Welcome to day two here, or day three, excuse me, of the TD Cowen Global Healthcare Conference. I follow tools and diagnostics. Really pleased to be joined with me here on stage, Zhenya Lindgardt, who is the President and CEO of Sera Prognostics. Zhenya, welcome.
Thank you.
Starting off with a high-level question, I think we'd love to hear from you about framing the issue of preterm birth. How important is this? How material is it or not? Is this something that the world should be really focused on?
It's a huge problem. I would call, especially in the United States, we have a preterm birth pandemic. It's been a very sticky and intractable issue. In the last 10-20 years, the numbers are not improving. They're actually getting worse, slightly worse year after year. Approximately one out of 10 babies are born preterm in the United States. Prematurity is a leading cause of death for neonates and babies under a year old. For 3.7 million births in the United States, about 20,000 babies die. Unfortunately, we as a healthcare system have not been able to address it. Economically, it costs the system about $25 billion, the cost of prematurity, because each delivery of a premature baby on average costs the system $65,000, which is orders of magnitude 10x of what a term baby cost would be.
How is preterm birth diagnosed today? Can you tell us about how Sera aims to change that?
Today, there are two risk factors that are definitively spelled out by the guidelines to be predictors for preterm birth, which is previous preterm birth, which clearly does not work for first-time moms because you do not have that history to go off of, and short cervix. Only fewer than 2% of moms present a short cervix early on. When higher risk factors are present, it is transvaginal ultrasound that allows us to monitor the mom and diagnose risk for preterm birth or screen for preterm birth. As you know, it is expensive and takes a lot of visits and ongoing monitoring. It is not optimal for spontaneous preterm birth. Spontaneous preterm birth accounts for more than half of all preterm birth in the United States, where the baby comes and there were no other risk factors that allowed the physician to potentially prevent it with treatment or preventive bundles of interventions.
The baby comes before 37 weeks of gestation, the definition of preterm birth. Therefore, for us, having developed a biomarker, which is a simple blood test administered between weeks 18 and 20 of pregnancy, allows the physician to know that risk, which exists in a healthy singleton asymptomatic pregnancy, is just the physician and the mom do not know it. It allows the physician to commence a preventive bundle of safe and efficacious treatments. In our case, we have proven in multiple clinical trials that low-dose aspirin, vaginal progesterone daily, and a weekly nurse call can make an enormous difference for the health of mom and baby by extending gestation of the baby in utero and have the baby being born healthier and stay in the hospital fewer days.
Great. Before we jump into the data, maybe it would be helpful to get some background on yourself. You came in as interim CEO back in May of 2023. You'd been at Uber before that and then a long career at BCG. What makes you the right person to lead Sera during this critical phase of corporate life since they just had their pivotal study, which we're going to get to in a moment here, reported out within the past few months? What skills and expIriyence from your prior roles can you draw upon to be successful in this role?
Absolutely. I first was introduced to Sera Story by my predecessor, Dr. Greg Critchfield, who led the company for over a dozen years. He called me up because I was an executive at Uber and I led the corporate incubator where my job was to scale small businesses under $100 million and get them to be multibillion-dollar businesses for Uber on the tech platform. We connected immediately because I'm a mom of three girls and I want them to have a wonderful expIriyence in their pregnancies and have many, many grandchildren in the next few decades. I told him that for women of childbearing age today, we need to introduce technology. In order to achieve adoption and drive density of adoption, we really need to blend screening, diagnostic tools, and technology in commercialization, and of course, the test performance.
What I bring to the table is an unusual combination of in-depth knowledge of the healthcare system in the United States and beyond from my 20 years in the Boston Consulting Group, having worked in life sciences in every sector from optimizing provider integrated delivery networks to serving payers to serving biotechs and diagnostics, bringing all of that and big tech unicorn expIriyence and scaling small businesses now to take Sera from this $1 billion-$ billion stage.
Terrific. Let's dig into PRIME. The PRIME study, which is your pivotal study, the abstract was out in early January, where you reported the study met both co-primary endpoints, excuse me, and showed a 25% reduction in neonatal morbidity and mortality or NMI versus a 19% reduction in the previous AVERT trial. You also had an 18% reduction in neonatal length of stay versus a 27% reduction in AVERT. AVERT was one of your prior studies. Maybe just give us a sense of early feedback from doctors, payers about the significance of this data. If you want to frame the data in your own words, that would be helpful.
