All right. Good morning. I'm Julia Qin, lead analyst covering life science tools and diagnostics at JPMorgan. It's my great pleasure to introduce you to our next company presentation by Natera. With that, let me turn it over to Steve.
Great. Thank you very much. This is the standard safe harbor information. Many of you know Natera, we are today the market leader in cell-free DNA technology. We launched our first test, Panorama, in 2013, which is a non-invasive prenatal test. We were the fourth company to market, today, we believe we have more than 50% market share. In 2020, we expanded, used the same technology, to move into the field of oncology and also into organ health. Looking across the portfolio, in women's health, we now have a full suite of services that we offer to physicians: Panorama non-invasive prenatal testing, Horizon carrier screening, and the Empower hereditary cancer testing. In oncology, we have our Signatera MRD test, Altera solid tumor comprehensive genomic profiling, and as you know, we're working on an early cancer detection product.
In addition, the oncology sales team is now also selling the Empower hereditary cancer test to breast surgeons and oncologists. In organ health, we initially launched our Prospera donor-derived cell-free DNA test for kidney transplant recipients. We've now expanded that to heart and lung. We also have a germline test that looks at patients with chronic kidney disease that we're distributing to the general nephrology practices. I'll talk a little bit more about each of those as we go on. One of the core drivers of our success is that our products are supported and driven by strong, real-world, peer-reviewed evidence. Today, in the women's health space, we have more than 77 peer-reviewed papers. In oncology, in support of the Signatera technology, we now have 39 peer-reviewed papers.
In organ health, in support of our donor-derived cell-free DNA and chronic kidney disease products, we have 24 peer-reviewed papers. Cumulatively, we've studied more than 1.3 million patients. When we look back at 2022, we had a great year. We processed more than 2 million tests, which is year-on-year growth of 30%, and we performed greater than 190,000 oncology tests, which was growth of greater than 150% year-on-year. In fact, these numbers would've been better, but because of the flooding that occurred right at the end of the year, we in fact had to not session samples for a day or so, and that sort of delayed things.
You know, again, we're usually conservative with these estimates, so we came in above these numbers, but we just wanted to give you sort of a benchmark to work from. We saw strong oncology momentum. Greater than 25% of oncologists used Signatera in the fourth quarter. We now have 39 peer-reviewed publications. We got Medicare coverage for muscle-invasive bladder cancer this year, or in 2022. That was the fourth coverage decision for Signatera. We published a landmark SMART 22q deletion study, and we got ACMG guidelines for 22q. We published 12 papers in organ health last year, including the heart and lung validation studies and including Trifecta, which is the largest prospective multi-site fully biopsy match study ever performed in the field of donor-derived cell-free DNA testing in kidney.
Now we're in a great position to scale, and we have big potential catalysts that will provide a lot of momentum as we move forward. Looking at volume, as I mentioned, we've seen excellent growth in volume, and this is coming across all areas of the business. We're seeing record volumes in each of the business units. The growth is now being particularly driven by oncology and the rapid uptake of Signatera. We were really pleased to come in now significantly above 190,000 units. You know, as I mentioned, though, we did have that flood impacting our operations at the end of the year. We were pleased to see significantly more than 25% of oncologists using Signatera in the fourth quarter. Interestingly, we're seeing, you know, very strong support in the academic centers as well.
In Q4, greater than 90% of the NCCN academic centers and greater than 87% of the NCI academic centers use Signatera in their practice. We think that's pretty impressive, as well as the uptick now significantly above 25% of oncologists using Signatera. Q4 again was particularly strong. We saw the highest number ever of new patients coming in using Signatera, the highest number ever, a record of recurrent patients, and the most physicians using Signatera that we've ever seen in a quarter. Again, very strong momentum. Now I want to take a step back and look at women's health. You know, one of the great news stories at the end of the year was the ACMG coverage of 22q.
