PM-477: Cure BV

Bacterial Vaginosis (BV), the number one vaginal infection, leads to severe complications. It is significantly associated with pre-term labor, increased risk of getting sexually transmitted diseases and cancer. Moreover, it has a major impact on quality of life and psychological wellbeing if frequently recurrent and strongly symptomatic. Current standard of care treatments with antibiotics often fail to eradicate the Gardnerella dominated biofilm, a hallmark in BV. Antibiotics treatment destroys the whole beneficial microbiome and has a high recurrence rate of up to 60% within 6 months.

 We invented new, precise, species-selective, phage-based therapy to treat BV. This novel therapy will have a huge impact on 400 million women that suffer from BV every year. It will positively affect their physical, emotional, sexual, and social conditions and life. It will be lifesaving for women and their children. And it will rebalance the health inequality among rich and poor women.

Bacterial Vaginosis (BV), the most frequent vaginal infection, infects ~400 million women yearly. It leads to severe complications such as pre-term labor (the leading cause of infant death), and it increases the risk of getting sexually transmitted diseases (~30% of new HIV infections due to BV) and cervical cancer (lower resistance to HPV infections). Due to ineffective standard of care antibiotic treatments, women face recurrent BV which has a severe impact on their quality of life and self-esteem.

During BV, the vaginal epithelial surface is covered with a dense collection of Gardnerella cells in a biofilm that is frequently resilient to treatment. Biofilms are adherent communities of microorganisms which are resistant to many negative stimuli (chemical disinfectants, pH extremes, host immune defences, antibiotics). Antibiotics often fail to eradicate the biofilm, so that recurrence rates are up to 60% within 6 months. Antibiotics wipes the vaginal microbiome, despite leaving some rests of viable biofilm, which opens this ecological niche for other pathogens (fungi, HIV, HPV). There is a great medical need for new approaches to treat BV, by selectively killing bacterial genus Gardnerella, preferably without harming the beneficial Lactobacilli while they re-populate the vagina and are crucial for vaginal health.

Our intention is to develop a high precision therapy for BV that is effective against one of the most pathogenic bacterium (Gardnerella) while leaving beneficial bacteria (Lactobacilli) intact and thus enable a rapid recovery of vaginal microbiome and significant lowering of the recurrence rate. The core of this novel therapy is a small phage-based protein – so called endolysin PM477 – that specifically kills Gardnerella bacteria. Applying our directed evolution platform technology we further optimized this protein to be more effective and stable. The protein consists of two parts, one part that specifically binds to Gardnerella (binding domain), and the part that acts as a scissor and cuts through the bacterial cell wall. Its binding domain is highly specific and will only bind to pathogenic Gardnerella bacteria. The protein was tested ex vivo by treating vaginal fluid samples of patients suffering from BV. The results show that this novel therapy has the power to disrupt Gardnerella dominated biofilms which were formed on vaginal epithelial cells. 

BV is the most common vaginal infection among women of reproductive age with recurrence rate of up to 60% and frequent adverse side effects from treatment. One in four women ages 15 to 49 will experience BV every year. This number is even higher within Hispanic and black women, whereby every third and every second women is positive for BV respectively. It is a highly unpleasant infection without optimal treatment, and it has a high negative impact on women’s health, quality of life and self-esteem. We performed patient surveys to explore women’s BV management approaches, their experience with a clinical care, and their needs. The women reported frustration and dissatisfaction with current treatment regimens and low levels of satisfaction with the clinical management of BV. They dislike taking antibiotics regularly, commonly experienced adverse side effects from treatment and feel frustrated at having symptoms recurring quite quickly after treatment. There is a huge need for a sustained therapy, which will be effective, but will not cause adverse side effects. This is exactly the type of therapy that we are developing – safe, precise, and effective. It will have a huge impact on physical, emotional, sexual, and social women’s life conditions.

BV is the number one cause for pre-term birth and complications during pregnancy, and pre-term birth is the leading cause of infant death and long-term childhood health problems. BV rubs salt in the wounds of health inequality, affecting poor women more than rich women, uneducated women more than educated women. African American and Hispanic American women have almost twice the rates of preterm birth as White women. These rates are much higher in African countries. A long-term cure for BV would be lifesaving for women and their children, and this is exactly the type of therapy that we are developing. 

