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A Novel ENaC Blocker/Osmolyte Inhalation Solution for the Treatment of Muco-Obstructive Lung Diseases

Award Number: R44HL174235
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 08/14/2025

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A Novel ENaC Blocker/Osmolyte Inhalation Solution for the Treatment of Muco-Obstructive Lung Diseases - ABSTRACT Muco-obstructive lung diseases, e.g., COPD, asthma, CF, and PCD, cause major health problems to many citizens of the US. Recent CT data have identified mucus plugging as a major contributor to the pathogenesis and mortality of muco-obstructive lung diseases, including COPD. Ironically in 2023, there are no therapeutic agents available dedicated to the clearance of mucus plugs from patients in need. CT data demonstrating that mucus plugs persist in COPD subjects for > 3 yrs suggest that current COPD therapeutics are not helpful in mucus clearance. A combination of in vitro biophysical studies and clinical research studies over the past decade have established that mucus plugging is a predictable consequence of the increased mucus concentration. Increased mucus concentration typically reflects defects in the epithelial ion/fluid transport pathways that control mucus hydration. A rational therapeutic strategy to clear mucus plugs from the lungs of patients in need is to rehydrate the accumulated, hyperconcentrated mucus. This application is designed to support the enabling studies of a novel mucus hydrator combination therapy, including a next-generation ENaC blocker (P-1155) formulated with an osmolyte, to IND status. The medicinal chemistry design of P-1155 builds off the success in the clinic of the P-1037/hypertonic saline (HS) combination for the chronic therapy of primary ciliary dyskinesia (PCD). The P-1037/HS experience strongly emphasizes the importance of both: 1) an osmolyte for effective clinical activity; and 2) high protein binding for a high degree of extra-renal excretion and, hence, safety. Based on the perceived need for a rapidly active muco-kinetic agent for the treatment of both stable and exacerbating COPD or asthmatic subjects, P-1155 has been modified to accelerate the kinetics of onset of action while preserving P-1037 safety attributes. Two specific aims encompass a two-phase development plan. Phase I will select the osmolyte for co-formulation with P-1155, the choices being NaGluconate vs HS/Sulfobutylether-β- Cyclodextrin (SBECD), based on: 1) P-1155 formulation/stability studies; and 2) efficacy studies in a muco- obstructive mouse model. Phase II will include IND-required aerosol formulation, ADME/PK studies, and a 28- day GLP rat inhalation toxicology study. Accordingly, the application proposes two Specific Aims: Specific Aim 1: Phase I studies designed to select a P-1155 formulation. SA1A: P-1155 formulation and stability studies. SA1B: 7/28d βENaC muco-obstructive mouse model efficacy studies. Specific Aim 2: Phase II studies designed to advance a P-1155 formulation to an IND. SA2A: Aerosol delivery formulation studies of P-1155/osmolyte solutions. SA2B: ADME/PK studies, including hepatic excretion, plasma protein binding, and P-1155 metabolism. SA2C: 28d rat GLP inhalation toxicology study of selected P-1155 formulation. The ultimate goal of the SBIR submission is to file an IND for P-1155 focused on subjects with COPD.


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	PARION SCIENCES, INC	2800 MERIDIAN PKWY STE 195	DURHAM	NC	27713	DURHAM	USA	Lung Diseases Research	000	2	5/4/2026	EXTENSION WITH OR WITHOUT FUNDS	$0
2026	2024	PARION SCIENCES, INC	2800 MERIDIAN PKWY STE 195	DURHAM	NC	27713	DURHAM	USA	Lung Diseases Research	001	1	5/13/2026	NEW	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $1,971,749 )
2025	2025	PARION SCIENCES, INC	2800 MERIDIAN PKWY STE 195	DURHAM	NC	27713	DURHAM	USA	Lung Diseases Research	001	2	8/14/2025	EXTENSION WITH OR WITHOUT FUNDS	$1,971,749
2025	2024	PARION SCIENCES, INC	2800 MERIDIAN PKWY STE 195	DURHAM	NC	27713	DURHAM	USA	Lung Diseases Research	000	1	8/14/2025	NEW	$0
														Subtotal = $1,971,749

Issue Date FY: 2024 ( Subtotal = $295,700 )
2024	2024	PARION SCIENCES, INC	2800 MERIDIAN PKWY STE 195	DURHAM	NC	27713	DURHAM	USA	Lung Diseases Research	000	1	4/26/2024	NEW	$295,700
														Subtotal = $295,700

Grand Total All Awards = $2,267,449

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A Novel ENaC Blocker/Osmolyte Inhalation Solution for the Treatment of Muco-Obstructive Lung Diseases

Award Number: R44HL174235

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 08/14/2025

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