Ladies and gentlemen, thank you for standing by, and welcome to the Exact Sciences Fourth Quarter 2019 Webcast and Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded.

[Operator Instructions] I would now like to hand the conference over to your speaker today, Megan Jones, Manager, Investor Relations. Thank you, please go ahead..

Thank you, and thank all of you for joining us for Exact Science's fourth quarter 2019 conference call. On the call today or Kevin Conroy, the company's Chairman and CEO; and Jeff Elliott, Our Chief Financial Officer. Exact sciences issued a news release earlier this afternoon, detailing our fourth quarter financial results.

This news release and today's presentation are available on our website at exact sciences.com. During today's call, we will make forward-looking statements based on current expectations. Our actual results may be materially different from such statements.

Reconciliations to GAAP figures are available in our earnings press release, and descriptions of the risks and uncertainties associated with Exact Sciences are included in our SEC filings. Both can be accessed through our website. It is now my pleasure to introduce the company's Chairman and CEO, Kevin Conroy..

Thank you for joining us this afternoon. The Exact Sciences team delivered another strong quarter to end a transformative year. During the quarter, we closed the Genomic Health acquisition. As a combined company, we intend to be the advanced cancer diagnostics leader for years to come.

We helped screen 477,000 people with Cologuard, and tested 41,000 patients with Oncotype, and delivered nearly $350 million in revenue on a combined pro forma basis.

The strong foundation we built for Cologuard and Oncotype, the capabilities of our combined team, and our financial strength will allow us to capture a significant portion of our combined 20 billion total addressable market, and deliver more innovative tests to people in need.

Today, we will review our fourth quarter financial performance and 2020 guidance. We'll also discuss our key accomplishments in 2019 and the path forward for our combined team, starting with their 2020 priorities. Our CFO, Jeff Elliott, will now review our financial results..

Thanks, Kevin. Good afternoon, everyone. My comments will reflect contribution from Genomic Health, starting with the acquisition closed on November 8, rather than for the entire quarter, unless otherwise stated. Total fourth quarter revenue was $296 million and $348 million on a combined pro forma basis.

In our screening business, which primarily includes Cologuard, revenue of $229 million increased 60% on strong Cologuard good volume growth. Average Cologuard revenue per test was $481, slightly above the third quarter level. We expect stable Cologuard revenue per test near term, and continue to see a long-term path to at least $500.

In Precision Oncology, which includes the former Genomic Health business, fourth quarter revenue was $66 million. Standalone Genomic Health revenue for the full fourth quarter would have been $119 million, an increase a 14%. Total fourth quarter gross margin, including amortization of acquired intangibles, was 72%.

Non-GAAP gross margin, which excludes amortization of acquired intangibles, was 76%. Fourth quarter Cologuard cost of sales improved $6 to $123 per completed test, in line with our guidance. Fourth quarter saw additional fixed costs from bringing in our new Cologuard lapa [ph] line to meet growing demand.

We expect to leverage these costs overtime with increased Cologuard volume and lab automation. We're confident in reaching our long-term cost per test goal of $100 or less. Total sales and marketing expense was $120 million, including the Pfizer service fee of $14 million.

G&A expense of $145 million included $53 million in transaction and integration costs related to the Genomic Health acquisition. R&D expense was $43 million. Relative to our guidance for standalone Exact Sciences, sales and marketing G&A and R&D expense were each slightly favorable, helped by timing. Fourth quarter adjusted EBITDA was $10 million.

Our definition of adjusted EBITDA adds back stock based compensation, acquisition and integration costs, and any lost unsettlement of convertible notes. Total fourth quarter CapEx was $34 million, including Genomic Health, bringing the full year to $182 million.

For 2020, expect CapEx of approximately $125 million, weighted slightly to the first half of the year, and including CapEx for the acquired Genomic Health business. We ended the quarter with cash and securities of $324 million. Turning to our 2020 guidance.

Based on underlying strength we're seeing in the business, we're raising our revenue outlook to $1.61 billion to $1.645 billion. This assumes screening revenue of $1.125 billion to $1.15 billion dollars, and Precision Oncology revenue of $485 million to $495 million.

We expect non-GAAP gross margin in the 75% to 76% range, with screening gross margin relatively flat year over year as we work to leverage the new lab, the system's $92 million dollars in amortization have acquired intangibles. In addition to the full year impact of Genomic Health, there are three main drivers of sales and marketing growth in 2020.

We're invested about $45 million in a primary care sales force expansion. We expect about $35 million in additional services fees paid to Pfizer that will see the full year impact of investments made in 2019.

We expect G&A to increase about $100 million, driven by the full-year impact of Genomic Health, the IT investments made in 2019, and additional headcount to support growth. We expect R&D of approximately $200 million, with about 75% of that related to our pipeline.

For the first quarter, we expect revenue of $349 million to $359 million, the system screening revenue of $230 million to $235 million, and Precision Oncology revenue of $119 to $124 million.

We expect first quarter operating expense to increase about $50 million from the fourth quarter, with the full-quarter impact of Genomic Health partially offset by reduction in acquisition integration costs.

We expect total sales and marketing to be around $185 million, including the full-quarter impact of Genomic Health, our premier care sales force additions, and an additional $10 million in Pfizer services fees, compared to the fourth quarter.

We expect total G&A of around $110 million, with a reduction in acquisition and integration costs of about $50 million compared to the fourth quarter, partially offset by the full-quarter impact of Genomic Health, and an increase in headcount to support growth.

We expect total R&D of about $52 million, with growth from the fourth quarter primarily due to the acquisition. As we've indicated over the past year, we don't plan to provide Cologuard or Oncotype test volumes and related metrics going forward. I will now turn the call back to Kevin..

