Welcome, everybody. Thanks for joining us at the Raymond James Institutional Investor Conference. I'm Andrew Cooper. I'm happy to be joined by Natera. We have CFO, Mike Brophy here, who's gonna talk to us a little bit first about just Natera in general, and then we're gonna dive into some Q&A as well. With that, I will just pass it straight to Mike.
Great. Thanks, Andrew. Appreciate the time and being here today. I'm just gonna do a couple of kind of basic kind of intro slides here. Natera is a leader in cell-free DNA technology. The first major product launch that we initiated was back in 2013. We launched our Panorama non-invasive prenatal diagnostic test, non-invasive prenatal test. That was a purpose-built test that utilizes a very flexible and sensitive PCR-based chemistry paired with a suite of algorithms that delivered really excellent performance in screening for fetal aneuploidies for NIPT. When we launched that product, we actually were fourth to market, and it was like a little startup, and it was up against some very large, deep-pocketed competitors.
Fast-forward to 2015, we kind of rocketed to the number one position in that market with about 1/3 of the market share and probably 600,000 or 700,000 women in the United States getting an NIPT at that point. Fast-forward to today, there's probably something like 2 million pregnant women that get an NIPT out of about 4 million pregnancies in the U.S. every day. We estimate that we've got about 55% market share, despite the fact that this has been an incredibly competitive area of molecular diagnostics, as many of you know. We've now kind of taken that core technology, and we've continued to hone and improve it in the pursuit of an ever better non-invasive prenatal test.
Now we've been able to leverage that same exact core technology in a couple of different other unmet needs within healthcare. In 2020, you see we've kinda branched out, we've launched in a couple of complete new areas, one in our organ health. We offer a test called Prospera, which is a kidney transplant rejection screening test. The concept there with Prospera is a kidney transplant recipient receives a kidney. The number 1 thing that you're worried about with a kidney transplant recipient is that their immune system is going to reject that kidney. Okay? Sometimes it's hard to tell if the patient post-transplant is just feeling green because they've just got a kidney transplant or if they're experiencing an acute rejection.
Historically, the standard of care there has been to intervene, including and up to a biopsy. You get, like, a large bore needle, stick into the kidney that you just transplanted. This is precious tissue, pull some out, and you biopsy that tissue to see how the organ is faring. Now what's available is a very sensitive and flexible plasma test that can give you a readout on the graft health non-invasively. A lot of overlap technologically between what we built for NIPT, and then we're able to leverage that in organ health. The next product that we launched was in oncology. We created an entirely new category of cancer care in minimal residual disease and recurrence and monitoring of cancer with our Signatera product.
The next slide is just like a snapshot of kind of the core products here in the first column here, Panorama, Signatera, and Prospera. You'll see a range of additional products that we've been able to launch that kind of wrap around that core product. They're often offered in the same call point and often offered to the patient at the same time as they're kind of getting this offering here on the left-hand side. That makes a huge difference for patients to be able to get additional information about their, about their healthcare situation, whether they be, you know, in the prenatal space, oncology, or the transplant setting.
For example, in the prenatal health setting, at the same time that you go in and you get a blood draw for the Panorama test, we can also take some tubes of blood, and we can run this Horizon carrier screening panel that screens mom to see if mom is a carrier for a range of inherited disorders, like for example, cystic fibrosis or Duchenne muscular dystrophy or so on and so forth. We offer kind of single gene carrier screening panels all the way up to 270 gene carrier screening panels. Now, you know, we launched that test as an ancillary offering to the NIPT.
Now fast-forward, you know, eight years later, for every 100 NIPTs that we offer, we also get orders back in for about you know, 45 or 50 carrier screening tests as well. As the NIPT market continues to penetrate, so too does our opportunity to serve patients with this carrier screening test. It's a similar kind of model as we've kind of replicated across the across these different call points. This is just a snapshot of kind of the recent progress in the business from 2017 to now in terms of total volumes. You've seen that things have really accelerated here. The revenue slide looks very similar to this.
