Chris Jackson, CEO and Founder of CiceroDx, maker of the ReceptivaDx test, has been in diagnostic lab testing for over 30 years focusing on health care sales and marketing. Mr. Jackson has launched over 35 products during his career, with the majority in the field of women’s health & reproductive medicine.
Chris Jackson 02:15
Right now what we're doing is helping women understand the potential of what unexplained infertility means. That shouldn't be a diagnosis. It's just a label given to someone where people are giving up and they don't know what to tell them, they run out of answers. And so what ReceptivaDx does is provide answers that are different from everything else that they're getting. And it's pointing towards the uterine lining and the information it might be able to provide as to why these people aren't getting pregnant. What we're picking up is very mild or asymptomatic endometriosis, which no one was thinking about, that could be impacting their ability to get pregnant, or stay pregnant. So the test is done when they would normally be trying to conceive, they would send it to our laboratory, they get results back in about four or five days. And then that information can be used by the doctor if it's positive to treat this person and give them a new pathway to pregnancy that they never thought would happen for them.
Georgie Kovacs 03:16
What resonates with me is unexplained infertility, and obviously more so because I have a personal story around it. I ended up going through 10 of the best doctors in the country constantly being told I had unexplained infertility. And I don't know if it's because I'm a dreamer or because I come from the healthcare field. I was very convinced that it just meant they either didn't know yet because science didn't catch up, or they weren't trying hard enough. And lo and behold, I had some immune blood work done. And the hypothesis was that I had endometriosis but happened to be asymptomatic. My surgeon went in with the laparoscopy and I had it and more than they had thought and I got pregnant the first IVF after.
Now, I'm not at all saying everyone go get surgery and you're automatically going to get pregnant. It wasn't that simple. But you know, I definitely hear what you're saying. And it's great that you guys are trying to solve this.
So let's back up to your background and your role with this and how you've got to today and then we can dive more into ReceptivaDx.
Chris Jackson 04:25
I've been in women's healthcare startups almost my entire career. I've been involved with genetic testing for things like cystic fibrosis. I was with the company at the launch. The first commercial test was involved in the test for preterm labor to assess women that are showing up in hospitals thinking they might be in preterm labor. So that's a quick assessment that has never been done before.
I have always gravitated towards women's health care and I've actually been a good friend and involved in a couple different business ventures with Dr. Bruce Lessey, who is the person behind all the research that the ReceptivaDx test is based on. He and I stayed in touch, and he let me know that he found something that was very, very exciting and spent some time with him and looked at it. And I said, “This is tremendous, but can we help the women? Everyone can find markers, and we don't know what they mean.”
He found this marker, it shouldn't be there when a woman is trying to get pregnant. But for some reason, all these women that couldn't get pregnant, that marker was there. So we thought we had something but now it's like, what do you do for them? So then the next step was to get involved with that. It’s been a blessing. We're helping a lot of people.
I never thought it'd be in this position, but we now have over 300 fertility centers. I just talked to somebody in Dubai, and we have a center there now that's doing the test. We've got people in Saudi Arabia, they're gonna be doing the test that just blows my mind that we start something and then we're helping women all over the world.
Georgie Kovacs 05:59
Right? The test looks at BCL6. And what exactly is BCL6?
Chris Jackson 06:08
BCL6 is that protein I was just talking about that we found. It's a marker of inflammation that's actually been used in lymphoma profiles to help people understand progression of their lymphatic disease. It just happened to be a part of these proteins that we looked at in the sequence - two that were showing up in abnormal uterine lining. When I say abnormal, meaning these folks couldn't conceive, versus women that had normal uterine lining that didn't have this, so we started working backwards.
What's happening there?
Not only is it a marker of inflammation, and you just think of any type of situation, where there's something going on that shouldn't be BCL6 is an inflammatory reaction to endometriosis somewhere else in the body. So it's not on the uterine lining, necessarily. It could be in the pelvic area, it could be on the ovaries, but the immune response for endometriosis is inflammation on the uterine lining.
