NovoNO Biotech Unveils Portable Nitric Oxide Generator INOwill to Transform NICU and Beyond

NICU refers to the Neonatal Intensive Care Unit. It is hard to imagine that human newborns, only days old, need to rely on “Viagra (sildenafil)” to “sustain their lives.” This is the current reality for neonates with Persistent Pulmonary Hypertension of the Newborn (PPHN) in the NICU. In clinical medicine, the underlying logic for treating neonatal pulmonary hypertension is to use nitric oxide (NO) to dilate the small pulmonary arteries, thereby alleviating pulmonary hypertension. The mechanism of action of sildenafil aligns precisely with this principle, as it enables neonates to increase NO levels in tissues through administration, thus improving oxygenation.

The mechanism of action of nitric oxide was elucidated in the 1980s by three American scientists: NO is a highly reactive free radical that is widely present in the body and serves as an important intracellular signal transduction molecule, playing a role in various cellular functions. NO primarily exerts its biological effects by increasing levels of cyclic guanosine monophosphate (cGMP). Vasodilation is achieved through the NO/cGMP pathway, and Viagra is a product of the translational research based on the physiological functions of NO. In 1998, the Nobel Prize in Physiology or Medicine was awarded to these three scientists in recognition of their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system.

However, the “miraculous effects” of nitric oxide are not limited to this. As the structurally simplest multifunctional biological signaling molecule in the body, it serves multiple physiological roles, including acting as a second messenger, a neurotransmitter, and an effector molecule. In terms of indications, nitric oxide is not only somewhat effective in treating pulmonary arterial hypertension but also used for conditions such as high-altitude sickness and high-altitude edema, refractory hypertension, and Raynaud’s disease. Furthermore, it plays a regulatory role in alleviating cardiovascular and cerebrovascular diseases, improving sexual quality of life for couples, resolving vascular inflammation, and enhancing sleep quality.

“Nitric oxide boasts numerous clinical benefits, yet it remains virtually an ‘untapped market’ in China,” Cao Guiping, COO of Nuoquan Biotech, told VCBeat. “In foreign markets, the treatment of neonatal pulmonary hypertension almost universally relies on delivering nitric oxide gas from cylinders equipped with flow control devices. Such systems are akin to high-end medical devices like ventilators and have seen little innovation over the past two decades. The inconvenience of cylinder-based NO delivery and its high transportation costs have long been pain points in clinical practice.”

Nuoquan Biotech’s mission is to address this pain point by developing next-generation integrated devices for nitric oxide generation and delivery. Nitric oxide is a first-line therapy for neonatal pulmonary hypertension. Over the past years, nitric oxide generation technology has progressively transitioned from laboratory research to industrial application. Since around 2015, the industry has witnessed explosive growth, with four companies internationally filing applications for novel point-of-care nitric oxide generators for the treatment of related conditions.

On March 20, 2020, Bellerophon received FDA approval for the use of inhaled nitric oxide (iNO) therapy in the treatment of COVID-19; one week later, VERO Biotech also obtained FDA approval for iNO therapy to treat COVID-19. Inhaled nitric oxide therapy delivers NO to lung tissue via a face mask or ventilator, thereby dilating pulmonary blood vessels, reducing pulmonary vascular resistance, enhancing oxygenation, and improving ventilation. Additionally, NO can kill and inhibit the growth and spread of coronaviruses within the lungs, thus improving prognosis and therapeutic outcomes. Currently, all inhaled nitric oxide therapies require storage and transportation in high-pressure gas cylinders, which is highly inconvenient. The high concentration of NO gas in these cylinders also poses safety risks. The storage and transportation of NO are labor-intensive and costly, making the development of an integrated all-in-one device “a long-standing dream.”

High-concentration nitric oxide (NO) is prone to side reactions during long-term storage and carries significant toxic side effects. Currently, the industrial-grade NO gas used in China relies on a single flow control device, making it difficult to apply in non-ICU clinical settings and for industrialization. In this sector, several U.S. companies are already developing portable NO generators for clinical use, while China’s participation remains virtually “zero.”

NO Generator Market Overview

Dr. Qin Yu, who has dedicated many years to the research and development of nitric oxide (NO)-releasing materials and generation technologies, currently serves as the Chief Technology Officer (CTO) of Nuoquan Biotech. Her globally leading technology has laid a solid foundation for the team to develop China’s own portable NO generator. A research expert at the University of Michigan in the United States, Dr. Qin has achieved internationally advanced results in the fields of clinical diagnostic testing and novel medical devices.

Nuoquan Biotech’s independently developed compact, portable NO generator (INOwill) can produce high-purity nitric oxide (NO) gas in real time, serving as an alternative to conventional NO gas cylinders. It is applicable for the treatment of pulmonary hypertension in various clinical settings. Additionally, INOwill has been shown to reduce inflammation and complications associated with the use of cardiopulmonary bypass systems during surgery, with hundreds of clinical cases already documented.

INOwill Physical Prototype

INOwill eliminates the burden of relying on traditional bulky high-pressure steel cylinders as a gas source, utilizing its own on-site generation capabilities to produceHigh-Purity NO Gas, equipped with a nitric oxide (NO) delivery device featuring precision sensors and flow controllers, ensuring that physicians can generate NO gas on demand for patients in real time.

Nuoquan Biotechnology utilizesUniqueNO Preservation and Sustained-Release Technology, enabling long-term storage of NO donors and the development of sustained-release formulations that achieve varied NO release doses and patterns tailored to specific application scenarios。

On the NO generation device, Nuquan Biotech utilizesUnique catalysts, electrode materials, and ultra-efficient gas-liquid separation materials, along with independently developed precise electrochemical NO sensors, ensure high-purity NO generation, collection, and monitoring, significantly reducing the cost of inhaled nitric oxide therapy.。

Since the underlying mechanism of INOwill relies on electrochemistry, once the nitric oxide (NO) gas is depleted, a sustainable supply can be ensured simply by periodically replacing the “micro-reactor.” In terms of supply capacity, “the NO gas released by one INOwill micro-reactor is equivalent to the capacity of three to four high-pressure NO cylinders,” described Cao Guiping. “During the treatment of persistent pulmonary hypertension of the newborn (PPHN), the amount of NO in ordinary cylinders typically sustains only about three days of treatment for neonates, whereasRelying on INOwill ensures a half-month supply of treatment dosage for newborns.。”

Cao Guiping told VCBeat: “Currently, the INOwill portable NO generator is primarily used in conjunction with ventilators in China. It is classified as a Class III medical device. Nuoquan Biotech has obtained the product registration test report and is currently conducting clinical registration trials. The earliest”Product commercialization is expected to be completed by the end of next year.。”

In addition to the INOwill portable NO generator, Nuoquan Biotech has also made strategic arrangements for other application scenarios of nitric oxide (NO). Its product pipeline includes NO antimicrobial coating materials, NO ultrasound devices, NO nasal irrigation solutions, and NO functional masks. Among these, the NO functional mask is an emergency product developed by Nuoquan Biotech in response to the COVID-19 pandemic this year, with its market launch expected in the near future.

Regarding the company’s long-term planning and strategy, Nuoquan Biotech has divided its development path into four stages: cylinder replacement, all-in-one machine expansion, indication expansion, and transition from medical to home use. Nuoquan Biotech is currently in the “cylinder replacement” stage and will gradually expand into more medical scenarios.

It is reported that Nuquan Biotech completed its angel round of financing last year and has now launched its Pre-A round, aiming to raise RMB 20 million to fund company operations in 2021 and 2022, including clinical trials as well as product research, development, and manufacturing.