This has been very much kind of up and to the right as we've experienced rapid growth in all three of these areas. I mentioned kind of the trajectory that we've seen in the women's health space, and that's now been added to by both the organ health space and especially Signatera in the cancer space. It's not just this kind of core technology that's driven all that success. One, we have had this kind of leading edge technology and a constant focus on innovation in these products, and we've just been able to stay in the lead in terms of our technology. We've been able to prove that out by having a very, very centered focus on delivering what we perceive as best-in-class clinical trial data. I'll give you one example in the women's health space.
Last year, we read out a five year, 20,000-patient prospective clinical trial to demonstrate our performance in detecting the 22q microdeletion with pregnant women. This is a test that is very broadly ordered within our prenatal health clients. No one had ever kind of prospectively characterized the incidence of 22q in the population. We were able to kind of really break new ground there. I think that data puts us in good standing for potential guideline inclusion for screening of 22q, just as an example. Let's skip forward here. I think the other two pieces I'll take kind of together. One is, you know, broad and talented commercial teams, and the other is just an extreme focus on user experiencing and the customer's experience, both patient and physician.
Our CEO, Steve Chapman, was actually the first commercial employee that was ever hired here at Natera back in 2013. He joined Natera after a very successful run at one of the first molecular diagnostics companies to ever exist, in Genzyme Genetics. Some of you guys may remember Henri Termeer kind of setting the stage with Genzyme Genetics and Genzyme more generally. Steve joined the company when this was a IVF, in vitro fertilization diagnostics business, led the launch of the Panorama product, and over the last, you know, 10- 12 years has built up a cadre of commercial leaders that have just demonstrated over time this type of commercial execution quarter-on-quarter, year-over-year.
We've kind of developed a way of going to market where we really focus first on the customer, and then we really kind of drive excellence in our responsiveness to what the customers need. Okay, good. I previewed this in terms of just our extreme focus on, you know, on data generation. We're very proud of this study. This is the SMART publication that came out last year. Partially, you know, in response to that study, you see new guideline inclusions happening already. More recently, within the last, you know, couple of months, we saw the American College of Medical Genetics and Genomics come out with a very, very fulsome recommendation in favor of 22q11.2 deletion syndrome screening for all patients.
It was a very strong recommendation, and we're hopeful that, you know, we may be able to get an ACOG recommendation, American College of Obstetricians and Gynecologists, recommendation as well. Similarly, we've been able to generate data in our carrier screening business. We saw, you know, over the last kind of five years, over the life of that product, we've seen a continued drumbeat in favor of coverage for a broad panel carrier screening. This is, you know, in addition to the cystic fibrosis and things like that, you can get a screen for up to, you know, 274 disorders in our case.
There's been a lot of clinical evidence, a lot of support that's been voiced for those broader panel carrier screening tests. Really valuable test to patients, and we just recently got this endorsement from the NSGC. Again, this is something that's a potential catalyst for the business going forward, to get a, you know, broader guideline inclusion for broad panel carrier screening. Okay. Just a quick plug on transplant, just to kind of level set you on the market. I think that the summary here on the left-hand side, you see the transplant test market. You see it's very under-penetrated today.
Really just launching into this space here in the last couple of years have seen a lot of good kind of sequential traction in the business and been able to help a lot of patients here. On the right-hand side, you know, this is an example of, you know, adding these additional products to our call points, you know, when we launched kind of the core technology. We've got a test called Renasight that's similar to carrier screening in the women's health space, will screen people who are suffering from CKD to see if they have the pathogenic mutation that's actually causing their CKD. Significant percentage of those patients who suffer from chronic kidney disease actually suffer from it because they have a pathogenic mutation, and knowing that has implications for how those patients are cared for.