Thanks, Jeff. The Exact Sciences team had three key priorities in 2019. Parrying our partnership with Pfizer, enhancing Cologuard, and advancing our pipeline of blood-based cancer tests. During 2019, we continued laying the groundwork to allow Cologuard to reach at least 40% of the U.S. colorectal cancer screening market from just over 5% today.

Our expanded sales team, innovative and evolving marketing campaign, and growing payer and health system relationships provide the key pieces to support Cologuard growth. Our Pfizer partnership is strong. We're pleased with the effectiveness of our partnership last year, and we expect even greater productivity from our partnership this year.

To support these teams in future growth , we also increased our lab capacity and made our IT system stronger and more flexible. The sales team now has advanced selling tools and capabilities through the Viva customer relationship platform, which we made available in December.

We implemented Epic's world class electronic health record system as the backbone of our IT infrastructure, and improved nearly every other aspect of our IT infrastructure in 2019. The team more than doubled our lab capacity to 7 million tests annually by introducing automation and opening a new lab site in Madison.

We've invested significantly to help establish Cologuard as a new standard of care in colorectal cancer screening. We've created a powerful brand, supported by a large body of clinical evidence, broad physician adoption, and a 1000-person commercial organization.

This will allow Cologuard to dramatically improve colorectal cancer screening rates in the U.S. Our second 2019 priority was to enhance Cologuard, including a label expansion to ages 45 to 49, and an improved version of Cologuard, the FDA-approved Cologuard's label expansion to include these 19 million average risk Americans last year.

This represents an important opportunity to screen people earlier, and to impact the rising incidence of colorectal cancer in younger age groups. Cologuard is a convenient, effective option that fits well with their busy lifestyles.

To increase adoption in this age group, we're enhancing our marketing efforts and working to raise awareness of the need for earlier screening. We also plan to publish results from our prospective study in the 45 to 49 year old age group this year, to further support Cologuard use.

The team also made progress on an enhanced version of Cologuard with the potential to further differentiate it as a frontline screening test. We presented promising data, showing new markers with improved specificity, while maintaining a high level of sensitivity when compared to the current version of Cologuard.

Based on this study, we kicked off a 10,000-patient prospective trial to validate performance. Our third priority was advancing our blood-based cancer diagnostics program. In November, we presented our third data set for our liver cancer test designed for patients with liver disease in need of more accurate and convenient testing options.

These data demonstrated the superior performance of our liver tests compared to the guideline recommended blood test, alfa-fetoprotein, with 80% sensitivity for all stages of liver cancer at 90% specificity.

We plan to make our test available in the second half of this year, with the goal of generating real world evidence to support guideline inclusion, broad reimbursement, and adoption over time.

We look forward to offering our test to the three million total eligible Americans, and demonstrating the power of our pipeline and the strength of this combined team. Exact Sciences is the leading advanced cancer diagnostics company globally.

Our people and infrastructure, combined with our financial strength, will help us extend our leadership in cancer diagnostics in the next decade and beyond.

Our partnership with Mayo Clinic, $200 million R&D budget, and our experienced R&D team of 250 scientists and engineers will allow us to accelerate the availability and growth of new innovative tests to patients in need.

We recently signed agreements to acquire Paradigm and Biomics, another step forward in extending our leadership position in advanced cancer diagnostics. Paradigm and Biomics have exciting DNA sequencing technologies and experienced scientists. Paradigm provides a therapy selection test for late stage cancer patients.

The test recently received a local coverage determination through the MolDX program, and is differentiated by faster turnaround times and a design that requires less sample input. Many patients today don't have access to therapy selection testing because it takes too long or there's not enough DNA in the sample to obtain a valid result.

This information is critical to support treatment decisions, and the Paradigm test will allow us to provide smarter, faster answers to more patients. Today, the Paradigm test is a tissue-based test. In the future, we plan to make available a blood-based version.

Over time, our Precision Oncology sales team will offer advanced cancer tests like these to patients and oncologists who need them, expanding our total addressable market by about four billion globally. Biomics, a team we've collaborated with for years, provides critical sequencing and biomarker discovery capabilities.

We've worked with Biomics in the past to identify unique markers we plan to use in pipeline tests. This talented team will bring additional resources to our world-class R&D organization, allowing us to serve more patients across the cancer continuum.

This technology and clinical lab testing capability will play a pivotal role as we work to bring blood-based therapy selection and minimum residual disease tests to patients and physicians. Building the leading advanced cancer diagnostics company starts with clear defined and well-communicated priorities.

In 2020, we are committed as a team to achieving these three core priorities, deliver more answers, enhance the customer experience, and power new growth. Delivering more answers means growing our core business, Cologuard and Oncotype, to impact more patients. We have a solid foundation and clear plan in place for both.

We want to enhance the customer experience by making every aspect of the testing process really easy for patients, physicians, health systems, and managed care organizations. Our experienced teams and infrastructure will make working with Exact Sciences across the cancer continuum simple and straightforward for all our customers.

We'll power new growth by continuing to lay the groundwork for future cancer tests. This is fueled by our 10-year collaboration with Mayo Clinic, our experienced R&D team, and our automated, accurate, and differentiated platform. We expect our liver cancer test to be the next of many innovations in cancer diagnostics from this team.

We look forward to providing updates on our progress toward these priorities throughout the year. We're now happy to take your questions..

[Operator Instructions] Your first question comes from Derik De Bruin with Bank of America. Your line is open..

Hey, good afternoon. Thanks for taking my question. So I guess the first question, the Cologuard guide for the first quarter, I think it was a little bit below where people were thinking.

Can you sort of talk about sales force productivity, and sort of contributions from Pfizer, and sort of what's going in with it? Just sort of walk us through how you got to that first quarter number..