That inflammation we found is enough to create havoc when a woman's trying to get pregnant. When it's not there, the women's chances are much better and IVF of people that have it, their chances for success if they don't do anything or less than 12% in IVF attempts, so very powerful information when that came out. And then we started looking at the treatment options to see if we could help.
Georgie Kovacs 07:41
Incredible given that there's just so little research right now and women's health. Even when you look at the numbers for endometriosis (at least 1 in 10 women have it), this is such an incredible finding.
Would you say that if you test positive for BCL6, you likely have it, and if you test negative, there shouldn't be a concern? Can you explain that nuance, please?
Chris Jackson 08:22
The only way to diagnose endometriosis is to go in with a laparoscopy and visually see it. So we use the word detect. When we say detect, this is an indirect measurement of that. So it's very similar to other things where you might be measuring something indirectly, but it's directly related to that condition, so a lot of tests are actually like that.
What we did in this study, when we looked at the BCL6 markers, we had 123 women in the original study, and they all had unexplained infertility, and that meant, over 35 try naturally, for at least a year, under 35, at least six months. They hadn't had any procedures like IVF. They had ruled out other male factors and female factors first, but all those women agreed to be biopsied. When the biopsies came back in those women, 65 of those 123 women tested positive for the BCL6.
Everyone in that study agreed to be scoped and so we're very pleased that, out of the women tested negative, the chances of seeing anything were less than 3%. So we felt really good that we weren't giving out any false negatives in that regard. On the other side of it, out of the 65 women that tested positive, 62 of them actually had visible endometriosis. So that's when we felt very comfortable. Now you're talking about sensitivity and specificity levels, about 90% and that's rare in a lot of things in medicine.
For the other three women in the study:
One, we could not see anything
The other had a blocked fallopian tube
The third one had adenomyosis, which is growth on the outer uterine wall that was there.
So other things can cause inflammation and trigger the BCL6 to be positive, but the majority of the time, you're probably looking at the endometriosis.
And if you don't mind, I just want to say something about endometriosis - this is not your mom's endometriosis. They're not doubling over and pain. They don't have painful intercourse. They don't have painful periods where they're just cramping severely. This is the first time they've even thought about it, and that's where that data came in.
Trust me. Introducing a test and telling a doctor, “These patients might have endometriosis” is hard. It's been out of sight, out of mind. No one's talked about it. No one's looking for it. And a lot of the reproductive endocrinologists (REIs) today don't offer up laparoscopy like they did 20 or 25 years ago. That was a standard procedure in fertility workups. They would find endometriosis all the time, but what happened is it just kind of got pushed to the side because laparoscopy was expensive. Insurance didn't want to cover it unless you had glaring symptoms like pain.
The focus has been more on embryos in the last 15 years. It's all been the quality of embryos The American Society for Reproductive Medicine always has known that endometriosis is probably one of the biggest factors and unexplained infertility. They just didn't have a way to define it because we weren't scoping people. It's hard to say, “Okay, I don't have any other signs or symptoms, go ahead and charge me a lot of money for elective surgery that there's no indication for yet.
The BCL6 biomarker comes along. It was just great timing for a lot of these women.
Georgie Kovacs 12:19
I commend Dr. Lessey for his research, and for you guys staying in touch and doing something with this because I was at the Endometriosis Foundation of America conference last year - unfortunately, this year with COVID, they had to cancel it, and I think they're doing some virtual things - but it was really interesting because you have this dilemma with endo, where it's not like every woman's going to walk around getting a laparoscopy, but the only way that you can determine if you have endo is to do it, but you're not going to randomly do the surgery.
Researchers can’t even determine what percent of women actually have it like when they say one out of 10. I'm wondering if that's even accurate. I've been hearing about some data that hasn't been published yet where people think the rate of endo is significantly higher. So the fact that you could have such great statistics in demonstrating that testing BCL6 is a pretty good marker, quite honestly, it is the best thing that is out there.