22q is a very common condition that has a very significant clinical utility behind screening. When you compare the incidence of the disease to other diseases that ACOG recommends, it's actually exceptionally common. Short, or just second behind trisomy 21, 22q is the most common genetic disease that's recommended by ACOG. It's more common than cystic fibrosis, it's more common than trisomy 13 and 18, and it's more common than SMA testing. When you look at the clinical utility, this is one of the leading causes of congenital heart defects. It's also one of the leading causes of inherited schizophrenia. Patients that are born with this disease are very difficult to diagnose. In fact, the average diagnosis time is about 4.7 years.
Interestingly, treatment with calcium at birth can prevent seizures and brain damage caused from hypocalcemia. There's a very strong intervention that can take place to help improve the lives of these children. It's for those reasons, in addition to the performance of the test in the Smart Study, that ACMG has come out and issued a positive guideline. You can see their recommendation. ACMG suggests that an non-invasive prenatal screening for 22q11.2 deletion be offered to all pregnant patients. We think this is a great move in the right direction by the societies. You know, we were, again, very pleased with the performance of the test in the Smart Study. We saw high incidence, about 1 in 1,500.
We saw very high sensitivity, 83% overall clinical sensitivity, that's for all 22q microdeletions, including those that are below 2.5 Mb. When a lot of groups talk about the performance data, they're talking about only those microdeletions above 2.5 Mb. We're including all microdeletions, all 22q microdeletions in that 83%. When you look at those just above 2.5 Mb, our sensitivity was actually greater than 99%. The specificity was also very high, leading to a positive predictive value of greater than 50%. If you look at historical screening tests like the Quad Screen, or first trimester screening, the biochemical screens for Down syndrome, they generally have a positive predictive value in the range of 3%-5%.
We're talking about orders of magnitude better than the historically accepted positive predictive values for screening tests. We look forward to seeing what happens as the year goes on with other societies. Now I'm gonna move into organ health. We think there's a significant opportunity in both the transplant setting and the chronic kidney disease setting. When you look in the field of transplantation in donor-derived cell-free DNA, we think there's about 1.2 million tests per year as the total available opportunity. We think that's only about 10%-15% penetrated. We have validated tests that perform very well on market today across all three of these indications.
When you look on the right-hand side, screening in the chronic kidney disease setting, this is a very under-penetrated opportunity, and we think as time goes on, this could end up being one of the biggest opportunities out there. About 10% of the population today in the United States is diagnosed with chronic kidney disease. There's been studies in The New England Journal of Medicine that show roughly around 10% or more of those patients actually have a genetic etiology. It's been suggested that when a patient is diagnosed with a genetic etiology, that more than 50% of the time, there's an intervention that can be taken. These are the types of statistics that I think set up nicely for very high clinical utility, very positive use case for genetic screening. Now, a couple of key happenings in organ health.
The first is Prospera. Heart has now or the category of testing donor-derived cell-free DNA testing has now been included in the ISHLT guidelines with a Class one, level B recommendation. We think this could pave the way for us to get both Medicare coverage and commercial payer coverage and see an increase in the TAM. Couple things to look out for in 2023 are two big studies that are coming out that are already completed enrollment. The first is the DTRT study. This was an NIH-funded seven-year multi-site prospective trial in the field of donor-derived heart testing that has more than 2,000 plasma time points. The results are in. They're being looked at by an independent third party right now who's leading the publication.
We expect that to be out in the first half of 2023. This will be one of the most significant papers that's ever been published in the field. If you look on the right, I talked about chronic kidney disease testing. The RenaCARE study, which was a multi-site prospective study that looks at the clinical utility of testing patients with chronic kidney disease, using a multi-gene panel. The results for that are also in. The paper is being written and is gonna be submitted in Q1. We think this could be a very impactful study as well that could open up that opportunity that I shared previously. Now moving on to oncology. A lot of our growth is coming from colorectal cancer.
If you recall, we think there's an estimated opportunity there of greater than 1 million tests per year. There's two primary indications. The first is adjuvant treatment decision-making. Is the patient MRD positive, yes or no? Should we treat that patient with adjuvant chemotherapy? Then the second is recurrence monitoring. Today, you know, the doctors may use CT scans or CEA, unfortunately, 85% of patients that recur are diagnosed too late for the physician to do a surgical intervention.