Hi, Derik. This is Jeff. First of all, take a step back here. The Cologuard business is very strong right now. When you look ahead to the year broadly, there's a robust set of growth drivers. You mentioned rep productivity. Obviously, that's a big one.

When I look at every cohort of reps we hired, whether a year ago or five years ago, every cohort continues to get more productive. And what we announced earlier last month is that we are expanding the sales team. We are adding over 150 new reps. So rep productivity will be a big driver this year.

With the other big drivers this year when it comes to three year rescreening, there's over 200,000 more patients due for rescreen in this year than last year. And we are seeing a higher capture rates on the rescreens.

Health System's a big part of the business and growing, electronic ordering, overseeing more and more health systems convert to electronic ordering. So the point here is there's a lot of growth drivers and the business is in very good shape.

When you think of phasing through the year, what we're signaling is expecting a typical phasing through the year. When I look over the last two years, '18 and '19, Q1 was about 20% of the volumes for the year. When you look at the 2020 guide, what we're signaling is Q1 will be about 20% of the revenue for the year.

So I would think of this is a pretty typical year for Cologuard..

Great, and any -- on the Genomic Health business, any specific upcoming milestones and things that we should be looking for in terms of clinical data releases for the next year?.

Yes, so that business continue to perform very well, which is exciting. Keep in mind that the second half of 2019 was arguably the strongest period of that company's history, right, and that came at a time during the acquisition announcement and the acquisition close.

The team at Genomic Health delivered two very strong quarters, so we enter 2020 with very good momentum. Really, a lot of this momentum stems from the continued benefit of the TAILORx study, which is now almost two years old, and as well as the team is a really high quality team. Top to bottom, a really high quality team.

So I would expect 2020 to be another good year of execution. When you look at the three main components of that business, the U.S. press franchise, we expect mid single-digit growth there. And that business now -- your two years post TAILORx, so semi ration to growth was to be expected.

Internationally, again, a really strong team, which will provide a valuable foundation for years to come as we bring new tests to market. Expect strong double-digit growth internationally. And prostate. Prostate ended the year last year with very good momentum. We expect strong double-digit growth in that business.

And even what you're seeing is even stronger revenue growth and volume growth, given improving reimbursement dynamics..

Great. And just one final follow up, going back to the first point. I guess, just third quarter, the fourth quarter of last year, I think people were a little bit disappointed in the numbers.

I guess the question being, your first quarter being a little bit softer on the Cologuard guide, I guess what's your level in terms of confidence on the backhand acceleration?.

When it comes to Q1, you have to keep in mind the seasonal impact on this business. We've talked about holidays before. Holidays lead to a pretty dramatic impact in primary care seeking behavior. So you think of the back half of December, even weaker Thanksgiving. Fewer people go to see their primary care doctor. That at least has some softness in Q4.

The bigger impact from the holidays is really felt in Q1, right, because there's about a 30-day lag between an order and a completed test, and you all look at completed tests. So the seasonality really hurts Q1 more than Q4. So that's something to keep in mind. I've said this before.

At some point, that Q1 Cologuard business will end up being down below Q4. There's no way around that. Now, when I look internally, I look at kind of daily order trends. When I look at that and think about all the drivers we have over the course of this year, I'm very confident in the outlook.

In fact, we're not pointing to a the higher Cologuard number at the higher overall revenue number that we had talked about previously. Short answer to your [indiscernible], we're very confident in the state of the business today..

Great, thanks..

Your next question comes from Brian Weinstein with William Blair. Your line is open..

Thanks for taking the questions.

Starting on the acquisitions that you guys were talking about Paradigm Biomics here, did you disclose what you paid there? And then specifically with each one of those, on Paradigm, how quickly do you think you can move that from a tissue to a blood-based test, and where is that in process now? And then on Biomics, you mentioned MRD testing there in particular.

When would we see something on that? How close are you to disclosing something there just more broadly on some of the biomarker discovery that they're doing? Where do we see some evidence of progress that they're making?.

We're really excited to have both of these businesses as a part of the Exact Sciences family. They provide deep DNA sequencing capabilities and a really important test that's differentiated from other therapy selection tests.

We're not giving timeframes at this point for when that test will be in the hands of the Precision Oncology sales force, or when the liquid-based version of that test will be available. Suffice it to say, we have the technical capability to deliver those solutions to oncologists who need them.

And it's important to note it's about a $2 billion TAM in the U.S., and about that same size ex-U.S., and we're a company with the proven ability, through the Precision Oncology international business unit, to deliver new, innovative, and life-saving, and life-changing tests to the patients who need them.

So we're really excited, Brian, about what Paradigm can do for patients looking out into the future. We're also -- we've already developed biomarkers with Biomics. We've had a long relationship with Biomics, and they have delivered to us biomarkers that are embedded in various products that we will bring to physicians and patients into the future.

I'm not sure that we'll ever really disclose exactly which biomarkers they develop compared to the Mayo Clinic relationship and our own internal efforts.

Suffice it to say, they are approaching biomarker discovery from a different direction than either we or we in combination with the Mayo Clinic, and we think that will make a big difference over time. We're really excited about these two acquisitions. We have not disclosed the purchase price..

Okay. And then kind of a higher level question here for you, Kevin. I mean, there's still a lot of people, I think, struggling to understand the potential for a blood-based screening test in colorectal cancer.

I mean, can you just review for everybody your take in terms of what you think is needed to not only just have a test approved, but also getting guidelines, get it reimbursement, ultimately used by clinicians? And when we're looking at data from whoever's putting it out there, what are the things that are most important in your view for people to be considering in terms of things like trial design, or statistical methodology, etcetera? Thank you..

