Cystic Fibrosis Foundation Awards $2.8 Million To Novoteris, LLC For Development of Inhaled Nitric Oxide CF Therapy

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by Charles Moore |

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Garden Grove, California based Novoteris, LLC has received $2.8 million in funding from Cystic Fibrosis Foundation Therapeutics Inc. (CFFT) to develop an inhaled nitric oxide antimicrobial therapy for people with cystic fibrosis (CF) who have airway bacterial colonization. CFFT is the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

A pilot trial of this therapy in Europe by Novoteris investigators found encouraging microbiological and lung function changes following two weeks of treatment with Gaseous nitric oxide in patients with CF. The scientists deduce that Nitric Oxide’s potent antimicrobial properties, lack of bacterial resistance, and small molecule penetration capabilities could make it a promising alternative non-antibiotic approach to treating infections in people living with the disease.

Novoteris plans to begin a Phase 2b study by Q3 of 2015 to be supported in part by the CFFT award. The program was based on nitric oxide antimicrobial research work pioneered by Novoteris Chief Science Advisor Dr. Chris Miller PhD, who notes: “The results from our pilot trial demonstrated more than a 15% increase in lung function following two weeks of therapy and we anticipate that we will be able to demonstrate similar outcomes in our Phase II trials.” Also supporting the program are 12th Man Technologies, Inc. of Garden Grove, California, with more than 30 years of experience developing technology for the medical industry, which will provide device development expertise, and Nitric Solutions Inc. of Vancouver, B.C. — a research and development corporation dedicated to developing new therapies and technologies to utilize the beneficial effects of Nitric Oxide in human and veterinary medicine will provide scientific and clinical guidance.

Cystic Fibrosis (CF) is a rare autosomal recessive genetic disorder genetic, life-shortening chronic disease that affects the lungs and digestive systems. In persons with CF, a defective gene and its protein product cause the body to produce unusually thick, sticky mucus that causes recurrent life-threatening lung infections and loss of lung function, restricts breathing, obstructs the pancreas, which stops natural enzymes from helping the body break down and absorb food and results in digestive problems. Patients with CF typically live only into their mid-20s, but that metric has been improving with greater understanding of the disease and development of better treatments.

Lifelong inhaled antibiotic therapy is routinely used to treat lung infections in people with CF, but tends to become ineffective as bacterial drug resistance develops, and resistance to available antibiotics is a major concern for patients with CF. Thick mucus pooled in the lungs also makes it difficult for antibiotics to penetrate bacterial colonies. Consequently, there is a great unmet need to develop alternative agents that can treat bacterial infection in people with CF.

Novoteris is a privately held corporation formed in 2013 and managed by a group of international industry veterans and clinicians dedicated to developing and producing innovative, cutting-edge for the sole purpose of bringing a novel inhaled antimicrobial drug product to the market for the treatment of Cystic Fibrosis, other serious respiratory infections or chronic airway colonization. The science and intellectual property that formed the basis of Novoteris was acquired primarily from 12th Man Technologies, Inc. and Nitric Solutions Inc., and includes drug delivery technology, the science base for the drug product and clinical trial data. The lead entity being pursued by Novoteris and its partners is its Thiolanox nitric oxide gas formulation. The company received Orphan Drug designations for use of inhaled nitric oxide as a treatment for Cystic Fibrosis from both the FDA and EMA in 2013.

The US Orphan Drug Act is intended to encourage companies to develop safe and effective therapies for the treatment of rare diseases and disorders. In addition to providing a seven year term of market exclusivity upon final FDA approval, orphan drug designation also positions Novoteris to be able to leverage a wide range of financial and regulatory benefits, including government and institutional grants, and waiver of FDA user fees for the potential submission of a New Drug Application.

Novoteris is focused on developing inhaled nitric oxide gas formulations to address some of the most serious and lethal respiratory tract infections. The company’s scientists have spent two decades studying and developing nitric oxide for the treatment of drug resistance infections in diseases such as tuberculosis, cystic fibrosis, bronchiectasis, and chronic sinus disease.

Nitric oxide, an endogenous molecule, is an important signaling molecule in the body that plays an important role in every organ system, including the body’s innate defense system against microorganisms. Exogenous nitric oxide has been demonstrated to be an effective antimicrobial agent against a broad spectrum of microbes, including drug resistant strains. A lower concentration of nitric oxide is already on the market from other manufacturers for the treatment of pulmonary hypertension in newborns. “This new application brings years of work with nitric oxide gas for antimicrobial uses to the clinical forefront,” observes Dr. Miller.

thiolonoxNovoteris’ Thiolanox is a pharmaceutical nitric oxide gaseous formulation supplied in high pressure cylinders at 5,000 ppm (0.5% v/v) blended with medical grade nitrogen. Thiolanox is an inhaled antimicrobial gas whose active ingredient is a gaseous molecule called nitric oxide (NO). It is administered to spontaneously breathing patients for 30 minutes, three to five times a day for multiple days and delivered to patients at a dose of 160 ppm nitric oxide. The company says the inhaled antimicrobial effect in patients with cystic fibrosis during pilot testing resulted in improved lung function, and that inhaled NO may potentially have other effects that might benefit CF patients such as its potential anti-inflammatory, smooth-muscle relaxation and secretion thinning effects.

Novoteris notes that the pharmacology, toxicity, and safety data for inhaled NO in humans for other applications are well-established through both previously approved drugs by EMEA (Europe), TPD (Canada), FDA (USA) and many published studies. The synthetic NO gas produced for blending into Thiolanox is an identical molecule to that naturally produced by the human body with no biochemical, pharmacokinetic or physical differences.

Thiolanox was first shown to be safe and effective at reducing those bacteria frequently identified in patients with CF infections. This was demonstrated in both the laboratory and with pneumonia models in two other species prior to human use. A phase I clinical study in 10 healthy adult volunteers, under the auspices of government regulatory authorities, investigated the safety of delivery and the physiologic effects of inhaled 160 ppm Thiolanox for 30 minutes, every four hours, five times a day for 5 consecutive days. The treatments were well tolerated without any significant adverse events.

The pharmacology, toxicity, and safety data for inhaled NO in humans for other applications are well-established through both previously approved drugs by EMEA (Europe), TPD (Canada), FDA (USA) and many published studies. The synthetic NO gas produced for blending into Thiolanox is an identical molecule to that naturally produced by the human body. There are no biochemical, pharmacokinetic or physical differences.

Alex Stenzler, President of Novoteris, says: “Based on the success of our pilot trial, and the broad spectrum of bacteria and fungi that our product has demonstrated effectiveness against, we anticipate a high level of patient eligibility and interest for our Phase II efficacy trial. We are expecting that our program will provide a novel and the first inhalable gaseous antimicrobial agent for the treatment of patients with this devastating disease.”

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