We think with Signatera and doing longitudinal monitoring, we can identify these patients, early and allow the physician to intervene and potentially save the patient's life. We've supported the use in Signatera in colorectal cancer with multiple peer-reviewed papers, but one of the most exciting is the CIRCULATE study that was presented at ASCO in GI in early 2022, about a year ago now. That was the first 1,000 patients enrolled in the study with 12 months of follow-up, and what we saw was excellent prognostic data. Very high disease-free survival rates for patients that were MRD negative, disease-free survival rates in the 50s for patients that were MRD positive. A good distribution there between the two cohorts of patients.
Very high hazard ratio of 13.3, and then the sensitivity from a single time point taken 30 days post-surgery was 67%. We were able to identify from one time point patients that would later go on to recur. If you do longitudinal monitoring of multiple time points, the sensitivity gets up above 90%, but this is just from that one single time point after surgery. What was even more exciting was not just the prognostic data, but it was the predictive data, and this was really the first time the predictive data had been shown. If you're positive, what does that mean for your care? Should you get chemotherapy or not? If you're negative, what does that mean? Will you benefit from chemotherapy?
What we were able to show is that patients that were MRD positive benefit from adjuvant chemotherapy, and patients that are MRD negative, in fact, don't benefit from adjuvant chemotherapy. We also were able to show that clearance of ctDNA was predictive of treatment efficacy. These are big findings, and what we're really excited about is that the study has continued to advance, and now the 18-month follow-up on these patients has been packaged and submitted for peer review, and it's now been accepted by Nature Medicine, and we think that will be published shortly, potentially as soon as this month. That could be a key opportunity to open up the next leg of growth in colorectal cancer testing and potentially an opportunity to submit that paper to the NCCN guideline committees and to commercial payers.
We've seen the consistent results across all different tumor types now at this stage, colorectal, breast, bladder, lung, but we've continued to validate now, you can see on the right-hand side, multiple different tumor types that we've tested Signatera in, melanoma, multiple myeloma, gastrointestinal, head and neck, pancreatic, ovarian, and they're all showing the same things. If you're MRD positive, you're destined to recur with a very high positive predictive value, and if you're MRD negative, your disease-free survival is going to be much better than it is if you're MRD positive. Our peer-reviewed publications continue to go along at a very high clip. We now have 39 peer-reviewed publications.
One of the things that we're most excited about, and we showed this slide, I think, on the Q3 earnings call, at that time, we said in the next 6 months, we're gonna have 7 additional peer-reviewed papers that have more than 500 plasma time points. To my knowledge, no other company has published even 1 paper that has 500 plasma time points in the MRD setting. We're gonna have 7 that are published, at that time, we said in the next publisher accepted in the next 6 months. Now we're executing on that. We've now had gastroesophageal, which is the fifth largest cancer type in the United States, accepted and published with 940 plasma time points. We just had our anal cancer paper published with more than 800 plasma time points. We've had the CIRCULATE-Galaxy study with 7,000 + time points accepted.
We've had our melanoma study with greater than 500 time points accepted, and we still have 4 additional studies across colorectal, breast, and pancreatic that we're waiting to have accepted. This level of data really has served to build, I think, a very strong foundation for us to go get Medicare coverage, and to get support from physicians and committees. When you look at our current coverage position, we have coverage from Medicare for what we believe represents about 2.3 million tests per year. You can see the expanded future opportunity is up to about 13 million tests per year.
As we start to submit for gastroesophageal, for breast, for lung, for some of these other indications like melanoma, we're gonna start to be able to tap into that additional opportunity as we further penetrate colorectal and, you know, get more than the current share that we have there today. We're also expanding the opportunity, and we can do that without validating a new test every time we go and do a new indication. It's the same test, it's the same protocol. It's validated now in a pan-cancer opportunity, and we just run the same test. It doesn't matter what your tumor type is. I wanna just take a step back at oncology and kind of summarize what we think are the key strengths, but also the key investments that we've made.
