with ALS and demonstrated encouraging signs of efficacy across multiple parameters. This data will soon be submitted for publication in a scientific journal," said Dr. Ilana Cohen, Immunity Pharma's VP of R&D. "If confirmed in a subsequent larger phase 3 study, the magnitude of reduction in ALSFRS-R progression observed in this study is greater than that achieved with currently approved drugs." "These early-stage data support further development of IPL344 as a treatment for ALS, and merit further investigation in a large number of participants. We intend to progress PL344 to a pivotal clinical trial in ALS," said Immunity's CEO, Eran Ovadia. About the Phase 2a ALS Clinical Trial The Phase 1/2a trial was an open-label study with once-daily IPL344 treatment administered IV (home administration). Subjects were allowed to stay in the study for up to 3 years. The study includes a 28-day Phase 1dose-escalating portion, after which subjects may continue to the Phase 2a portion of the study. The study was conducted at the Hadassah Medical Center in Jerusalem (NCT03652805, NCT03755167). The Phase 1/2a study included nine participants with probable or definite ALS and a progression rate >0.55 points/month on the ALS functional rating scale-revised (ALSFRS-R) that received open-label treatment with once-daily IPL344 for up to 36 months. Efficacy outcomes included the rate of progression on ALSFRS-R, slow vital capacity (SVC), weight, and survival compared with historical placebo from the PRO-ACT database and ceftriaxone study. The statistical analysis included a method previously proposed by Dr. Schoenfeld designed to quantify inter-center and inter-study variability, to pinpoint whenever ALSFRS-R slowdown exceeds the normal variability. This analysis shows that, despite the small number of participants the magnitude of ALSFRS-R slope reduction is larger than the threshold needed for significance and is beyond that expected by inter-study variation. About IPL344 IPL344 is a biologically active peptide that stimulates therapeutic cell-signaling processes including activation of the Akt pathway, which is down-regulated in neurodegenerative diseases. IPL344 was discovered in the Weizmann institute of Science, Israel, at Prof. Irun Cohen's Laboratory. IPL344 is being developed as an intravenous injection for the treatment of ALS initially through a Phase 1/2a clinical trial in ALS patients. IPL344 received orphan drug designation from FDA and EMA, which grants exclusivity for at least seven years. About Immunity Pharma Immunity Pharma Ltd. (IPL) is a privately-held clinical-stage neurology-focused biopharmaceutical company that develops therapies for neurodegenerative diseases, with an initial focus on Amyotrophic lateral sclerosis (ALS). IPL's drugs are biologically active peptides that stimulate therapeutic cell-signalling processes and mitigate progression of neurodegenerative diseases by inducing intra-cellular survival-supporting processes. IPL's drugs are being developed as treatment for ALS, Parkinson's disease and other neurodegenerative diseases. For more information, please visit SOURCE Immunity Pharma