Meredith Kaya - Director, IR Peter Hecht - CEO Tom Graney - CFO.

David Lebowitz - Morgan Stanley Geoff Meacham - Barclays Irina Koffler - Mizuho Boris Peaker - Cowen Eric Joseph - JP Morgan Divya Harikesh - Goldman Sachs Tim Chiang - BTIG David Nierengarten - Wedbush Securities Etzer Darout - Leerink Partners.

Hello, ladies and gentlemen, and welcome to Ironwood Pharmaceuticals Fourth Quarter and Full Year 2016 Investor Update Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be given at that time.

[Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the call over to Director of Investor Relations, Ms. Meredith Kaya. Please go ahead..

Good afternoon, and thanks for joining us for our fourth quarter and full year 2016 investor update. Our press release crossed the wire earlier this afternoon, and can be found on our website, www.ironwoodpharma.com. Today’s call and accompanying slides include forward-looking statements.

Such statements involve risks and uncertainties that may cause actual results to differ materially.

A discussion of these statements and risk factors is available on the current Safe Harbor statement slide, as well as under the heading Risk Factors in our quarterly report on Form 10-Q for the quarter ended September 30, 2016, and in our future SEC filings.

All forward-looking statements speak as of the date of this presentation and we undertake no obligation to update such statements.

Joining me for today’s call are Peter Hecht, Chief Executive Officer, who’ll provide a few introductory remarks; and Tom Graney, Chief Financial Officer, who will review Ironwood’s fourth quarter and full year 2016, financial performance and provide 2017 financial guidance.

We will provide a more comprehensive update on the business at our R&D Day which is being held on March 9th at our offices in Cambridge. Peter and Tom will be referring to slides available via the webcast. For those of you dialing in, please go to the Events section of our website to access the webcast slides.

I would now like to turn the call over to Peter..

Thanks, Meredith, and good afternoon, everyone. We appreciate you joining our call today. It was great seeing many of you at the H&Q conference last month where we highlighted Ironwood’s strong momentum driven by excellent commercial and R&D performance in 2016.

On the commercial front, we’re very pleased to be serving patients in two very large markets with innovative medicines. LINZESS is the branded prescription market leader for IBS-C and CIC with 38% sales growth year-over-year and rapidly increasing profitability.

ZURAMPIC, our first drug for uncontrolled gout launched late in 2016, and we expect DUZALLO, the fixed-dose combination of lesinurad and allopurinol to launch in the second half of 2017, if approved.

Both LINZESS and the lesinurad products have a potential to help millions of patients and to grow for many years, driving continued top-line growth and expanding operating leverage.

On the R&D front, our investments in innovations delivered important milestones including positive Phase 2b data for linaclotide colonic release; advancement of our sGC stimulators, IW-1973 and 1701 into Phase 2; submission of the DUZALLO NDA; and full enrollment of the IW-3718 Phase 2b trial for uncontrolled GERD.

We look forward to continuing our momentum in 2017, anticipating strong LINZESS volume-driven growth, further market development for lesinurad including the DUZALLO launch in the second half of the year, and at least four important clinical data readouts from our pipeline including Phase 2b data for IW-3718 midyear.

Looking beyond 2017, we expect our linaclotide and lesinurad products to continue to grow throughout their branded exclusivity period into 2031 for LINZESS, the mid 2030s for colonic release 1, and 2028 for ZURAMPIC and DUZALLO, providing us the opportunities for a long period with rapidly increasing Ironwood revenues.

As a near-term signpost along the way, we expect greater than 25% revenue CAGR between 2016 and 2020. And these are just the early days from which we expect to continue to drive sustainable, high-margin growth as these first products are augmented by current pipeline assets coming to the market.

We look forward to providing a more detailed review of our strategy and key programs at our upcoming R&D Day, here at Ironwood on March 9th. We hope to see many of you here then. With that, I’ll turn it over to Tom..

R&D expenses of $145 million to $160 million and SG&A expenses of $235 million to $250 million; total 2017 marketing and sales expenses for LINZESS to be in the range of $250 million to $280 million; net interest expense to be approximately $40 million in connection with our 8.375% notes on which we will begin paying quarterly interest in June 2017 and our 2.25% convertible debt; finally, cash used from operations to be less than $100 million.

In summary, we are on track to build a top performing commercial biotech with an expected greater than 25% revenue CAGR between 2016 and 2020, and continued margin expansion.

