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An Intermediate-Size Expanded Access Protocol (EAP) for NUZ-001 in People with Amyotrophic Lateral Sclerosis (NUZ-001 EAP)

Award Number: U01NS153995
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2030

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An Intermediate-Size Expanded Access Protocol (EAP) for NUZ-001 in People with Amyotrophic Lateral Sclerosis (NUZ-001 EAP) - A hallmark of ALS is the presence of cytoplasmic inclusions containing mislocalized, TAR DNA-binding protein 43 (TDP-43). This proteinopathy is found in ~ 97% of people with ALS, establishing it as the central molecular lesion in the disease. TDP-43 normally resides in the nucleus. In ALS, TDP-43 accumulates as insoluble cytoplasmic aggregates, which are key drivers of neuronal stress and toxicity, leading to a breakdown of protein homeostasis (proteostasis). Motor neurons are uniquely vulnerable to proteostatic imbalance due to their axonal length, high metabolic demand, and limited regenerative capacity. Maintaining proteostasis relies on three coordinated pathways: the ubiquitin–proteasome system, the autophagy–lysosomal pathway, and the endoplasmic reticulum (ER) stress response. NUZ-001 is a small molecule with a differentiated mechanism of action that intersects multiple pathways within the proteostasis network. NUZ-001 has been shown to enhance proteasomal function, boost autophagic flux, and modulate the ER stress response, preventing TDP-43 aggregation and supporting neuronal homeostasis, providing a strong rationale for advancing it into clinical evaluation for ALS. A Phase 1 study involving 12 people with ALS, followed by a long-term open-label extension (OLE), yielded preliminary observations after daily oral administration of NUZ-001. Comparison with historical control data from the PRO-ACT database using the rate of decline in ALS Functional Rating Scale-Revised scores and overall survival over the course of the Phase 1 study and OLE suggested potential beneficial effects on disease progression. The safety and efficacy of NUZ-001 (same dosage proposed in this EAP) are currently being evaluated as Regimen I inthe HEALEY ALS Platform Trial. This trial includes a 36-week efficacy randomized controlled trial (RCT) followed by an active treatment extension. Due to the RCT eligibility criteria, a large segment of the ALS population is ineligible to participate in the RCT. We propose an expanded access protocol of NUZ- 001 at approximately 20 physical study sites and one national virtual study site across the US, for 200 individuals with ALS who are ineligible for clinical trials, with participants receiving the drug for up to 96 weeks. The physical study sites are part of the HEALEY ALS Platform Trial, while the national virtual site, offered through Synapticure, enables fully remote participation across all 50 states. This study will provide real-world data by assessing the drug's effects in a broader population than the efficacy trial and by collecting safety, clinical, and biological outcomes over longer-term exposure.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $8,276,544 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/28/2026	NEW	$8,276,544
														Subtotal = $8,276,544

Grand Total All Awards = $8,276,544

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An Intermediate-Size Expanded Access Protocol (EAP) for NUZ-001 in People with Amyotrophic Lateral Sclerosis (NUZ-001 EAP)

Award Number: U01NS153995

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2030

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