International Medical Conference Endometriosis 2025:
Endometriosis 2025: Your Mother Should Know, Your Doctor Should Know Better!
Discussion: Familial and Hereditary Penetrance of Endometriosis
Thank you all for a wonderful session on the familial hereditary penetrance of endometriosis Time for any questions
Kind of in my clinical practice I do scoring. It's true. You want to know how real? Because many times peritoneal endometriosis, there's obviously, there's no biomarker, there's no positive imaging is what the patient says. They have pain and the doctor, whether they believe or not is another story. But you got to listen to patients. So when you put the probe in and check the areas, I start a conversation totally irrelevant. The patient may think what this doctor is really talking about. In the meantime though, I check what areas are sensitive. So amazing. Genius work is very exciting, non-hormonal approach, but just for pain, I think this is so exciting. I want to be a scientist. I wish I was young, younger, so it's so much challenge and unknown this there. I really appreciate it.
I can help making this comment about this. I'm going to be very right to the point. The people who are in this committee of naming or coding endometriosis for especially peritoneal versus superficial business, and I see no peritoneal word there, they are not clinicians. They are stuck in hardcore academical practice of surgery. Even they don't see the patients who are going around for 10 years for pain and they have so every lesion, they're seeing patient for 10 minutes and moving on for surgery. I am coming from the trenches. I know that peritoneal endometriosis is not superficial Endometriosis. Endometriosis is not a superficial disease. You're downgrading the whole world of magnificent peritoneum that covers from your bottom all the way to the tox continues to be pleura there. That whole bio, the magnificent impact of that organ graze anatomy recognizes peritoneum as an organ, not visceral.
Also splenic, also mesentery covering all bowel. It's a bigger area surface than our skin. So I'm just, maybe I'm partial because half of my practice is this in one, I'm going to present my data tomorrow, thousands of excisions all verified by pathology. So in that sense, I'm a little bit political. I do not refuse. The point of endometriosis may regress, it may not be symptomatic. Every peritoneal lesion is not serious. Has to be, there has to be fibrosis that really designates the disease. In the absence of fibrosis, 80% of the women may have peritoneal. We really don't know. So I hope I was nicer to this comment. Thank you.
There's a question back there.
Hi there. This is a somatics related question. So you spoke a lot about how you're almost trying to emulate what we see in oncology with the move to precision medicine away from clinically defined. So I was just thinking with the somatics pipeline, are you already thinking about how treatments may for specific subtypes of endometriosis and how we might reach a treatment landscape of true biomarker led diagnostics, led treatment for endometriosis?
Yeah, so it's spot on the perfect question. We really, in addition to seeing this as the first I think potentially really cure this disease and not just manage it, we also see it as potentially the first truly precision medicine story in our field. Because what I didn't get to share, but I know that it will be shared by others, is that the work that Steve Palmer was doing at Baylor College of Medicine, there's an important collaboration with, why can't I pronounce Reed's last name? Now I'm embarrassed. Tara's Group at NextGen Jane, you may know about their work. So they are taking menstrual effluence and they were looking at genetic signatures basically that are up and down regulated in that. And so there's some really interesting work showing that we can potentially subset people and actually see a treatment response. And this is groundbreaking. When we pitch this story to investors for funding, we have to tell a very straightforward drug story.
Like here's a mechanism of action to address pain. And here's the LPS model showing that it addresses pain and here's a safety profile. We have to tell a straightforward story. But behind the scenes, what is also really important to us is what you're saying, which is that ultimately we need to be able to more rapidly identify not only patients with endometriosis, but patients who will benefit from this drug. One of the challenges with really being out and proud about it being something that we think could be a precision medicine drug is that that then becomes kind of a funding killer for a program like this. Because then they say, oh, well great, now f FDA's going to want you to do surgery at the beginning of the clinical trial and surgery at the end of the clinical trial to demonstrate your claims that you're causing lesion regression and treating the underlying disease.
So we're navigating that with our clinical trial steering committee, but I think we're not there yet. Follow us for more progress. But I think where we're evolving to is rather than saying that we're causing lesion regression or making claims like that, I think we might make it around recurrence because we know that with endocrine disrupting approaches, and even with surgery, there's a high recurrence rate certainly with treating just painkillers. So there might be some more tractable clinical endpoints just around recurrence that we can do as a secondary endpoint that doesn't require an invasive procedure. But what we're really hoping is that re's work catches up and gets funded as well in parallel. And then we actually have a molecular signature that's noninvasive to show remission of disease. This is all, we're all growing up together, our different efforts, but it's certainly the vision for the program. Again, I'm up here as the face of it, but Dr. Katina Clemente is here from our team who did a lot of that first 10 years and the subsequent five, five years. And then Dr. Steve Palmer. I feel a little bit like I'm kind of not an awesome megaphone for this program this morning with my brain, but this is, a lot of people are working on this j and k story. It's not just us. Linda.