Thank you so much. The endpoints that we studied in both AVERT and PRIME are the same. That is, as you highlighted, very important because we want to show consistency of performance of the test to the clinicians, to guideline-setting bodies. That continuous and consistent performance is something I wanted to highlight first. Number two is whatever the percentages are in reduction and in the endpoints that you laid out, what is really critical to remember is the difference between the two studies. One has a historical control arm and one has a prospective control arm. What is critical is that if you blend and analyze the data together, they both achieve a really nice stable with a p-value that is very credible and strong, 22% reduction in each, the health of the baby, the severe outcomes for the baby, and in the length of stay.
That shows to us that the performance is spectacular in ability to be translated from a single study location to a 19-center national trial and prospective control, and the performance is the same.
What are you hearing so far in terms of the endpoints either here that we just mentioned or any other secondary endpoints that are early on resonating with doctors and/or payers from your early conversations?
From the conference where we presented the data, Dr. Iriye presented the data at the late-breaking session, the first number that jumped out at everybody was keeping babies out of NICU. The 20%-22% reduction of NICU admission absolutely was perceived as a breakthrough. Basically, one out of five babies doesn't go into NICU, and those who do end up in the NICU have a reduced length of stay because of the screen and treat intervention bundle. That was the first major, major positive reception of the data. Of course, because everybody saw the AVERT data, the primary endpoints everybody was excited by, but said, great.
The second most well-received was actually a number needed to screen, which is a metric that payers frequently use, but clinicians know about, where you measure the effectiveness of the screening or diagnostic test on how many women need to be screened in order to achieve an outcome. We measured that number needed to screen for saving a NICU day and for reducing a NICU admission. It is just three or between three and four women that you need to screen in order to save one NICU day, which is incredibly powerful as a number. For other tests and treatments, that number is orders of magnitude higher. When you look at how many women need to be screened to prevent a NICU admission, we only need about 41.
That is more than three times better than the screening test I mentioned in the guidelines, which is transvaginal ultrasound. You need to screen with transvaginal ultrasound 150 women in order to save one NICU admission. For us, it is just 41. It is more than three times better.
Interesting. How about in terms of early pushback on the data? Has it been any? What are some of the doctors or folks kind of pointing to?
The first thing they ask is, okay, you guys have this preventive bundle of aspirin, progesterone, and care management. Which is it? What drives the most impact? Because the test is intended to spot abnormalities from multiple etiologies or biological reasons for future development of preterm birth complications, the test does not specify which is the complication that is driving the higher risk. Therefore, it is not one particular bundle component that drives the most of it. We constantly talk about why it is important to drive all three, because for physicians, the symptoms will develop later on in the pregnancy and they will know what condition is emerging. These three components of the bundle have shown to be very effective at ameliorating the effects of it on the newborn mom and, of course, the hospital stay.
We'll take a look at that question because a lot of clinicians came to us and said, let us research and explore the data to see which component. We have launched an investigator-initiated research program. Maybe they can help us look at the data.
Okay. When do you expect to publish additional analysis on what drove the reduction in NMI? Some of the KOLs that we've spoken with are interested in knowing which morbidities in the NMI scale were reduced, as well as whether the reduction in NMI was more driven by days in the NICU or these morbidity events.
That will be broken down in the manuscript and the publication that is under review, and we're hoping will be published in the coming months.
Okay. Do you think the preterm birth could enhance the use of the effectiveness of corticosteroids in the future? We know there'll be a secondary analysis on the effects of corticosteroids during the trial, but can you speak to any of the effect you saw for the use of steroids in the trial? That was some feedback that we heard from doctors is that steroid use, if you kind of have a sense when the birth's going to come, that actually is effective at delaying that birth. Just speak to how steroids were used and kind of how you think that'll be analyzed.
We heard the same, and we're definitely going to take a look at the data. For now, what we showed, what Dr. Iriye showed at the conference, was the level of corticosteroid use in the intervention and in the control arm, which is 4.3% and 5.6% respectively. Of course, more data is forthcoming as we do this analysis.
You talked about NICU admission just a moment ago, just one in five babies are spared going to the NICU. Can you frame what that means in terms of an economic cost perspective?