This is driven by expected growth from our two marketed products and innovation that we expect to deliver two commercial launches and at least four mid-stage data readouts in 2017. With that, I’ll hand it back to Andrew to begin the Q&A portion of the call with a reminder that we are hosting an R&D Day in a couple of weeks..

Thank you. [Operator Instructions] And our first question comes from the line of David Lebowitz with Morgan Stanley. Your line is now open..

Certainly in the last quarter with the -- last month, with the recent competitive launch from Synergy and Trulance, has there been any qualitative commentary from the various physicians in your market about the new drug and as far as how they compare?.

When we first launched into this market four years ago, we saw a great opportunity to develop that market. And we’ve been very successful in that respect with LINZESS with now two indications and three doses and clear market leadership. We really focus on bringing OTC patients into the RX market.

We see that as a clear long-term growth opportunity in this space; and in that respect, the more competitors, the better.

In terms of generating noise, we feel like with our portfolio and the clinical profile of LINZESS, we’re in a great position to take advantage of the commercial experience and investments we make behind the brand as well as the exceptional payer access we have. So, we’re excited to be introducing 72 this quarter as well..

With respect to that, has the initial uptake -- has already been initial uptake of the 72?.

We have not yet made it commercially available, we will by the end of the quarter..

Okay, fair enough. Thanks for taking my questions..

And our next question comes from the line of Yin Huang with Bank of America Merrill Lynch. Your line is now open..

Hi. Thanks for taking our question. This is Amanda on for Yin.

So, maybe first thinking about the pricing environment and then given that LINZESS taking price increases in the past, and what’s your thought for pricing strategy going forward?.

Sure, thanks Amanda for the question. When we first launched LINZESS, we priced the drug very responsibly.

And again, with the market where you’ve got 40 million potential patients, you want to ensure that if you’re generating demand for the drug and getting prescriptions, you want those prescriptions filled at the counter and you get that through having really strong payer access. So, we did not -- the payer to be a barrier to the uptake of LINZESS.

We worked very hard with Allergan to make sure that it was in fact the case.

To the point now where most patients with commercial coverage are able to get access to LINZESS for about a $1 a day, we continue to evaluate the environment both, the competitive landscape and also the payer landscape to make sure that LINZESS is appropriately priced to ensure access but also to make sure that we’re getting rewarded for the innovation and our shareholders benefit as well..

I think the only thing I’d add is -- if it’s okay, this is Peter. With both of these products, as Tom mentioned, the key is to ensure availability and access. And in both cases, we see the vast majority of our opportunity for growth in patients’ volume and consistent patient use, not largely in price increases.

That’s one of the benefits of these large patient categories..

Great, thanks. And I wonder if you guys can comment on also your plans for improving the launch for ZURAMPIC..

Well, we launched ZURAMPIC late in 2016, as you know and we are incredibly excited to be bringing what we really believe is an advancement in care for these patients. This is a large patient population with very little treatment options.

And when you look at the clinical profile of ZURAMPIC, it fits very nicely in addressing the unmet need for these patients. This category has had very little innovation in the last 30 years. So, as we introduce ZURAMPIC into the market, it does require some physician education.

But, the feedback we’re hearing, both from physicians and payers as we talk to them about the dual mechanism of action that works with an XOI and also ZURAMPIC, the feedback we’re getting is very strong and very consistent that they recognize the unmet need and see a real place in the treatment regimen for these patients.

So, we will -- as Peter mentioned, we filed the NDA for DUZALLO and expect to launch that in the back half of this year, which as a fixed dose combination we think will bring even more simple solution for physicians and patients and the dual mechanism being captured in one pill once a day..

In a category that hasn’t seen real innovation in 35 years, we recognize we have a lot of hard work to do. And we took this product on from AstraZeneca in the middle of the last year, and we’ve really launched from a standing start since.

And we -- again, we recognize a need to do quite a lot of hard work to grow awareness to get payer access, to get payers and physicians educated. Having said that, everything we’ve seen and heard since we took the product on is very consistent with the fundamental pieces we laid out at the time we did the deal.

We are very excited about the opportunity; the product profile is quite good; and everything we hear about the product from patients and physicians that have used it, has been quite encouraging. So, we are quite pleased with the opportunity and we recognize the hard work we have to do..

And our next question comes from the line of Geoff Meacham with Barclays. Your line is now open..

I just had one for Tom. So, as earlier questions, it looks like reimbursement access hasn’t back then strong, but looking at the profile of a new start today versus when you first launched, I guess I am just trying to get a sense for what is unmet and what you can tackle with subsequent formulations? Thanks..

