Rebecca Chambers - Vice President-Investor Relations & Treasury Jay T. Flatley - Chief Executive Officer & Director Francis A. deSouza - President & Director Marc A. Stapley - Chief Financial Officer & Senior Vice President.

Tycho W. Peterson - JPMorgan Securities LLC Doug Schenkel - Cowen & Co. LLC Daniel Arias - Citigroup Global Markets, Inc. (Broker) Jonathan Groberg - UBS Securities LLC Ross Muken - Evercore ISI Amanda L. Murphy - William Blair & Co. LLC William R. Quirk - Piper Jaffray & Co (Broker) Isaac Ro - Goldman Sachs & Co. Dan L.

Leonard - Leerink Partners LLC Steve C. Beuchaw - Morgan Stanley & Co. LLC Dane Leone - BTIG LLC Bryan Paul Brokmeier - Cantor Fitzgerald Securities Jack Meehan - Barclays Capital, Inc..

Good day, ladies and gentlemen, and welcome to the Illumina, Incorporated, Fourth Quarter 2015 Earnings Conference Call. At this time, all participants are in a listen-only mode. Following the speaker's remarks, we will host a question-and-answer session and instructions will follow at that time. As a reminder, this call is being recorded.

I would now like to hand the call over to Rebecca Chambers. You may begin..

Thank you, Trisha, and good afternoon, everyone. Welcome to our earnings call for the fourth quarter and fiscal year 2015. During the call today, we will review the financial results released after the close of the market and offer commentary on our commercial activity, after which we'll host a question-and-answer session.

If you have not had a chance to review the earnings release, it can be found in the Investor Relations section of our website at illumina.com.

Participating for Illumina today will be Jay Flatley, Chairman and Chief Executive Officer; Francis deSouza, President; and Marc Stapley, Executive Vice President, Chief Administrative Officer and Chief Financial Officer.

Jay will provide a brief update on the state of our markets, Francis will comment on product performance, and Marc will review our fourth quarter and fiscal year 2015 financial results as well as detail our guidance for 2016. This call is being recorded and the audio portion will be archived in the Investors section of our website.

It is our intent that all forward-looking statements regarding our expected financial results and commercial activity made during today's call will be protected under the Private Securities Litigation Reform Act of 1995. Forward-looking statements are subject to risks and uncertainties.

Actual events or results may differ materially from those projected or discussed. All forward-looking statements are based upon the current information available and Illumina assumes no obligation to update these statements.

To better understand the risks and uncertainties that could cause actual results to differ, we refer you to the documents that Illumina files with the Securities and Exchange Commission, including Illumina's most recent Forms 10-Q and 10-K.

Before I turn the call over to Jay, I would like to let you know that we will participate in the Cowen Healthcare Conference in Boston the week of March 7. For those of you unable to attend, we encourage you to listen to the webcast, which will be available through the Investor Relations section of our website.

With that, I will now turn the call over to Jay..

Thanks, Rebecca, and good afternoon, everyone. As we shared a few weeks ago, fourth quarter results surpassed our expectations with revenue of $592 million, an increase of 15% over the prior-year period and our 17th consecutive quarter of sequential growth.

During the quarter, we witnessed robust trends across the business, including year-over-year total sequencing growth of 19%, and 30% shipment growth to clinical and translational customers. Demand from clinical oncology customers contributed to the strong Q4 result with approximately 40% growth compared to the prior-year quarter.

We're very pleased with the commercial uptake of the TST 15 product, and the TST 170 development program remains on track. These panels are based on initial standards defined by the Actionable Genome Consortium and were developed to drive adoption of NGS in the translational market and by pharma partners in their clinical trials.

Encouragingly, we recently announced that Amgen will be utilizing the IUO version of TST 15 as part of a new oncology development program, and we're in discussions with other potential pharma partners as well. In early January, we formed GRAIL, a new company focused on the cancer screening market.

We're currently working to transfer our ctDNA programs, the MSK partnership, and the employees working on these projects to GRAIL. We're in the late stages of recruiting a CEO and have identified a potential lab and office space in the Bay Area.

We've begun work on the detailed planning necessary to embark on a large-scale clinical trial in 2017 with the goal of demonstrating a stage shift in diagnosis. In our reproductive and genetic health business, we saw strong adoption of both our IVS and NIPT products in the fourth quarter.

Sales of our pre-implantation genetic screening or PGS products increased close to 25% compared to the fourth quarter of 2014. Further, we completed enrollment in the STAR trial ahead of schedule, which will measure the impact of PGS in embryo morphology on IVF success rates. NIPT revenue grew more than 50% compared to the fourth quarter of 2014.

Test send-out volumes were slightly lower sequentially at 45,000 as one of our large customers began to shift testing in-house. This transition will decrease service revenue and increase product sales in the coming quarters. Partially offsetting this impact will be continued penetration of the average risk opportunity.

Currently, we estimate more than 70 million lives or 25% of the U.S. population has coverage with Anthem and regional Blue Cross, Blue Shield carriers who've made a favorable coverage decision for average risk.

Moving to arrays, shipments grew 1% versus the fourth quarter of last year and revenue was down 2%, with ASPs sequentially stable for the second quarter in a row.

With strong demand from agriculture, DTC, and biobanking customers as well as the launch of our new arrays, Methyl EPIC and ImmunoArray, we shipped 1.6 million samples during Q4, a new record. We project slight array growth in 2016 supported by the entering backlog and the availability of Infinium XT later this year.

In summary, the momentum in the fourth quarter was largely driven by the continued penetration of clinical genomics in the oncology and reproductive health markets.

This trend together with our strategic investments in market and platform development will enable us to deliver on our mission to unlock the power of the genome and further penetrate the many large and untapped opportunities ahead of us. Lastly, as you may have read in our 8-K yesterday, Dr.

