Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Targeting eNAMPT-TLR4 signaling with the novel ALT-100 mAb to slow IPF progression

Award Number: R41HL180035
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2025
PERIOD OF PERFORMANCE END DATE: 09/19/2026

Group Awards By:

View Award Description

Targeting eNAMPT-TLR4 signaling with the novel ALT-100 mAb to slow IPF progression - ABSTRACT: There is a major unmet need to identify novel therapies for idiopathic pulmonary fibrosis (IPF), a rapidly pro- gressing fibrotic lung disease often resulting in fatal respiratory failure. Current IPF drugs only moderately slow the progression of the disease and fail to halt or reverse fibrosis development. Many IPF patients are ineligible for lung transplantation, the only IPF treatment option, and often expire prior to transplantation. Consistent with recognition of innate immunity-driven inflammatory responses as key contributors to IPF development and sub- sequent progression, we identified eNAMPT (extracellular nicotinamide phosphoribosyltransferase) as a novel damage-associated molecular pattern protein (DAMP) and therapeutic IPF target that binds and activates Toll- Like Receptor 4 (TLR4) to evoke innate immunity-mediated inflammatory and fibrotic pathways. Expression of eNAMPT in plasma, lung tissues and PBMCs is strongly linked to the severity of human IPF, including 3 year survival. Importantly, we have manufactured a humanized eNAMPT-neutralizing mAb (6 gms/L expression) that attenuates lung fibrosis progression in two models of preclinical models of lung fibrosis (radiation, bleomycin). In this R-41 application, we will optimize the dose of subcutaneously-delivered ALT-100 mAb (1 mg/kg, 2 mg/kg, 4 kg/kg, 6 mg/kg) that most effectively ameliorates established lung fibrotic injury in preclinical models of radia- tion-induced lung fibrosis (Specific Aim #1A) and intratracheal bleomycin-induced lung fibrosis (Specific Aim #1B) utilizing C57Bl6 mice. Specific Aim #2 will utilize the bleomycin IPF model to assess responses of the optimized dose of ALT-100 mAb in combination with the FDA-approved IPF drugs: i) pirfenidone, and ii) nintedanib. Murine phenotyping will include histologic lung fibrosis scores, physiologic lung stiffening (re- sistance/elastance), expression of key fibrosis-related proteins (TGFb, SMAD, thrombospondin), and single-cell RNA sequencing of SA #1/SA #2-derived murine lung tissues to identify the primary target cells and signaling pathways rectified by ALT-100 mAb therapy. Supporting ALT-100 mAb feasibility as an IPF therapy, we have completed Phase 1A ALT-100 mAb safety studies in healthy human volunteers (zero serious adverse events) and initiated a Phase 2A clinical trial of ALT-100 mAb for ARDS (NCT05938036). IV ALT-100 mAb exhibits a T1/2 half-life of 16-27 days and recently completed IND-enabling chronic pharmacokinetic and 6 month toxicity studies with subQ ALT-100 mAb showed a T1/2 half-life of 10-14 days in rats and no discernable toxicity in rats or pigs. These studies leverage the strong academic-private biotech partnership between the University of Flor- ida and Aqualung Therapeutics and will yield valuable histologic/biochemical/genomic evidence that validates eNAMPT/TLR4 as a druggable IPF target and ALT-100 as a novel strategy to directly address the unmet need for therapeutics that reduce IPF severity. Successful completion of these Phase I Specific Aims will allow us to proceed to receive IND approval from the FDA to conduct safety studies in healthy volunteers and clinical trials to evaluate ALT-100 mAb as a novel therapeutic approach for subjects with IPF.


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 = $0 )
2026	2025	AQUALUNG THERAPEUTICS, CORP	450 OCEAN DR APT 1205	JUNO BEACH	FL	33408	PALM BEACH	USA	Lung Diseases Research	000	1	1/30/2026	NEW	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $284,699 )
2025	2025	AQUALUNG THERAPEUTICS, CORP	450 OCEAN DR APT 1205	JUNO BEACH	FL	33408	PALM BEACH	USA	Lung Diseases Research	000	1	9/17/2025	NEW	$284,699
														Subtotal = $284,699

Grand Total All Awards = $284,699

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeting eNAMPT-TLR4 signaling with the novel ALT-100 mAb to slow IPF progression

Award Number: R41HL180035

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/20/2025

PERIOD OF PERFORMANCE END DATE: 09/19/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer