Selection of a lead candidate for the development of an ASO therapeutic for NF1 cognitive and social deficits - neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting 1 in 3,000…

The National Institute of Neurological Disorders and Stroke awarded Infixion Bioscience Inc. $478,799 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to develop and select a lead candidate antisense oligonucleotide (ASO) therapeutic targeting cognitive and social deficits associated with Neurofibromatosis Type 1 (NF1).

The project develops steric-blocking antisense oligonucleotides designed to increase NF1 protein levels, normalize altered downstream signaling (particularly RAS hyperactivation), and mitigate NF1-related cognitive and social deficits at their source. Up to 80 percent of individuals with NF1 experience these deficits, which include impairments in attention, executive function, learning, memory, and social development. The approach is mutation-agnostic, targeting the underlying NF1 haploinsufficiency common across diverse NF1 mutations.

Performance takes place in San Diego, California from September 1, 2026 through August 31, 2028. This Phase I Small Business Innovation Research award supports lead candidate identification and validation for advancement to pre-Investigational New Drug stage evaluation.

Selection of a lead candidate for the development of an ASO therapeutic for NF1 cognitive and social deficits - neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting 1 in 3,000 births and over 2.5 million people worldwide. Up to 80% of individuals with NF1 experience cognitive and social deficits (csds), including impairments in attention, executive function, learning, memory, and social development, often diagnosed as autism. These challenges significanuy impact academic performance, necessitate individualized education plans (ieps), and contribute to increased anxiety, depression, loneliness, reduced employment opportunities, and lower quality of life. Despite their prevalence, NF1-associated csds remain an unmet clinical need, with no approved therapies direcuy addressing their root cause. Current therapeutic efforts primarily focus on downstream NF1 signaling targets, such as MEK inhibition, which fail to comprehensively address NF1-associated pathophysiology. Since NF1 is a haploinsufficient disorder, restoring NF1 protein levels represents a promising therapeutic approach. Given that micrornas (mirnas) regulate NF1 expression, we propose a novel strategy using steric-blocking antisense oligonucleotides (sbasos) to increase NF1 protein levels, normalize RAS and other altered signaling, and mitigate NF1-related csds at their source. This mutation-agnostic approach holds potential for broad clinical impact across the diverse spectrum of NF1 mutations. Research background increasing NF1 protein expression has been shown to reverse RAS hyperactivation, and overcomrg haploinsufficiency has demonstrated therapeutic benefit in other haploinsufficient genetic disorders ( e.g., SIM1, PAX6). By leveraging sbasos as highly specific gene-targeting agents, we aim to develop a mutation-agnostic CNS therapy for NF1, addressing csds in the vast majority of NF1 individuals, regardless of their specific NF1 mutation. Specific aims we will develop and validate lead sbaso drug candidates for n F1 csds by 1) designing and screening sbasos targeting the NF1 3'UTR to block mirna binding and enhance NF1 protein levels, 2) verifying specificity and functional impact on NF1 protein expression in a CNS-relevant cell line, and 3) demonstrating in vivo efficacy I1 an NF1-relevant mouse model. By the end of this program, we will establish in vivo proof-of-conceptfor NF1 haploinsufficiency correction using sbasos. This will position infixion for intellectual property (IP) protection, a phase 2 sbir grant, and pharmaceutical partnerships for follow-on efficacy, safety, and toxicity studiesadvancing a first-in-class therapeutic approach for NF1-associated csds.