TUCSON, AZ., May 27, 2020 - In June 2019, Aqualung Therapeutics received a three year $1.7M dollar NIH Fastrack Award, for development of a novel immune-based anti-inflammatory therapeutic antibody for critically ill patients with acute lung injury. Due to progress in completion of the initial Fastrack Phase I studies, the company has received National Heart Lung & Blood Institute approval for Fastrack Phase II Funding. Aqualung has now begun IND-enabling pharmaco-dynamic, pharmacokinetic and toxicology studies that will advance their lead therapeutic ALT-100 into human studies to treat Acute Respiratory Distress Syndrome (ARDS). ALT-100 is a humanized monoclonal antibody designed to neutralize circulating extracellular NAMPT, as a novel biologic to suppress lung and systemic inflammatory cascades, inclusive of Covid-19-induced ARDS.
Aqualung Therapeutics Corporation was awarded an NIH FASTRACK AWARD (R42 HL-145930) in June of 2019 with Phase I to support mid-stage identification and development of the lead monoclonal antibody (ALT-100) examined in various preclinical ARDS/acute lung injury models. With early success and completion of these studies, the NIH has granted Aqualung approval for funding of Phase II in ALT-100 development. “We have completed in compelling fashion all of the proposed Phase I studies of this STTR grant and have selected ALT-100 as the lead humanized monoclonal antibody. Based on this early resounding success, the NIH has funded us to begin our Phase II IND-enabling PD, PK and key animal toxicity studies” states Joe GN Garcia MD, CEO and Founder of Aqualung Therapeutics. Upon completion of Phase II of the STTR, Aqualung will file an IND with the FDA and seek to initiate human safety and proof of concept studies with ALT-100 for the treatment of Acute Respiratory Distress Syndrome(ARDS) and Ventilator-Induced Lung Injury(VILI).
On June 2, 2020 Aqualung announced they received a $2.3 Million National Institute Of Health (NIH) Fast-Track Award To Aqualung develop a novel therapeutic antibody for patients with radiation-induced lung injury.
Dr Garcia also states: “there is a serious and ongoing unmet therapeutic need for COVID-19-induced ARDS cases as well as for the nearly 500,000 ARDS patients in the U.S. alone who annually develop ARDS from sepsis, trauma and a myriad of diverse stimuli and experience a 30-40% mortality. Currently there are still no new ICU therapies to treat ARDS other than supportive care.“ Aqualung believes targeting a novel upstream inflammatory agonist, eNAMPT, with an eNAMPT-neutralizing therapeutic mAb ALT-100, will successfully inhibit inflammatory cascades, shorten the duration that patients remain on mechanical ventilation, and thereby reduce ICU healthcare costs and improve ARDS and ICU survival. The Aqualung team continues to advance this lead therapeutic compound and the eNamptorTM platform (ALT-100, eNAMPT biomarker assay, NAMPT genetic test) to key inflection points and the support of this NIH grant demonstrates a need to address conditions of severe unmet medical needs.
About Aqualung Therapeutics Corporation
Aqualung is an early stage biotech company developing immune-focused therapeutic antibodies for patients suffering from disorders characterized by acute and chronic lung and systemic inflammation. Founded in 2016 and led by a physician-scientist, Aqualung’s rigorous science-driven approaches led them to the identification of nicotinamide phosphoribosyltransferase (NAMPT) and other key proteins expressed in both acute and chronic inflammatory diseases. Aqualung Therapeutics is developing eNamptor™, a Next Gen platform comprised of: i) humanized eNAMPT-neutralizing monoclonal antibodies- ALT-100; ii) eNAMPT-Plex-a plasma-based biomarker panel comprised of cytokines including eNAMPT, which predicts ARDS mortality; and iii) NAMPT-Gene, a genotyping assay that identifies individuals with NAMPT genetic variants at increased risk for ARDS mortality. The Aqualung pipeline is designed to target a range of serious inflammatory diseases, including ARDS, ventilator- and radiation-induced lung injury, prostate cancer, pulmonary hypertension, pulmonary fibrosis, cardiac ischemia, non-alcoholic steatohepatitis or NASH and chorioamnionitis or intrauterine infection. These conditions all exhibit a significant unmet medical need with significant morbidity and mortality. For additional information about the company, please visit www.aqualungtherapeutics.com.
Aqualung Therapeutics Corporation
Tel: +1 (312) 618-7337
Joe GN “Skip” Garcia, MD, CEO & Founder
skip@aqualungtherapeutics.com
These ARDS stimuli all have in common the activation of inflammatory cascades which result in a cytokine storm which causes blood vessels to leak fluid into the lung filling the air sacs producing profound shortness of breath and respiratory fatigue.