William Rastetter stepped off the Illumina board in order to invest and serve as a board member of GRAIL. I would like to thank Bill for his enormous contributions during his 17 years as a board member and 11 years as chairman. I'll now turn the call over to Francis who will provide a detailed overview of our product results..

Thanks, Jay, and good afternoon, everyone. I'm pleased to provide further details on the performance of our products in the fourth quarter. To begin, interest in the HiSeq high throughput portfolio remained strong with HiSeq 2500 and HiSeq 4000 orders both exceeding our expectations.

Versus the prior year, shipments were lower due to challenging comparisons in HiSeq X and HiSeq 2500. Demand for HiSeq X was generated from customers adding capacity, as well as new X sites which totaled 27 at the end of the fourth quarter.

While orders are expected to be relatively steady in the 20- to 30-per-quarter range, shipments depend on customer readiness, which we expect will result in fewer than 20 shipments in Q1. Demand for HiSeq 2500 exceeded expectations in Q4 due to commercial customers with validated workflows who value the rapid run mode this product offers.

During the quarter, we received a multi-unit order from an NIPT customer as well as orders from commercial customers looking to add throughput to their laboratories. HiSeq 4000 also benefited from capacity additions including multiple unit orders from HiSeq X customers looking to expand the application breadth of their respective fleets.

HiSeq 4000 again was the leading platform sold, which lifted ASPs for the family of instruments compared to the prior year. Moving to our benchtop instruments, we saw a rebound in demand in the fourth quarter as MiSeq orders approached record levels and NextSeq orders were the highest in any quarter since launch.

These order trends were the result of delivering on the strong pipeline we saw exiting Q3. Heading into 2016, our MiSeq and NextSeq pipelines remain stable, but at a more normalized level than seen entering the fourth quarter. Clinical and translational centers drove demand for NextSeq instruments, accounting for more than 40% of orders.

Continued interest came from our NIPT partners in China, reproductive health customers focused on PGS and NIPT, and oncology customers. New-to-sequencing customers accounted for approximately 55% of MiSeq orders in the fourth quarter with our new-to-NGS bundle contributing to this dynamic.

MiSeqDx orders were also at record levels in the quarter and we recently submitted our registration document for IVD designation on MiSeq in Korea. We're continuing to work closely with the FDA to update the intended use of the MiSeqDx to include a claim for DNA, isolated for multiple sample types.

Both of these activities will further support the global demand for MiSeqDx units. Moving now to our newest benchtop instruments, I'd like to share some customer feedback on MiniSeq. Approximately 4,600 attendees have signed up for our webinars to learn more about MiniSeq, our largest-ever registration for a new product.

Early customer feedback indicates only a slight overlap with MiSeq, and as a result we expect minimal cannibalization in the range of 20% to 25%. In addition, we believe many of the customers who choose MiniSeq over MiSeq will opt for multiple units to optimize the throughput and sample flexibility of their fleets.

With these early indicators of demand, we're pleased with how the pipeline for MiniSeq is building and expect its customer friendly features to further democratize sequencing. In Informatics, we continue to increase the level of integration with BaseSpace.

We have completed the planning and design of the Clarity LIMS-BaseSpace integration, which we intend to release towards the end of Q1. We believe this will enable better visibility on lab metrics and shorten turnaround time for our customers.

BaseSpace now includes more than 70 apps as well as an upgraded dashboard and analysis manager to improve monitoring and control of reports.

These enhancements combined with the introduction of the BaseSpace Professional and Enterprise editions will enable researchers to enrich their informatics experience, while improving efficiency in sequencing labs. I'll now turn the call over to Marc, who will provide a detailed overview of our fourth quarter results..

Thanks, Francis. As we shared a few weeks ago, Q4 closed out a solid year for Illumina. Revenue for the year grew 19% versus the prior year to $2.22 billion, which equates to 23% on a constant currency basis.

Fourth quarter revenue was slightly better than our preannouncement at $592 million, 15% growth versus the prior-year period and 19% constant currency-adjusted. This strong quarterly result can be attributed to better-than-forecasted demand for benchtop instruments as well as strength in sequencing consumables and services.

Shipments in the Americas grew 25% year-over-year in Q4, while European and APAC shipments increased 5% and 10% respectively over the same period. Growth in our international regions was slightly muted due to the impact of currency.

Further, Europe faced a challenging HiSeq X comparison while the Asia Pacific region continue to experience weakness in the Japanese funding environment.

Consumable revenue was $346 million, an increase of 19% compared to the fourth quarter of 2014 as higher demand for sequencing consumables, including record library prep shipment was partially offset by a slight decline in arrays. Consumable revenue represented 59% of total revenue, up from 57% in the prior-year period and the 58% we saw in Q3.

As we've previously shared, sequencing consumable revenue was robust, growing to approximately $280 million, up close to 30% over the prior year.

This result was driven by our growing installed base of instruments and strength in NextSeq consumables, which saw utilization well above our updated guidance range of $100K to $125K per instrument annually. This is the first quarter that NextSeq has exceeded our range, so we are not updating our utilization guidance at this time.

MiSeq utilization was in our projected range of $40K to $45K, and HiSeq pull-through per instrument excluding HiSeq X was in our projected range of $300K to $350K. HiSeq X utilization fell short of our recently increased pull-through guidance range due to order timing.

We continue to project HiSeq X utilization of $650K to $700K per instrument over the course of 2016. However, the timing of a single order of $4 million or more would be sufficient to move pull-through outside of our projected range in any quarter, given the size of our installed base.

Services and other revenue, which includes genotyping and sequencing services as well as instrument maintenance contracts, grew approximately 50% versus Q4 2014 to $94 million.

This improvement was driven by growth in NIPT services, which benefited from increased test send-out revenue and IP fees, extended maintenance contracts associated with the largest sequencing installed base, and genotyping services.