Yeah, and actually, we're excited to publish that data, hopefully in a peer-reviewed journal as another publication to show the health economic impact. If we do a back of the envelope on the basis of number needed to screen, we do have a reimbursement code from CMS at about $750. Given the number needed to screen is between three and four, so roughly you look at $2,200 to save one NICU day. The cost of one NICU day on average in this country is $5,000. Right there, you're saving almost $3,000. Now, for some babies who are born really premature, that cost is about $20,000 if there's a lot of procedures and machinery that is used to keep the baby alive and growing in the NICU. Those savings could be much, much more.
That's, again, just a back of the envelope with a number needed to screen, but a lot more data will be forthcoming. Needless to say, it looks really good. Our partner, national payer Elevance, has run their model to show $1,600 savings per member tested. Of course, we're looking forward to show the data from our trials to show how well the test performed to compare to that initial estimate from Elevance.
Right. So what did they use? $1,600 versus you're showing $3,000. You're almost double what they were showing. What were some of the impacts?
It all depends on the cost of aspirin, progesterone, care management, what you include. I did the back of the envelope.
Got it. Okay. Talk about guidelines are going to be critical, right, and the commercial outlook now that the data's out. Walk through your high-level plan and framework for getting the data published, working towards developing any additional evidence for guidelines, and then we can kind of go from there.
Of course, first and foremost, we stay in touch with guideline-setting bodies and ask them, what can we do to help them make a recommendation for usage of the test and screen strategy in the community? What they told us is publish, publish, publish, which was delightful because they did not say run three more studies. They just said publish more data out of this spectacular data set that we have pulled together. We are going to do just that. We are going to offer all of the 19 PIs in the study to research more and make the data set available to them and support them to get as much as possible of the data out. That is strategy number one, as recommended by the professional societies themselves.
Second is they recommended that we work together with some partners to lay out what is the protocol and how to implement it, and importantly, how to help physicians get paid for it. We will work to make sure that that is really clear, whether it is in collaboration with a professional society or they do it themselves. The societies felt like that would be really important. Fourth thing we are going to do is, of course, get the major institutions to start adopting this protocol based on the published data so that it nudges the questions to professional societies that these institutions are using the test, clinicians are using the test. What is your position on usage of this test so that it can be prioritized for guidelines review?
It's important to note that ACOG Bulletin 234, which currently governs protocol for preterm birth management, already mentions biomarkers in development and cites our validation study that we've done many years ago. For us, it's about updating the guidelines, which means it needs to be prioritized to be one of two or three, just two or three per year that gets updated when a committee of about 20 people of OB-GYNs, MFMs, health economists, neonatologists gets formed to review the evidence that has emerged in the last three years to update this bulletin. Last time it was updated was August 2021. It's really good timing on the coattails of breakthrough data and hopefully several publications that we aim to make available to this committee should this topic be prioritized quickly.
What are the types of publications? Because I know investors or scientists and guidelines, I'm sure, look at the level of quality. New England Journal of Medicine is always like a premier publication, obviously. But for this particular area for women's health, what are the types of publications that kind of in an A category, the B category? How do we think about that? Is that important?
Of course, impact factor of the journal is important, generally speaking. That said, guideline-setting bodies, specifically ACOG and SMFM in our space, but of course, the USPSTF, which is a very important, I would say, uber guideline-setting body that payers look at, also look at specific publications to that specialty. For us, it's of course AJOG, American Journal of Obstetrics and Gynecology, which is the top journal. There are many in that roster. We've published there. We've published in many other journals. Not to be forgotten, the new journal that Society for Maternal-Fetal Medicine launched just this year called The Pregnancy, which is poised to be the leading journal in the next 10 years for specifically higher-risk pregnancy management.
We're looking at which journals are important for our space, as well as general readable journals by physicians so that we have a mix of journals with these half a dozen publications that are imminent. What's important to know is that there is grading level when guidelines are set. There's a grade assessment of the quality of evidence. It's not just the publication quality itself, but the study design. Of course, the gold standard level one is an RCT, which is what we have with PRIME. Then acceptable are level twos and level threes, which is like an RWE study, which we're launching actually as we speak. We hope that AVERT and our future RWEs and all of the investigator-initiated research we're going to sponsor and support are going to make it into the grade assessment and the evidence that will be evaluated in the guidelines.
In terms of trying to influence guideline members, I know you've gotten or you do have a fair number of guideline members that were involved with the clinical trial. Could you just speak to that a little bit? Because I know there are other diagnostic companies that have had this really rigorous process towards trying to promote their test and ensuring that guideline members are involved throughout the process. Just speak to the strategy that Sera's followed there.
