NuvOx Pharma Files for IPO: Pioneering Oxygen Therapeutics Platform Targets Hypoxia Across Multiple Critical Diseases

Since its founding in 2008, NuvOx Pharma has received multiple Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants from the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute, all under the U.S. National Institutes of Health (NIH), to support preclinical and clinical studies.

In 2017, the biotechnology company received a $3 million grant from the NIH. They used this funding to conductIIPhase b clinical trials have demonstrated the safety and efficacy of oxygen therapy in treating glioblastoma. These findings support NuvOx Pharma’s pursuit of FDA approval. Moreover, this funding serves as a form of validation, attracting numerous additional investors to NuvOx Pharma, which has secured $15 million in private financing to date.

In 2008, Evan Unger co-founded NuvOx Pharma with Jenny Johnson and Terry Matsunaga. They planned to use a novel approach to deliver oxygen to patients experiencing hypoxic symptoms. In addition to clinical trials focused on stroke and glioblastoma, NuvOx is also exploring the use of its oxygen therapy for the treatment of COVID-19, traumatic brain injury, sickle cell crisis, myocardial infarction, and hemorrhagic shock.

On June 29, 2020, Health Canada approved NuvOx Pharma’s NanO for COVID-19 patients with acute hypoxemic respiratory failure (AHRF)₂ ofIIPhase I clinical trial.

Some cases of AHRF may progress to more severe forms of disease, such as acute respiratory distress syndrome (ARDS). ARDS is associated with pulmonary inflammation leading to hypoxemia and is also a leading cause of death in patients with COVID-19. Data from NuvOx Pharma in several animal models indicate that,NanO₂Restored oxygen levels under hypoxic conditions caused by ARDS or acute lung injury.

In addition to COVID-19, hypoxia is also one of the causes of death in cancer and stroke patients. Reduced oxygen flow from the lungs to the blood and from the blood to the tissues poses a life-threatening risk to patients. Current care methods for hypoxia mainly involve supplemental oxygen, hospital ventilators, or hyperbaric chambers, but many issues arise during actual implementation. For example, ventilator masks may leak air, leading to difficulty falling asleep, nasal congestion, and dry mouth.

NuvOx Pharma’s drug therapy primarily relies on NanO microbubbles mixed with dodecafluoropentane emulsion (DDFPe)₂ (Microbubbles: gas bubbles in water with a diameter of less than 1 millimeter but greater than 1 micrometer). These microbubbles are smaller in diameter than red blood cells, making the injection of DDFPe into human blood highly safe. The microbubbles then travel to the lungs, where they absorb oxygen during pulmonary circulation and subsequently deliver it to hypoxic tissues.

Research has demonstrated:

• Although dodecafluoropentane (DDFP) boils at 29°C, it remains stable when stored as a liquid nanoemulsion, thereby enabling DDFP to serve more effectively as an in vivo oxygen carrier and delivery agent.

• DDFPe absorbs 3 times more oxygen than perfluorocarbons at 21°C and 7 times more at 37°C.

• At less than 1% of the perfluorocarbon dose, NanO₂Demonstrates its potential efficacy: improving oxygen flow between blood and tissues.

  
  

Based on these findings, Dr. Unger secured the patent license and ownership of the DDFPe regulatory documentation, and initiated the development of NanO₂plan.

As NuvOx Pharma's flagship drug, currently, NanO₂Possesses data demonstrating its safety and efficacy across different clinical stages for more than seven indications,It is the most effective oxygen therapeutic among 78 clinical-stage compounds.

NuvOx found in its preliminary study on triple-negative breast cancer (TNBC) that NanO₂can enhance the efficacy of immunotherapy in TNBC mouse models. Compared with immunotherapy alone, NanO₂Co-administration with immunotherapy can significantly delay tumor growth. This study is based on a previous clinical trial conducted by NuvOx Pharma in patients with brain cancer,The results indicate that NanO₂Improved tumor-induced hypoxia and increased survival rates after radiochemotherapy.

There are more than 20,000 patients with triple-negative breast cancer (TNBC) in the United States each year. Chemotherapy is the most common treatment modality; however, a high proportion of patients experience disease recurrence and progression to end-stage disease. Therefore, there is an urgent need for new therapeutic alternatives for TNBC. As a breakthrough therapy for certain cancers, immunotherapy has demonstrated some benefits in a subset of TNBC patients. A preliminary preclinical study conducted at the University of Arizona Cancer Center demonstrated thatNanO₂Holds great potential in improving the response to immunotherapy for triple-negative breast cancer (TNBC).

On February 11, 2022, the U.S. Department of Defense (DOD) announced that NuvOx Pharma had received a grant from the Congressionally Directed Medical Research Programs (CDMRP) Breast Cancer Research Program. Through this grant, NuvOx will conduct research on NanO in triple-negative breast cancer.₂Clinical trials combined with immunotherapy.

In addition to TNBC, NanO2 has also demonstrated favorable clinical efficacy in two Phase Ib/II studies: acting as a radiosensitizer in glioblastoma multiforme and as a neuroprotective agent in stroke.

NuvOx Pharma's R&D Pipeline

Source: NuvOx Pharma Official Website

To improve NanO₂Quality Management System for Clinical Trials and Manufacturing: On April 30, 2021, NuvOx Pharma completed the construction and commenced operations of its GMP manufacturing facility at its plant in Tucson, Arizona. The facility comprises an 1,800-square-foot hard-walled space, which houses a 900-square-foot ISO Class 5 cleanroom.