Turning now to gross margin operating expenses, I will highlight our adjusted non-GAAP results, which exclude non-cash stock compensation expense and other items. I encourage you to review the GAAP reconciliation of non-GAAP measures included in today's earnings release.

Result from projections includes Helix and projections now also include our GRAIL business. Accordingly, all subsequent references to net income and earnings per share refer to the results attributable to Illumina's stockholders after non-controlling interests.

Our adjusted gross margin for the fourth quarter was 71.7%, a decline compared to 73.2% in the third quarter, primarily due to the lower mix of sequencing consumables and a higher mix of arrays and services. Year-over-year, adjusted gross margins contracted 60 basis points due to a higher mix of services revenue.

Adjusted research and development expenses for the quarter were $103 million or 17.5% of revenue, higher compared to $90 million or 16.4% of revenue in the third quarter due to the impact of additional head count and spending associated with the launch of MiniSeq, Project Firefly, and clinical trials.

Adjusted SG&A expenses for the quarter were $124 million or 20.9% of revenue, an increase compared to $115 million or 20.9% (sic) [18.9%] of revenue in the previous quarter due to the impact of additional head count.

Adjusted operating margins were 33.4% compared to 36% in the third quarter and 37.7% in the prior-year period, due to the impact of lower gross margin, higher head count, and previously mentioned investments.

In the fourth quarter, our stock-based compensation expense equaled $35 million, better than projected due primarily to cancellations associated with the management changes that we announced in December.

Our non-GAAP tax rate for the quarter was 26.5% compared to 16.2% in the fourth quarter of last year, higher than expected due to a one-time international restructuring charge. As a reminder, Q4 2014 was impacted by favorable adjustments related to multiple prior-year provisions and higher-than-expected stock deductions.

Non-GAAP net income was $121 million for Q4, resulting in non-GAAP EPS of $0.81. This compares to non-GAAP net income and EPS of $129 million and $0.87 respectively in the fourth quarter of 2014. Included in the Q4 2015 non-GAAP EPS result is approximately a $0.01 of dilution from Helix.

In addition the impact of foreign exchange lowered Q4 non-GAAP EPS by approximately $0.05 relative to last year.

We reported GAAP net income of $104 million or $0.70 per diluted share in the fourth quarter, compared to net income of $153 million or $1.03 per diluted share in the prior-year period, which reflected a gain associated with the settlement of the Syntrix litigation, partially offset by legal contingency costs related to the Sequenom patent pool agreement.

Cash flow from operations equaled $240 million in the fourth quarter. Q4 DSO decreased to 64 days compared to 68 days last quarter due primarily to improved shipment linearity. Inventory increased to $271 million, largely due to a build-up of sequencing instruments and safety stock.

Capital expenditures in Q4 were $35 million, resulting in $205 million of free cash flow. For the fiscal year, cash flow from operations equaled $660 million and capital expenditures were $143 million, resulting in $517 million of free cash flow.

During the quarter, $29 million of the 2016 0.25% convertible bonds were settled, leaving approximately $75 million remaining, which will come due in the first quarter.

We repurchased over 1.3 million shares at an average price of $151.44 utilizing $202 million under our previously announced buyback program, leaving us with more than $255 million of authorization remaining under this program. We ended the quarter with approximately $1.39 billion in cash and short-term investments.

Moving now to guidance, as we shared a few weeks ago, we expect total company revenue growth of 16% in 2016 or 17% on a constant currency basis based on today's rates.

Underlying this guidance is an assumption of sequencing consumables will generate the vast majority of growth while sequencing instruments are expected to be relatively flat versus the prior year given a strong HiSeq X backlog shipments in Q1 2015, resulting in a challenging comparison.

Non-GAAP EPS is expected to be $3.55 to $3.65, including the impact of $0.15 and $0.10 of dilution from GRAIL and Helix respectively. Additionally, we project approximately 73% gross margin, a full year pro forma tax rate at 26%, and full year weighted average non-GAAP diluted shares outstanding of 149 million.

We expect the net loss attributable to non-controlling interest of approximately $30 million. Specific to the first quarter, we are projecting flat to slightly higher revenue sequentially as a result of the stronger-than-anticipated Q4 result.

Additionally, operating expenses are projected to increase by approximately $20 million sequentially based on the ramping of investment in Helix and GRAIL as well as the head count additions from strong hiring momentum coming out of 2015.

We are off to a good start in 2016 and believe that the important investments we are making in the business, including Helix and GRAIL, will catalyze significant long-term revenue growth for the company as we continue to drive the broad adoption of genomics. Thank you for your time. We will now move to the Q&A session.

To allow full participation, please ask one question and rejoin the queue if you have additional questions. Operator, we'll now open the line..

Thank you. Our first question comes from the line of Tycho Peterson with JPMorgan. Your line is now open..

Hey, thanks. I guess, question on the instrument guidance for flat placements, I'm wondering if you can provide a little bit more color. It sounds like you mentioned more normalized MiSeq and NextSeq orders, so maybe start with expectations there.

And then with HiSeq 3000, HiSeq 4000, if you could just talk to how you are thinking about the upgrade cycle given the strength you're still seeing with HiSeq 2500, that would be helpful..

Let's say first, Tycho, that we're entering 2016 with a pretty normalized backlog in terms of all the instruments in the product line. When we entered 2015, we still had a very large backlog of HiSeq Xs, which we shipped largely out in the first quarter.

So that was a pretty significant impact overall on the instrument number for the year, was the makeup of that backlog. So, we don't have that situation coming into 2016.

MiniSeq, of course, is going to be a positive lift for the instrument line during the course of the year, partially offset by some cannibalization across the MiSeq part of the product line.