We've developed this panel. We're gonna be reading out a large prospective data set, supporting the clinical utility of this panel, in clinical practice later this year. Just another, hopefully, you know, another case study and example of our core strategy. Okay, good. I'm gonna spend a couple slides on oncology. This is just the trajectory and the volumes of our Signatera business since we launched back in 2019. You see now we're, you know, 2022, we recently announced that we did almost 200,000 Signatera tests in 2022. Obviously very, very rapid trajectory here. We now estimate that more than 30% of oncologists in the United States are ordering Signatera, up from zero just a few years ago.
This was, you know, this is a technology and a market that we created here at Natera. I think, over time, we've demonstrated, one, that the test works kind of on a technical basis. Two, that there's enormous clinical utility. Three, that payers want to reimburse for this test. Finally, most importantly, doctors and patients desperately, you know, need this test. This is a large unmet need, and you can see the trajectory there. Recent example of a big win we saw on the data side was, we just got the 18 month prospective readout of our CIRCULATE study in colorectal cancer. I'm just gonna give you just an example of just how Signatera works, and use colorectal cancer as the example.
This example, I think, pertains pretty broadly to most solid tumor types. If you have colorectal cancer, it's a very dangerous disease. You go in, like, that afternoon or as quickly as you can, and you have a surgery to have the tumor removed. That surgery is quite good. Something like two-thirds of people are cured by the surgery. You know, you had a colon in your tumor, you had the tumor removed, and you're now cancer-free. The remaining 1/3 of patients are going to have a remission of their cancer or a relapse of their cancer post-surgery, and it's very hard to tell who is who immediately post-surgery, okay?
The standard of care is if your tumor is graded out in kind of mid-stage II or stage III or higher, then you're indicated for chemotherapy post-surgery, okay. Even though payers, patients, and physicians all know that a large majority of those patients have been effectively treated by the surgery, they're still going on to chemotherapy, okay. What ends up happening is a very inefficient triaging of these patients. You have, like, a large set of patients who are indicated for the chemotherapy. The physician would prefer that they go on and do their chemotherapy, but the patients, you know, has, like, kids or a job or they're not tolerating their chemotherapy. They know the odds are in their favor because the surgery is quite good, and they drop out of chemotherapy.
Physician would prefer to keep them on, it's hard to keep everyone on. It's hard to give chemotherapy as a doctor, people want to watch and wait. You have people that kind of against the physician's preferences end up kind of de-escalating and watching and waiting. This is where Signatera comes in. Go have your surgery like you normally would. Go home and rest for a month like you normally would post-surgery. In that intervening time period, we're gonna take a slide of the tumor tissue from your path lab. We're gonna run an exome on that tumor, which is just a survey of the 20,000 genes or so that actually code for proteins in your genome.
It's kinda like flying like a small airplane over a small town and kind of mapping that small town. What we're mapping are the variants in that tumor, okay? As a general matter, tumor DNA is highly aberrant relative to healthy tissue DNA. The variants that are the most common in my tumor are gonna be different than the variants that are most common in Andrew's tumor, okay? It's a little bit like a thumbprint. What we do is we just get the list of those most common variants, and using this same cell-free DNA technology that we've been honing for the last decade plus, we build for each individual patient a DNA base that is tailored to track the variants in their tumor, specifically tailored to their tumor, okay? Come on back a month later like you normally would.
Get us a blood test. FedEx that blood to us in our lab in Austin, Texas, we'll run a plasma test on that blood that you gave us. If a month after your surgery, using this sensitive assay, we're able to detect cell-free DNA from your tumor still in your bloodstream, those folks are relapsing an overwhelmingly high % of the time. Even though the tumor may or may not be visible, usually it's not still visible, you still have plasma, you still have tumor DNA still in your bloodstream, you're very likely to have a relapse.
The reverse has also been largely true, that if using this assay that's been tailored for your tumor, we can't find any evidence of cell-free DNA from the tumor, you're most likely you're in the category where you can at least afford to watch and wait. This data is very important because this is 18 month prospective data off of the strength of one plasma time point post-surgery, okay? These patients came in, they got their surgery as I described. Some were positive, some were negative. The positive patients, it was roughly 50/50 in this arm, you know, went on to chemotherapy and the other half didn't. For the patients that were positive for Signatera, saying, you know, we think they're gonna relapse, Signatera says they really need to get their chemotherapy, those people had a statistically significant benefit from chemotherapy.