We've invested an enormous amount to get to where we are today, and we've built a huge moat around the product and around the opportunity. The first is on the commercial side. We have a very large pan-cancer sales team, customer service team, and medical affairs team. In fact, more than 350 people across those departments are dedicated in oncology, and that's already built into our operating expense. Calling on community oncologists in academia. We're now accepting pan-cancer testing coming in ahead of reimbursement. Now, that's costly for us to do because generally the insurance companies aren't paying for those tests, but, you know, we think it's important to generate evidence to help move the market forward. We've done excellent executing our market access and reimbursement strategy, now with four different coverage decisions.
We think this year we're gonna submit an additional four tumor types to Medicare, and we're gonna see the first commercial reimbursement decisions for Signatera. We've executed a very strong user experience, and we've built scale. We have mobile phlebotomy capabilities. Physician portals were integrated, pre-installed on all of the Epic systems when people upgrade to the new software. We put extensive investments into COGS, into scaling up and building the lab. As I mentioned, we now have, you know, more than 75 customer service people that are dedicated to the field of oncology. The type of scale investment that we made is very significant, I think hard to replicate for somebody new coming in. Now, most importantly, our data leadership. 39 peer-reviewed publications now for Signatera is unprecedented, but that's just the beginning.
We have more than 100 clinical trials and datasets that we're working through that we're gonna be reading out over the next couple of years, including some of the most significant trials ever to be done in the field. We're not stopping just where we are today. We're working on improvements to the Signatera technology, and we're also working on a portfolio of tests that are gonna surround Signatera so that when we put our big commercial team to work, they're not just selling Signatera, they're selling the additional content as well that surrounds that. Two quick things as I know I'm 1 minute over here. In addition to our investments that we've made in our direct team, we're also pleased to announce our partnership with Foundation Medicine. We think this is a great opportunity.
Many of you know, they're building a FoundationOne or Tracker off of the FoundationOne CDx, so there's no need to really do the whole exome sequencing. They're just building it off the comprehensive genomic profiling that they're already running today. They have a significant base of installed patients that, you know, as soon as we move into full launch, we're in pilot launch right now in the clinical setting, we can just flip the switch and run Foundation Tracker for any patient that has historically gotten FoundationOne CDx or that perspectively gets FoundationOne CDx. It's now fully available. It's no longer in pilot mode in the IUO setting, so for prospective pharma studies. We're looking forward to continuing this partnership. They've been a great partnership.
We submitted to MolDX off the strength of two peer review papers that have already been published. There's a lot more data coming. Finally, I just wanna summarize. You know, today, we have established products with strong market position. Unmet clinical needs are being met with our products. We have strong volumes, excellent ramp coming out of 2022. We have a leadership position in peer review data. We built and made a major investment into the commercial team. Now we're at peak levels of spending in R&D and commercial and operating expenses. We don't have to increase that in order to meet the goals. We can keep our operating expenses flat and go out and grow the volume on top of this on our path to getting to cash flow break even.
In the future, we have big catalysts coming, microdeletions guidelines, NCCN guidelines, commercial payer coverage, additional MolDX coverage opportunities. We're investing in COGS and scalability while we keep our operating expenses flat, so we can get on a path to cash flow break even in the range that we described previously. With that, I'll open it up for Q&A. Thank you.
Sure.
Thank you, Steve, for the great overview. Definitely a lot to look forward to in 2023.
Thanks.
Perhaps we can start with, you know, 4Q volume trends. You obviously announced very solid numbers and very robust trends for Signatera volume as well. Maybe talk about, you know, what surprised you to the upside, and give us an update on the current mix, you know, between covered and non-covered indications and, any notable pieces to call out?
Yeah, I mean, look, I think to be where we are in the launch and to be seeing this level of support from both community and academic physicians in the ordering patterns, I think is really unprecedented. you know, as we mentioned now in Q4, significantly more than 25% of oncologists use Signatera. 90% of NCCN academic centers use Signatera, and more than 87% of NCI academic centers use Signatera. you know, that I think bodes very well for where the technology is going, both from a utilization standpoint and from a guideline standpoint in the future. Colorectal is just the beginning, though, as you saw on the slide. it's only making up, you know, slightly less than one-tenth of the overall opportunity long term.