But it's really overcoming that extra shipment we had in Q1 on a comparable basis from the HiSeq Xs that caused us to give guidance to relatively flat instruments for the year. With respect to the upgrade cycle, we think it's continuing from – so, HiSeq 3000s and HiSeq 4000s from the HiSeq 2500.

But we've been actually pleasantly surprised, I would say, by the fact that we continue to get more orders for HiSeq 2500s than we expected, and that's largely because of clinical customers that have the instrument validated in their workflows and from those customers liking the rapid run mode, which we don't currently have implemented in the HiSeq 3000s and HiSeq 4000s..

Okay.

And if I could ask one follow-up, can you just discuss any feedback you've had from your existing pancancer panel customers with regards to GRAIL?.

We don't have any pancancer screening customers. So, GRAIL occupies an absolute unique niche in the market with a pancancer assay target for screening.

And it's strongly our belief that no customer that we have or anyone else has in the sequencing market has the ability to implement a screening test for asymptomatic individuals across all cancer types or most cancer types anytime in the next five years because of the economics required to sequence as deeply as we think will be necessary to make that test as specific and sensitive as required.

So we've not seen any negative reaction from any existing customers..

Okay. Thank you..

Thank you. And our next question comes from the line of Doug Schenkel with Cowen. Your line is now open..

All right. Thank you and good afternoon. The Q4 service revenue was quite robust.

How material a driver to services growth was average risk NIPT reimbursement and also population genomics programs? And what does your guidance embed for services revenue growth for the year, given it seems like the two things I mentioned would seem to be trends that would continue, but you do have an offset where one of your major NIPT customers did bring NIPT in house rather than sending out volumes to you?.

Yeah. I don't actually have the statistics, Doug, of what the average risk dollar contribution was to the NIPT component in the services line. We did mention in the script that the actual number of samples we did in the quarter went down a bit.

And that's because of a large customer of ours who has been in the process of moving the technology in-house, and that will continue through the course of the year. Population genomics really is one account now, largely Genome England. And if anything, that's running somewhat behind our expectations in terms of sample volume.

We expected to start ramping significantly in 2016, but in 2015 it's probably gone a little bit slower than we might have expected. As we look at services revenues for 2016, there are going some offsetting factors. We have some consumer business there that will continue to be very robust.

We expect through 2016 average risk will help to some extent, but that would be offset by one of our largest NIPT customers moving the test in-house. We will have GeL accelerating there as well. So there is some pluses and minus, puts and takes in the services line..

Okay.

But in the quarter, then, recognizing those puts and takes, and also recognizing that you had a – still a pretty big sequential step up, is there something you could call out as being the material driver to that?.

Well, because the installed base continues to grow, our overall warranty service contract business is growing very, very nicely, our maintenance contracts. And then, I would say the other big plus is how well we're doing in the consumer business and services..

Okay.

And then I guess just given all the moving parts at the R&D line, I was hoping that you might be willing to provide some breakdown, at least on this call, of R&D expense allocation, maybe something along the lines of how much you're allocating to sequencing platform development, really, technology development, how much is bioinformatics, maybe sample prep, and maybe something on the clinical study or consumer market, however you want to break it out.

Would you be willing to give us a little bit of detail there and how that's evolved and how you expect it to evolve in the years ahead?.

I would say not a dramatic change, although probably in 2016, we're working a bit more on the platform side because of the launch of MiniSeq and getting that all wrapped up, and also the significant investments that we're putting in place for Firefly. So we're probably slightly more biased toward platforms than we have been historically.

We've never given an exact breakdown of how we spend R&D, and I don't think we're prepared to do that today. But that tweaking on the margin probably is a little bit more toward platforms..

Okay. Thank you..

Thank you. And our next question comes from the line of Derik De Bruin with Bank of America Merrill Lynch. Your line is now open..

Hi. This is actually Mike Ruskin (25:37) calling for Derik. I had a quick question about the cancer moonshot that President Barack Obama and Vice President Joe Biden announced.

If you could comment on how much of an impact you're expecting to see from that especially with the recent news the other day that they're planning to spend another $195 million on cancer research at the NIH this year..

Yeah, and it's certainly going to be a plus. We're excited about the program and the fact it actually has some funding behind it. It's a little early to know specifically how much of that activity is going to be allocated towards sequencing, but they've called out specifically the work to identify the molecular basis of tumors.

Clearly, the kinds of things that we're doing in early detection are going to be very important. So I would say, qualitatively, we expect there to be a nice tailwind for our business from that, but it's too early to quantitate it..

All right. Thank you..

Thank you. And our next question comes from the line of Dan Arias with Citigroup. Your line is now open..

Afternoon. Thanks guys. Francis, can you expand on the MiSeq-MiniSeq dynamic just in terms of the selling strategy or the criteria that you're using to determine whether MiniSeq is the right box or whether maybe an upsell to the MiSeq is more appropriate.

And then if I could sneak in a follow-up, Marc, just curious how the margin profile for the MiniSeq will compare to the rest of the instrument portfolio once it's scaled up. Thanks..

Sure. The MiniSeq really targets sort of the long tail – the very long tail, we believe, of labs, the majority of which are new to sequencing. And so these are labs where, either because of capital constraints or frankly they just don't have the volume of samples to justify buying a MiSeq, and so for them, the MiniSeq is the perfect instrument.

And in some cases, if they have even more budget, they're more likely to get two MiniSeqs, because of the flexibly that gives them in terms of managing samples and workflows. If you have a larger volume of samples, then you tend to go to the MiSeq today.

And so what we're seeing is either a lab that have more samples or clinical labs that value the Dx designation off the MiSeq platform. And so that's sort of how it's breaking out. We had a thesis that the MiniSeq was going to open up a new segment for us and would not be largely cannibalistic.

