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Novel Therapeutic Antibody Targeting of Extracellular NAMPT in Ventilator-Induced Lung Injury (VILI)

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R42HL145930-02
Agency Tracking Number: R42HL145930
Amount: $750,000.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA18-575
Solicitation Year: 2018
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-05-15
Award End Date (Contract End Date): 2022-04-30
Small Business Information
Tucson, AZ 85718-6617
United States
DUNS: 097938637
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 (860) 605-3285
Business Contact
Phone: (312) 618-7337
Research Institution
KANSAS CITY, MO 64110-2241
United States

 Domestic nonprofit research organization

Mortality rates in intensive care units (ICUs) are unacceptably high and are directly related to the duration
of mechanical ventilation that is required to support patients with respiratory failure. For example, acute respiratory
distress syndrome (ARDS) is a vexing acute inflammatory lung disease requiring mechanical ventilatory
support as the result of severe hypoxemia and respiratory failure. The estimated 200,000 ARDS cases/yr (U.S.)
exhibit a mortality rate of 30-40% with ventilator-induced lung injury (VILI), a potent stimulus for lung inflammation
and release of multiple inflammatory cytokines (known as cytokine storm), a significant contributor to
ARDS severity and mortality. VILI may also ensue in mechanically ventilated patients with respiratory failure in
intensive care units (ICUs) even when ARDS is not present. As no clinical therapeutic intervention in the ICU
has significantly addressed VILI, there remains a serious unmet need for effective preventive therapies for VILI.
Aqualung Therapeutics scientists have identified nicotinamide phosphoribosyltransferase (NAMPT) as a
novel upstream therapeutic target in the development of VILI, and have developed human monoclonal antibodies
(Fabs or fragment antigen-binding) designed to neutralize circulating extracellular NAMPT (or eNAMPT).
Given the lack of approved VILI therapies, ALT seeks to improve ICU outcomes by developing the human monoclonal
Fab, eNamptor™, as an innovative strategy to reduce or eliminate VILI, targeting circulating eNAMPT.
eNamptor™ will be given prophylactically at the time of intubation in critically ill ICU patients receiving mechanical
ventilation, a marked advantage compared with prior ICU strategies. We expect that eNamptor™ will reduce or
eliminate VILI incidence and severity, reduce the number of days ICU patients require mechanical ventilation,
reduce healthcare costs, and improve ICU survival. With this background, the goal of this STTR Phase I/II Fast
Track application is to evaluate NAMPT-neutralizing pegylated and non-pegylated human monoclonal eNamptor™
Fab candidates for efficacy in attenuating eNAMPT-induced NFkB in vitro signaling and preclinical
murine VILI in vivo models (STTR Phase I). In addition, we will conduct pharmacokinetic/pharmacodynamic and
toxicology studies with lead eNamptor™ Fab candidates in rat and canine models (STTR Phase II). This STTR
Phase I/II Fast Track application represents a collaboration between a biotech startup company (Aqualung
Therapeutics Corporation), an academic entity (University of Arizona) and a private company (Gennova Biopharmaceutical
Ltd.). Together, we will address a serious and important unmet need by validating eNamptor™ as a
viable VILI therapeutic approach. We anticipate these efforts will lead to submission of a IND application to the
FDA to promote eNamptor™ as a therapeutic strategy for VILI in man.PUBLIC HEALTH RELEVANCE:
Acute respiratory distress syndrome (ARDS) is a devastating inflammatory lung disease (estimated 200,000
cases per year in the United States) with an unacceptable high mortality rate of 30-40%. Mechanical ventilation
directly contributes to de novo lung injury in ARDS patients as well as in mechanically ventilated ICU patients
with respiratory failure (estimated 700,000 U.S. cases/yr) due to a condition known as ventilator-induced lung
injury (VILI). Despite recent advances in care of the critically ill, there remains a need for therapeutic options to
address the extremely harmful consequences of VILI. This Fast Track Phase I/II STTR seeks to utilize a novel
therapeutic strategy targeting extracellular NAMPT to reduce VILI morbidity and mortality.

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

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