We think we're just getting started, and we're gonna continue to see very strong momentum.
How much of your current Signatera volume today is, you know, covered versus non-covered? You know, non-cover, how much is the colorectal.
Yeah. Today we have coverage in colorectal from Medicare. We have coverage for muscle-invasive bladder cancer, and we have coverage for immunotherapy monitoring. We're seeing utilization in other tumor types outside of those, and we're also seeing utilization from commercially insured patients. If you consider those as sort of covered, you know, I think together those make up, you know, probably in the range of, you know, 75% of the orders or something of that, in that range.
Gotcha. You recently noted, you know, the trend that, you know, Signatera volume growth in non-covered indications is kind of outpacing the growth in colorectal. Help us understand some of the dynamics that's going on there, because, you know, theoretically, we could think that, you know, it should be relatively easier to push your CRC utilization.
Yeah.
volume 'cause, you know, it is, you know, the beachhead indication, the most established in terms of data and reimbursement, et cetera.
Yeah.
Like, how much of that is driven by your intentional strategic choice to, you know, establish a footprint with as many accounts as possible, and then you can cultivate these physicians over time versus, you know, how much of that is purely driven by, you know, end market demand?
Yeah. You know, I would say now at this stage right now, we're seeing consistent growth in colorectal in covered indications as well as non-covered indications. I think when we first enabled the kind of broader pan-cancer offering, we saw an uptick, but that's now normalized and we're seeing, you know, solid increases in colorectal, you know, record quarters every quarter basically, along with now muscle-invasive bladder really starting to tick up and continued success in IO. In fact, I would say, you know, rather than focusing on the non-covered indications, we're actually going the other way.
I think we've established ordering patterns for some of these non-covered indications, but we're putting our sales team's effort on the covered indications, and we think that's the right path forward. As things get covered by Medicare, we're gonna open those up. You know, we're not rejecting samples, but we're not incentivizing our sales reps to go out and kind of focus on non-covered indications.
Gotcha.
Yeah.
Between the sales force focus and your expanding indications, we should see the mix of covered better.
Yeah. The mix will be, I think, relatively stable and as things open up. You know, for example, if we got breast coverage, you know, we'll start to see that kind of increase, you know, relatively speaking with respect to the broader book.
Gotcha. Can you remind us when the next NCCN guideline meeting is taking place?
We're waiting for the 2023 schedule to come out. In fact, we still don't have the results of the 2022 meeting that took place in August. Like we've said before, we think it's pretty unlikely that they've included Signatera into that guideline just based on the fact that the Circulate study wasn't published at the time that they held the meeting. We still think the Circulate publication could be a big upside opportunity for us and look forward to that coming. I think it's possible that could get published this month. We're gonna have to wait and see. You know, what we look forward to seeing the NCCN calendar as it's released for 2023.
You're pretty confident that with what you have by now, you know, It should happen with pretty high certainty?
I mean, you know, look, When you look at the paper when it comes out, it's a very strong paper. That combined with the DYNAMIC trial, which was the randomized trial out of Australia, I think is, you know, a very strong position for MRD testing.
Mm-hmm. Is it still your expectation that when the guideline comes, it'll endorse MRD testing in adjuvant therapy escalation only, or will we see, you know, guideline for both escalation and de-escalation? How much of the addressable volume falls into each category?
You know, I think, you know, when you look across our data, I think it's been very strong in adjuvant, for both escalation, de-escalation, and then also in the longitudinal monitoring where we're looking at, early detection of, or detection of cancer recurrence. You know, I think from what we found, you know, historically, physicians making a decision to not do something, you know, that they're used to doing is always a little bit of higher bar, versus them, you know, maybe making a decision to do something, when they're, you know, otherwise uncertain. I do think that there's a higher bar for de-escalation. I mean, the results that we've seen have been really solid across all different indications.
you know, I think we just have to kind of wait and see how things pan out. We'll go from there.
Great. I'll pause briefly to see if there are any questions from the audience. All right, let's continue on with Signatera. You recently discussed potential plans to develop IVD kits for Signatera. In the meantime, you know, one of your peers recently decided to exit the IVD strategy.
