DDW Editor Reece Armstrong speaks to Dr Piraye Yurttas Beim about the unmet need for patients with endometriosis and how research could lead to new treatments for ovarian health.

RA: What are the current unmet needs for women with endometriosis?

PB: Endometriosis is an inflammatory pain condition estimated to impact more than 10% of girls and women between the ages of 14 and 45, and there is a 10-year delay to diagnosis on average. This means that many women with the condition are not aware that it is what underlies their pain and other potential issues like infertility. For women who do receive a diagnosis, unfortunately there are no first line, disease altering therapies that have been approved. Standard of care involves disrupting the endocrine signalling that promotes growth of the endometriosis lesions through the use of birth control pills or GnRH agonists/antagonists and surgical interventions. These interventions are focused on managing the symptoms and recurrence, even after multiple surgeries is common. Additionally, endometriosis pain is managed with NSAIDs and other pain medications and women with endometriosis are at a nearly 4x increased risk for opioid use and overdose. Taken together, the biggest unmet needs in endometriosis are for more rapid diagnostics and also for pain treatments that are non-endocrine disrupting, non-surgical, non-opioid, and disease altering in a way to reduce the rate of recurrence.

RA: What are some of the biggest drug discovery challenges for endometriosis and ovarian health?

PB: One of the biggest drug discovery and development challenges for both endometriosis and ovarian health is attracting investment dollars to progress innovation. 80% of women’s health companies are founded by females and female founders receive less than 2% of innovation dollars from venture capitalists. While drugs that are targeted at conditions that uniquely or disproportionately impact women make up over 40% of pharma blockbuster sales, less than 1% of biopharma innovation dollars are reinvested into women’s health innovation. Lack of funding across the board from academic research to pharma R&D has also meant that an understanding of underlying disease mechanisms for women’s health conditions like endometriosis have lagged behind better funded conditions like cancer. This is why we focused the first decade of our research efforts at Celmatix on decoding the molecular drivers of conditions like endometriosis. Our Celmatix Therapeutics JNK drug programme resulted from our early understanding that dysregulated inflammatory processes are a key driver of endometriosis. This understanding has unlocked novel mechanisms of action that will help us achieve our aim to treat endometriosis pain in a way that is non-endocrine disrupting, non-surgical, non-opioid, and disease altering in a way to reduce the rate of recurrence. Also because we understand the mechanism we are targeting, it opens the door to better PD endpoints in clinical trials and monitoring disease progress and remission over time.

RA: How could Celmatix’s JNK programme address other health conditions that affect women such as polycystic ovary syndrome (PCOS) and ovarian ageing?

PB:  Our research has shown that inflammation is a common mechanism across women’s health conditions, including PCOS and ovarian ageing. By targeting the JNK signalling pathway, our therapeutic has the potential to reduce inflammation and improve symptoms associated with these conditions as well.

RA: What are some of the wider health implications that affect women with poor ovarian health?

PB: Most people associate ovaries with babies and menopause with hot flashes. However, the ovary has a myriad of functions beyond reproduction and the loss of ovarian function during menopause impacts women’s health beyond infertility. While there is growing awareness of the health risks that result from menopause, many people don’t realise that up to 15% of women globally suffer from poor ovarian health early in their lives due to conditions like PCOS. In fact, there have been as many as 300 distinct symptoms reported to date as a result of poor ovarian health, including things like heart palpitations, anxiety, and sleep disturbances, which people wouldn’t normally attribute to ovarian function. When left untreated, these symptoms can evolve into serious conditions like health disease, stroke, and dementia.

RA: Why have hormonal treatments been the standard therapy for so long?

PB: Rather than addressing the root causes of ovarian dysfunction, the standard of care has long centred around modulating steroid hormone levels to manage the symptoms of conditions like endometriosis and PCOS. These are cheap drugs that in many cases date back to the middle of the last century. And while they are effective at managing some of the worst symptoms of these conditions, long term exposure to these drugs is often not possible because of side effects and risk factors like blood clots and osteoporosis. Also, because the underlying disease is not being treated, many women develop resistance and need to escalate to surgical interventions that also have the risk of disease recurrence after a few years. In the absence of significant innovation in the space, these drugs have persisted as the standard of care because alternatives simply don’t exist. We are looking to change that with our JNK inhibitor programme.

RA: Could you discuss the immunotherapy approach Celmatix is taking?

PB: Celmatix Therapeutics is not only targeting endometriosis-associated pain through a new mechanism that is non-endocrine disrupting but we are also going after the cloaking mechanism whereby endometriosis evades clearance by the immune system. As with cancer immunotherapies, the idea is to enable the body to heal itself through retraining the immune system to effectively clear the disease.

RA: What was it like being selected for funding by the Advanced Research Projects Agency for Health (ARPA-H)? 

PB: Being selected as the only awardee of a SPARK Award in the ovarian health category of the ARPA-H Sprint for Women’s Health (SWH) was validating of the pioneering work we have done in ovarian ageing, dating back to 2009. The SWH was highly competitive and had a less than 1% funding rate, with very few of the awardees being drug companies. Initiatives like the SWH are important because they shine a spotlight on the pressing need for more research and investment in women’s health.

RA: Why was multi-omics key to recognising inflammation within the pathophysiology of endometriosis? 

PB: In the era of genomic technologies, many conditions like cancer have transitioned from being clinically defined to molecularly defined diseases. Molecular insights have subsequently led to a sea change in how cancers are prevented, diagnosed, and treated. Conditions that uniquely impact women, like endometriosis, have lagged decades behind other fields of medicine. Celmatix, together with countless academic collaborators over the years, has been on the forefront of catalysing this same sea change in women’s health. One of the biggest signals that emerged from our multi-omics efforts was the central role that immune function, in particular inflammation, plays across women’s health conditions. This insight allowed us to see the huge impact that targeting JNK signalling could have on women’s health conditions.

From DDW Volume 26 – Issue 2, Spring 2025 Read the digital issue

Biography:

Dr Piraye Yurttas Beim has 20-plus years of experience in women’s health. She founded Celmatix Therapeutics to advance precision medicine, pioneering breakthroughs in ovarian health and developing first-in-class therapeutics.