Ladies and gentlemen, thank you for standing by and welcome to the Ironwood Pharmaceuticals Third Quarter 2019 Investor Update Conference Call. At this time all participants are in a listen-only mode.

And after the speaker’s presentation there will be a question-and-answer session [Operator Instructions] I'd now like to turn the conference over to your speaker today, Meredith Kaya. Please go ahead ma'am..

Good morning, and thanks for joining us for our third quarter 2019 Investor Update. Our press release crossed the wire this morning 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 June 30, 2019, 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. Also included are non-GAAP financial measures, which should be considered only a supplement to and not a substitute for or superior to GAAP measures.

To the extent applicable, please refer to the table at the end of our press release for reconciliations of these measures to the most directly comparable GAAP measures.

During today's call, Mark Mallon will begin with an overview of the quarter; Tom McCourt will highlight our commercial and development progress; and Gina Consylman will close by discussing our third quarter financial results and 2019 financial guidance. Mike Shetzline will also be available during the Q&A portion of the call.

We will be referring to slides via the webcast. So those of you dialing in please go to the Events section of our website to access the webcast slides. With that I will turn the call over to Mark..

to accelerate LINZESS, advance our pipeline and continue to deliver profit. First, LINZESS. LINZESS U.S. prescription demand continues to show double-digit year-over-year growth hitting all-time high during the period in both extended units and new-to-brand, translating into $215 million of sales in the third quarter.

As a result of this continued momentum, we now expect mid-single-digit percent year-over-year growth in net sales. This compares to our previous guidance of low to mid single-digit growth. Second, our GI pipeline is advancing further into late-stage clinical studies.

Top line data for 7246, our product candidate in Phase II for treatment of abdominal pain associated with IBS-D is now expected in mid-2020 instead of the second half of 2020 due to faster than expected enrollment.

We are excited about both 7246 and 3718, our Phase III product candidate for the treatment of persistent GERD as they each represent new and innovative potential treatment options for two large and underserved patient populations.

And third, we recorded GAAP and non-GAAP profitability for the third quarter, which was driven by strong operational execution, our amended ex U.S. linaclotide partnerships with Astellas and AstraZeneca and disciplined investments.

As a result, I'm pleased to announce today that we are raising our 2019 revenue and adjusted EBITDA from continuing operations guidance. Gina will talk more about this later on the call. But again I would like to congratulate the team for their hard work and continued focus on our business.

Beyond these great results, we made significant progress across a number of other critical areas core to our strategy. We secured our second commercial partnership in less than six months. The team is thrilled to be working with Alnylam to build awareness within the GI community about Acute Hepatic Porphyria or AHP.

And if approved, we will help bringing Alnylam's givosiran to AHP patients, who are in desperate need of treatment. The sales force is already increasing awareness among physicians about AHP, further enhancing their productivity in combination with their promotional efforts for LINZESS and VIBERZI.

Additionally, we are excited about the emerging area of digital therapeutics. Pear Therapeutics announced just yesterday that we entered into an agreement with them to explore developing their innovative prescription digital therapeutics or PDTs for the treatment of selected indications within the GI space.

We believe digital therapeutics have the potential to become an important tool for patients in the future and we're looking forward to working with Pear to evaluate PDTs specifically within GI. Lastly and importantly, we strengthened Ironwood by adding strong senior leaders in regulatory biostatistics, finance, corporate development and HR.

Our leadership team is energized and committed to delivering on our mission to bring new medicines to patients living with GI diseases. We have made significant progress since our launch as a new company last April, as evidenced by these achievements, but we recognize that we have more to do to deliver on the value creation potential of Ironwood.

First and foremost, we must continue to execute on our core priorities. We believe there is tremendous value yet to be unleashed within our existing portfolio. Beyond that, our management team and Board are exploring options to further strengthen our business and deliver on our mission.

With that, I'll turn it over to Tom to discuss our commercial and pipeline performance.

Tom?.

Thanks, Mark. Our commercial performance during the third quarter was driven by the continued growth of LINZESS. LINZESS prescription demand, increased 15% compared to the third quarter in 2018. And impressively, our new-to-brand, prescriptions were up 12% year-over-year during the third quarter.

For the first time ever, during the third quarter, LINZESS became the number one prescribed IBS-C and chronic constipation treatment, meaning it is prescribed more than any other branded or generic option. LINZESS U.S. sales grew nearly 5% to $215 million compared to this time last year.

We attribute this growth to a number of factors, including the continued impact from the withdrawal of generic prescription MiraLAX for occasional constipation from the market, the launch of our DTC campaign last April and then the refreshed consumer materials introduced in September and our positive Phase IIIb abdominal symptom data that we announced in June.