Right.
You know, help us think through the rationale there. You know, do you think the market is ready to embrace a more, you know, decentralized model?
Yeah.
Like, are you ready to lock down the technology in terms of performance and everything despite, you know, the evolving competitive landscape?
I think this was an area of confusion actually. When we said IVD, we didn't necessarily mean distributed kits. In order to run interventional trials like the CIRCULATE-US study, for example, you have to have a certain regulatory threshold. In order to do companion diagnostic partnerships and do some of the bigger trials, the Phase III clinical studies that we've announced in breast cancer that will open up that opportunity to treat patients on molecular recurrence, you have to have a CDX level regulatory status. you know, when we said, "Look, we're going for IVD," that's no different than, you know, Guardant360 CDx being FDA approved or FoundationOne CDx being FDA approved. It's that same regulatory status that we're going with Signatera.
We're not planning on doing a kitted strategy, to bring Signatera, you know, around the world at this time, although that's something, you know, that we are open to, in the future. I think for right now, you know, we're focusing on driving, the CLIA lab volume in addition to this sort of IVD-level regulatory volume out of our existing lab.
Got it. That's helpful clarification.
Yeah.
A couple follow-ups. one is, how should we think about the timeline?
Yeah.
on the IVD front? Number two is, how do you balance kind of, you know, this, need to get IVD to get
into more, you know, companion and pharmaclinical trials versus the flexibility to continuously, you know, iterate on your product because, you know, your competitors are also, you know, continuously evolving their panels for higher-. Yeah.
sensitivities and
Solomon, do you wanna talk about that a little bit?
Sure. Solomon Moshkevich, general manager, oncology for Natera. In terms of timing, which is your first question, that's gonna be driven largely by the companion diagnostic roadmap that's laid out by our pharma partners. We've got several trials that we've announced previously, and were on the, on the board when Steve was presenting, specifically the IMvigor011 trial in partnership with Genentech, that's in muscle-invasive bladder cancer, and the ZEST trial, in partnership with GlaxoSmithKline in triple negative breast cancer and BRCA mutant HR positive breast cancer. As those trials get close to reading out, and our pharma partners get close to submitting to the FDA for approval of the drugs in MRD positive patients, we would submit alongside them.
I would suggest you talk to Genentech and to GSK about how those trials are going. We're very pleased and we're heavily invested in making those trials successful. If they're successful, that opens up a significant new reimbursed indication, presumably with level one guidelines, recommendations for patients to get Signatera testing if they could fit into the current inclusion criteria of the trial, and full commercial and government, payer coverage as well. That's a very important approach and we're, you know, we have a pipeline full of other studies of that nature, in other indications. How do we balance that against innovation?
What we see is that the current Signatera product, which is supporting those trials, is actually nearing a pretty good level of maturity where we feel comfortable having run the thousands and thousands of tests that we've described, and we've learned a lot. We've made over 100 improvements to the assay, and we are ready to lock that down and take that through the FDA, as a single site PMA, or 510K if the FDA sees it that way. At the same time, we can continue to innovate on our LDT assay, and stay on the cutting edge there as well.
Gotcha. Just dovetailing on that, you know, how are you thinking about, you know, what's your latest thinking on tumor-informed versus tumor naive? I think we can all see that, you know, so far you guys have, you know, gotten a lot of success and traction with a tumor-informed approach. Do you see the landscape, you know, staying the same or maybe, you know, changing a bit going forward as, you know, tumor naive approaches, you know, they have broader panels and.
Yeah, I mean, I look, I think, we're really focused on delivering the, to the doctor what the doctor wants and, you know, that we're gonna stay focused on that. I think so far what we've seen is tumor-informed is being accepted, you know, very nicely. And we're continuing to see record growth numbers. We're excited about innovation on Signatera and innovation in the oncology portfolio overall. If you look at the history of Natera, one of the things that's driven our success is continued innovation and continued improvements to the performance of the test and continued additional content. I think we're on, like, the ninth version of Panorama, something like that now, if you look back at the prenatal test. You know, we've got a lot of cool stuff that's coming.
