Joe G.N. Garcia, Founder & CEO, Aqualung Therapeutics
Joe G.N. Garcia, founder and CEO of Aqualung Therapeutics, spoke with Invest: about the development of a monoclonal antibody designed to reduce inflammation. “Un remitting inflammation is a major killer today in patients with chronic disease as well as patients in ICUs on a ventilator. Our drug blocks this uncontrolled inflammation to save lives. I want people around the world who need this drug to have access to it. I want to reduce mortality from inflammation.”
With the PUERTA (Pioneering the Utility of an eNAMPT Reducing Therapy in ARDS/VILI) Phase 2A ARDS trial underway, what early signals are you monitoring most closely?
As a pulmonary and critical care specialist, I have spent most of my career studying the mechanisms that drive lung inflammation and injury. The cornerstone for Aqualung Therapeutics came out of my lab when I was Chief of Pulmonary at John Hopkins, where we first identified eNAMPT as a key driver of inflammation and fibrosis in acute lung injury. Twenty years later, we have developed a humanized monoclonal antibody that blocks inflammation, our lead therapeutics, ALT-100. After a successful Phase 1 trial to show that it is safe, Aqualung now has five clinical trials underway across multiple indications. The PUERTA trial is focused on patients with acute respiratory distress syndrome (ARDS). ARDS is a devastating illness many individuals suffered from during the COVID-19 pandemic, which required some patients to be put on ventilators. I started out as an ICU doctor, and have seen what these patients on ventilators have had to endure, and wanted to make a drug that would address the high mortality rate for this horrible disease. In our initial cohort of 15 patients, we saw very strong signals of clinical efficacy with reduced duration of mechanical ventilation, prevention of intubation in some patients, and clear reductions in inflammatory markers. We feel that these are major outcomes for a disease with historically limited treatment options. We will soon start the next leg of the trial and believe we have a transformative therapy.
How has the clinical trial landscape changed since your FDA clearance for PUERTA in 2023?
It hasn’t changed a great deal from the standpoint of conducting the trial. PUERTA remains a ICU, hospital-based clinical trial, which is inherently complex to run. What we have observed is the lack of enthusiasm from investors when it comes to ARDS. Despite the fact that this disease affects 500,000 people every year in the United States and it has a 40% mortality rate. There is still deep skepticism in the investment community, I am guessing because, to date, no pharmacologic therapy has ever worked. I understand their hesitancy, but we are pushing ahead. ARDS is not a rare disease, it’s a common and lethal syndrome that ICU doctors see every day. This is why Aqualung is pushing forward, the science is strong, the target is validated and the need is there. My hope is that the PUERTA data will continue to show meaningful outcomes and we can shift that narrative. We intend to be the company that changes their perception after we deliver our results.
With your eNamptor platform, what has been learned about the correlation between biomarkers/genotypes and patient outcomes?
The eNamptor platform is designed to bring precision to inflammatory disease. It has three integrated components. First we developed a humanized monoclonal antibody that targets a protein called NAMPT, a potent driver of inflammation and tissue injury. Second we measure NAMPT in the blood, a biomarker for disease severity. The last part is the genetic part. We have sequenced the NAMPT gene and identified specific variants in the gene associated with worse clinical outcomes. Used together, they provide the foundation for a precision medicine approach, In diseases like liver fibrosis, where the trajectory is slower, we would utilize this platform to identify patients at higher risk to find genetic variants, to help guide both prognosis and therapeutic decision making. The challenge with ARDS is we don’t have time to measure everything. These patients are critically ill and decisions have to be made quickly. The eNamptor platform is proving to be incredibly valuable in clinical trials, where we have more time to study therapeutic response with genetics and biomarker studies.
Funding is always a critical issue. Since 2025 is likely a pivotal year, how has your Series A, late-stage financing progressed?
