June 26, 2020 || NuvOx Pharma has the potential to transform COVID-19 care with its NanO₂™ emulsion for oxygen delivery. With approval from Health Canada to proceed with a Phase IIa clinical trial, NuvOx Pharma is making strong headway in COVID-19 innovations.

Evan Unger is the co-founder, CEO, and president of NuvOx Pharma. Previously a practicing radiologist, he attended the medical science training program at UC San Francisco and completed his residency at the Washington University in St. Louis. He is an inventor on over 118 issued US patents and has several years of experience in the medical industry from his work building two previous companies. His first company, ImaRx Pharmaceutical, was centered around ultrasound contrast agents of gas-filled liposomes and was eventually sold in 1999. Unger then went on to work on microbubbles to treat vascular thrombosis in his second company, ImaRx Therapeutics, which later went public in 2006. His experience with these companies led him to start working on NuvOx, which is focused on developing an oxygen therapeutic, NanO₂^TM, to treat life threatening diseases where hypoxia plays a role. Since its founding in 2008, NuvOx Pharma has won various awards including the AZBio Fast Lane Competition where NuvOx Pharma was selected as one of the top 3 life sciences companies in Arizona for 2017.

1. Tell us about your start-up company.
2. How did your company pivot due to the COVID-19 pandemic?
3. What got you interested in this particular industry? 
4. Do you still work as a radiologist?
5. Do you have any personal anecdotes about the changing VC/investment space? 
6. Have you had any changing relationships with regulatory agencies because of COVID-19?
7. What’s the next step for your company?

NuvOx Pharma began when I discovered that microbubbles work well for oxygen delivery and made it to market with my FDA approved microbubbles. I licensed the patent of a competing company which dropped their project and got ownership of the regulatory documents. The FDA agreed we could reference those documents in support of the development of therapeutic applications. Then, we developed new patents, improved the formulation, and got composition claims and method of use claims. The first data with NanO₂ demonstrated that we could reverse hypoxia and improve response to radiation therapy, and we performed clinical trials in brain cancer patients and stroke patients that showed improvement in survival and that it was safe.

Virtually all of the COVID-19 deaths are going to have hypoxemia as one of the major factors in death. If you look at ARDS patients, they all get hypoxemia and approximately 30-50% of patients die. The survivors often have long-term morbidity due to the hypoxemic insult that they suffer, lung damage from the ventilators, and inflammation in the lungs. COVID-19 is a new area, but COVID patients are experiencing a lot of the same things that the ARDS patients experience.

When the pandemic hit, we already had several animal studies showing that we could restore hypoxemia to normoxia in these models of acute respiratory distress syndrome (ARDS), which is what kills COVID-19 patients. This data catalyzed us to pivot towards this COVID-19 solution and run clinical trials. We now have authorization from Health Canada to conduct a study and we will likely hear back from the FDA this week. We are planning on conducting a Phase IIa study in COVID-19 patients, and we have several sites in Canada and the US. If we don’t get FDA authorization, we’ll start in Canada initially.

However, COVID patients also get cardiac damage and small strokes, and we have data with our drug that shows we can reduce cardiac damage and alleviate damage from traumatic brain injury. Potential administration of the drug could help not only the hypoxemia and pulmonary inflammation but also some of the other complications that COVID patients are getting which are important factors in the morbidity of the disease.

Check out the below video from NuvOx Pharma on ARDS and COVID-19.

I studied architecture in college for three years and my brother and father were architects. Architects are designers, and I like trying to design and invent things. Also having a medical background helps me to understand what might be useful. When I was in my radiology residency at the Washington University in St. Louis, I was doing some of the first work in the world done on MRI contrast agents, and I saw that there were companies patenting and trying to develop the same things I was making in the lab.

I worked until maybe 8 months ago, when I took myself off the clinical schedule. I was a professor of radiology and biomedical engineering at the University of Arizona, and I did some teaching — most of my work was in imaging, interventional biopsies, and different kinds of procedures. Then as I began to work more on product development, it wasn’t really possible to continue working on invasive radiology. I enjoyed it, but I decided that for the rest of my career I was just going to focus on product development.

I’m an angel investor myself. My general sense is that investors are holding their capital closer to their vests and are having hard thoughts about making new investments at this time. On the other hand, there is an opportunity for those with COVID-related technologies. At NuvOx we have seen a tremendous amount of grant opportunities and have been working very hard to apply for these grants. I think in general, this pandemic is making it more difficult for companies to raise capital. At NuvOx, we have a large grant from the National Cancer Institute to fund much of the brain cancer trial, but we weren’t able to start the trial since COVID hit. New trials are hard to get going unless they are COVID-19-related.

I think that our relationship has been collegial with the FDA in our interactions with NuvOx. With the COVID-19 pandemic, the FDA has tried to accelerate getting new drugs into trials, but they are still just as concerned about patient safety and welfare as they were before. It’s remarkable what happened with Canada — we submitted the IND in Canada and it was approved in about a week and they were very responsive. In the US, we submitted a pre-IND, and they’ll get back to us in 2 weeks. It also seems to me that over the past 5 years, the FDA has become more collegial and cooperative, whereas 20 years ago, it seems as if we didn’t have as strong of a relationship. I think the NIH has stressed clinical translation more which has made it easier for us to get grants and start clinical trials. I hope that the NIH continues to receive the support it needs to continue to fund biomedical research in the US.

We’re applying for a lot of grant funding, and there are a lot of grant opportunities. We need some resources to get the trials started. At the same time, we’ll be reaching out to potential investors and partners to try to raise additional capital to not only finish this Phase IIa trial in COVID subjects, but also to try to get Phase II trials going in stroke. We already have funding to do most of the brain cancer trials in subjects, and hopefully, we’ll be able to get that back on track with the sites. We’d like to get those other two trials going, and really try to execute well on the COVID trial since the ICUs are full. The goal of the trial is to give sustained 24 hour IVs to COVID patients who are hypoxic and to try to keep them from needing invasive ventilation. If that’s successful, it could have a really big impact; if you can keep them off invasive ventilation, you should be able to really improve outcomes as well as decrease healthcare costs.

Hunniwell Lake Ventures (HLV) is a Palo Alto-based VC firm that invests exclusively in medical devices. Its mission is to make surgery safer, more accessible and less invasive by investing in innovations that help surgeons visualize the operative field better, employ surgical tools using improved and advanced technologies to treat the patient, and ensure their speedy recovery through the best wound closure and tissue healing technologies available.