We generally, you know, don't talk about it until it comes out, but, there's a lot of cool stuff coming on Signatera.
Sounds great.
Yeah.
On cancer screening program, I know it's still early, but you guys are planning to share some early validation data this year. Is that right? Could you maybe give us a sneak peek of the underlying technology? Is it based on ctDNA only? Is it based on methylation or maybe multi-omics?
Yeah.
What kind of performance advantage can that potentially, you know?
I mean, we, you know, we really don't have any, as I think we've said before, like, we have a very limited investment on early cancer detection, probably like $5 million in the range of that per year. I mean, it's, although we're seeing great technology improvements and we hope to be able to put out case-controlled data this year, the investment's very small.
Mm-hmm.
We don't have any updates right now versus what we said, you know, previously. You know, I'll just point people back to kind of what was said before. I'm excited about it. I think the early data that we're seeing is very strong, but it's a very low investment.
Gotcha.
Yeah.
I mean, as you think about or as you make the decision of whether or not to, you know, continue to maintain investment at a modest level versus, you know, stepping it up and pushing full force, what kind of data or performance bar do you need to see to kind of gonna make that trigger?
Yeah. I think, I think when we get the results of our sort of early case control study, I think at that point we're gonna kinda have a better feeling about whether we should be, you know, pushing forward in a more significant way or not. We're gonna do that in a way that I think makes sense, where if we move forward and fund additional investments, it's gonna be obvious to everybody that that was the right decision. For right now, our strategy is very low investment, you know, in the $5 million range, you know, and we think that's the right approach.
Gotcha.
Yeah.
Any questions from the audience? All right, let's maybe move on to women's health. Great to see the ACMG guideline endorsement. What's your latest thinking in terms of ACOG timelines and how quickly payers will follow suit?
Yeah, I think we just have to wait. I mean, I think the meeting is in April. It could come before then or could come after or could not come. You know, I think we feel positive that ACOG has endorsed with a very strong guideline. You know, a lot of the ACOG guideline members in women's health are also ACOG, you know, members, OB geneticists, and are very tuned in to sort of the status of things. You just have to go back and look at the fundamentals. Is it a common disease? Is there a cost-effective way to screen for it? Does it have a high sensitivity, high specificity, high positive predictive value? Is there a clinical intervention?
When you look at all those things, the basic criteria that ACOG and ACMG have outlined, it checks all the boxes. You know, the reason why we did this study in the first place eight years ago was because we know that it takes this type of study in order to move the needle. If guidelines do come out, this will be a good example of us making an investment, doing the right study, taking the long-term approach, and having it ultimately generate guideline and coverage. That's the same model that we're following with Signatera now, with more than 100 different clinical trials that are underway.
it builds a moat, and it makes it, I think, challenging for others, that don't put that level of rigor into the clinical data to come in and launch products successfully.
Mm-hmm. Great. Any updated thoughts on the net potential impact of the California program?
We've actually done very well in California. I think, you know, we've seen, probably, you know, 50% increase in the volume, something in that range in the state of California. If you remember, the state program volume is at a much lower price because they're only purchasing a very small panel of tests. We have a separate product that we sell for the state program in California that's not the Panorama product. You know, I think, you know, most people are aware that there was an injunction that prevented the state from enforcing the program fully. We've been able to continue to offer Panorama. We've seen that volume kind of normalize now, where there's some customers that want the state program, and where they want that, we're able to service that.
There's some customers that want to order Panorama directly, and when the customer wants that, we're able to service that. We have to see how things evolve, but I think, you know, being, you know, in the position that we're in right now, I think is fine, and as things evolve, we'll evolve our strategy.
I mean, you already enjoy, you know, more than 50% of market share in NIPT. Is it fair to assume that, you know, even without a California program, you can still enjoy, you know, significant market share while enjoying a much higher AD?
Yeah. Yeah. I think we think NIPT over the next three years is gonna get up to close to full penetration and, you know, we're in the best position to ride that wave up as things continue to penetrate.
All right. We're out of time. With that, thank you everyone.
Great.
Thank you to the management team.
Thank you.