Well it’s no secret that the funding landscape for biotech has been challenging, the words “nuclear winter” comes to mind. Investors are very conservative, shaped by post-COVID and the broader economic and geopolitical environment. There used to be dozens of IPOs every year, but in 2025, we will only see three. For early stage companies like Aqualung, that environment is tough. However, Aqualung has been successful not only because of investors, but through non-dilutive federal funding from the National Institutes of Health (NIH). These grants have enabled us to move our antibodies through preclinical development, GMP manufacturing and early-phase human trials to get a first-in-class therapeutic platform with early clinical promise. We are actively seeking investors to help us finish out the PUERTA trial. Biopharma companies like Regeneron, Eli Lily, and Merck are following us closely. I bring the scientific leadership and credibility but what investors ultimately want to see is clinical efficacy data. They need to know the drug works in people. We think it does, we have seen meaningful signals in early cohorts, but we need more patients to show that it does. The opportunity here is significant, to be the first to deliver a successful therapy for ARDS and with the right backing, we can get there.
What are the biggest manufacturing or CMC (Chemistry, Manufacturing, and Controls) challenges facing Aqualung in 2025?
Fortunately, this is an area we have been above the curve. Several years ago, I developed an antibody against NAMPT in mice, and with limited funds, took the steps to de-risk the manufacturing pathway early on. I partnered with a company in Northern Ireland to humanize the antibody, marking a key milestone. With very little capital, but with a humanized antibody I found a manufacturer, a spinout from Lonza, who was just starting out as a monoclonal antibody manufacturer. Thankfully, I was able to structure a performance based agreement, allowing us to begin production with minimal upfront cost. In the course of the first year of our work they got bought out by Wuxi Biologics, one of the world’s leading monoclonal antibody manufacturers, responsible for roughly 25% of the world’s antibody production. Because of our prior agreement, WuXi inherited and honored the terms of Aqualung’s original agreement. As a result, I now have a major monoclonal antibody manufacturer making our clinical-grade antibody for almost nothing. This strategic windfall has positioned Aqualung very well. We now have enough of the drug to support all ongoing and near term trials over the next couple years. For investors, this means our resources can be directed squarely toward clinical execution and value inflection, not infrastructure or supply constraints.
What is your strategy for long‑term safety monitoring, and what preclinical or early clinical data are you generating or expecting in 2025 to support that?
Our long-term vision extends far beyond ARDS and into chronic inflammatory disease. We are extremely interested in chronic diseases like lung fibrosis, liver fibrosis, inflammatory bowel disease, and autoimmunity. In these areas, there are publications supporting the role of NAMPT and showing our antibody works in each of those diseases. These are models where treatment is sustained in animals for weeks or months to show that it works over time. In our preclinical work, we found no evidence of toxicity. We’ve also completed the FDA required IND enabling studies for chronic indications to show the drug is safe, which provides the critical regulatory foundation for expansion beyond acute care. We just finished those studies and have submitted our submissions to the FDA for the use of our antibody for chronic disease. Monoclonal antibodies are always safer than a small molecule inhibitor. In 2025 we expect to generate additional preclinical and early clinical safety data that will satisfy regulatory requirements and give our investors and partners confidence in the durability of our platform.
With increased attention to cost and reimbursement, how is Aqualung thinking about the eventual commercial model for ALT‑100?
Well, many companies are charging a very high price for monoclonal antibodies, some therapies can cost hundreds of thousands of dollars. That is not the path we envision for ALT-100. We would want the price to be much lower, it’s not expensive to make the antibody. ARDS is a global disease with a high mortality rate, and we believe that cost should not be a hurdle to access to life saving therapeutics. From a manufacturing perspective, the expression levels are high, and the cost of goods is very low. I want this drug to be used around the world. Our strategy is to set a price point that ensures adoption in the U.S. market, while also allowing access to people around the world who need this drug, especially in regions where ARDS continues to be a major unmet need. For me, the goal is to change the trajectory of a devastating disease, and our commercial model will reflect that commitment.
Looking forward, what significant scientific, regulatory, or market risks could derail or delay your path to approval and commercialization?
I believe we’ve done a good job at de-risking many of the typical challenges that early-stage biotechs face. The main concern would be if in the course of doing a chronic study we found a safety signal, that would be problematic. Based on our preclinical work and what we have seen so far, we have every reason to be confident in the safety and durability of our antibody. The antibody was humanized, scaled and manufactured efficiently and we have a good supply to support our current and upcoming trials. Biopharma companies also worry about when the patent will run out, but my patent is good until 2041, providing plenty of runway for commercialization and value creation. Nothing comes without risk, but I feel that Aqualung is in a great place, scientifically, operationally, and strategically to bring this therapeutic through approval and to patients who desperately need it.
