Women’s Health Landscape and New Treatment Approaches on the Horizon

There are many therapeutic areas in women’s health that are woefully undertreated and lack targeted therapies. Women undergoing in-vitro fertilization (IVF) procedures often have asymptomatic vaginal dysbiosis, which is an imbalance of microbiota that can cause local vaginal inflammation, and it has an impact on IVF treatment success. Freya Biosciences, a trans-Atlantic biotech company with a focus on women's reproductive health, is currently pursuing a proof-of-concept study on its asset, FB101, an investigational vaginal microbial immunotherapeutic. Researchers are planning to assess its effectiveness in women seeking infertility treatment and undergoing IVF who have asymptomatic vaginal dysbiosis.

In this exclusive Q&A with Pharmaceutical Executive^®, Colleen Acosta, CEO and co-founder of Freya Biosciences, shares insights into the women’s health landscape, where the pharma industry is currently excelling in women’s health, areas for improvement, microbial immunotherapies, and an inside look into its work with FB101 to improve IVF success.

Pharm Exec: How would you describe the women’s health landscape in the US as it currently stands?

Colleen Acosta, CEO and Co-Founder, Freya Biosciences

Acosta: There have been a lot of advancements in women’s health in the US, especially over the past three decades that deserve [to be] highlight[ed]. But there’s a long way to go, and progress can’t come fast enough. Compared to women in other high-income countries, US women have the highest burden of chronic illness, rates of maternal mortality, and preterm births.^1-3 These are glaring statistics. Americans have long struggled with accessing healthcare because of high costs—a disparity even more pronounced for women needing access to contraception, reproductive, and maternity care. Additionally, funding for many conditions that exclusively or disproportionately affect women has been traditionally less than for those affecting men.

Growing recognition of these gaps, however, is encouraging. This combined with a rapidly expanding women’s health market, clinical data on women and new technologies have sparked a notable uptick of investments in women's health companies and startups. Venture capital firms, private equity funds, and impact investors are recognizing the market potential and social impact of addressing women's specific healthcare needs. Recent examples of big successes have been seen especially in the medtech space, including digital health, artificial intelligence, and health services for women. Overall, however, investments in women’s health remain small compared to other sectors. Investment drives innovation, and more is needed of both—especially in developing new therapeutics for women (an area still lagging and with largely untapped potential).

Pharm Exec: Where is the pharma industry currently excelling in women’s health in the US?

Acosta: There are a number of areas where the pharma industry is excelling in women’s health in the US. Most notable are developments in contraception, including hormone replacement therapy to manage menopause symptoms and promote bone health in postmenopausal women as well as targeted therapies for breast cancer (such as HER2 inhibitors and hormonal therapies like selective estrogen receptor modulators and aromatase inhibitors). These have improved outcomes for women with, or at risk for, breast cancer. The pharma industry has also played a role in the advancement of reproductive technologies, such as IVF and assisted reproductive techniques. Medications for ovarian stimulation, hormonal support, and embryo transfer optimization have contributed to the success rates of assisted reproductive procedures. Additionally, HPV vaccinations have reduced the rates of cervical cancer and play a central role in the World Health Organization’s global elimination initiative for the disease.

Pharm Exec: Where are there still areas for improvement in women’s health in the US?

Acosta: Women’s health concerns approximately half the world’s population—and more when considering the impact on families. So, this is hardly a “niche” market, a concept which women’s health is often relegated to. Additionally, the breadth of women's health is wide, spanning conditions that only affect women to conditions that disproportionately (and differently) affect women. In view of the scope, a healthcare paradigm shift from niche to mainstream is needed to comprehensively tackle the health challenges women face.

In the US, these include areas such as maternal health, gynecological conditions, women's reproductive health, menopause management, and mental health. In addition to the alarming fact that maternal mortality rates in the US remain higher compared to other developed nations, there is a long list of conditions for which there are no approved therapeutics available. This is true not only for the US but also for women globally. For example, one in ten women are estimated to have endometriosis, with millions suffering from severe associated pain and infertility.⁴ Yet there are still no therapies available to combat the disease itself. Additionally, more than one in ten babies are born prematurely in the US—a trend that has been steadily increasing with devastating consequences for those born severely preterm.⁵ Yet there are no preventive therapeutics for women at risk (beyond medicines to slow or stop contractions temporarily once preterm labor has started). These are some of the areas where Freya is working to make a difference.

Integral to addressing these issues is addressing health disparities among marginalized populations and increasing funding for research specifically focused on women's health. After being underfunded for decades, the science of women’s health conditions is playing catch-up. But sufficient attention can drive meaningful change for women's health now and in the future.

Pharm Exec: Your company is working on microbial immunotherapies. Can you describe this type of therapy a bit more?

Acosta: Microbial immunotherapies are communities of microorganisms, mainly bacteria, that work to prompt immune system changes that confer a health benefit. These microbial communities are then developed as drug products for specific conditions. At Freya, we are pioneering microbial immunotherapies that directly target the reproductive tract microbiome—the entire community of microbes that women have in their reproductive tracts. By doing so, we aim to reduce inflammation locally, which is known to be detrimental to reproductive outcomes.