In February 2022, the production facility shared by NuvOx and another Tucson-based biotechnology company received ISO 7 certification. To secure FDA approval for its Phase IIb clinical trial, NuvOx further certified the drug filling area within this facility to meet ISO Class 5 standards under ISO-14644.

“These infrastructure upgrades are critical to our Phase IIb trials in glioblastoma (GBM) and stroke,” said Evan Unger, CEO of NuvOx. Rong Wang, Chief Operating and Financial Officer of NuvOx, stated, “Improvements in our manufacturing environment help us prepare for upcoming clinical trials and other studies, thereby advancing our drug toward market approval.”

Evan Unger, President, Chief Executive Officer, and Co-Founder of NuvOx Pharma, possesses extensive professional expertise and management experience. As a radiologist, he is a pioneer in minimally invasive techniques and holds over 120 patented inventions. Mr. Unger has served for four years as a member of the NIH’s Gene and Drug Research Division, as an ad hoc reviewer for multiple nanotechnology research divisions, and as a reviewer for the NCI Cancer Center Imaging Program.

NuvOx Founder & CEO Evan Unger

Image source: NuvOx Pharma official website

Evan Unger has founded a total of four biopharmaceutical companies. His first company, ImaRx Pharmaceutical, developed three FDA-approved drugs, includingDefinity, the world's best-selling ultrasound contrast agent.In October 1999, DuPont acquired the patents and global market development rights for Definity and its backup compounds by purchasing all outstanding shares of ImaRx Pharmaceutica.Evan Unger Achieves Over 20x Return on Investment Through This Acquisition, and retained the right to use microbubbles in treatment.

Evan Unger’s second company, ImaRx Therapeutics, conducted the world’s first clinical trial of microbubble- and ultrasound-based therapy for ischemic stroke.and was listed on the NASDAQ on October 17, 2008.

In 2016, Evan Unger founded Microvascular Therapeutics (MVT), a company dedicated to developing diagnostic and therapeutic applications for microbubbles (MB) and phase-shift microbubbles (PSMB), supported by the NIH-funded Molecular Imaging and Therapeutics Program.

Based on PSMB technology, MVT has developed a novel, improved ultrasound contrast agent, MVT-100, via the 505(b)(2) regulatory pathway. This product is currently undergoing testing for sonothrombolysis to restore blood flow and open the blood-brain barrier using ultrasound. With a diameter approximately one-tenth that of conventional microbubbles (MBs), PSMB offers advantages in theranostic applications.

In May 2017, NuvOx Pharma stood out among 47 healthcare companies at the MedCity INVEST Perfect Pitch Contest, winning first place as the “Most Investable Startup.”

Top 5 “Most Investable Healthcare Startups” at MedCity INVEST 2017

Source: MedCity INVEST

As a major healthcare investment conference in the U.S. Midwest, MedCity INVEST is dedicated to identifying startups with strong growth potential and uncovering co-investment opportunities for innovative enterprises in the fields of biotechnology, medical devices, digital health, diagnostics, and pharmaceuticals. Participating investment firms include, but are not limited to, AbbVie, Qualcomm Ventures, Mayo Clinic Ventures, Baxter, and Venture Investors.

NuvOx has managed to stand out among numerous innovative enterprises, offering several highlights that other startup teams can learn from.

First is technological innovation. NuvOx is not the first company to treat hypoxia. For decades, scientists have been experimenting with oxygenated perfluorocarbons, but NuvOx’s DDFPe is active at less than 1/200th the dose of perfluorocarbon agents. A lower dose means fewer side effects. In March 2022, NuvOx’s paper “Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized Controlled Dose-Escalation Trial,” published in the prestigious neurology journal Journal of Vascular and Interventional Radiology, was selected by a review article on stroke neuroprotective agents as“One of the 30 Most Notable Studies.”

Additionally,This is also a highly capital-efficient company.. Although Tucson’s talent pool is relatively small, NuvOx has successfully recruited qualified professionals, offering company equity as part of their compensation package. CEO Evan Unger also receives his remuneration entirely in additional equity rather than cash, ensuring that all equity remains within the team.

In October 2017, NuvOx Pharma received the Fast Track Award from the Arizona Biomedical Industry Association (AZBio) for its progress in clinical trials for brain cancer and stroke, as well as its continued development in preclinical stages for indications such as heart disease. In the same month, it also won the TechConnect Defense Innovation Award.

In May 2022, NuvOx Pharma’s “Compositions of Fluorocarbon Nanoemulsions and Methods for Their Preparation and Use” was granted a U.S. patent.

NuvOx’s current clinical programs are based on dodecafluoropentane emulsion (DDFPe). This new patent covers perfluorohexane emulsions for use in oxygen therapeutics,Provides an active pharmaceutical formulation that can be used to develop other products.

Dr. Nina Ossanna, Senior Vice President of Strategy at NuvOx Pharma, stated that theyPlan to develop a differentiated product for the treatment of life-threatening diseases caused by hypoxia.This patent may broaden NuvOx’s extensive portfolio of perfluorocarbon-based therapeutic formulations, further enhancing the efficacy of hypoxia treatment.

Currently, NuvOx boasts a robust intellectual property portfolio: 8 patent families, 6 issued U.S. patents, and 8 applications pending approval, securing 12 years of market exclusivity in the United States.