Some of the REIs I’ve spoken to since my fertility journey said that there was data showing that it didn't matter if you did the surgery or not. And that's why they stopped doing it, which I find really interesting.
Chris Jackson 13:54
To their credit, they were thinking of endometriosis. They were talking about it being on the ovaries for the tube, something that's in the reproductive tract, and not thinking that somewhere else in the body and the pelvic region would have anything to do with implantation. If you have a problem that's local, don't worry about it, we're going to do IVF we're going to take the eggs, create the embryos, and we'll put them right there. So we've avoided this system where the egg needs to get from point A to point B by doing this for you. There are cases of women with endometriosis where they've gotten pregnant.
When I introduced the test, REIs shared, “I understand everyone's paying for everything out of pocket for the most part, and here comes the test with some data but not a ton of data. And you're asking us to screen everybody.” I shared, “You guys are good at what you do. You get the majority of the people pregnant, but the the reality is that some of these women are going to…”
Imagine going into 100 women coming into a Mercedes dealership all putting down $40,000 or $70,000, but only about 40 to 60% of them leave with the Mercedes. Would you do that proposition? That's what's happening in the fertility world - it’s statistics are amazing.
There's still a flipside to that, where there's still a lot of women that are going through this process and ending up without answers. That's where our test fits in. ReceptivaDx is for that group of women that have just about given up, have exhausted everything, they're now finding out about this test and finding out that there may be a new pathway to pregnancy, because no one had talked about endometriosis.
Now, doctors are introducing the test much earlier, they're introducing it after the first failed IVF transfer. Doctors are a lot more proactive now. And now I'm getting a lot more engaged in discussions with doctors because they want their success rates. They want to do the right thing for their patients, and they don't want a patient to come in and say, “Why didn't you tell me about this test that I just pulled off the internet $40,000 ago? There's a lot more healthier discussions going on now because there's a lot more data.
Georgie Kovacs 16:41
What is the cost of the test?
Chris Jackson 16:48
Our test is $690. And that includes not only the BLC6 marker test, but it's also a pathologist giving you a full pathology report.
Georgie Kovacs 17:15
Tell me about the transformation in helping doctors understand the value of the test. When we first met, I believe it was mostly the West Coast of the US where the doctors really thought that this was of great value. What would you say helped really move the needle?
Chris Jackson 17:48
Well, we're a small company, too. I don't have an army of people out there marketing the test. It takes a while for doctors to accept new things, and they get hit with so many new things. How do you sift through that? For us, there were a couple key centers, one in particular in New York, that started using the test from the beginning. And I had some on the West Coast. Patients were leaving these other practices because they couldn't get pregnant and getting consultations at these centers, which ended up getting them pregnant. Not all of them, but the majority of them did and offered them our tests.
One particular doctor, Dr. Aimee Eyvazzadeh, up in Northern California, known as "The Egg Whisperer," is communicating with patients and talking about not just our test, but other tests. Her attitude is, “I want all this information up front.”
Those centers were offering the test up front or after a failure and getting great results and letting people know, “We want you to do this test. We don't want to keep going down this route.”
You also had women that had a prior egg retrieval. So maybe they had limited embryo reserves at that point. So throw the kitchen sink at it not expecting a different result.
You had other other women that maybe had their fertility benefits through, for example Starbucks. They were excited to have fertility benefits, but finding out they only went so far before they had to go into their own pocket by the time you go through the whole process. So people are wanting to know what can I do up front before I just exhaust all these funds? That makes sense.
It's really up to women, as a consumer, and the families to figure out do they want to do tests like this up front? Do they want to give it a try first and see how it goes for them?
The area that we're now focusing on in addition to that is women that can get pregnant, they just can't stay pregnant. They're losing the baby in the first trimester, and we're finding our marker is present in those situations too. So it's not only preventing them from implanting, but it's preventing them from keeping that pregnancy to term.