We are developing a novel antibacterial therapy for the treatment of BV. We are the first to discover a protein – so-called endolysin PM477 – which is specific for pathogenic Gardnerella bacteria, acts like a scissor and cuts through the cell wall of these pathogenic bacteria. Furthermore, we developed a platform technology that enables us to further optimize this protein, making it even more effective and safe. This therapy is different from anything else currently on the market or under development. It has a completely new mode of action and is proprietary. Currently, BV is treated with broad-spectrum antibiotics, that eradicate the whole microbiome but are not able to destroy biofilm formed by pathogenic bacteria which leads to very high recurrent rates. Current treatments under development are just new formulations of existing antibiotics. To our knowledge, our approach is the only specific therapy for BV and is completely proprietary.

Antibiotic resistance is one of the biggest threat to our Healthcare. A vast set of medical interventions from chemotherapy to surgeries rely on effective anti-bacterial therapies. Developing the next generation of antibacterials is therefore critical to ensure our ability to continue advance healthcare and extend our lifespan. At PhagoMed we develop precision anti-bacterials that work where antibiotics fail. With our “ε2 Directed Evolution Technology” we use the principles of directed evolution to naturally engineered phages and phage-derived proteins (phages are viruses that infect and kill bacteria) to hunt and kill pathogenic bacteria. Phages and their proteins have the ability to selectively kill bacteria. We use this ability to develop drugs that only kill pathogenic bacteria in our microbiomes, while sparing the beneficial microbiome. 

We performed ex vivo analyses of vaginal samples from women suffering from BV. All these women developed already chronic form of BV. They were all treated with antibiotics, even some of them for 20 times already. However, the biofilm was not eradicated, and BV was recurrent. We treated vaginal samples of such patients with our drug candidate. We analysed the number of remaining Gardnerella cells by qPCR (quantitative polymerase chain reaction) analysis and performed FISH (fluorescence in situ hybridization) microscopy analyses in order to visualize the potential disruption of the Gardnerella biofilm. All untreated samples contained a high amount of Gardnerella bacteria and a thick biofilm was visible under the microscope. After treatment with our drug candidate, vastly amount of Gardnerella bacteria was destroyed, whereby no beneficial Lactobacilli were affected. The FISH analysis clearly demonstrated that this new treatment is able to destroy the biofilm, without having a detrimental effect on the beneficial microbiome. We are currently working on a scientific paper explaining the mode of action and showing the results. 

Bacterial Vaginosis (BV) is the number one vaginal infection. BV rubs salt in the wounds of health inequality by affecting much more poor and uneducated women. If left untreated, BV leads to severe complications and conditions: preterm birth, infertility, increased risk for acquiring sexually transmitted diseases (increased risk of both acquiring and transmitting HIV), increased risk for developing cervical cancer, depression. 

Our major goal is to develop convenient therapy which solves these problems. A therapy that is effective, precise, and safe, can be easily stored and administered all over the world. We succeeded in the early, preclinical development of this therapy. We discovered a phage-derived protein that specifically binds and lyses pathogenic Gardnerella bacteria, the one responsible for biofilm development on vaginal epithelial cells, and with this for BV development. Our next goal is to accelerate this drug into the clinic and bring it as soon as possible on the market. This novel therapeutic approach will restore vaginal microbiome and secure vaginal health for millions of women. On the long term, it will lead to decreased rates of preterm births, decreased HIV infections, increased health equality between women of all races and social status, and increased women’s health in general. Because women’s health matters.

Our solution is currently in development. We showed ex vivo that it works. We collected vaginal samples of women suffering from BV and treated those with our drug. The results show that our novel drug can destroy the biofilm that forms on vaginal epithelium by killing the pathogenic Gardnerella bacteria, and with this cure the BV. We are currently accelerating our drug candidate into the clinic and plan to start clinical development in 2022. We plan to market the drug and make it available for a large patient population. Once on the market, our solution will serve to millions of women. 

We are currently in fundraising which will enable us to accelerate our BV drug candidate into the clinic. This year's goal is to complete all ex vivo analyses and to close the Series A. We plan to conduct and finalize toxicological and stability studies next year, and to start the clinical development in 2022. During clinical development, several hundreds of women will have access to this novel therapy across different countries. Once on the market (planed for 2027) the access to our drug will be granted to millions of women. 

The current results are very promising, and we are confident that this new drug will revolutionize the treatment of BV. To achieve this, we need both, scientific and financial support. We managed to build a world-class scientific advisory board that is helping us to establish the best possible development plan for our drug candidate. We received both private and public funding for this program, however, we need additional funding to be able to move forward fast. Therefore, we are currently in fundraising with a goal to close the round by the end of 2020. The current COVID situation slowed down our progress and changed the focus of VC money. Achieving this goal on time is our biggest barrier right now. 