Thanks, Geoff.

Just to clarify, you are talking about LINZESS, I guess?.

Yes, sorry. Yes..

Well, we see typical with the primary care category and a highly symptomatic space, the early adopters when we first came on to the market were for the thought leaders and gastroes who saw a lot of patients who were very highly symptomatic.

And as they’ve gotten comfortable with the drag and certainly as primary care physicians have gotten more experience with it now with overall 180,000 physicians having written LINZESS, as they get experience with it, they are able to better identify a broader range of patients that can benefit from the profile of LINZESS.

And that was really well set into us bringing the 72 to market as well. It was feedback from physicians saying they wanted greater dose inflexibility because this is a very heterogeneous patient population with a broad range of severity of symptoms. So, it’s really important to have alternate doses.

So, now, we will have three doses, we’ll two indications. And then, as you mentioned with the formulation, what we saw in the colonic release data, it was really encouraging that we’ve got a different profile in the CR1 formulation of linaclotide, which was cited to be moving into Phase 3 during 2017 for IBS-C.

And we think it will take a broad portfolio to address the most available patients..

Okay. And then, just a quick follow-up for GERD.

I know you will be talking about the clinical details at your R&D Day, but is there a hurdle you are looking for with respect to addressing the need, maybe just help kind of frame how you view the market this early on before the data obviously?.

Yes, Geoff; it’s Peter. We’ll take you through that in quite a lot detail in a couple weeks at R&D Day here. Just to frame up briefly for those that are in deep in the details, IW-3718 is being developed for patients with uncontrolled GERD.

These are patients who are taking proton pump inhibitors like Prilosec and Nexium, and are receiving either partial or no symptom relief despite being on the PPI’s chronically. And there’re about 10 million patients who suffer chronically from uncontrolled GERD, and there’s really been no effective therapies.

And so, even a small improvement would be important benefit in this category. There’re number of potential predicates to triangulate by -- to get a feel for what minimally acceptable might be from a regulatory endpoint and to give you a feel for what might be clinically meaningful, again we’ll triangulate.

But in the Phase 2b study, we have a PRO measure included. So, we’ll be able to correlate patient response on the key clinical endpoints with patient response within the trial. Again, we’ll take you through that in the R&D Day to give you more details on that..

And our next question comes from the line of Irina Koffler with Mizuho. Your line is now open..

I just wanted to explore expenses a little bit.

So, for SG&A, should we directionally expect commercial spend to go up in the second half of the year when you’ll be launching the DUZALLO? And then on R&D, because you’re not going to be doing the collaboration or I should say the colonic release program is not going to start till the back half of the year, should we expect a little bit of lighter R&D spend within the JV for Allergan at that time?.

I would say on the SG&A front that there’ll not be a large inflection with the launch of DUZALLO. We essentially are laying the groundwork for that launch throughout the year and will just be kind of dropped in to our commercial infrastructure that we already have in place.

So, I would say phasing of SG&A would be pretty similar to typical year and there really won’t be an inflection point there. On the R&D side, we do expect, as you noted to, initiate a Phase 3 as part of the collaboration with the colonic release 1 version of linaclotide.

In addition, we’ve said that we’re exploring further development of the colonic release 2 version for non-constipated subtypes of IBS. So, as we get better insight into the timing and extent of those trials, we’ll have a better idea of how much of the R&D would be part of the collaboration and how much would be as part of the independent pipeline..

And just to remind you, we have ongoing post marketing commitments as part of that collaboration, our ongoing trials, our pediatrics trials are still enrolling both in chronic constipation and in IBS. And we have an immunogenicity study enrolling. We have a few other trials ongoing still.

So, this steady state is not the right way to put it but there’s ongoing R&D expenses in the collaboration..

And our next question comes from the line of Boris Peaker with Cowen. Your line is now open..

My first question is on the 72 mg dose.

I’m just curious how do you plan to market it and specifically like what is the reason would you tell doc that they should prescribe it versus the higher dose of a LINZESS and will you in some way position it against Trulance or not?.

As I mentioned before, when we were discussing bringing forward to market an additional dose, it was really based on physician feedback, on the desire to have a different dose based on the way patients present their symptoms.

And as such, we chose the 72 microgram dose, which in the trial for registration was a better tolerated dose than the 145 dose; and essentially it just gets physicians the opportunity to select the dose that they think is most appropriate for the patient in front of them as well as consider LINZESS for a broader range of patients..