Intensive care units use ventilators to keep patients alive when their lungs fail and they are exhausted from breathing with fluid-filled lungs. The ventilator is clearly life-saving, however, we and others have shown that being placed upon mechanical ventilation can cause lung injury (VILI) and contribute to the staggering 30-40% ARDS mortality rate in the US. This must be factored into acute COVID-19 treatment.
Aqualung Therapeutics was founded by renowned physician and scientist, Dr. Joe GN Garcia, a member of the prestigious National Academy of Medicine who has relentlessly been pursuing an effective ARDS therapy well in advance of the current COVID pandemic.
“The majority of patients today that are dying of COVID-19 infection are dying because they develop ARDS due to severe unchecked inflammation brought on by the virus and the ventilator, resulting in severe damage to the lung and other vital organs leading to death,” said Garcia.
Aqualung scientists have shown COVID ARDS patients have markedly elevated eNAMPT levels in their blood, the target for the ALT-100 mAb which has shown dramatic anti-inflammatory activity and lung protection in animal studies. With impending movement to ALT-100 mAb manufacturing, the path towards an IND filing with the US FDA appears very straightforward.
NEW MILESTONES TOWARDS SERIES A FUNDRAISING
With a heightened awareness of the linkage between ARDS and COVID-19 mortality, Aqualung has had a renewed interest in recent weeks with potentially interested investors. The Aqualung focus is to obtain an initial tranche of a $5M capital raise (A round). However, with the time to initiate cGMP production of the ALT-100 mAb looming in the next 8 weeks, Aqualung has been in advanced discussions with investors and family office groups who would consider accelerated financing as another convertible note. Aqualung is open to another convertible note with highly favorable terms in order to access capital to initiate manufacturing in a timely manner.
The company is now actively engaged with US government agencies such as the National Institutes of Health (NIH) and the Department of Defense for additional funding opportunities. Applications have been submitted to BARDA as well based on COVID-19 and our focus on being the only upstream target to combat unchecked inflammation.
HOW AQUALUNG WILL TREAT ARDS
Specifically, Aqualung Therapeutics is developing eNamptor™, a NextGen platform comprised of:
- ALT-100- a humanized eNAMPT-neutralizing monoclonal antibody (ALT-100)
- eNAMPT-Plex- a plasma-based biomarker panel comprised of cytokines, including eNAMPT, which predicts ARDS mortality
- NAMPT-Gene- a genotyping assay that identifies individuals with NAMPT genetic variants at increased risk for ARDS death.
Aqualung Therapeutics identified an upstream protein, extracellular nicotinamide phosphoribosyltransferase (eNAMPT), and its receptor, Toll-like receptor 4 (TLR4) which are important in regulating the upstream inflammatory cascade that contributes to ARDS morbidity and mortality. Supported by strong preclinical and human data, combining the elements of the eNamptor™ platform technology has the potential to define high-risk ARDS individuals as well as identify patients most likely to respond to ALT-100 and reduce downstream inflammation that contributes to death from COVID-19 infection and ARDS. eNAMPT is a highly novel target, discovered in the Garcia laboratory while he was Chief of Pulmonary and Critical Medicine at Johns Hopkins) and is unique when compared to other mAbs being evaluated for ARDS which tend to focus on a downstream individual cytokines. The Aqualungs biologic therapy, ALT-100, targets neutralization of an upstream protein (eNAMPT) that is involved very early in activation of the inflammatory cascade and thus can potently attenuate the development of the entire cytokine storm.
Additionally, there are rapidly accumulating data that certain phenotypes or subsets of COVID-infected patients (obese, diabetic, hypertensive, African Americans, Latinos) experience higher progression to ARDS and mortality with COVID-19-induced ARDS. Aqualung believes their novel biomarker and genotyping assays will help in identifying patients most likely to progress to ARDS and most likely to respond to ALT-100 therapy. This precision medicine platform is significantly unique compared to other products in development or others being studied. This platform, in fact, provides significant risk mitigation.
“It’s all about regulating the inflammation," he adds. "By reducing inflammation, vascular leak is greatly reduced and gives the patient time to absorb the fluid that has leaked into their lungs which improves blood oxygen and reduces need for mechanical ventilation. Reducing runaway inflammation will get patients off the ventilator sooner. Every additional day on the ventilator is increasing their risk of mortality.”
“We've worked a lot on this gene [NAMPT] and protein [eNAMPT] and we’ve found out how the protein works to produce inflammation. More importantly, we have devised a powerful and effective way to control this inflammation in a very personalized medicine manner .”
