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Inhaled IRK inhibitors as a novel therapeutic for IPF

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44HL151067-01
Agency Tracking Number: R44HL151067
Amount: $1,515,600.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NHLBI
Solicitation Number: PA18-574
Solicitation Year: 2018
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-02-10
Award End Date (Contract End Date): 2021-08-31
Small Business Information
Somerville, MA 02144-2935
United States
DUNS: 116955235
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (617) 497-6789
Business Contact
Phone: (617) 858-4045
Research Institution

ABSTRACTThe overall objective of this project is to develop MPX-111, an inhaled remodeling kinase inhibitor
(IRKI) as a 1st-in-class, disease-modifying medicine for idiopathic pulmonary fibrosis (IPF), with superior
medical benefit and improved safety and tolerability than current treatments. The main goals of this proposal
are the testing of the efficacy of inhaled MPX-111 in an animal model of IPF, and inhaled toxicology studies.IPF is a chronic, progressive and fatal fibrotic lung disease, with a median survival of 3-5 years after
diagnosis. Current treatment options for IPF are limited with minimal efficacy and significant tolerability issues.
It is estimated that about 5 million people worldwide suffer from IPF. Thus, IPF represents a serious, common
disease with a massive unmet medical need for new medicines that will improve morbidity and mortality.Metera Pharmaceuticals (Metera) in-licensed the proprietary IRKI Program from Janssen, which identified
novel classes of inhaled, small molecule compounds that potently inhibit PDGFR, VEGFR and FGFR.
Inhibition of these receptor tyrosine kinases is the mechanism of action of oral nintedanib which is approved for
the treatment of IPF. However, nintedanib has significant safety and tolerability issues which reduce
compliance and likely impact its clinical effectiveness, by limiting the doses that can be given. The IRKI
Program focused on identifying compounds with the inherent pharmacological profile of nintedanib, but are
optimized for local delivery to the lung, to minimize systemic exposure and reduce side-effects. Metera
recently selected MPX-111 as the clinical development compound, based upon its overall biological, DMPK,
physicochemical and developability profiles which are very favorable for an inhaled medicine, including high
sustained lung levels in rodents after local administration, and low oral bioavailability (andlt;1%). In addition, a
stable crystalline, micronized form of MPX-111 that is amenable to large-scale synthesis has been identified.In Specific Aim 1, the effects of intratracheal of MPX-111 will be compared with those of oral nintedanib in
a standard model of IPF, bleomycin-induced pulmonary fibrosis in rat, using both prophylactic (to assess the
impact on extracellular matrix markers) and therapeutic (to evaluate the effects on ongoing, developed
disease) treatment paradigms. The plasma and lung levels of MPX-111 and nintedanib will be measured so
that their PK/PD relationships can be determined. For Specific Aim 2, key inhaled toxicology and toxicokinetic
studies with nebulized MPX-111 will be performed: non-GLP 7-day dose-range-finding and then GLP 28-day
studies in rat and monkey, two of the species used previously to evaluate the toxicological profile of oral
nintedanib. Metera will fund the rest of the IND-enabling studies required to complete an IND application.The results from this Phase II project will expand the scientific rationale for a small molecule IRKI inhibitor
as an innovative, disease-modifying inhaled therapy for IPF treatment with improved safety profile compared to
current oral medicines and will lay the foundation for an IND filing and the clinical development of MPX-111.Narrative
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease of the lung, which
is estimated to affect 5 million people worldwide, and which only has an average survival of 3-5
years after diagnosis We are conducting research, including the use of disease-relevant animal
models, on a new type of potential medicine, an inhaled remodeling kinase inhibitor (IRKI), for
IPF that has the potential to provide superior medical benefit and improved safety (by its local
delivery to the lung) compared to current treatments, and will increase survival and the quality of
life for IPF patients. The results from the studies outlined in this application will be an important
step towards the clinical testing of an inhaled IRKI compound in patients with the deadly disease
of IPF.

* Information listed above is at the time of submission. *

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