Periodic Reporting for period 3 - NEFERTITI (A Novel Eco-Friendly, dually Efficient and Resistance-free Treatment of vaginITIs) Période du rapport: 2021-09-01 au 2022-06-30 Résumé du contexte et des objectifs généraux du projet Bacterial vaginosis (BV) and vulvovaginal candidiasis (VCC) are common vaginal infections caused by Gardnerella and other anaerobic bacteria or by Candida fungi. The infection can occur once - the acute form - or recur repeatedly over the course of a year or even several years. Every year, about 68m women in Europe and the US have at least one vaginal infection. Vaginal infections cause intense physical discomfort, adversely affects quality of life and have heavy socioeconomic costs. Many women opt to self-treat with non-prescription over-the-counter antifungals which fail because the causative microorganism has not been properly identified. Antibiotics for BV are encountering increasing levels of drug resistance. Combination of misdiagnosis, misuse, non-compliance, overconsumption leads to low efficacy and high recurrence rates for vaginal infections.Our solution is pHyph, a pessary based on glucono-δ-lactone that is a highly effective cure for acute and recurrent vaginal infections, providing a far better alternative to antibiotics or antifungals. We have confirmed the commercial and economic viability and biological safety of pHyph and have developed a comprehensive roadmap to complete clinical development and reach commercialisation. This project has been a crucial step to execute these plans and enter the vaginal infection treatment markets. NEFERTITI project objectives were to fine tune the formulation of pHyph followed by a full clinical testing program to demonstrate efficacy of pHyph treating vaginal infections and preventing their recurrence. In total, 152 patients participated in pHyph clinical trials at ten clinical investigation sites. The safety and efficacy of pHyph in treating and preventing BV and its recurrence, as well as secondary VVC infections was confirmed by clinical diagnosis in the CL3/NEFERTITI study. Data gathered from the clinical studies has been essential on our route to comply with the European CE mark approval requirements, and consequent market launch in Europe, leading to a strengthened company position when negotiating with pharmaceutical enterprises to complete our distribution value chain. To support commercial viability, we have performed market maturation activities including supply chain maturation, market surveillance, legal and regulatory matters, IP protection as well as communication and dissemination activities. Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent We have successfully reached all project objectives and milestones. We have achieved the appropriate release and concentration of glucono δ-lactone confirming its biocompatibility with human tissues (WP1) and obtained ISO 13485:2016 certification for Medical device Quality management system. We conducted clinical trials testing the pHyph pessary for its performance against VVC and BV (WP2). The safety and efficacy of pHyph in treating and preventing BV as well as in preventing secondary VVC infections has been confirmed. A total of 152 patients across ten clinical investigation sites were included in the study.. Within the value chain development and commercialisation activities (WP3-4), the key stakeholder groups in our value chain were identified and an engagement strategy has been developed presenting a convincing business case to each supply chain partner. We have finalized our Communication Plan investigating the pathways to communicate optimally with all our stakeholders (WP5). We have completed the work on the regulatory landscape and held a pre-IND FDA-meeting, confirming the development plan and clinical phase 3 study design. We have prepared for market readiness and initiation of commercial manufacturing. Finally, we have ensured efficient project and innovation management (WP6), including risk management and mitigation measures related to the COVID-19 related delays, as well as developing the interim and final Business Innovation Plan (BIP) and Commercialisation Plan. Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent) pHyph is an OTC antibiotic-free and antimycotic-free pessary that rapidly restores the vaginal pH to a healthy 4.0 and reverses the formation and proliferation of biofilms on the vaginal mucosa and promotes a healthy vaginal microbiome. The main novelties distinguishing pHyph from state-of-the-art antibiotics and antifungals for vaginal infection treatment are:-its dual action in treating and preventing bacterial and candida vaginal infections without provoking resistance.-the use of biologically safe glucono-δ-lactone.-its gradual release from the pessary.-its mode of action against pathogenic microorganisms when dissolved in the fluids of the vaginal mucosa.-the promotion of a normal and highly beneficial microflora balance in the vaginal mucosa.The NEFERTITI project contributes to the following expected impacts:-Economic: pHyph is intended to give a permanent solution to recurrent vaginal infections which antibiotics and antifungals frequently fail to achieve. pHyph has shown a cure rate for BV in line with many antibiotic products on the market, but with substantially less recurrence and secondary VVC infections. Our commercial roll-out will see pHyph being used to treat in 14.1m women in Europe by 2026 and 2.75m women in the USA in the same year to treat vaginal infections, cutting their workplace absences and thereby avoiding lost workplace productivity by up to €10.7bn in Europe and €2.2bn in the USA.-Industrial and technological: Antibiotic resistance is one of the biggest threats to global health, food security, and development today. It is undermining the efficacy of antibiotics and antifungals. Past misuse or overuse has selected for drug resistance and loss of clinical efficacy, and the healthcare sector is searching for alternatives that do not provoke resistance. pHyph is a very strong candidate to take their place. pHyph acts by rapidly restoring the normal pH and disrupting biofilm formation. pHyph can be used repeatedly for giving lasting protection for recurrent vaginal infections as well as acute cases. It does not select for resistant strains or genotypes, regardless of its mode of use, and it does not cause drug resistance to build up in the population. -Innovation capacity: GED are pushing pHyph as the first of a series of OTC healthcare products with glucono δ-lactone as the active ingredient. The OTC sector is worth €160bn. Growth is driven by low cost and ready availability compared to prescription drugs. Breaking into the market with pHyph will establish scientific credibility of glucono δ-lactone, and stimulate interest from the healthcare industry to join us in further R+D with glucono δ-lactone to treat other types of infections. -Competitiveness and scale-up: Commercialisation of pHyph will have a major economic impact on the industrial partners. pHyph is planned to be launched in 2023 into the European market and into the US in 2025, and targeted at 68m women who suffer from acute or recurrent vaginal infections. -Societal: VVC and BV are both major issues for women’s health. They cause intense discomfort and physical pain along with psychological distress. pHyph alleviates the physical symptoms that vaginal infections bring. Initial trials in Sweden have shown a cure rate of over 82% in BV patients when used for six days and also the current NEFERTITI trial confirmed that 70% of patients treated with pHyph were totally absent of symptoms after treatment and only 14% experience recurrence after a month. phyph.jpg