And based on the early feedback we're getting from the interest in the MiniSeq, that thesis seems to be true. And so we believe there will be minimal cannibalization between those two instruments to the order of 20% to 25%..

And remember, MiSeq has some unique features that MiniSeq doesn't. It's got the Dx version; of course, we have the long reads, 2x400s, 2x350s on MiSeq, which we don't have on the MiniSeq. And of course, if you're doing something like deep cancer panels, you need more throughput.

And that would tend to bias toward MiSeq, where MiniSeq will be much more targeted..

And Dan, on the gross margin question, I would say, the margin for MiniSeq is pretty typical of our benchtop instruments, and I would compare it more to MiSeq than anything else.

And in fact, as it's typical with any time we launch a new instrument, the initial warranty and installation experience, we tend to estimate to be on the high side, and certainly, in the first couple of months or maybe in six months, it is. And then that settles down over time as well..

Got it. Thanks very much..

Thank you. And our next question comes from the line of Jon Groberg with UBS. Your line is now open..

Thanks. Jay, can you maybe talk a little bit about the decision to keep a majority ownership stake in GRAIL and also in the variable interest of Helix? And then also I'd love just kind of any update on Helix.

You mentioned the growth in your – on your large consumer customers who – I think talked about pretty spectacular growth in the last quarter there, but also maybe a little bit of reticence to move to Helix or to sequencing..

Sure. You can imagine on both Helix and GRAIL, we had significant internal debate about what the right structure for these entities should be. At the end of the day, the key considerations came down to the nature of the business itself.

And in the case of (30:22-30:27) than Illumina's core business, one being very focused on a new market, that being the consumer; and the second, being a business that will very likely be a global services company. And neither of those are directly what Illumina does. So that was quite important.

We thought both of these needed to operate in sort of the high-velocity startup mode, and we wanted to have the ability to recruit the best possible talent early on into these companies.

And so we thought the best structure for that was to spin them out of the core of Illumina, have a separate management team, separate board, but retain majority ownership. So that Illumina, as these companies, be as successful as we hope, we'll get the majority of the benefit from these.

With respect to Helix, JPMorgan announced the second set of partners, so a total of four are now announced. The two largest consumer companies so far have not been announced as joining Helix. It's certainly our ambitions to try to get them to join, but you can imagine as an incumbent in this space, there might be some initial reluctance to do that.

So it's imperative for us to really build this ecosystem out and to demonstrate that we have the capability to deliver a better experience and better economics to the incumbents than what they do independent of Helix.

We're working on a large number of other potential partnerships within Helix as well, and we're very active in recruiting a CEO and hope to get that done here in the next month or two..

I don't know if I can have a quick follow-up there, but is your sense that there's a desire for sequence data, or on the consumer side is – are you learning that maybe that's just not so important to them right now? There's some other factors, I guess?.

No, I don't think that's the key determinant, Jon. I think everyone wants to move toward sequencing. I think it's a question of really economics and to what extent Helix can subsidize the upfront economics to allow the consumer price points that exist today and the margins that are being delivered in the existing consumer companies.

But the whole idea of having the full content database and being able to go back to that content without having to rerun or recreate a chip, I think, is appealing to everyone. So there's no resistance on that front..

Thanks..

Our next question comes from the line of Ross Muken with Evercore ISI. Your line is now open..

Good afternoon, guys.

So, just quickly on the Q1 guide, I mean, aside from, obviously, the downtick on the HiSeq Xs seemed temporal, I guess as we just think about sort of the sequential movement, obviously we'll get a little bit less box placement, in least a few of the pieces is just that seasonal, but were also the other key deltas – I'm just taking back the historical step-ups off of Q4.

And they're, I don't know, 5%, 6%, and this is obviously a bit less. So I'm just trying to see how much – what other sort of flex points there are on that sequential movement..

Ross, let me mention two things. Marc may have some more to throw into this after I start the answer here. I'd say one thing is that we had a very strong Q4, that we actually outperformed all of our forecasts in Q4, and so that's caused us to temper our expectations a little bit for the percentage growth into Q1.

I'd say the second factor is that we're a little bit cautious whenever we announce a new instrument like MiniSeq, that sometimes customers take a little bit of time to make a decision. So there is a chance that we may slow down at some orders in Q1 because customers are deciding between MiSeqs and MiniSeqs.

And that will cause some instruments to get pushed probably out into Q2 that otherwise may have come in, in Q1.

Marc, anything else to add?.

Yeah. The only thing I would add is if you look at it geographically, Japan has often been a very strong contributor to Q1, both instruments and reagents. And we're not entirely counting on that to be the case this quarter, given the funding challenges that we've seen over there..

Got it. And maybe just following up on MiniSeq, you gave the number in terms of individuals signing up for sort of the webinars.

Can you just help us put that in context of what you think the total addressable market opportunity is here? And then secondarily, the staffing needs to ensure that you can sort of execute on that part of the market, which is likely to be slightly different, obviously, than some of your other platforms just in terms of user base and sales, what sort of OpEx needs in terms of what you guided to already are sort of being allocated there?.

Yeah. I mean I think the OpEx considerations are built into the guidance that we'd provided, so there should be nothing incremental to what we've done in the guidance. So – and the commercial team clearly has been thinking about this for quite some time. We think it is largely opening up a new market segment.

We need to become more efficient to sell systems effectively that are priced at $50,000 and ultimately below with Firefly. And so we're a tremendous amount of work in the commercial organization to sort of tune our organization, hire people that perhaps are earlier in their careers and at lower price points.

We're working on our services model, and of course it requires that these instruments be fundamentally more robust to reduce the amount of service and training that's required. So all that commercial work is going on now and is built into the guidance that you've seen.

In terms of the addressable market, I think that the – if you think about the 50,000 labs out there, there's probably half of them would want to have a MiniSeq if they could, but the funding won't support that.