The reverse was also true, where there was basically no DFS, there was no significant disease-free survival benefit for Signatera negative patients to go on and get their chemotherapy. This, this prospective data reinforces the data that we've been able to show in different tumor types over time. We've been able to really have a significant triaging of these patients, between those who are going to have a relapse and those who are not, okay? This data was on the cover of Nature Medicine, here this year, which we're very excited about. This plus other data sets that we've been producing, we think will ultimately support, you know, guideline inclusion in the NCCN guidelines for colorectal cancer treatment. Okay, good.
Another recent win that we had is Medicare decided to award a coverage decision in favor of Signatera for breast cancer. This is breast cancer patients in the adjuvant setting, phase II-B and higher are now covered by Medicare. Within our mix of our Signatera volumes, about 15% of our volumes are breast cancer patients, okay? This kind of speaks to the pan-cancer nature of Signatera in that even though our focus in terms of the education to physicians has been in these GI cancers like CRC, because breast cancer is such a common cancer, we're seeing these breast cancer patients come in for Signatera.
The test works perfectly well for breast cancer as well as any other tumor type because again, I'm agnostic to the tumor type. What I'm focused on are the specific variants in that individual's tumor. Okay. Even without, you know, a significant push from us, we already have a significant minority of our volume is breast cancer volume, this is an enormous win for us, important beachhead for reimbursement in breast cancer. Okay, good. I'm just gonna do a couple more financial slides, and I swear I'll quit talking. I'll let Andrew talk. He's a handsome guy. I wanna get him up here. On the revenue line, we guided $980 million-$1 billion in revenues this year.
This implies, you know, roughly 20% growth year-over-year vs. last year. On the bottom line, we're guiding to burn about $300 million-$325 million in cash, which is about $150 million less than what we burned last year. We're kind of on that trajectory to getting to cash flow breakeven. This is the last slide I'll show you. This is just operating expenses on an absolute dollars basis, 2022 vs. our 2023 guidance. You see on an absolute basis, operating expenses are actually gonna decline, and that's because we've kind of reached a solid base where we've got established products in each of these three key areas.
We've got established commercial teams in each of these areas. Now we can continue to drive volume with those established products and teams and actually get a little bit leaner as R&D projects roll off, as clinical trials roll off, and as we get more efficient with our commercial offering. We've actually run this playbook once before, specifically in the women's health call point, where late 2019, I laid out a similar slide for just the women's health effort. We said, "Hey, look, by the middle of 2021, we think the women's health effort will be cash flow generative based on this same kind of math." It's, hey, you've got a very established product.
You've got the clinical trial set, and we're getting increasingly more efficient on the, on, you know, sales and marketing while volumes continue to grow. We met that timeline. By middle of 2021, we were kind of cash flow breakeven in the women's health business. Now it's time to just replicate that same playbook for the overall company, which now incorporates a very large investment in organ health and oncology. That's the strategy, continue to execute with these core products and the core technology and continue to get operating leverage with these commercial teams that we've built. That's it.
Despite your compliment, I promise nobody wants to see or hear me. Happy to be up here.
Yeah.
Maybe just first thinking about, you know, that 30% of oncologists ordering is a really impressive number given sort of how fast this all happened.
Yeah.
As we think about the path forward there, you know, is there something that is a bigger inflection point? Is there, hey, first time you're in NCCN guidelines for something, that's it? What drives kind of that hockey stick that I think is still, you know, potentially on the come?
Yeah, these things are hard to predict. I mean, I would never have predicted that we'd be at this scale this quickly post the launch, not because I didn't think that we could do it just because, you know, one doesn't predict that type of a trajectory. So far, things have, you know, really progressed, you know, really rapidly. I think there are a couple of, you know, data sets, catalysts that can drive, you know, significantly broader adoption. I think you hit on one. I think footnote inclusion in the NCCN guidelines for colorectal cancer would be a good example of that.