Immunotherapies are widely known for their role in cancer treatment and certain immune-related disorders. There are various classes of immunotherapy drugs, such as checkpoint inhibitors and monoclonal antibodies, each with different mechanisms of action but with the shared goal of enhancing or restoring the immune system's ability to recognize and destroy abnormal cells. Freya’s immunotherapies work differently by replacing or significantly shifting the microbiome—thereby, also shifting the local immunology and reducing inflammation in the reproductive tract.

Pharm Exec: Vaginal inflammation associated with asymptomatic vaginal dysbiosis plays a critical role in the conditions that your company is targeting for treatment. What is asymptomatic vaginal dysbiosis, and how is it currently being treated?

Acosta: The reproductive tract microbiome plays a crucial role in protecting against infections and maintaining reproductive health. A healthy vaginal microbiome is characterized by the dominance of Lactobacilli species of bacteria and low levels of pro-inflammatory and pathogenic bacteria. When the balance is reversed, this is known as dysbiosis.

Many women have vaginal dysbiosis without ever knowing it because, in most cases, there are no symptoms—this is asymptomatic dysbiosis. When women do have symptoms; this is known as bacterial vaginosis, which can usually be treated with antibiotics. Vaginal inflammation associated with asymptomatic vaginal dysbiosis, on the other hand, is not usually treated. However, there is a large body of literature linking vaginal dysbiosis (and bacterial vaginosis) with inflammation and then also [linking] inflammation with a host of reproductive health problems. Some of these are IVF failure, preterm birth, infertility in endometriosis, and more. Currently, there are no treatments available that specifically target the underlying inflammation in these conditions. And antibiotics have so far not been shown to confer an effect on inflammation. Freya’s immunotherapies work by adjusting the microbiome—thereby, reducing inflammation to potentially provide a solution to those health problems.

Pharm Exec: Tell me more about FB101, your investigational vaginal microbial immunotherapeutic. How does it work, and what led you to pursue this particular candidate?

Acosta: FB101 is our first-generation investigational drug candidate to improve pregnancy success in IVF. Several studies have indicated that dysbiosis of the reproductive tract leads to immune activation and inflammation, negatively affecting IVF success. Unpublished data from a large cohort study that Freya conducted in collaboration with Boston IVF, a major US clinic, have pointed to lower pregnancy rates in women with a dysbiotic inflammatory vaginal microbiome compared to women without this condition when undergoing IVF.

We recently announced positive topline results from a first proof-of-concept clinical study of FB101. These data allow us to advance the clinical development program with FB101, which has the potential of becoming the first targeted therapy for the IVF population with vaginal dysbiosis.

Additionally, these data lay the groundwork for further pipeline programs with Freya’s immunotherapeutic candidates for other conditions within women’s health. Freya has a discovery platform that de-risks and accelerates the development of our next-generation drug candidates. We can then use those second-generation candidates to target other indications with large populations, such as preterm birth, which affects one in 10 babies. These candidates are in development.

Pharm Exec: As I understand it, you are the CEO of Freya Biosciences and formerly worked at WHO on Ebola and other global outbreaks. Can you share a bit more about your background and what led you to co-found Freya Biosciences?

Acosta: I’ve always been fascinated by the impact that microbes have on human health and how health interventions can change the lives of many. That’s why I became an epidemiologist. I was lucky to have the opportunity to do my PhD (DPhil) in epidemiology with leading experts at the University of Oxford, focused on how pathogens in the reproductive tract are associated with poor maternal and infant health outcomes. After spending some extremely rewarding years at WHO, it was a natural decision to work on Freya with an all-star team and group of co-founders. There are no therapeutics yet available in the areas of women’s health that Freya is focused on, but [there are] lots of unmet needs. It’s quite plain to me that the unique and novel approach that Freya is using to develop new therapeutics can have a huge impact on the lives of women all over the world.

References

1. Gunja, M. Z., et al. What is the Status of Women’s Health and Health Care in the U.S. Compared to Ten Other Countries? Commonwealth Fund. 2018. DOI:10.26099/wy8a-7w13.
2. Hoyert, D. L. Maternal Mortality Rates in the United States. CDC. 2023. DOI:10.15620/cdc:124678.
3. Bronstein, J.M.; Wingate, M.S.; Brisendine, A.E. Why Is the U.S. Preterm Birth Rate So Much Higher than the Rates in Canada, Great Britain, and Western Europe? Int J Health Serv. 2018. 48(4):622–640. DOI:10.1177/0020731418786360.
4. WHO, “Endometriosis,” accessed August 2023. https://www.who.int/news-room/fact-sheets/detail/endometriosis
5. CDC, “Preterm Birth,” accessed August 2023. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm

Meg Rivers is the managing editor of Pharmaceutical Executive^®.