Does that mean you are not going to specifically promote the 72 mg dose, just let them know that it’s available and that will be the extent of it?.

Well, we will promote the whole range of LINZESS, both indications and all three doses.

Again, the opportunity here is to continue to grow the market and bring patients in, so the prescription market who are dissatisfied on the OTCs that they are on which is what we’ve been successful of doing since launch and will continue to do with 40 million patients and only a 1.5 million been prescribed LINZESS, we’ve got a long way to go..

Great. And my next question -- thanks for that answer. My next question is on DUZALLO. This is a rather unusual situation I think when you have a label saying that two drugs need to be combined in practical treatment then when you file for approval.

I’m just curious what is the FDA actually looking for in its regulatory review when it already says to combine these two drugs on the label?.

The clinical trials we’ve done with the two drugs is separate, not a fixed dose combination. And what the FDA wants to make sure is that the fixed dose combination provides the same bio-equivalency as the two drugs in a standalone therapy. So, you -- straight way you can manufacture the product, so that it will have the same relief..

So, it’s basically just to focus on PKPD and manufacturing.

It doesn’t seem like they would be much clinical review here?.

There was no new clinical data in the filing..

And our next question comes from the line of Anupam Rama with JP Morgan. Your line is now open..

Hey guys, this is Eric in for Anupam.

Just wondering if you could maybe provide a little color on where you are with respect to formulary approvals or payer access for ZURAMPIC, maybe some color around percent of target account interactions, hit rates? And also wondering whether to any extent with DUZALLO potentially being approved later in the year where that puts a limit on some of your current conversations with payers over ZURAMPIC?.

To answer your second question first, it does not put a limit on the conversations we are having with payers. Depending on the payers’ policy, it will be a line extension, once it comes to market.

We’ve been having very constructive conversations with payers, which starts out with really a clinical conversation to make sure that payers understand the mechanism and the clinical data that serves as the approved basis for the approval of ZURAMPIC.

And in those conversations, it’s been clear to us that payers recognize that this a patient population for whom the current formulary really doesn’t have a suitable treatment option for. So, we’ve been very encouraged by that. We have had some formulary wins and we continue to have ongoing discussions.

I think in terms of providing measures and metrics, we’ll look forward to updating you throughout the launch as we get clarity on the timing and physician -- formulary physician that we’re able to secure with ZURAMPIC. So, we’ll give updates throughout the year but so far so good on the payer front..

Great, and maybe just a follow-up on LINZESS 72 microgram. Just actually curious whether or not you’re making any use of sampling that differs currently from what you’re currently doing with 145 and 290 micrograms. Thanks..

No, we do provide samples for LINZESS and we have since launch as a way to make sure that we get uptake of the product. And we will not be deviating from our normal sample strategy with the 72..

And our next question comes from the line of Jami Rubin with Goldman Sachs. Your line is now open..

Hi. This is Divya Harikesh on behalf of Jami Rubin. Just a couple of questions. Your LINZESS SG&A spend of 250 to $280 million is higher than last year. As you think about -- you’ve talked about commercial margins for this product in a goal by 2020.

What is driving this incremental expense going forward? Are you increasing the sales force for the 72 microgram or is it in order to increase your presence relative to competition? Just trying to understand the nature of what’s driving that incremental expense. And the second question being R&D spend is roughly flattish year-on-year.

How should we think about this going forward, especially as you start bringing these sGC compounds into late stage development? Thank you..

Thanks Divya for the question. On the LINZESS commercial spend, really since launch, we have been in a pretty tight range around $250 million a year us and Allergan investment behind LINZESS. The guidance, you are correct, is now kind of 250 to 280, so picking up a little bit but not a drastic change from where we’ve been historically.

I think really the takeaway message there is we continue to focus on growth in LINZESS, in maximizing growth.

We’ve been happy with the quality of our sales growth through prescription and volume growth over the last year and want to take advantage of the fact that this is a very large market with a lot of patients left to be helped with LINZESS and the fact that we’ve had very strong payer coverage.

So, we want to make sure that with the combination of personal promotion and also what has been a very successful DTC campaign over the last three years that we continue to drive top-line on LINZESS.

On the R&D side, you’re right, as we advance the pipeline for sGC, we’ve got the opportunity there for many very-high value indications which would require R&D investment.

We’ll be watching along with you to see how those programs develop, certainly within 2017 for the guidance we have given, we plan on fully funding the opportunity in the sGC program..