I think just getting this data published, this, you know, 18 month prospective clinical trial data published in colorectal cancer is absolutely critical. It's, you know, it's early days, but I'm encouraged about the, you know, the response we've seen from the field here. Breast cancer is maybe the third one that comes to mind, where we really haven't put a, you know, put our shoulder behind an education drive around the data that we do have in breast cancer. Now that we have this important kind of reimbursed area within Medicare, you know, we feel more comfortable doing that. I think there's an opportunity to really drive growth there as well.
Okay, helpful. You know, you mentioned the sort of 15% or so of volume that's breast cancer. You said in the past 60-65 were sort of the previously covered by Medicare indications.
Yeah.
About 80% of the total. How does that trend and how do we think about that in context of, you know, coverage begetting other testing, right? Whether it's an indication that's not covered within breast or it's a different cancer type that's not covered, you know, how do you, how do you plan for that as well in sort of the guidance in the P&L?
Yeah. Well, in the guide, it's really simple. I mean, I don't. We try not to do aspirational guidance as it relates to, like, additional coverage decisions. I mean, I think there's a kind of an organic way for average selling prices within oncology just to increase over time as your mix evolves towards some of these these reimbursed indications.
In terms of, you know, just getting reimbursement in additional tumor types, I really, I still think about that as very specific to the data in that tumor type, and we're very committed to just producing data in a given tumor type, in a given indication, submitting that data, getting it published in the top-tier journals, taking it to Medicare, taking it to the commercial payers, and there's no way to replicate just kind of going down that path, and we've done that now in a very broad range of tumor types.
Great. We only have a few minutes, so maybe I'll make sure we hit on kind of the reproductive health side, the women's health side of the business as well. You know, if we wake up tomorrow and there's a headline, ACOG's changed guidelines for, let's start with carrier screening, expanded carrier screening. You know, how do you think about the impact there on not just the ASP side, 'cause I think that's pretty clear of, hey, if there's coverage, there's coverage.
Yeah.
Potentially the volume and the mix side and what that does to the business.
Yeah, I mean, I think the first thing that comes to mind is, I think it's just incredibly important for prenatal care. I mean, I think the rank and file physicians appreciate the utility of those tests. I think that it would just be kind of matching up with the reality that you're seeing in the field for the use of those tests. I really think about carrier screening tests as coming alongside, like in lockstep with the non-invasive prenatal test. That's, you might think that you'd go get a carrier screening test before conceiving, but as a practical matter. Most people are like me.
My wife and I got our carrier screening test at, you know, when we were, you know, expecting one of our kids, because that's kind of when you're thinking about these things. What I've seen over, you know, since we've launched that product in, you know, 2015 is a ramp that's really been driven by the adoption of NIPT also begets this kind of adoption of, you know, of carrier screening as well.
Okay, helpful. Maybe kind of similar question on microdeletions.
Yeah.
When we think about, you know, the potential for coverage there. When you think about those two in, you know, in conjunction with each other.
Yeah.
How should we be thinking about the cash flow that that women's health business can actually generate?
I mean, I think it can generate a significant amount of cash, just based on the fact that, you know, based on just the leadership position, you know, that we're in there. That's important because if you can't generate cash, you cannot care for patients. You know, you gotta have a path to delivering that. Again, I mean, it's kind of the same answer. I mean, amazingly, you know, if there's 4 million, you know, plus pregnancies in the United States, only 2 million women are getting an NIPT, despite the clear and obvious, data benefits that have been demonstrated in NIPT vs. older technologies that have been around since the 1980s.
There's just a lot of room to run in terms of improving prenatal care in the United States, and we're excited to be part of that.
Maybe tagging on to the back end of that, thinking about that NIPT penetration.
Yeah.
I think you've commented in the past 80%-90% is sort of realistically the goal over some period of time. I think you said about 50% just now.
Yeah.
What's the, you know, maybe what's the mix of folks who aren't doing it?
