KNOW bio Combines Nitric Oxide Therapy with Precision Phototherapy to Redefine Gas-Based Therapeutics

In 1998, the Nobel Prize in Physiology or Medicine was awarded to three American scientists—Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad—in recognition of their contributions to the discovery that nitric oxide (NO) serves as a signaling molecule in the cardiovascular system, marking the rise of gas therapy.

As a widely recognized gaseous signaling molecule, nitric oxide (NO) functions in signal transduction pathways. Currently, inhaled NO therapy has been extensively applied in clinical practice for the treatment of diseases includingPersistent Pulmonary Hypertension of the Newborn (PPHN), Pulmonary Arterial Hypertension (PAH), Pulmonary Fibrosis, Chronic Obstructive Pulmonary Disease (COPD), Acute Respiratory Distress Syndrome (ARDS), Diabetic Foot, and Coronavirus Disease 2019 (COVID-19)).

In 2019, the global market size for inhaled nitric oxide (NO) therapy reached RMB 6 billion. According to a report by Market Research Network, the COVID-19 pandemic has accelerated the development of the inhaled NO therapy market. The global market size is projected to grow to RMB 15 billion by 2026, with a compound annual growth rate (CAGR) of over 14.8% from 2022 to 2026.

Currently, numerous companies both domestically and internationally are actively developing the functionality of inhaled nitric oxide (NO) therapy for various clinical scenarios. Through its research on NO gas molecules, KNOW Bio has strategically positioned itself in four application scenarios.

KNOW Bio is a subsidiary of Novan Inc. Novan Inc. is a clinical-stage biotechnology company focused on dermatology, currently listed on the NASDAQ with a market capitalization exceeding $100 million. After discovering that nitric oxide (NO) gas molecules and phototherapy have beneficial effects in the treatment of skin diseases, Novan Inc. established KNOW Bio, a life sciences incubator, in 2015 to focus on the innovative development of NO gas molecules.

KNOW Bio is headquartered in North Carolina, USA, a major hub for companies specializing in inhaled nitric oxide (NO) therapy. Having completed three rounds of financing, KNOW Bio has raised a total of $52 million to date.

Through in-depth research on nitric oxide (NO) gas molecules and precision phototherapy by KNOW Bio, it has currently developed targetedCystic Fibrosis (CF), Alopecia, Diabetes Mellitus, Respiratory Infectious Diseasesand other therapeutic approaches for different indications. To address these various indications, KNOW Bio has established four subsidiaries.

Neal Hunter is the Founder and CEO of KNOW Bio, with 25 years of investment experience. Previously, Neal co-founded the publicly traded company Cree Inc. and served as its CEO, later acting as a founder or investor in multiple startups. Meanwhile, he was a founding investor of the parent company Novan Inc., serving as its Chairman for eight years and orchestrating over $100 million in private financing.

As an incubator, KNOW Bio has established subsidiaries focused on nitric oxide (NO) gas therapy for specific diseases, providing supporting infrastructure and related services to help them evolve from biotech startups into publicly listed companies in the clinical stage. To date, its subsidiaries have raised over $20 million in financing.

NO gas molecules, as a trace substance, canNervous System, Digestive System, Respiratory SystemandImmune Systemplay a role. Since the 1990s, the development of nitric oxide (NO) gas molecule-related therapies has spanned only about two decades. Although the academic community has fully recognized the effects of NO gas molecules, continuous improvements are still needed in delivery methods and generation technologies.

Phototherapy is a common clinical physical therapy that utilizes natural or artificial light sources for the prevention and treatment of diseases, primarily includingUltraviolet Therapy, Infrared Therapy, Visible Light TherapyandLaser Therapy. The mechanism of phototherapy involves the application of spectral energy at a specific wavelength to the human body, thereby triggering a cascade of biological responses to achieve therapeutic objectives.

KNOW Bio’s incubator comprises four subsidiaries, throughCombining Nitric Oxide Gas Therapy with Precision Phototherapy, developed therapies for different indications.

EmitBio, founded in 2020, initially focused on developing home-based treatments for COVID-19, with the goal of deploying a series of new therapies for respiratory diseases.

In 2021, EmitBio announced that it had been granted a patent covering an oral device that uses light to inhibit or eliminate a broad spectrum of pathogens, including the SARS-CoV-2 virus that causes COVID-19.

Previously, EmitBio published a peer-reviewed article titled “Visible Blue Light Inhibits SARS-CoV-2 Infection and Replication,” demonstrating thatInhibiting SARS-CoV-2 infection and replication by irradiating human respiratory cells and tissues with safe visible light to trigger the release of stored nitric oxide (NO) molecules in the body。

Nitric oxide (NO) is a key component of the immune response, capable of preventing viral entry into the body and inhibiting viral replication and release, while simultaneously alerting neutrophils, macrophages, and natural killer (NK) cells to help contain, attack, and eliminate the virus.