And our next question comes from the line of Tim Chiang with BTIG. Your line is now open..

I just wanted to follow-up on the SG&A figure, because I guess you are going to spend much, an incremental $60 million to $75 million this year versus 2016.

And I am sort of wondering, is that incremental spend tied to ramp ZURAMPIC, DUZALLO, ramping that product up or is it more tied to LINZESS 72 microgram; I wasn’t 100% sure, or is it just a combination of it?.

Sure, thanks Tim. Well, as we’ve just talked on the question Divya asked around LINZESS investment, we continue to focus on the top-line for LINZESS.

Really what you are seeing in SG&A on the Ironwood guidance is essentially the full year impact of the ZURAMPIC investments we made in the fourth quarter as we -- in the third and fourth quarter, as we geared up the launch of ZURAMPIC. As you know, we expanded our sales force.

So, you are going to have the annualization of those fourth quarter expenses for the full year..

And maybe just one follow-up, are you going to keep your sales force as around 300; is that what’s included in your financial guidance for 2017?.

We currently have about 300, as you mentioned. And in the guidance for 2017, we haven’t disclosed what, if any changes, we expect to make to our sales force. But the spending covers whatever action we are going to take..

And our next question comes from the line of David Nierengarten with Wedbush Securities. Your line is now open..

I have a just a couple, one quick one. What was the gross to net in the quarter? And then, next one is a little bit more complicated.

Just to go back to question on the cash guidance -- cash burn guidance, do you see -- I mean, I assume that is mostly coming from the build out of the ZURAMPIC launch and SG&A and not a significant change in operating margins for LINZESS? Thanks..

What we saw in a fourth quarter was 34% growth year-over-year in LINZESS. And as we mentioned, the vast majority of that when you consider prescriptions and also script size, we see -- continue to see expansion in the average size of a prescription; it was about 26% of that 34%. So, you see overwhelmingly really volume driven.

We haven’t really talked about gross to net in a couple of years now. What we have said is that over time, we expect to realize gains in net price. But really, as we’ve been talking about on this call, it’s all about accelerating growth and maintaining growth of LINZESS by bringing additional patients into the category.

And as the market leader, we expect to capture more than our fair share of those incremental patients. On the cash burn piece, it’s important to remember, when you are looking year-over-year to that in 2016, we had $30 million in milestone payments that we don’t expect to have in 2017.

So, what we have in 2017 is kind of base business 2016 without those milestones, plus the annualization of the commercial spent behind ZURAMPIC and DUZALLO..

And our next question comes from the line of Jason Gerberry with Leerink Partners. Your line is now open..

Hi. This is Etzer filling in for Jason. Most of our questions have been answered. I just wanted to know if you could comment quickly of any conversations occurring on the reimbursement front, on the formulary access or as Trulance prepares to come onto the market as an additional option in constipation.

I just wondered if maybe you foresee any changes as far as LINZESS reimbursement or formulary dynamics in 2018..

We’re thrilled with the formulary position we’ve been able to achieve with LINZESS.

And I think that because of the strong clinical profile of the drug and the high degree of patient and physician satisfaction that payers have seen LINZESS now on the market for four years and with 180,000 physicians having written a prescription for over 1.5 million patients.

I think that track record really has enabled us to maintain a very strong payer position, which as I mentioned before, most patients who have commercial plans, can get LINZESS for about a $1 a day, which puts us in great position where the payer is not kind of getting in the mix, and is actually helping to make sure that patients who can benefit from LINZESS are able to actually get it.

With respect to our pricing strategy going forward, we’ve been very consistent that we think access is really important. We priced LINZESS responsibly since we launched it.

And we’ll continue to drive value in the market by innovating, and that starts with the introduction of the 72-microgram and also later on with the colonic release version of linaclotide CR1 if that’s approved..

Alright. At this time, I’m showing no further questions. So, with that said, I’d like to turn the conference back over to CEO, Mr. Peter Hecht, for closing remarks..

Thanks for your help Andrew, and thanks everyone for your time and attention. Just a reminder, we’ll be around this evening and tomorrow. So, if you have any follow-up questions, please reach out to Meredith. And one final flag, we look forward to seeing as many of you as can make it here, here at Ironwood on March 9th for our R&D Day.

We have a full agenda and lots of exciting data and strategy to take you through. So, we’ll look forward to seeing you here. Thanks again..

Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program and you may all disconnect. Everyone, have a wonderful day..