# Development of Novel Mycolytic Therapies for Lung Disease

> **NIH NIH P01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $2,173,973

## Abstract

The overarching therapeutic goal for the UNC tPPG renewal is to clear the hyperconcentrated, adherent
mucus that promotes airways obstruction, inflammation, and infection. A straightforward approach to treat
muco-obstructive diseases is to rehydrate airway surfaces. However, recent experimental and biophysical
analyses have identified that thickened adherent mucus can be modified to generate “permanent” gels
resistant to clearance by hydration. The therapeutic strategy identified to clear permanent mucus gels is the
reduction mucin molecular weight (MW). Consequently, the tPPG is configured to take advantage of novel thiol
mucin MW reducing agents, e.g., a di-thiol P2176 and a monothiol P2114, and has assembled a full drug
development team to quickly and safely bring these molecules into patient populations in need. The tPPG will
be overseen by a decision making Project Development/Statistical Core (Core A, Richard C. Boucher, MD, PI)
that will guide selection and development of thiol class compounds and oversee selection of drug dose, dosing
frequency, drug formulation and clinical trial designs. Projects/Cores overseen include: Project 1 (Michael
Rubinstein, PhD., PI: Mechanism of Action of Mucolytics in Improving Mucus Clearance in Lung Disease), will
focus on the relative roles of MUC5AC (an “asthma” mucin) vs. MUC5B (a “CF/COPD” mucin) as disease
specific targets and generate biophysical measurements to assist in compound selection and as biophysical
assays for the clinic. Project 2 (Richard C. Boucher, MD, PI: PK/PD Requirements for Mucolytic Therapeutic
Agents In Vitro and In Vivo), will utilize in vitro, small animal, and large animal models to compare P2176 with
P2114 with respect to mucolytic dose, dosing frequency, and the requirement for a hypertonic saline (HS)
formulation. Project 3 (Scott Donaldson, MD, PI: Treatment of Mucostasis and Airways Obstruction in Cystic
Fibrosis with a Novel Mucolytic), will test the safety and short term efficacy of P2176/P2114 in CF populations.
Project 4 (David Peden, MD, PI: Treatment of Mucostasis and Airways Obstruction in Asthma with a Novel
Mucolytic), will test on the safety and short-term efficacy of P2176/P2114 in patients with asthma under basal
and allergen challenged conditions. The projects will be supported by three cores: (1) Core B, Analytics for
Mucolytics (Mehmet Kesimer, PhD, PI), will provide a broad spectrum of biophysical and biochemical
measurements of mucolysis; (2) Core C, In-vivo Imaging of Mucus Obstruction and Clearance (William
Bennett, PhD, PI) will provide imaging of subjects, including radio-nuclide mucociliary clearance
measurements and F19-MR ventilation imaging; and, (3) Core D, The Pharmacokinetics/Pharmacodynamics
(Charles Esther, MD, PhD, PI) will provide measurements of pharmacodynamic and drug pharmacokinetic
measurements of thiol compounds. The tPPG deliverable is to mobilize our experienced drug development
group to advance a novel class of IND-ready therapeuti...

## Key facts

- **NIH application ID:** 10001578
- **Project number:** 5P01HL108808-09
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Richard Charles Boucher
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,173,973
- **Award type:** 5
- **Project period:** 2017-09-07 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001578

## Citation

> US National Institutes of Health, RePORTER application 10001578, Development of Novel Mycolytic Therapies for Lung Disease (5P01HL108808-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10001578. Licensed CC0.

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