This therapy willNon-Ultraviolet Precise Monochromatic WavelengthGuided to the posterior pharynx, it eliminates invading pathogens and stimulates host defenses. Clinical trials have demonstrated that applying this therapy to patients other than those with severe disease,SARS-CoV-2 viral load reduced by an average of 99.9% (including the Omicron variant)，Symptoms of COVID-19 resolved more rapidly and were milder than those in the control group.Moreover, viral load continues to decline even after phototherapy is discontinued.

Currently, this therapy has completed three clinical trials and is preparing to re-engage with the FDA to obtain an Emergency Use Authorization or pursue other regulatory pathways.

Vast Therapeutics, founded in 2017, is a clinical-stage drug development company focused on breaking the vicious cycle of infection and chronic disease in respiratory conditions.

Vast is developing a nitric oxide prodrug for inhalation via dry powder inhalers, nebulized solutions, and other formulations, indicated for the treatment of respiratory tract infections. Upon administration, the drug begins to degrade into nitric oxide once it deposits in the lungs, with release durations ranging from one hour to 24 hours, depending on its stoichiometry.

Nitric oxide (NO) is regarded as an alternative to antibiotics, exhibiting broad-spectrum antimicrobial activity. It can kill bacteria through multiple mechanisms, including nitrosation and oxidative stress that damage DNA, proteins, and iron-sulfur clusters.

Vast holds four patents, including those covering various nitric oxide (NO)-releasing compounds and their pharmaceutical formulations. Its lead candidate, ALX1, has demonstrated in vitro activity against multiple strains of Pseudomonas aeruginosa (PA) bacteria as a treatment for patients with nontuberculous mycobacterial (NTM) lung disease. Another candidate, BIOC11, has been designated as a “Qualified Infectious Disease Product” (QIDP) by the U.S. Food and Drug Administration.

Currently, Vast plans to develop new drugs and therapies for a variety of respiratory diseases, including bronchiectasis, nontuberculous mycobacterial (NTM) lung disease, cystic fibrosis, tuberculosis (TB), aspergillosis, hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP).

Revian, founded in 2016, is a medical technology company specializing in hair loss treatment. In 2018, Revian’s LED-based hair loss treatment, Revian Red, received FDA approval and was officially launched on the market.

Revian Red delivers high-output LED light at two precise wavelengths—620 nm and 660 nm—By combining light at these two wavelengths, the production of natural growth factors (such as nitric oxide) can be stimulated, thereby promoting blood flow, reducing inflammation, and inhibiting DHT (dihydrotestosterone).。

Clinical results showed that patients with at least 80% adherence to Revian Red had an average increase of 26.3 hairs per cm² after 16 weeks compared to those who did not receive light therapy (n = 18).

In 2019, KNOW Bio acquired Clinical Sensors and renamed it Diabetic Health. Diabetic Health focuses on developing technologies in the field of diabetes management.

Diabetic Health leverages KNOW Bio’s nitric oxide-releasing technology to develop new coatings for patients with diabetes, which can mitigate foreign body reactions (FBR) in continuous glucose monitoring (CGM) sensors and insulin infusion sets.

In the daily management of patients with diabetes, continuous glucose monitoring (CGM) sensors and insulin infusion sets are indispensable medical devices. However, due to their short and mismatched service lives (7–14 days for CGM sensors versus 3 days for insulin infusion sets) and their subcutaneous placement, these devices induce a foreign body response (FBR), which limits their performance and usable lifespan.

To address the aforementioned issues, Diabetic Health has developed nitric oxide (NO)-storing and -releasing nanoparticles dispersed in medical-grade polymers and deposited onto device surfaces to form a thin film. During use, the film on the device surface releases nitric oxide, protecting the device from foreign body reactions (FBR) and extending its service life.

In 2019, KNOW Bio announced the establishment of a new wholly-owned subsidiary, Digestive Health Therapeutics, to develop nitric oxide-based biotechnologies for gastroenterology. In the same year, KNOW Bio secured $30 million in a new round of financing.

In the field of nitric oxide molecular therapy, KNOW Bio is actively pursuing a multi-dimensional and comprehensive strategy, aiming to integrate nitric oxide into treatment regimens for various indications. As a trace substance widely present in the human body, nitric oxide serves as a signaling molecule in diverse signaling pathways. Its byproducts exhibit minimal side effects, highlighting its potential to enhance existing therapies for multiple indications.

During the COVID-19 pandemic, inhaled nitric oxide (NO) therapy garnered significant attention. Inhaled NO therapies from international companies such as Bellerophon and VERO Biotech sequentially received FDA approval for the treatment of COVID-19, fueling a surge of interest in overseas markets.

Compared with overseas markets, inhaled nitric oxide (NO) therapy started relatively late in China, with low clinical adoption rates and fewer companies involved. Currently, the market for inhaled NO therapy remains a blue ocean. In 2022, China’s first inhaled nitric oxide therapeutic device received official approval, marking a breakthrough from zero to one.

With the continuous discovery of the functions of nitric oxide (NO) molecules, an increasing number of related products have emerged. A variety of products, including portable NO generators, NO-based antimicrobial coating materials, NO ultrasonic devices, NO nasal irrigation solutions, and NO-functionalized masks, have gradually entered the market, positioning the NO market for accelerated growth.