Thanks, Brian. I think the most important thing to consider when you look at the opportunity in colon cancer screening is that there are 106 million Americans in the average risk screening population between the ages of 45 and 85. 106 million. There are 15 million who today are either not screened or out of compliance with screening. 15 million.

As you know, we have delivered results to about 3.5 million people, and so we've barely gotten started, and that is a huge opportunity for Cologuard.

And we think -- and I think it's important to understand that the current tests available with colonoscopy and Cologuard, clearly the two most sensitive tests, which is the goal of screening, is to be able to detect cancers and pre-cancers at a high rate. And colonoscopy and Cologuard are above the rest of the pack that fit an FOBT test.

When you think about a blood-based test, you have to consider what is the sensitivity and specificity, and to date, the folks who have worked on this, including Exact Sciences, have delivered case control studies that are not particularly impressive relative to colonoscopy and Cologuard, and we think that it's a long effort to make a difference.

So I think there is a role for blood-based tests. We think that will be a smaller role compared to those tests with a longer interval testing, Cologuard, three years, colonoscopy, 10 years.

Also keep in mind that the brand awareness of Cologuard is significant in the mind of consumers and physicians, and over the next four or five years, that is only going to continue to build. And we have the largest commercial presence and capability to bring a blood-based test to physicians.

So that's our view of this, and that view has been consistent over time. And we think that it's time that we'll prove out that that with Cologuard, we can get to a significant percentage of those 50 million unscreened Americans..

Thank you..

Your next question comes from Brandon Couillard with Jefferies. Your line is open..

Thanks, good afternoon.

Kevin, if we look at health systems, can you just sort of update us on where you stand in terms of the incremental progress that's been made since Pfizer came on board? How much should the volume for Cologuard today do health systems account for? And should we think about that as more of a '21 story, kind of post the Epic ordering functionality rollout? Or will it be a material driver, you think, to the business this year?.

Thanks, Brandon. The health systems productivity and impact is increasing each quarter. We had a very strong fourth quarter of HL7 implementations, and that's a piece of software that goes between a health system EHR system and our lab system, making it easy for a physician within one of those systems to order Cologuard electronically.

And we expect that to continue into the first quarter. We're not going to break out the number of health systems who get HL7 interfaces. It's a pretty significant step up from the first half of 2019, and we expect that to continue throughout this year.

Then there will be a large impact towards the end of this year when Epic rolls out the ability to electronically order Cologuard within their version of Epic. About 45% of primary care physicians use the Epic EMR system. Then as those systems update to the new instance of Epic, it in 2021 will start to feel an even greater impact.

Basically, it takes -- for the new -- for health systems that implement an HL7 interface, after about a year, they are ordering 95% more Cologuard tests than a system that doesn't have an HL7 or electronic ordering capability. Hopefully that gives you some direction in terms of the impact here.

Over time, it will be an important growth driver for us in '20, '21, and beyond..

Thanks. And a two-part question for Mark, if he's there. Just curious if there's any metrics or anything you can share with us as far as the impact of Viva rollout, which I think happened in early December.

And then part two, just curious if you could share with us how you expect the marketing message to kind of evolve as we move through the year in terms of new content and press, when we might begin to see some messaging around the Cologuard 45. Thanks. .

Let me start with this, and then Jeff will answer. Since we now have a business unit, Mark is not on this call, but certainly would be available if you want to chat with him offline. So Jeff, if you want to take this one..

So Brandon, the first question on Viva rollout, you're right, Viva rolled out, went live, in December. The team did a phenomenal job of bringing the sales force in and training them on the new system. Early feedback has been fantastic. Too early to share any metrics on that one, considering we're very early in that roll out.

But the feedback has been very good. Viva enhances a rep's ability to do very sophisticated call planning and call routing. So over time, we think this will be a very big driver of incremental productivity. When you think of our ability to partner with Pfizer, it worked well together. Now, both the Pfizer reps and our reps are on the same platform.

So Viva is just a fantastic tool. Really excited to have it. On the marketing messaging, I think you mentioned on 45, rest on 45. What has happened is we are working to update all of our marketing materials to make sure we're driving awareness on the expanded label for Cologuard. So that has already started to happen.

If you've seen our ads, you'll see that they now talk about Cologuard 45. There's additional marketing content that we'll roll out through the year. It's important that you keep these T.V. ads fresh. T.V. ads have been an absolute homerun for us. They are still the biggest driver of new ordering physicians.

As well, Kevin talked about this brand that we've created when you think over the life of Cologuard. Today, we're -- with the budget for this year, we are approaching $1 billion of marketing and sales investment in this brand. So this is creating a very strong brand that will have a long, long runway out there.

So we will continue to evolve the messaging over time, and stay tuned for some new ads this year..

Very good. Thank you..

Your next question comes from Doug Schenkel with Cowen. Your line is open..

Hey, good afternoon, guys. Maybe starting on reorder rates, you sounded a bit more positive on this in your prepared remarks than I think you have over the past few quarters. Not on the opportunity, that's been consistent, but really on converting patients to get them to reorder.

Is that right? And if so, what's changed, and what are you factoring into 2020 guidance on reorder rates at this point?.

Hi Doug, this is Jeff.

I think -- is your question on the three-year with retesting?.

Yes..

Okay. So rescreening, huge opportunity. This year, there are over 370,000 patients coming up for three repeat testing, which I mentioned before. That's over 200,000 patients more than last year. So it's a huge opportunity. And longer term, as we continue to drive a higher capture rate, we expect rescreens to become over half of our revenue.

So it's important, it's an important driver today, and it is a material driver. What we're seeing internally is increasing capture on that three-year repeat customer. When I look month on month, we are seeing a higher capture rate.

And I think what this boils down to is we're doing a better job at both reaching out to the patient and making sure the patient is aware that they're due, and to the physician. So we've given our sales team new tools to make sure that they can communicate with a physician that the patients are due for screening.