So getting below the $50,000 price point, we think, opens up certainly the opportunity to get to many, many thousands of these instruments placed.

We talked about our installed base of the MiSeq at the JPMorgan conference, and I would suspect if we went out a few years on MiniSeq that the installed base would be some multiple of the installed base of MiSeqs..

Great. Very helpful. Thanks, Jay..

Thank you. And our next question comes from the line of Amanda Murphy with William Blair. Your line is now open..

Hey. Good afternoon. I just had a quick question on the X platform.

So in terms of funding, it seems like while the NIH-derived large-scale funding might be sort of down year-over-year, that perhaps we're seeing some increased funding from other agencies within NIH in terms of large-scale sequencing, and then obviously positive potential trends going forward here in NIH, as well as industry buyers maybe that are a bit different than we've seen in the past in terms of pharma biotech and then even some clinical customers.

So I guess I'm just curious, do you agree with that statement? And then secondly, what might drive an acceleration in X placements beyond the 20 to 30 that you talked about? Is that something that's feasible if you think out two to three years from now?.

Well, I definitely agree with sort of your analysis of the funding opportunities there for Xs. I would say that we have placed an awful lot of Xs now with 27 customers. And if you recall back a couple of years ago when we first launched this, we had talked about 5 to 10. And so we hit a awful lot of the large customers around the world with this.

And so the incremental brand-new customer is naturally – has to be created from scratch almost because they generally won't be somebody who already exists.

The other thing to be a little bit cautious about is the fact that many of these customers are also going to want to run the full breadth of applications, so they may be opting for HiSeq 4000 rather than HiSeq Xs. So that's another consideration in terms of calculating how many Xs we may place. There's a couple of other things that could happen.

Population sequencing projects – you know we're tracking (39:28) and other places like Australia, which is an interesting opportunity for a POPSEQ project. China's announced that they're going to do some very large population programs, but nobody quite knows the specifics or timing around that, but that could certainly be an upside to Xs as well.

So I think, like so many parts of our business, there're some puts and takes here, and it's caused us to kind of keep the guidance the same at that 20 to 30 per quarter until we know anything different than that..

Got it. Thanks very much..

Thank you. And our next question comes from the line of Bill Quirk with Piper Jaffray. Your line is now open..

Great. Thanks and good afternoon, everybody. Jay, I just wanted pick up on a comment that you just talked about in terms of China. Certainly, I guess the new five-year budget plan is expected here as soon as March, and there's a lot of talk, certainly at a conference last week, about this being a pretty substantial long-term investment.

So I'm just curious kind of what you guys are hearing on China? And then I've got a follow-up. Thanks..

Yeah. And we're hearings big numbers, but none of that is official yet. So it's a kind of leaking out in bits and pieces. We don't know how much of it will be sequencing-directed and what the timing of that might be.

Some of these programs, if they begin, spend a year or two collecting samples, and they don't actually start doing any large-scale sequencing for a while. That's certainly the case, for example, in the U.S. PMI program, so there's no sequencing actually budgeted yet in the PMI program.

So we're just going to have to wait and see what the strategy of this is. The alternative could be that they're going to start collecting and start sequencing them just as they come in, which would be very favorable to us. So – and we're just waiting to hear more specifics in March..

Okay. Got it. And then on a follow-up, I guess a follow-up to the warranty question earlier. And that is, in terms of kind of that the increase in the warranty expense, obviously your installed base is growing.

Is this at all any reflection of kind of the diversification of your customer base? In other words, some of your translational customers may be hanging on to some of the systems longer, and so we could potentially see some more, I guess, sustainable growth within the warranty side. Thanks..

If by warranty expense – and what I was talking about as warranty revenue or maintenance revenue being a significant (41:52).

Yeah, warranty and service revenue. Sorry, Jay. I should have clarified that..

Yeah. I wouldn't say we're seeing necessarily people hold on to systems longer, although there probably is some of that going on. I think we're doing a great job of getting renewal contracts compared to any other business I've seen.

The fraction of customers that renew their contracts is very high, and our gross margins are great on these maintenance contracts. So we tend to do pretty well in that business, and we have a team that is totally focused on making sure that customers get their maintenance contracts in place.

So I think it's just largely a function of the growth of the installed base more so than it is, at least now, people holding on to systems longer..

Okay. Got it. Thank you..

Thank you. And our next question comes from the line of Isaac Ro with Goldman Sachs. Your line is now open..

Thanks a bunch. Question on the guidance this year regarding OpEx, I was sort of thinking through the puts and takes you guys mentioned, and curious if you could talk at all about whether or not there are any internal initiatives to support the scale-up of GRAIL this year, putting aside the ownership structure that we should keep in mind..

All of the initiatives to build up on GRAIL, Isaac, are going to be in the GRAIL business. So we will have our share of those expenses, and that's in the dilution numbers that we've already talked about. But there's nothing in addition to that other than some minor coordination kind of activities that will be slightly incremental expense to Illumina.

But those are kind of in the noise level.

Marc, anything else there?.

Just on the geography and how that's accounted for, I mean, we get the full extent of the expenses for both Helix and GRAIL in the R&D and SG&A lines, and you'll see that. And then we get the credit down below the line for that in the non-controlling interest shares.

So you'll see it kind of look like a higher uptick for Illumina in the OpEx line, but the benefit is down below..

Got it. And then maybe a follow-up, I was reviewing the comments that you guys made last month regarding GRAIL timelines, and was curious if you could perhaps talk little bit about some of the key milestones operationally you guys want to hit with GRAIL this year, pursuant to the clinical trial start in 2017.

Is there – are there any specific guidance, maybe not dates, but events that we should be thinking about to signal that you guys are on track?.

