Neuren secures FDA Orphan Drug Designation for NNZ-2591 in neonatal HIE, advancing preclinical development ahead of a planned 2027 IND submission.
Written By: Sravani Pamanji, PharmD
Reviewed By: Pharmacally Editorial Team
Neuren Pharmaceuticals has received Orphan Drug Designation (ODD) from the US Food and Drug Administration (FDA) for NNZ-2591 (ercanetide), its investigational drug candidate being developed for neonatal hypoxic-ischemic encephalopathy (HIE). The condition occurs when a newborn’s brain receives insufficient oxygen or blood flow before, during or shortly after birth, potentially resulting in permanent neurological injury.
The designation provides regulatory incentives for the programme as Neuren advances preparations for clinical evaluation. However, NNZ-2591 remains in preclinical development for HIE, with an additional juvenile animal safety study required before the company can initiate its proposed clinical study.
FDA Orphan Drug Designation and Regulatory Benefits
The FDA’s Orphan Drug Designation programme supports the development of treatments for rare diseases affecting fewer than 200,000 people in the United States. Eligible sponsors can receive incentives, including potential seven-year marketing exclusivity following approval for the designated indication and exemption from applicable prescription drug user fees for marketing applications.
For Neuren, the designation strengthens the regulatory position of NNZ-2591 in HIE. However, orphan designation does not constitute marketing approval or establish the candidate’s safety and efficacy. The drug must still complete clinical development and regulatory review.
Neonatal HIE: A Significant Unmet Medical Need
HIE is a serious cause of neonatal mortality and long-term neurodevelopmental disability. According to Neuren, many thousands of children experience the condition annually. Survivors may develop developmental delays, cognitive impairment, cerebral palsy and seizures, with complications potentially continuing into adulthood.
Although therapeutic hypothermia is an established treatment for eligible newborns, significant long-term neurological complications remain a concern. Additional treatment approaches are therefore needed to improve outcomes in affected infants.
NNZ-2591 and Its Potential Neuroprotective Mechanism
NNZ-2591 (ercanetide) is a synthetic analogue of cyclic glycine-proline (cGP), a peptide involved in regulating insulin-like growth factor 1 (IGF-1) availability in the brain. By modulating IGF-1 signalling, the candidate is being investigated for its potential to support neuronal survival and brain function. This mechanism is relevant to HIE, where oxygen deprivation can trigger brain cell injury, inflammation and neuronal death. Preclinical studies have reported neuroprotective effects of NNZ-2591 in models of hypoxic-ischaemic brain injury, although its therapeutic benefit in newborns remains to be established clinically.
FDA Feedback Shapes NNZ-2591’s Clinical Development Pathway
Neuren’s HIE programme has progressed through regulatory discussions with the FDA. In February 2026, the company received written feedback on its proposed Investigational New Drug (IND) application and initial clinical study.
The FDA generally accepted the proposed study design and NNZ-2591 doses but requested additional juvenile animal safety data before clinical evaluation could begin. Neuren is conducting the required study and submitted its protocol to the FDA in May 2026.
The proposed initial clinical study is intended to evaluate the pharmacokinetics, tolerability and safety of NNZ-2591 in neonates and infants with HIE. The additional preclinical work is required to support dosing in this vulnerable population.
Neuren now plans to submit its IND application in the first half of 2027, later than its previously anticipated fourth-quarter 2026 timeline. The company also expects further discussions with the FDA on the programme’s development pathway.
NNZ-2591 Development Across Four Neurological Conditions
Neuren is developing NNZ-2591 for four neurological conditions: Phelan-McDermid syndrome, Pitt-Hopkins syndrome, Angelman syndrome and HIE. All four programmes have received FDA Orphan Drug Designation.
The candidate is already in clinical development for the first three conditions, including the Phase 3 Koala trial evaluating NNZ-2591 in children with Phelan-McDermid syndrome. These programmes have also received additional FDA Fast Track and Rare Pediatric Disease designations.
The HIE programme, however, remains at the preclinical stage. Its progression will depend on completion of the juvenile animal safety study, submission of the IND application and subsequent regulatory clearance to begin clinical evaluation.
The latest designation expands NNZ-2591’s development portfolio, but the next significant milestone for HIE will be completion of the required safety work and progression towards its first clinical study.
Reference
FDA grants Orphan Drug Designation for NNZ-2591 to treat HIE, Neuren Pharmaceutical, 02 October 2026
Corporate Presentation, 2 September 2026, Neuren Pharmaceuticals, 02 September 2026
About the Writer
Sravani Pamanji is a PharmD (LinkedIn) professional with experience in scientific writing, medical literature review, drug profile preparation, and clinical case documentation. She has contributed to scientific publication and presented at the 74th Indian Pharmaceutical Congress. Her training includes ICH GCP E6(R3), scientific research, and medication safety. She is passionate about evidence-based medical communication and accurate dissemination of clinical and pharmaceutical information.