When I look up over the course of 2020, there's some really new exciting tools coming in place, and this is really all enabled by the IT investments we made last year in both Epic and Viva. So let me give you one example on Viva.

Now that the reps have the Viva platform, which is a really high quality IT system, when they communicate with a physician, they will be prompted if that physician has patients due for three-year reordering.

Now, the plan is this year to make it so a physician -- we can communicate a list of patients right to the physician, fax, email, however the physician prefers, that when a physician has a list right in front of him or her to respond to, to make sure that patient is still eligible and very easily through -- ideally through the click of a button, to place that three-year reorder.

So getting better tools in place and better programs around this has allowed us to start capturing a higher percent, and I expect that momentum to continue throughout 2020..

Okay. And then given a lot of those tools, while exciting are new, presumably it's probably too early for you to get too aggressive in incorporating any real upside associated with the implementation of those tools over the course of the year..

So there is rescreen revenue in the base. So obviously, we have a pretty good line of sight into the near-term impact, Doug, so it begs in what we know. Potentially, obviously, there's a long runway ahead for years to come. So this is going to be one of the key growth drivers for many years to come..

Okay, understood. Pivoting to M&A and strategic partnerships, I guess another guidance question.

How are Paradigm and Biomics treated in your revenue targets for the year, if they're included at all? And what's your bandwidth to do more agreements along these lines over the course of 2020?.

Biomics is primarily an R&D partnership. Again, as Kevin mentioned, this is a really high-quality partner that we've worked with for many years. Paradigm does have an on-market test. We're not bringing out the contribution; however, it is factored in the guidance. It is not a material contributor this year.

It's primarily about laying the foundation for the future and putting this into the hands of the really high-quality Precision Oncology sales team, and opening up a much broader part of the cancer continuum..

In terms of our bandwidth, Doug, we are so -- we're thrilled with the quality of leadership and individuals that are part of the Precision Oncology team. That really gives us an incredible opportunity to bring more impactful tests to physicians and to patients who need them.

And that means that there's an opportunity for us to in-license technologies that we think are impactful, to acquire companies who have gotten to a certain place but really need access to a large commercial organization and payer team to be able to activate those tests and get them into guidelines, and to help them bring those tests to the physicians.

And remember, we have 1,000-person commercial organization, which really differentiates us. So we have the bandwidth and capability to do more things like this, and an incredible R&D team.

Now, combined with the Genomic Health scientists and engineers, we think we're going to be in a great position to keep innovating and adding to our portfolio of products, now and over a long period of time..

Okay, that's helpful. And just a couple quick ones to wrap up. Act Bold. This is a 7,500-patient study that you quietly did over the course of last year, collecting blood and stool as part of your efforts to advance next generation Cologuard. That study, I believe, is supposed to read out maybe in March.

Is it possible you would share any readout data from that study over the course of 2020..

So Act Bold, the plan is to have that finished enrolling in the near term, Doug. That would give them some time to then process the samples and generate any evidence. I expect at some point there will be a read out on it.

As of now, the primary intent of Act Bold is to use those samples to finalize the design of Cologuard 2.0 and our [indiscernible] blood assays..

Okay, and last one on guidance. Just going back to Derik's question, the first question on the call, on Q1 guidance. I just want to make sure I'm doing the math right.

I mean, it seems like one, while you're not necessarily assuming an increase in completed orders per provider based on seasonality, you're likely assuming an increase in kits ordered per provider, which again, I think would speak to the seasonality you described, Jeff.

And then secondly, just to be clear, it seems like your expectation based on your Payson commentary, is that after you move past Q1 seasonality and any potential blue impact, that we should expect a more notable sequential increase in orders per practice along the lines of what we saw Q1 to Q2 last year? Is that right?.

The typical seasonal pattern for orders, which is what we really look at internally -- the typical seasonal pattern is you start the year coming out of the holidays with a steep ramp, and we can see that the steep ramp orders per doctor ramps very strongly all the way up until above Memorial Day timeframe.

The reason is around Memorial Day, families with children, people start to go on vacation more commonly, so you see the steep ramp continuing through about the end of May. Over the summer, you have some temporary disruption from holidays and summer vacations. And then about mid-August or so, the seasonal trends start to improve again.

You see another steep ramp in orders per doctor all the way through Thanksgiving. So that's the typical seasonal pattern. Again, holidays, Thanksgiving, Christmas, New Years are the biggest areas of seasonal weakness. That's not unique to us. That's pretty typical of any primary care focus company. The flu happens every year.

We are seeing some impact on the flu this year. That is baked in the guidance. I want to be clear about that. We did assume that in the Cologuard Q1 guidance in the annual guidance. It's important to keep in mind, if you look back to 2018, 2018 was the worst flu year at that time in about 10 years. We did have some impact on the business back in '18.

However, more importantly is that that impact was temporary. In fact, when you look at the remainder of the year, the business not only recovered, it actually accelerated coming out of the flu. So to the extent that we have any more meaningful impact this year, I would say look, it's going to be temporary.

It has been historically, and we'd expect a nice ramp through the year. When you look at all the different growth drivers that we have lined up for 2020, it's going to be a very exciting year. .

Okay, thanks a lot. Appreciate it..

Your next question comes from Dan Arias with Stifel. Your line is open..

Hey, thanks. This is Daniel Macik on for Dan Arias. So what does the outlook assume in terms of the 45 to 49 year old population contributing to the mix, and with that as well, what should we look for in terms of coverage for that population? Thanks..

Thanks, Dan. This is Jeff. So, take a step back and look at what 45 to 49 means, right? This this target age group, this age group has 19 million average risk Americans, and we estimate that nearly all of them are unscreened. Cologuard, given that it's a very patient friendly, non-invasive test, fits into their lifestyles very well.