There are. So the key things that we're working on – a key goal for 2016 is to make sure that we've down-selected to the final or near-final assay method. We're pursuing in parallel a number of different techniques here. We're likely to have both DNA and RNA, maybe even methylation work going on in parallel.

And then, deciding on what the ultimate format of this test will look like by the end of the year could involve running sequential tests or multiple tests in parallel, and maybe across DNA and RNA. So that work has to happen this year.

We're also moving ahead as rapidly as possible on the MSK partnership to help understand many of the fundamentals about what happens in cell-free DNA in the blood and to begin to correlate what we've learned there with what actually is happening through biopsy of solid tumors.

And so all that kind of fundamental work that hasn't been scaled before is an important goal for us in 2016. Third thing I'd say is getting the clinical trial very well-defined in getting it structured in a way that when we push the button, start collecting samples, we have the ability to do that, and to do it at scale.

And that's going to require a lot of background work and potentially some partnerships at GRAIL we'll we need to form to get large-scale sample access. All of those things, we hope to finish in 2016 to be able to begin large-scale clinical trial work in 2017..

Got it. It's very helpful color, really exciting. I appreciate it. Thank you..

Thank you..

Thank you. And our next question comes from the line of Dan Leonard with Leerink Partners. Your line is now open..

Thank you. First question on the MiSeq versus – I'm sorry, the MiniSeq versus the Firefly.

Do you think that the announcement of the Firefly could impact interest at all in the MiniSeq? And if not, why not?.

We don't, Dan. We thought a lot about that, and we wouldn't have said anything if we thought it did. If you look at the relative output of those boxes, it's pretty dramatically different, a factor of six times, and the capital cost is going to be somewhere just above half – little more than half for the Firefly.

So I think that the kind of applications you're going to want to run on a MiniSeq are very different than what we're going to do on a Firefly. And for those reasons, we just don't think there's going to be any cannibalization in the near-term. It's a different market segment in our view..

And Jay, can you elaborate a bit more on your efforts to, I think you said, tune the sales force? You have talked in the past, it is sometimes tough for the lower-priced product to get attention when you have big ticket items..

Yeah, it is. I think we're beginning to introduce some very specific things here, and Francis can elaborate on some of this. But Christian and Francis have been working on defining how we do specialist overlays, and I think for the first time, we're actually considering creating a part of the sales force that doesn't sell the high-end instruments.

And as you know, up until now, we've taken the philosophy that salespeople know the best place to go and they know how to maximize their overall revenue and we let them be essentially market animals to go figure that out. But I think, for the first time, we're going to have to develop a sales force that sells just the desktop platforms.

So, Francis, maybe you want to give an update on where (47:51)..

Yeah, sure. As Jay said, look, there are number of things we're doing to more effectively and more efficiently get at that much larger, sort of low end of the market.

So, one thing we are doing is we're looking to bring in a targeted sales force that targets that low end of the market, primarily people that are maybe earlier in their careers, and so are less on a per-head basis than more experienced salespeople, and also primarily people that are working the phones.

And so we'll be expanding our inside sales capability to sell those products. In addition, we are looking to expand our ability to digitally get to those customers through expanding our e-commerce capability as well as being smarter about using our instruments to drive additional sales.

And then we're also looking at targeted areas where we can add specialization by market into the sales force that will allow us to target some of the smaller labs that we haven't been able to get to yet. So those are the kinds of things that we're doing in the commercial team..

Appreciate all that color. Thank you..

Thank you. And our next question comes from the line of Steve Beuchaw with Morgan Stanley. Your line is now open..

Hi. Good afternoon, and thanks for taking the questions here..

Sure..

One for me, you guys have been really helpful giving color over the last couple of years on how things are progressing in the clinical channel. I wonder, as you think about the plan for 2016, how you would imagine growth for clinical progresses relative to what we've seen over the last year or two..

I'd say overall, we expect that to be far and away the strongest growth area for us, fueled in part by average risk coverage in the NIPT space. The kind of things we're doing in the PGS and IVF markets, I think are going to accelerate the number of IVF cycles that use various forms of sequencing.

So, we think that's in the earliest stages of adoption, and we'll get into the higher part of the growth curve during 2016 and 2017. We're waiting for the inflection point yet to happen in the oncology market, and as I said, we're seeing good uptake of TST 15.

I think we need to really define what the regulated and reimbursed strategy is going to be in the oncology market after we get this next round of guidance from the FDA. And once we get that, I think it will help us clarify what kinds of products we want to push through the FDA and actually get approved.

And that, I think, puts a serious inflection in the curve if we can figure out how to do that efficiently in ways where the time it takes to get approval doesn't mean that the product you ultimately get approved is obsolete by time it gets there. And so, those are the key issues. But the oncology market is still very, very, very early.

And so we're not even up on the accelerating part of that growth curve, which we think will happen in the next couple of years..

Okay. Got it. And then on the Bio-Rad collaboration, I wonder to what extent you might be able to expound upon the plans there. I mean, given some of the chemistry and the work that we've seen come out of Bio-Rad, it's perhaps a little too easy to let our imaginations run in terms of what that could turn into.

Can you expound a little bit on where you see that going? Thanks..

Yeah. The collaboration is based on integration of their fundamental droplet technology, which they have working very well in other implementations for different applications, coupled obviously with our library prep and sequencing.

The initial target of the collaboration is around single cell and their droplet approach is very effective for doing high-efficiency single-cell sample prep. So we're excited to move that program forward.

As I mentioned at JPMorgan, I think that the method that is used there is quite extensible, and so we're exploring other applications that we may decide to put on that platform. And we're using both sales forces to sell this into the marketplace. So we're real excited about it, and we're getting good data already very early on in the collaboration.

And as we said at JPMorgan, we expect to have it out on the market late this year or early 2017..

Got it. Thanks so much..

Thank you. And our next question comes from the line of Dane Leone with BTIG. Your line is now open..