We deploy the playbook that works in the industry, number one. Number two is we aim to do it the right way without biasing the guideline committee and making sure that the evidence speaks for itself. We are doing our job to make sure that all of the stakeholders are aware and we bring them the data. We keep them updated on our publication plans, on the studies, what questions they might have that we should look into. That collaboration without overdue influence, which can backfire in them saying, you guys are too close to us, let us do our job. We are letting them do their job and following their recommendations on what we can do.
You do have, I mean, there were a number of guideline members that were involved with the study. Is that fair?
Yes, that's exactly right. We also have a number of ex-presidents of the society that have worked with us in the 17 years that Sera has been in existence. We are not a spring chicken. That's why the community knows us. It's also a small community. That's why we feel we're well positioned. That said, we also understand that in the guideline-setting process, we want to make sure a broader set of KOL leaders know us, not just a few influencers, because some of them may have to recuse themselves because they've been affiliated.
You mentioned earlier that you said when you spoke with the guideline members and you asked them what to do, they said publish and they didn't say run another study. Would they have told you to run another study? Is it an official statement back from the guidelines? How does that communication go?
There is no guideline-setting process that is laid out really nicely in ACOG bulletins. What does it take for the guidelines to be revised? Industry should not influence that. Industry can ask questions, and that's what we're doing. There is no official advice. It's not like an FDA, which is a rigorous process and you know what to expect. We understand fully the process, but our job is to create evidence, and clinicians and researchers' job is to discuss that evidence and make conclusions.
Got it. In terms of, are there any surrogates that you might point to in terms of the pathway forward to have your tests actually get into guidelines in terms of how long it would take or the level of evidence that you've put forth?
Definitely. For us, of course, ACOG and SMFM, two professional societies, collaborate on guidelines. There has been one precedent when one society, SMFM, went alone. It is actually a recent one. I want to zoom out and look at three previous tests that have become ubiquitously adopted in the community: Panorama, Cologuard, et cetera. How long did it take the NIPT? How long did it take them to get into guidelines? I will not tell you something you do not know. Many of you are experts in this space. For Exact Sciences, it took seven years, for example, to get into guidelines with their test. For Panorama, it took 10 years. For NIPT, for broad-based adoption, it took even longer. It took shorter to get into the higher-risk population.
It is important to note, however, that the world is evolving and preterm birth is a big challenge for the community. There are no other tools. This is a breakthrough innovation and is recognized as such. There is a catalyst to look and perhaps move faster. That recognition will help change the timelines. Additionally, the change of guidelines may come gradually with levels. For example, commentary letter, not a full-blown recommendation and change in the bulletin, recommendation or practice advisory, which already will start being a huge support to the community to start experimenting and adopting this innovation.
What can you do now? What could, in terms of your commercial plans while you're building the evidence and producing future evidence and working with publications and things of that sort, consulting with doctors, how about on the front of beginning to market this test? When will that start while you have this time period, which could be hopefully a lot sooner than 7- 10 years, but we don't know.
Yeah. We hope so as well. Usage in the community. It's a big, big, big factor because, of course, when clinicians say, we're using this test, society, please share your position on how this test should be used in practice. That is number one lever we have. The more opinion leaders in major institutions that are recognized as leading obstetric and gynecology centers or maternal-fetal medicine specialists are using it, the more opportunities for that dialogue among clinical leaders to take place. That's number one, and we're driving that. Number two, of course, is reimbursement. As payers are starting to recognize the value, clinical and economic value, this test brings to the country, that also makes a huge difference.
What we're doing right now is creating local ecosystems where clinicians are excited to be putting the test to use in hard-hit by preterm birth areas and payers and moms and clinicians and make sure that we drive the density of adoption to showcase what this can do economically and clinically for high preterm birth prevalence areas.
In terms of your cash runway, you just did the $50 million raise. What are your thoughts in terms of having that cash wave last you into the future?
We are unique and very fortunate in the diagnostic space for a company that is just launching their broad-scale adoption journey to have at least through 2028 cash runway. That is not even including any proceeds from revenue. For sure, it will be extended much farther as we ramp the revenue. We think that's plenty of time to get to significant scale and maybe even break-even timescale.
Terrific. I think with that, we're out of time. Zhenya, thank you very much for being here.
Thank you for the amazing questions. Good to see you.
Thank you.