So we're very optimistic longer term about the potential in this age group. Given the timing of the FDA approval last year, late in the year, it wasn't a material contributor, as expected in Q4. That said, I do expect it to be a material driver of growth this year, and for many years to come. We are seeing some increasing adoption.

The important early efforts are around making sure physicians are aware of the need to start screening earlier.

What the evidence show, and really why the American Cancer Society lowered its screening recommendation to age 45, is that there's been a rapid rise in incidence, over a 50% rise in incidence in the younger population over the past 20 years. So we need to get more people screened, and again, Cologuard fits well into that lifestyle.

So making sure physicians are aware of that. The sales team has been trained on the expanded label. They're out there educating physicians. I mentioned before the marketing campaign has been updated. So now we're out there trying to reach patients through an updated marketing campaign.

Unless they're working with the payers and guideline committees, it is also important. So we want to make sure there's broad commercial reimbursement in this age group. What we've seen so far is that when patients in this age group get Cologuard, the vast majority are covered in full. Today, over 70% are covered in full.

We want to make sure that number goes up over time. Keep in mind that overall, Cologuard has about 95% of our patients pay zero. We want to make sure that the doctors and patients are confident that Cologuard will be covered in full. So there's some work to be done on the on the coverage side still..

Right, thanks.

Just to clarify that too, so on the payer side, the conversations you're having there are pretty consistent with your previous commentary then?.

Yes, we continue to see progress with the payers. They see that the evidence is very solid for screening patients at a younger age. And as I mentioned, over 70% of eligible patients in this age group are covered in full by the payers..

Okay, great.

In terms of the pipeline, the liver cancer assay, is there anything we should be on the lookout for in terms of data, maybe in the first half of the year?.

The next big milestone for liver is we plan to make that test available in the second half of this year. There likely will be some additional data published this year. Haven't said which conference yet, but there will be some additional data published. The plan is to get some additional data out there, and then use that as a basis to launch the test..

Okay, thanks. And then one last quick one. Just switching over to Genomic Health, the OncotypeDX in terms of reimbursement in Germany and France, and if you could just provide the latest there. Thank you..

Yes. So there's some exciting news in Germany last year with the establishment of the reimbursement code. So that is moving forward. And we expect Germany to be one of the more major growth drivers for that business. Really, this all stems from the TAILORx study, which is published back in 2018.

So that study has led to improving reimbursement globally, and Germany's one of the bigger drivers this year. I would say France, as we said before, does like that a bit. But given the strength of the evidence here, we expect reimbursement to continue to improve for years to come..

Okay, thank you..

Your next question comes from Amanda Murphy with BTIG. Your line is open..

Hi, good afternoon. So I have two questions. I guess one, I feel like I'm beating the cadence for the year to death, but I'm going to ask it again. So sorry about that, Jeff. But I just was curious.

Obviously, you've got a lot of experience in some of these dynamics, like reordering rates and the primary care productivity at Pfizer, and you've obviously brought on reps before in terms of understanding their productivity.

But then you've got maybe some newer dynamics with bringing online Epic, and kind of incremental strategies on marketing, and then EHR integration with the health plans.

I just wanted to get a sense as you think about the year and guidance, and how your caveating some of these newer dynamics that maybe -- not that you have less experience with, but just trying to get a sense again of where the upside, downside might be, what you're thinking about in terms of at least the back half of the year where there could be -- just trying to get a sense of how you thought about incorporating all these into the numbers, especially areas where you may not have years of kind of knowledge of how these things work..

Hi, Amanda. This is Jeff. When I think about guidance, what I try to do is bake in my best expectation for all these various growth drivers. So whether it's rep productivity, three-year restreams, electronic ordering, 45 to 49, try to bake in everything I know up until that point.

And many of these things we've also -- we have contribution in the base already. So you talked about Pfizer. Well, we've been working with Pfizer for over a year. As you mentioned, we've added reps before. So we have good experience and very good line of sight into what the expected contribution will be. That said, there's always new things that come up.

We've got a really talented commercial team running Cologuard. So they continue to find new ways to keep driving that business forward. And we'll keep pressing them and setting high expectation. So I think that the guidance is appropriate, and bakes in everything we know as of today..

Okay, fair enough. And then Jeff -- and I guess this is a question for both of you. You talked about with the new acquisition, this idea of screening across a cancer continuum, and I thought that was really interesting. And maybe you could talk about that a little bit more.

Obviously, there's lots of discussion around early cancer detection in different indications. Some other folks out there doing therapy selection. I think there is also a big opportunity in terms of cancer recurrence.

So I was hoping maybe you could take a step back and maybe look long term about how you see in a distance of what you've already talked about with your liquid biopsy focused with Mayo, kind of how you see the business evolving from a pipeline perspective, based on that that one comment that you made earlier on that continuum of cancer..

Thanks, Amanda. It's Kevin.

Historically, if you look at the introduction of new cancer tests, there's been a very long cycle to get those tests adopted, and there have only been a handful of companies that have been particularly successful, and there are -- we look at as there are three major impediments and things that you need to do to make a new test successful.

One is a tremendous R&D clinical trial capabilities, evidence generating capabilities. Second is the ability to reach and gain traction with insurers. And finally, is a commercial presence. We have what we consider to be top tier R&D, incredible reach into payers between the OncotypeDX and Cologuard brands.

You have near universal coverage or nearing universal coverage in a commercial organization. That is pretty remarkable.

So this means that we -- our strategic plan is to press on the accelerator and to bring more tests through our R&D team, our team that deals with large insurers, and importantly, our commercial organization, because we know that cancer diagnostics -- that you're at this dawn of a new era in molecular medicine, and with the new cancer therapies that are coming to patients, we think that by detecting cancer earlier, and detecting recurrence earlier, you can change outcomes with new therapies that are showing to be more effective, the smaller the tumor load is.