Hi. Thank you for taking the questions.

Just from a high level on your 2016 guidance for relatively flat instrument growth but somewhat robust consumable growth, can you help us – just give some color on how historically generally consumable growth in the following year of instrument growth has been lower but you kind of expect the opposite in 2016, as instrument revenue growth was a little bit lower in 2015 but it seems like you expect consumable growth in the following year to be a bit higher?.

Mark, do you want take that?.

The way the math works with the increased installed base that we built this year, that plus the increased utilization and the mix of instruments is what drives consumable growth to be so much higher next year.

So if you kind of look at this year's trend of instruments by quarter and you look at the continued growth in sequencing, it's always around the high – sequencing is always around – consumables, I'm sorry, always around high 20%s, low 30%s, even to mid-30% growth. And the flat instrument placement is sufficient to drive that..

And Dane, we're not implying an acceleration in sequencing consumable growth in 2016 versus 2015. We're just saying that sequencing consumables will be a large component of the growth next year..

Exactly..

Got it.

And on terms of MiniSeq, that 20%, 25% cannibalization rate, is that on a unit or dollar basis?.

That's on a unit basis..

Okay. Thank you..

Thank you. And our next question comes from the line of Bryan Brokmeier with Cantor Fitzgerald. Your line is now open..

Hi, thanks for taking the questions. You mentioned that the HiSeq X was below the anticipated range, but that's due to the order of timing.

Since several quarters since you began working with the – from your lower-utilization customers on improving their own utilization, have the utilization of those customers picked back up into an acceptable range?.

Yeah. I think, the best way to describe it is that we've got a handful of customers at the very high end that are using their machines all out, and whenever they need to add any bit of capacity, it means, they have to buy a new machine. We have a middle group of customers that on average continue to move up the curve. They're getting more efficient.

They're getting more sample access. They're getting better at running the overall pipelines. And so that continues to be kind of an upward pressure on the number. And then we have a small number of customers at the very bottom that frankly aren't doing very much and almost no matter what we do, it's hard to influence them to do more.

It's either funding issues or a couple of these vanity buys that we've talked about or customers who are just waiting for something structurally to happen in their environment that's going to cause them to actually start using the units. And there is a small number of those at the bottom end of the curve..

And you mentioned the weak funding environment in Japan, but could you provide some color on what you're seeing in China as well as in Europe? Thanks..

Yeah. I would say in Japan that things are starting to feel a little better. So in the fourth quarter, things got little bit better. It's not anywhere near back to where it was, so it's still got a long ways to go, which is why we remain a bit cautious about Japan as we've looked into our guidance for 2016.

In China, the research markets have been a bit challenging over the past year or two in terms of overall funding. But having said that, we have a couple of unique vectors into the Chinese market, one being the HiSeq X systems.

There's a sort of disproportionate number of HiSeq Xs in China, which gives us good reagent pull-through and incremental potential sales into those customers. And our NextSeq sales there are good because of our NIPT business.

So the downward pressure perhaps is the overall health of the research funding environment, but NextSeqs and HiSeq Xs are the strong uplift. Europe's been pretty steady. In Q3, we talked about the fact that we had some business that we think got pushed out to Q4, and you saw that we had very strong results in Europe in Q4.

So I think we recovered that business and more normalized the pipeline. When we exited Q3, we talked about a strong desktop pipeline that didn't quite make it over into Q3 revenue, and we're able to recapture that in Q4. So I wouldn't read anything into the Q3 weakness there. I think overall, Europe's pretty stable..

Okay. Thank you..

Thank you. And our next question comes from the line of Jack Meehan with Barclays. Your line is now open..

Hi. Thanks. Good afternoon. I wanted to start on GRAIL, and just curious if you began soliciting any feedback or received anything from managed care payers, just given the magnitude of the investment you're planning on making the next few years.

And then maybe off of that, just what do you think the criteria you need to demonstrate is in the clinical trials to earn reimbursement?.

It's a little too early to be talking to the managed care companies. We need to figure out exactly what this assay method is and get our own economic models done around knowing which stage of cancer we can detect. So there's some work we need to do before we actually embrace that community.

With respect to the clinical trial itself, what we're trying to do is demonstrate a stage shift. So we will screen a large population, identify on average for that small subset of that population that has cancer at that stage when they don't know they have cancer, what stage on average we detect it.

We'll filter them out of the population and then sequence the remaining group a year later and then two years later, and demonstrate that on average the stage of detection is earlier.

So that's a clinical trial design which we think will be sufficient to demonstrate that screening this population can be dramatically improved outcomes, but also improve the overall economics of cancer care..

Got it. That's really helpful. And then just one wrap-up with Marc, on the balance sheet, I'm curious just given some of the moves in the market to start the beginning of the year. I'm curious how you're thinking about capital deployment and just the repurchase program or M&A from here. Thanks..

Yeah. I mean, no real change. We'll continue to – and our intention always has been to try and offset employee stock issuances with repurchases where it make sense. We still have a fair amount of discretionary at our disposal. The one thing we need to be cautious of in terms of repurchases is our U.S.

cash, and that's something we continue to look at very carefully; no challenges or concerns right there at the moment. And then beyond that, we always want to make sure we've got plenty of opportunity for M&A should opportunities come up. And you've seen us do a few smaller ones in the past.

And then continued investment as you saw in the 2016 guidance..

Thank you. And I'd now like to hand the call back to Rebecca Chambers for any closing remarks..

As a reminder, a replay of this call will be available as a webcast in the Investors section of our website as well as through the dial-in instructions contained in today's earnings release. Thank you for joining us today. This concludes our call and we look forward to our update following the close of the first fiscal quarter..

Ladies and gentlemen, thank you for participating in today's call. That does conclude the conference. You may all disconnect. Everyone have a wonderful day..