Yeah.
Meaning are they doing legacy? Are they doing nothing? How do we make that push higher?
Yeah. A lot of people are doing the quad screen, which is I think sometimes there's a misunderstanding that NIPT has kind of heralded this new era of non-invasive prenatal testing or screening, and that's not at all what has happened. Non-invasive prenatal screening has been standard of care in the United States since the 1980s. It's just that people have used this older test that has a 5% positive predictive value, meaning that for 20 positives using the quad screen, there's one true positive. What that meant was that there's a huge amount of volume of follow-up, like amniocentesis being run in the U.S., that volume has really been cut down with the advent of NIPT.
It's hard to explain exactly how do you get to 50%, it's not like 90% the next day, but you see this in other areas. You know, it's just, it's a grind, and it takes time, and you've seen kind of steady evolution toward that kind of broader, you know, broader penetration.
Doctors are stubborn and don't change their practices.
Well, I don't even know if it's about physicians. It's just, you know, it's just one of those things. It's, it can be clinical practices in certain ways. It can be access to care, is critically important. That's something that we try and spend a lot of time on. The number one thing that we try to do is just offer the test very broadly and deliver the data necessary to get people comfortable that the test is safe and effective, and we've tried to do that.
Okay, helpful. We've got just a couple of minutes, so maybe transition a little bit to the P&L.
Yeah.
You know, gross margins, I think is a big topic.
Yeah.
You know, been kind of present, especially in the guide. Maybe talk about kind of the mix perspective and how you plan for kind of this transition and maybe the breakout of margins as best you can between, you know, the three segments.
Yeah, I mean, the gross margins this year, are lower than they have been in years past, and yet the EBIT line was a little better than it has been in years past, and that was on purpose. Okay? We intentionally have taken on a couple of opportunities that are volume-based bets, if you will, or opportunities, where the reimbursement is not where it can be what we think in the relative near term. We think that's gonna change. We're gonna take on some lower margin volume here in 2023, and we think that can turn into something better in 2024 and 2025. Top of mind for me are, you know, the California program for non-invasive prenatal testing. I'm sorry for those who are new.
I didn't have time to kinda get into that. Many labs opted to actually leave the state of California when that program was first launched. Despite the fact that the margins were quite poor initially, Natera and I believe Quest opted to stay in California. We felt like that was one very consistent with our mission, to care for those patients. We're originally a California company, we care a lot about those physicians and those patients. Two, we felt like there was a way forward there to get, you know, to get the program working in a way that companies can economically continue to serve these patients. Well, down the path now with the preliminary injunction on the program. That's step one. Number two, Signatera.
Those gross margins are still dilutive to corporate gross margins. As we've talked about in the past, you know, ASPs in 18 months ago were in the $500s. Now they're in the mid $700s for Signatera Clinical. Cost of goods sold exiting 2022 or in the mid of $500s. Exiting 2023, we'd like to see them in the mid of $400s. That's on scale, and that's on some lab operations, you know, projects that we have launching this year. You kind of see that gross margin kind of getting to the right place. In the interim, we wanna continue driving volume because we've got a ton of momentum, even though that's a little bit dilutive to gross margins this year. You know, the final one was around carrier screening.
Given some of the reimbursement challenges that have been seen in the space, you know, we saw a number of players actually go out of business. Okay? Very high-quality labs going out of business because of that. We wanted to take on that volume. Again, consistent with our mission, we feel like there's great clinical utility for these offerings. We feel like a guideline can come that will help clarify things in terms of reimbursement, in which case, you know, that'd be, you know, very positive for us. These are all things that we did intentionally. In return for that, in order to cover that, we engaged on some tough but I think important kind of cost-cutting to kind of get back to neutral on the EBIT line. You know?
I was gonna ask about that cost-cutting, but we are unfortunately at the end of time, so we'll save it for the breakout.
Yeah.
Down in Amarante day one, I believe.
Okay. Thanks for the time.
Thank you so much.
Yeah, cheers. Yeah.