Insights on NervGen Pharma’s Positive Phase 1b/2a Data for NVG-291 in Spinal Cord Injury

Daniel Mikol, MD, PhD

Earlier this month, NervGen Pharma, a clinical-stage biotech company, announced topline data from its phase 1b/2a trial (NCT05965700) assessing its lead drug candidate, NVG-291, as a potential treatment for spinal cord injury (SCI). The study featured 2 separate cohorts of individuals with cervical motor incomplete spinal cord: chronic (1-10-years post-injury) and subacute (20-90 days post-injury), to test a fixed dose of the agent using electrophysiological and MRI imaging measures, functional clinical outcome measures, and blood biomarkers.

According to the latest data update, the trial met its co-primary end point demonstrating improved motor connectivity in individuals with cervical chronic SCI receiving NVG-291 (n = 10) compared with placebo (n = 10). In addition, NVG-291-treated patients achieved a 3-fold increase in the strength of motor connectivity to first dorsal interosseus, a vital hand muscle, measured by change in normalized motor evokved potentials amplitude. While the study’s second co-primary end point of connectivity in tibialis anterior did not meet statistical significance, positive trends were seen in the secondary end point of change in Graded Redefined Assessment of Strength, Sensation, and Prehension (GRASSP) test.

To gain better insights on the data, as well as the mechanism and rationale of NVG-291 to treat SCI, NeurologyLive^® reached out to Daniel Mikol, MD, PhD, chief medical officer at NervGen Pharma. Mikol provided commentary on the difficulties with treating SCI, given the heterogeneity of the disorder, as well as some of the notable takeaways from the trial, such as the drug’s impact on improved motor recovery. Furthermore, he commented on what remains next for the agent and where clinicians and patients can turn to for more information on the trial.

NeurologyLive: What is the rationale and mechanism behind NVG-291? Why do we believe it can be successful to treat SCI?

Daniel Mikol, MD, PhD:

• NVG-291 is a peptide that is derived from the intracellular wedge domain of the CSPG receptor protein tyrosine phosphatase sigma (PTPσ).
• In preclinical studies, NVG-29-R has been reported to interfere with CSPG signaling resulting in enhanced repair mechanisms that are normally inhibited by CSPGs, such as regeneration, myelination, and plasticity.
• This is a novel, first-in-class technology and NervGen is currently conducting PK, ADME and exploratory omics work to further elucidate the mechanism.

Why has SCI been so difficult to treat?

SCI is a heterogeneous condition that is difficult to investigate for several reasons. After SCI, connections between the brain and the rest of the body can be interrupted resulting in loss of motor, sensory and autonomic function. A glial scar forms soon after the injury to protect adjacent neural tissue from further damage, but this scar tissue effectively blocks repair due to inhibitory substances such as CSPGs. Spontaneous recovery can occur after SCI, but the extent of recovery varies and recovery plateaus around one year after injury. Given the complexity of SCI, there are many important variables to consider in defining a clinical trial population, such as the type, level and severity of injury. Also, the timing of intervention in relation to the injury needs to be determined. Most SCI trials are acute intervention studies, with treatment administered within the first ~24-48 hours, because results of preclinical studies supported early but not late (“chronic” SCI) intervention. Conducting acute SCI trials can be very challenging operationally, but also these studies have to contend with a placebo effect given that participants are within the window of greatest spontaneous recovery. Importantly, SCI trials to date have enrolled either a broad population in terms of severity, or have enrolled a severe “motor complete” population consisting of individuals who have no voluntary motor function below the level of the injury. But there is a disconnect because in the preclinical models of SCI animals do have motor function below the injury.

Recognizing this disconnect and to increase the probability of successful clinical translation, we took a different approach in designing our trial by enrolling a “motor incomplete” population with some preserved voluntary motor function below the level of the injury. We also considered that another reason for potential failure of past trials might be that clinical outcome measures used may be insensitive to discern a treatment effect. We, therefore, incorporated electrophysiological testing as a quantitative biomarker of motor recovery in addition to using a range of clinical outcome measures. Finally, we decided to enroll two cohorts in our clinical trial, chronic (1-10 years post-injury) and subacute (20-90 days post-injury), given that preclinical efficacy was demonstrated when NVG-291-R was administered soon after injury or after motor recovery had plateaued – essentially, we have two trials in one. We remain hopeful for individuals with SCI that NVG-291 can potentially break the pattern of negative trials and open the possibility of living a life with more function and greater independence.

Describe some of the Phase 1b/2a data that was presented at ASIA 2025; what stands out from a clinical perspective?

NervGen reported positive results from the chronic cohort (1-10 years post-injury) of its Phase 1b/2a clinical trial, CONNECT SCI study, evaluating lead drug candidate, NVG-291, as a potential treatment for SCI. The data supports the therapeutic potential of NVG-291 and represents a step forward in advancing NVG-291. The study met its primary endpoint demonstrating that NVG-291 increased electrical connectivity between the brain and an important hand muscle (first dorsal interosseus) in individuals with cervical SCI.The study also showed a positive trend in the secondary endpoint evaluating change in Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) score, a measure designed specifically to assess hand function in people with cervical SCI.

NVG-291 is the first pharmaceutical candidate to show improved motor recovery based on increased motor evoked potential amplitude. These study results represent a significant scientific advance in the potential to treat SCI, where there remains no approved pharmaceuticals to enable sustained functional recovery.

What are the next steps in advancing this therapeutic?

NervGen received Fast Track designation from the U.S Food and Drug Administration (FDA) for NVG-291 in SCI, and we are focused on advancing NVG-291 to the next stage of development. We intend to review the results and propose a plan with the FDA to determine next steps.

At the same time, enrollment of the Phase 1b/2a SCI trial for the subacute cohort (20-90 days post-injury) is ongoing; we had announced in February 2025 that the first patient had been dosed in the subacute cohort. More information about eligibility criteria for the subacute cohort is available at www.connectscistudy.com.

NervGen’s goal is to hopefully bring solutions to the market that address significant unmet medical needs for people with nervous system damage.