Here I'll just quickly and then throw it back to you. Sorey just arrived and wasn't here to hear me slaughter your name initially, but I fixed it. So there's reading from next gen Jane. I got the question about what about precision medicine for the JK program. So anyway, here you are. So yes, so just sidebar, this is the foundation hosting this. I discovered I had endo pretty much with my first period. So as you've educated me on and I've learned through the foundation, this is primarily a pediatric disease initially, and we don't think of it that way, but I think it is important to remember that and that there may be, and Stacy actually was the one who opened my eyes to, there may be a fundamental difference between people who have endo with their first period and people who develop endo later in life, and it could end up being a type one versus type two diabetes type of thing.
And so I think that's evolving, but to your point, from a clinical standpoint, what we see for a pediatric onset is that parents are reluctant to treat with endocrine disrupting interventions and they're reluctant to do surgery on their teenagers. And so I think that's in part what also really excites me about the j and k program, and we've talked about this, Linda, is that if you say to a parent, here's something that's non endocrine disrupting, it's not invasive and it's relatively safe, I actually think it's going to be a game changer because also because it targets the transmission of pain to the central nervous system and that central nervous system sensitization as we know, because there's such a long lag to diagnosis for a lot of these girls, it fundamentally changes their biology to be developing the last stretch of their lives. In this context of the central,
The clinical trial, how will you do the clinical trial? Just real quick, how will we do, can you do patients who are 16 in your clinical trial or are you going to do your initial trial? I mean, how do you even think about that? We can answer that later
At lunch. Yeah, thank you for nudging us on that. I don't
Have a good answer. Yeah, let's talk about that. But Stacy, Stacy, the one thing I would like to point out or ask you real quick when I read that paper, because I got asked to comment on it by some people in the press, as you know, I referred them to you, it seemed like the patients were really fairly old and also that the types of cancer they were diagnosed with were the more indolent types of ovarian cancer at the end of your paper. And so is there any diagnosis bias that some patients who may not have gotten diagnosed with a more indolent ovarian cancer phenotype got diagnosed because they were having surgery for endometriosis? So in other words, was there bias toward diagnosing more cancer because they were having endometriosis surgery and it was a more indolent form of the cancer, so maybe they just got diagnosed early because they were having surgery anyway.
Yeah, absolutely. That direction of bias is also possible. One thing, and I want to not step on the toes of far and Paolo who are also going to be presenting and addressing some of this is the Tui's team also in their letter pointed out very low absolute risks, which we have to much more clearly infer to patients. And just the reality that with all of these biases, there's still very solid evidence that there is an increased risk. But clinically and in terms of action, it's very different if you have a subgroup that truly has a 20 fold increased risk that requires a clinical and a response different from a very low absolute risk and a two to fourfold change. So the argument is not that this is all a mirage, the argument is we just have to be much more precise. And this also comes to the great work that's happening at Somatics and at NextGen Jane, is that because we're seeing and embracing this diversity of patients that informs the underlying pathways, it informs the treatment, both exposure and response, it may inform diagnostic success and treatment successes.
It doesn't mean exactly as prey so nicely described. It doesn't mean that there won't be things that are common to all endometriosis. It just means that when we find something that is associated effective, highly evident in a group, we have to do the work of proving that that does apply or does not apply to all these different patient types. And if it doesn't apply, it doesn't mean that that finding isn't valid and effective and impactful. We just have to be really precise about it. And if it applies to everyone, that's fantastic. We just have to prove it.
I have one more question if I to Stacy and Dr. Go. It's very interesting. A hormone dependent disease joins tracks with non-hormone dependent other diseases. We know rheumatoid arthritis is more female dominant, but however there is something happening here, maybe two, there's something pushing endo into a pro fibrotic stage that goes on uncontrollably. And I think that's the challenge we are facing today. And I'm solidifying my thinking in that deeper and deeper for that. I appreciate all the beautiful presentations that you made. Do you have anything to add to that?
Thank you. I will just add, and again, similar to these excellent other presentations that we have been offensively not curious about women and female bodies and female specific health. And so we know that for many of those conditions associated with endometriosis, they actually also are more prevalent in women autoimmune conditions, chronic overlapping pain conditions. The cardiovascular disease presents differently in women than it does in men. And we know and understand very little about these sex and gender specific differences that and the more we learn in the space, hopefully the more we push curiosity focused intention of understanding better. And so again, part of the argument is the more we learn about these multiple across the life course impacts that are experienced by those with endometriosis, we learn about the endometriosis and we learn about these other conditions and we learn new important understanding of women's health across the entire life course.
We do have to wrap up the session. Dr. Go has a last
Okay, so the first question was do we think our mouse models will translate? I don't know. We have time problems. We have time problems. What I will say is that we need better translational models. So we're working with the ones we've got and we could have a whole day dedicated to all the flaws, but we acknowledge them fully. So thank you for bringing that up. And no, we are not concerned about abnormal uterine bleeding, but let's pick that up over lunch.
