Mr. Mike Kelly reports

NERVGEN PHARMA REPORTS POSITIVE TOPLINE DATA FROM THE CHRONIC COHORT OF ITS PHASE 1B/2A CLINICAL TRIAL EVALUATING NVG-291 IN SPINAL CORD INJURY

Nervgen Pharma Corp. has released positive top-line results from the chronic cohort (one to 10 years postinjury) of its phase 1b/2a clinical trial evaluating its lead drug candidate, NVG-291, as a potential treatment for spinal cord injury. NVG-291 met one of its co-primary end points and demonstrated promising changes in the graded redefined assessment of strength, sensation and prehension score, a measure designed specifically to assess hand function in individuals with cervical SCI.

Top-line results from the trial support the potential of NVG-291 to promote nervous system repair. The trial met a co-primary end point, demonstrating improved motor connectivity in individuals with cervical chronic SCI receiving NVG-291 (n equals 10) compared with placebo (n equals 10). Data showed that subjects receiving NVG-291 achieved a threefold increase in the strength of motor connectivity to an important hand muscle (first dorsal interosseus) as measured by change in the normalized motor evoked potential amplitude (baseline/week 12 actual results: 6.207 out of 18.773 for NVG-291 versus 6.527/7.760 for placebo, p-value 0.0155). The second co-primary end point evaluating connectivity in a leg muscle (tibialis anterior) did not achieve statistical significance. The co-primary end point approach to the trial design is intended to permit only one of the co-primary end points to achieve statistical significance, though with a more rigorous p-value of less than 0.025 being required.

"As a scientist and clinician dedicated to enhancing rehabilitation outcomes for individuals with SCI, I am encouraged by the results from the chronic cohort of the NVG-291 clinical trial," said Monica A. Perez, PT, PhD, scientific chair, arms and hands lab, Shirley Ryan AbilityLab and principal investigator of this trial. "A threefold increase in MEP is generally considered substantial, and, in this study, the data separation from placebo is clear. I believe that data demonstrating changes in motor connectivity underscore the potential of this new drug candidate to provide functional restoration and improve the quality of life for people with SCI."

"We are excited to have achieved positive study results demonstrating both improved hand motor connectivity and improved function in the chronic cohort of our phase 1b/2a trial. This data supports the therapeutic potential of NVG-291 and represents a big step forward in advancing this drug candidate," said Mike Kelly, Nervgen's president and chief executive officer. "This data demonstrates, for the first time, that a drug candidate can assist in achieving functional improvement for individuals in the chronic stage of SCI who have plateaued in their recovery. It is important to highlight that changes in upper extremity motor function can provide individuals living with SCI the opportunity for meaningful improvements in their performance of daily functions as well as their independence. Lastly, on behalf of the entire team at Nervgen, I would like to thank the investigators, all those involved in the trial at Shirley Ryan AbilityLab and the individuals with SCI who participated in this trial."

Positive trends were also seen in the secondary end point evaluating the change from baseline in the graded redefined assessment of strength, sensation and prehension test, with the strongest improvements being in quantitative prehension. GRASSP is a validated test of hand function, sensation and strength composed of four tests and is designed specifically to assess hand function in individuals with cervical SCI. The quantitative prehension performance subtest scores an individual's ability to carry out specific gross or fine motor tasks, and requires control, orientation of the hand, strength and endurance. A positive trend, though not sufficient to reach statistical significance, toward improvement in the quantitative prehension score, was observed (actual change from baseline at week 12: plus 3.7 for NVG-291 and plus 0.4 for placebo; linear mixed effects modelled results: plus 3.1 for NVG-291 1.0 for placebo group, p equals 0.1416); 50 per cent of the individuals receiving NVG-291 versus 10 per cent in the placebo group had an improvement of at least four points.

"What I am particularly excited about are the changes in GRASSP scores as these are very important clinical outcomes for patients living with SCI," said James Guest, MD, PhD, FACS, professor of neurological surgery at the University of Miami. "For individuals with cervical SCI, their level of independence depends on their hand and arm functions. Based on my clinical experience, if an individual with a cervical SCI had to pick what is most important to them, upper extremity function is most often what they would choose. An increase in quantitative prehension can allow for a meaningful improvement in independence."

In preliminary post hoc analyses, positive trends toward improvement were also seen for changes on the nine-hole peg test (9-HPT), a measure of upper extremity dexterity. Although not statistically significant based on top-line analyses, these results in the secondary end points warrant further analysis. The company did not see any clear effects on changes in the other secondary end points of pinch force, the 10-metre walk test, and upper and lower extremity motor scores, although additional analyses are continuing and have the potential to provide additional insights into the data and NVG-291's therapeutic effects.