Georgie Kovacs 20:14
Interesting. And where are you with that research now?
Chris Jackson 20:16
We've already published a paper on that. We are looking at the ReceptivaDx test to understand their recurrent pregnancy loss. A lot of times, it may be genetic reasons. Patients may not have had the eggs tested and the embryo might have had some type of genetic defect that happens in a good amount of the situations. Yet there's a lot of women that may never be able to access advanced fertility services, but they want to know why they can't get pregnant or stay pregnant. That's something I hope next year that we'll have out in full force for any woman to be able to buy the kit from us. They'll take it to their OB GYN, have the test done and send it to our laboratory. There may be a treatment option for them that is very simple and allows them to be able to get pregnant the next time and hold on to that pregnancy. So very excited about that possibility.
Georgie Kovacs 21:13
What are the treatment options? So you test positive for BCL6. What's next?
Chris Jackson 21:27
The gold standard was always laparoscopy. Let's go in and look for it. And you know, I had to deal with that a lot at the beginning, because there were no other treatment modalities that were published. And we really can't talk about treatment modalities unless we've got some published data. That just does a disservice. So laparoscopy was the first. They would go in and they were finding it in a lot of these patients. So instead of being used as a diagnostic tool, it was being used as a treatment tool to confirm and then to treat those affected areas.
The other exciting part of it is that we used a hormone suppression therapy, which involves Depot Lupron, the brand name of the therapy that was used. It puts women basically in active menopause for 60 days. The idea of that doesn't sound thrilling to a lot of women. They associate that with hot flashes or worried that their reproductive system won’t be the same, but it's been used for a long time now.
We published a study a year and a half ago that compared laparoscopy to the women who do the hormone suppression therapy, and got almost the exact same results. There were just under 60% on the live birth rates for both on the very next transfer. So these are women who did the hormone suppression therapy for 60 days and went right into a frozen embryo transfer protocol. In that study, a 58% live birth rate was reported - a little bit higher than the clinical pregnancy rate, but the live birth rate is what I look at so that was really exciting. That gave doctors permission to rethink given there's valid research to present to the patients.
Since then, we've been collecting information on our top referring centers, and they're even getting better success rates from that we're seeing an average of about 63- 64%. We've got outcome data on about 350 patients, and I'm hoping by the end of this year, first quarter next year, we'll have that up to about 1,200.
We've got this shared network program where our biggest centers are letting us know what kind of treatment options they used on the positive patients and then what the outcomes were. It's great because anyone can access this data. We share that with anybody that's out there. So it's not published, but it's their own colleagues, their own network of reproductive endocrinologists seeing that other doctors are using it and getting results.
Georgie Kovacs 24:27
A question about the two modalities of treatment. The way I view it is they're basically dealing with two decisions, both of which have their own pros and cons that I think are really important to take into account and that women may not be aware of. Given that you see data from a broad perspective, I'd love for you to react.
Surgery: I interviewed Dr. Seckin, who's an endometriosis surgeon, and he started the Endometriosis Foundation of America. He, by the way, loves the test and thinks it's a game changer. One of the things he really talks about in the podcast episode is how there's really few surgeons in the world who, I think he said, maybe 100 to 200, who can effectively do the surgery. So if you need to get it done, and you don't live in a place where you have the world renowned surgeons and their team in cases where you may have endometriosis in your bowel, it's a really tough place because you need it done.
Depot Lupron: I've connected with some folks in the advocacy world, and they are really against it because of the bone density loss. I think they're more concerned for those who are on it long term, and I think here you're talking more about 60 days. I personally had a really bad experience with Lupron, so I will never go on it again.
It's a hard decision because Depot Lupron is cheaper, but you can have all these risks. Then you have laparoscopic surgery, which has its risks, but then you also have to make sure you find the right surgeon and it's way more expensive.
I'm curious to hear your reaction to the statement that I'm making and words of wisdom for women.