And so we're excited about what the future holds. And this is across the continuum. Screening, incredibly large opportunities. Diagnostics, like our liver cancer test for people who are already at very high risk of liver cancer, do they or don't they? OncotypeDX tests, the Paradigm therapy selection test.

You're now starting to span this continuum, and you're doing it with an incredible team. Our goal is to stay world class at everything that we do so that the physicians who choose to order a test for their patient has a high degree of competence that it's reliable..

And just one quick follow up there. So you've talked a lot about cost of goods. That's obviously a big focus for Cologuard.

I understand it's a different modality with next gen sequencing, but I guess how do you think about that as you -- again, thinking long term, bringing some of these areas to market or tests to market, where next gen sequencing, obviously, there's some cost there? Again, what's your view there and in getting the cost base right to be competitive, and still sort of adding value, adding clinical utility, just curious there too?.

I think that the key thing is to use the right tool for the particular clinical challenge. And if it's therapy selection, sequencing is clearly the right tool. And as sequencing costs come down, there's an opportunity to use sequencing in an additional array of potential tests.

One of the reasons that Cologuard works is because the cost of goods of the assay itself are low, and that's important as you're trying to reach 106 million Americans in that particular population. It'd be very challenging to make DNA sequencing work in that setting.

But things change, and we're thrilled to have a deep capability of DNA sequencing on board, and we will grow that and look for incredible scientists who want to join our exciting company..

And Amanda, this is Jeff. Just to add to what Kevin said, we're part of the cost of launching a product, in fact, one of the biggest costs, is the commercial team. Now, we're in a very good position with the talented team from Genomic Health that today, as you know, has about 1,000 oncology reps with deep experience.

About a third of those reps have over 10 years' experience out in the field, building relationships with oncologists. So that cost we already have, right, we sort of baked into our model for Oncotype. Now, as you bring new products to market, we'll get very good leverage on that model.

There's a lot less incremental investment for us to make as we bring new products in..

That makes sense. Thank you very much..

And adding to what Jeff just said to the combination of the Precision Oncology sales force broadly, including the urology sales force and our primary care sales force also creates opportunities for us to think about a test that would help with prostate cancer, and bladder cancer, and beyond.

So this commercial organization is a dynamic one that will partner with our different groups of our sales teams to end up impacting patients in a positive way..

Okay, great. Thank you. .

Your next question comes from Patrick Donnelly with Citi. Your line is open..

Great. Thanks, guys. Maybe just one on the hiring side. You guys have called out the hiring adds a few times. Obviously seen an uptick.

Can you just talk through the strategy here? I understand the primary care market is fragmented, but to add, to protract a little higher than we anticipated, given the Pfizer agreement, supplementing the sale side as well.

Can you just talk through the give and take there on your end?.

When you think about a primary care launch, you would typically not launch a really significant product without at least 1,000 reps, and on a combined basis between Pfizer and Exact Sciences, we have more than 1,000 reps focused on this.

And that's important when you realize that there are 350,000 prospective ordering healthcare providers in primary care offices. And so, it's important to be able to reach those ordering healthcare providers, and reach them on a frequent basis.

There is a reason that large primary care drug companies have been very effective with large sales forces because it's that reach combined with the frequency, and so that 150, the new team members that have recently joined us and will become impactful over the course of this year and next year, is a start.

You can expect over time that that will increase as we have a greater reliance on our own. And we want to reach those 350,000 physicians. And every group of new primary care reps that have joined us have become more productive. We haven't seen any of those cohorts, their productivity flat now..

Patrick, this is Jeff. Just to add to what Kevin said, we approach the investment in sales reps the same way we approach any investment. We look at the return on investment. And what we see is that the ROI on reps is very high, and it continues to grow over time as they get more productive and we give them more tools.

So to the extent the ROI is strong, we will make the investment, and expect that to continue for many years, given how early we are in the penetration. Also keep in mind that over the past year, we had a 50,000 new order in providers.

So we need to make sure that our sales force is right sized to keep driving Cologuard growth amongst that growing physician base..

That's helpful. And then maybe just to stay on the sales rep and the Pfizer side, can you just talk about their engagement now the disruption around Lyrica is a few months behind us, just the activity there? And then has there been any compensation structure changes there with them kind of more heavily emphasized in Cologuard? Thank you..

I think what we have articulated is that we believe that in 2020, there will be a greater focus within the Pfizer field force on Cologuard. The compensation depends upon the position in the Pfizer bag that Cologuard is carried.

I think, on average that compensation will be higher in 2020 than it was in 2019, indicating a relative higher positioning in at least a portion of the overall team. Pfizer's been a tremendous partner across not only sales, but also marketing. I'll give you an example.

On 60 Minutes on Sunday night, there was a placement of brought to you by Cologuard for one of the 60-minute segments. And that is -- it's a hallmark of the Pfizer marketing team that thinks creatively and has the reach and access to that type of advertising placement.

And they are just a ton of examples where we have gotten better because of our Pfizer partnership..

Thanks, Kevin..

Your next question comes from Catherine Schulte with Baird. Your line is open. .

Thanks for the questions.

First on BLUE-C, any comments on how enrollment is progressing so far?.

Hi, Catherine. This is Jeff. As you know, BLUE-C just initiated in the fourth quarter. So we've got dozens of sites up and running, enrolling patients. We're not going to break out each quarter where enrollment is trending, but we're off to a good start there..

Okay.

And going back to the recent sales force expansion, recognizing you guys just talked about reps taking six months to 12 months to get productive, but they're getting typically more productive more quickly What are you assuming in guidance in terms of when those reps start meaningfully contributing? Do we start to see a benefit in the second quarter? Or do you view that more as a back half impact?.