We believe that only through promotion, networking, and good visibility we can achieve our fundraising goal. Although BV is the number one vaginal infection, and although it is linked to severe conditions, the awareness is still not where it should be. Therefore, we are very active in participating in different accelerator programs and promoting the medical need for BV. We also managed to receive support from world-class KOLs who are working in the field of BV. 

15 FTEs with different functions are working on our solution. 

PhagoMed successfully builds up a team consisting of both, business experts and scientists with an excellent track record and biotech experience Furthermore, PhagoMed understood how important dialog with KOLs/clinicians and regulatory authorities in early development is, and is in continuous discussion with all.

Currently, we have a research partnership with Ghent University, Belgium, on vaginal microbiome incl. ex-vivo work with patient samples.

Developing novel phage-based pharmaceuticals is PhagoMed’s core capability. The business model is therefore focused on developing novel drugs and demonstrating initial clinical efficacy and safety. Once a clinical proof-of-concept has been established, PhagoMed seeks to partner with established pharmaceutical companies that have the ability to secure the late-stage development of the program and commercialize the novel drugs. First out-licensing for our BV is therefore expected to be achieved by 2022 once a clinical proof-of-concept has been established.

Our funding strategy is a combination of investment capital and public grants. We are currently seeking additional investment capital (equity financing or partnership) to fund clinical development.

We are convinced that the Solve community would help us in promoting the high medical need for new treatment of Bacterial Vaginosis and would enable us to meet potential partners all over the world. We believe that only together, through exchange and networking we can succeed in achieving our goal – improving women’s health all over the world.

We put a lot of effort to build a strong network within Europe, however, we do not have a strong network and exposure in the US and globally. And this is where Solve’s global network and expertise would be of huge advantage. 

We are interested in partnering with organizations working in the field of women’s health, have a strong global network, have access to patients, can educate broad women populations. It is highly important to bring effective and safe therapy to all women suffering from Bacterial Vaginosis. And it is also very important to further inform and educate women on Bacterial Vaginosis and its impact on their health. Working closely with such organizations would hand in hand improve women’s health.  

Bacterial Vaginosis (BV) is the most common vaginal infection among women of reproductive age with a high negative impact on the quality of life and self-esteem. It is a highly unpleasant infection without optimal treatment. It is linked to more severe conditions such as preterm birth and increased risk for HIV infections, and it even leads to depression in many cases.

BV is currently treated with antibiotics. Those are failing in several fields: First of all, antibiotics and the vagina is a horrible combination. Antibiotics kill the good bacteria in the vagina, which leaves women vulnerable. Vulnerable to additional infections, vulnerable to sexual diseases, vulnerable to cancer. And on top: antibiotics have a bad cure rate. 50% of women will have recurrent episodes within three months despite antibiotic therapy.

We are working on precision and specific therapy that is effective against pathogenic bacterium leaving beneficial bacteria intact, and at the same time enabling rapid recovery of vaginal microbiome and significant lowering of the recurrence rate. We discovered and optimized a phage-based endolysins for specific and precise treatment of BV. We now need to accelerate its development and would use this prize to support this.

This novel therapeutic approach will restore vaginal microbiome and secure vaginal health for millions of women. On the long term, it will lead to decreased rates of preterm births, decreased HIV infections, increased health equality, and increased women’s health. It will have a huge positive impact on women’s physical, emotional, sexual, and social condition and life.  

Bacterial Vaginosis (BV) rubs salt in the wounds of health inequality. It affects much more poor women than rich women and uneducated women than educated women. In Africa, 40% of black women living in poverty have BV. Those women are at higher risk of both acquisition and transmission of HIV. It has been estimated that BV accounts for roughly 30% of new HIV infections among African women.

Increased preterm rates are another huge problem affecting low-income women. BV is the leading cause of preterm birth. And the preterm birth is the leading cause of infant death. Many of those that survive will have lifelong health issues such as chronic asthma, brain damage or blindness. One in ten babies born in the US will be preterm, but these rates are over 15% in low-income communities, Africa and South Asia.

Effective and convenient BV treatment would help to decrease those cases. And this is exactly our goal. We are working on precision and specific therapy that is effective against pathogenic bacterium leaving beneficial bacteria intact, and at the same time enabling rapid recovery of vaginal microbiome and significant lowering of the recurrence rate. We discovered and optimized a phage-based protein, so-called endolysins, for specific and precise treatment of BV. We now need to accelerate its development and would use this prize to support this.

On the long term, this novel treatment will lead to decreased rates of preterm births and decreased rates of HIV infections. It will help to increase health equality all over the world and improve women’s health.