"This is the first placebo-controlled trial of which we are aware that an investigational drug candidate has achieved statistical significance on a primary end point, in this case a quantitative biomarker of motor connectivity," said Daniel Mikol, MD, PhD, Nervgen's chief medical officer. "We are highly encouraged by the clear trends in improved GRASSP scores, and we look forward to additional forthcoming analyses to gain further insights into the results already observed. Results from this trial will also guide us in the design of future trials in SCI. We plan to meet with the FDA in the coming months to discuss these results and the path forward for NVG-291. In addition, we continue to enroll participants in the subacute cohort (20 to 90 days postinjury) of the trial."

The company believes that the preliminary efficacy signal observed in the chronic cohort in this study supports clinical advancement of NVG-291 in chronic SCI. NVG-291 was generally safe and well tolerated. The most common adverse event was mild/moderate injection site reactions. There were no treatment discontinuations or serious adverse events in the NVG-291 group.

SCI results in a loss of connectivity that sends and receives electrical signals to and from the brain, and can cause changes in feeling, movement, strength and body functions below the site of injury. NVG-291 is a potential first-in-class therapeutic peptide that targets the body's natural inhibitors of repair. It is thought to promote natural repair processes (such as axonal regeneration, neuroplasticity and remyelination) to improve the connections disrupted by SCI. Since there are currently no approved pharmaceuticals to enable functional recovery in SCI, Nervgen's study represents a meaningful and significant step forward for the SCI treatment landscape.

Asia presentation details

Nervgen will present results from the chronic cohort of the continuing phase 1b/2a study of NVG-291 as an oral presentation on Tuesday, June 3, 2025, at 1:40 p.m. EDT, at the 52nd Asia Annual Scientific Meeting being held June 2 to June 4, 2025, in Scottsdale, Ariz.

Presenting author:  Daniel Mikol, MD, PhD, chief medical officer, Nervgen Pharma

Session name:  general session 6: Clinical Trial Updates: Clinical Trials: What's the Latest and When Will it Get Here?

Session date:  Tuesday, June 3, 2025

Session time:  10:40 a.m. to 11:40 a.m. MST

Location:  Arizona ballroom I, Grand Hyatt Scottsdale Resort, 7500 East Doubletree Ranch Rd., Scottsdale, Ariz.

Analyst/investor call details

The company will host a conference call for analysts and investors on Tuesday, June 3, 2025, at 4:15 p.m. EDT, to discuss the results from the chronic cohort of the continuing phase 1b/2a study of NVG-291. To join the call, dial toll-free 1-877-407-0789 or international 1-201-689-8562, conference ID 13753321. Participants can use the dial-in numbers provided and be answered by an operator for telephone access to the event. A webcast will be available.

About phase 1b/2a trial

The double-blind, placebo-controlled proof-of-concept phase 1b/2a clinical trial (NCT05965700) evaluates the safety and efficacy of NVG-291 in two separate cohorts of individuals with cervical motor incomplete spinal cord injury: chronic (one to 10 years postinjury) and subacute (20 to 90 days postinjury), given demonstrated efficacy in preclinical models of both chronic and acute spinal cord injury. The trial is designed to evaluate the safety and efficacy of a fixed dose of NVG-291 using electrophysiological and MRI imaging measures, functional clinical outcome measures, and blood biomarkers that together will provide comprehensive information about the extent of recovery of somatic and autonomic function postinjury. Specifically, the co-primary objectives seek to assess changes in corticospinal connectivity of defined upper and lower extremity muscle groups following treatment, based on changes in normalized (as a percentage of the maximum motor response following direct electrical stimulation of the corresponding peripheral nerve) motor-evoked potential amplitudes. Secondary objectives evaluate changes in multiple clinical outcome assessments focusing on motor function, upper extremity dexterity, grasping and immobility, and additional electrophysiological measurements. The cohorts will be composed of 20 subjects each and will be evaluated independently in a blinded manner as the data become available. The trial is being partially funded by a grant from Wings for Life, which is being provided in several milestone-based payments and will offset a portion of the direct costs of this clinical trial.

About NVG-291

Nervgen holds exclusive worldwide rights to NVG-291, a first-in-class therapeutic peptide targeting nervous system repair. NVG-291's technology is licensed from Case Western Reserve University and is based on academic studies that demonstrated the preclinical efficacy of NVG-291-R, the rodent prototype of NVG-291, in animal models of spinal cord injury. These studies implicated several potential molecular and cellular mechanisms by which NVG-291-R promotes neurorepair and functional improvement in both central and peripheral nervous system injury models. The implicated mechanisms include the promotion of neuronal sprouting, or plasticity, remyelination, and promotion of a non-inflammatory phenotype in the microglial cells. Nervgen has received fast-track designation from the Food and Drug Administration for NVG-291 in individuals with spinal cord injury.

About Nervgen Pharma Corp.

Nervgen is a clinical-stage biotech company dedicated to developing innovative treatments to promote nervous system repair in settings of neurotrauma and neurologic disease. The company is testing the clinical efficacy of its lead candidate, NVG-291, in a phase 1b/2a clinical trial in spinal cord injury and has initiated a preclinical test of concept evaluation of its pipeline candidate, NVG-300, in models of ischemic stroke and spinal cord injury.

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