So, thanks for the question. I think you'll start to see some benefit early, but that historical timeframe is still there, right, typically six to 12 months to get productive. But that team -- it's a high-quality team that we've hired, and we've put in place a lot of tools like Viva to help make sure they get productive.

I think that the real contribution will be in the back half, but we'll see some early contribution starting really in the second quarter..

Okay, and then last one for me.

I know it's only a few [indiscernible] at this point, but are you happy with the progress so far with the new GI sales force, and how are you measuring success when it comes to that group?.

So the GI sales force, it's about 60 reps that we put in place last August. There's really three key reasons why we hired that team. The first is on making sure that GIs have the proper background knowledge, the proper clinical evidence on Cologuard, because GIs are often considered the thought leaders in colon cancer screening.

That way, when they're out there talking to all their physicians, they're equipped with the right data. And our market research has shown when the GIs have the basic facts on Cologuard, they're much more optimistic. They're much more supportive of the test. So that's the first.

And the way we'll measure that is on the order rate on the surrounding primary care doctors in a territory. The second is on the direct orders from a GI themselves. So GIs live and breathe colonoscopy and colon cancer screening.

However, there are certain patients that perhaps would decide they don't want to do another colonoscopy, or perhaps Cologuard is the better alternative. So for those patients of the GI cannon, and many do order Cologuard. In fact, well over half of all GIs have ordered the test.

So there is an opportunity for that GI team to drive incremental utilization amongst GIs. And third is that, starting with liver cancer, we need GI sales team.

Liver cancer -- that product should be available later this year, and over time, as we bring new products to market like esophageal cancer, pancreatic cancer, these tests will be carried by that GI sales team. So three main reasons why we're pleased that we have that team. We expect the benefits to grow in 2020..

Great, thank you..

Your next question comes from Dan Brennan with UBS. Your line is open..

Great. Thanks for taking the questions. So Kevin and Jeff, just wondering back to -- and I think a few questions have already been asked, but just wanted to get your perspective.

When we look at, from an annual basis -- well, I know you're not going to give any Cologuard testifying data anymore, but nonetheless, when we think about that utilization number, is it kind of -- what is baked in kind of implicitly in 2020? Does utilization -- does it go up as much as it occurred in 2019? Is it less than that? I'm just trying to get a flavor for how we think about that because that's something I'm sure we're still all going to try to track ourselves..

So Dan, this is Jeff. When you look at the Cologuard market, obviously, you know today we have about 5% market share within a given physician's practice. We've only captured somewhere between 5% and 10% of their eligible patients. So we're still very early. We do expect that test per doctor number to continue.

Like you mentioned before, it has grown over time, and in fourth quarter, it grew 22% year on year. So we expect that number to continue going up over time. You can get a good sense of where it's headed if you look at the revenue that we report.

And keep in mind what I said about revenue per test, expected stability in the near term, and slight improvement over time. That will give you a pretty good sense on where tests per doctor are trending. But we do expect it to go up this year, and for many years to come..

Okay. And then Kevin, I know you mentioned the prepared remarks and there's been a few questions on Pfizer. But you discussed how you think productivity, I think will accelerate in 2020, or you used a word that would signify it's going to get better in 2020.

Can you just characterize how we think about that in terms of your guidance? How does that productivity increase factor into the guidance?.

Yes. Well, all of our factors, Dan, figure into our guidance for 2020. And we won't break out any one component relative to another. Suffice it to say, Pfizer is incredibly experienced. They have deep relationships with their primary care physicians, and they are getting better at and more knowledgeable with Cologuard just as all of our reps do.

It typically takes about a year before reps become really effective. And now the Pfizer reps have had Cologuard for five quarters. So we expect good things, and it's embedded in our guidance. .

Great, thank you for that, Kevin. And then maybe just on liquid biopsy, obviously other companies are continuing to progress and running studies, and I'm just wondering if you can give us an update and when you think we can expect to see data from your own program..

We think that we are the leader in the liquid biopsy or colon cancer screening from a blood-based test. We're in a position that we don't have to show our R&D, all of the studies that we're doing, and we just continue to focus on doing great science, and at the appropriate time, we'll release that data.

And again, what I want to emphasize is the Cologuard brand, and the deep resources, and incredible investments that we've made are pretty powerful, and create a sustainable advantage for us, both for Cologuard and a potential blood-based colon cancer screening test that we bring to physicians and patients.

We're excited to be the leader in this space..

Great, and then maybe the last one. I know there's been a few questions on Paradigm, and I know you -- but I don't know if you disclosed it on the call. I was surfing on their website.

Did you disclose anything with regards to the revenues today, number of tests, what's differentiated about the technology? And if not, when would we expect to get more color on this acquisition? Thank you..

We haven't disclosed the purchase price. The revenues aren't material. And you'll have an opportunity to learn more about Paradigm and Biomics over time.

The first job is to make sure we do a great job with integration and to do -- take all of the right steps to make sure that the scale is there in the lab to meet the demand that we expect to generate..

And Dan, for modeling purposes, the Paradigm business will generate revenue within the Precision Oncology reporting line..

Got it. Okay, thank you..

Ladies and gentlemen, we have reached the end of the allotted time for the question-and- answer session. I will now turn the call back over to the presenters..

Thank you for joining us today to review our fourth quarter results, progress made in 2019, and our plan for 2020 and beyond. Thanks to the entire Exact Sciences team for your hard work and continued commitment to our mission.

We've never been more excited about the future of Exact Sciences, and have complete confidence this team will continue to change the way cancer is diagnosed and treated. Thank you..

This concludes today's conference call. You may now disconnect..