Let me briefly talk about each one of these. First, the withdrawal of prescription MiraLAX last November was a major disruption in this category. Not only are patients, now seeking different prescription options, but physicians are choosing LINZESS for more of their IBS-C and chronic constipation patients.

And this seems to be having a lasting effect, contributing to the strong LINZESS growth that we have seen this year.

Regarding our Phase III abdominal symptom data, in July, our sales force began communicating to physicians about the benefit LINZESS delivered in relieving overall abdominal symptoms of bloating, pain and discomfort in patients with IBS-C.

We also refreshed our consumer materials in September to include disease state information about IBS-C, including a reference to the abdominal symptoms including bloating and discomfort. We plan to file a supplemental new drug application with the FDA later this year.

Looking ahead, we believe that there's significant life cycle management opportunities to continue to grow the brand.

We and Allergan are evaluating several, including expanding our addressable patient population, such as in pediatrics or possibly other indications and enhancing our understanding of the mechanism to continue to strengthen the clinical utility of linaclotide. Turning to our pipeline.

I'll start with 7246, our delayed-release formulation of linaclotide that we and Allergan are developing as a nonopioid intestinal pain relieving agent for patients suffering from abdominal pain associated with certain GI disorders.

Estimates suggest that a significant portion of patients with GI conditions including IBS use opioids chronically to treat their GI pain. Given the risks associated with opioid generally and the potential adverse events specifically for patients with GI disorders, developing a nonopioid GI pain drug is of critical need.

We are initially exploring 7246 for the treatment of pain associated with IBS-D and initiated a Phase II study this past May. Enrollment in this study is going very well. And as a result, we are now expecting topline data in mid-2020 versus our original expectation of data in the second half of 2020.

If these Phase II results are positive, we would expect to initiate a Phase III pivotal trial with 7246 as early as the end of next year. We presented data last week at the American College of Gastroenterology meeting showing that, as desired 7246 did not impact bowel movement function or stool consistency in a Phase I study of healthy volunteers.

These data complement our positive Phase II data for 7246 relieving abdominal pain associated with IBS-C and further supports our rationale for exploring the effect of 7246 to relieve abdominal pain related to IBS-D. Turning to 3718, our bile acid sequestrant for the potential treatment of persistent GERD.

The Phase 3 trials continue to enroll patients. These trials are designed to evaluate safety and efficacy on the two most bothersome symptoms of persistent GERD; regurgitation and heartburn. As a reminder, these are rigorous studies intended to ensure appropriate patients are enrolled in the trial.

Patients are required to have a positive Bravo test, meaning they test positive for acid reflux which requires an endoscopy. Additionally, we are enrolling both erosive esophagitis patients and non-erosive GERD patients. We have enrolled over half of the study to-date.

But due to the demands of the study, enrollment has been slower than we originally expected. At this time, we continue to target topline data in the second half of 2020. We have already taken actions to further support enrollment such as introducing central recruiting and are monitoring it closely.

We are also considering a number of additional opportunities to support enrollment and expect to continue to update you as we move forward.

We are very excited about the potential for 3718 as we believe it represents an important opportunity to improve care for an estimated 10 million patients who continue to suffer from both heartburn and regurgitation despite taking standard of care PPI. We look forward to sharing more with you on this program as we do move forward.

As I mentioned, a team of us were at the ACG Meeting and the buzz around Ironwood and our GI portfolio is noticeable. There continues to be significant excitement about 3718, 7246 and LINZESS among both key opinion leaders and the broader GI community, further establishing Ironwood as a leading GI company.

With that, I'll turn the call over to Gina to discuss our financial results for the quarter..

Thanks Tom. As Mark mentioned, the third quarter was one of our strongest quarters to-date and that is especially true as it relates to our financials.

We recorded $131 million in total revenue, our highest revenue recorded ever as well as $21 million in GAAP net income from continuing operations and $76 million in adjusted EBITDA from continuing operations.

Over these next few minutes, I will outline the steps that we have taken to simplify our business, strengthen our capital structure, and continue to grow profits. Further, I will review our updated 2019 financial guidance. Please refer to our press release for additional details on our financials for the quarter.

First, we simplified our business by amending two of our ex-U.S. linaclotide partnerships with Astellas in Japan and with AstraZeneca in China.

Both of these partnerships were amended with these objectives in mind; to eliminate manufacturing responsibilities and focus our strategy in the U.S.; to enable strong partners like Allergan, Astellas, and AstraZeneca to bring linaclotide to patients globally, and to continue to share in the value creation from each of these opportunities.

In aggregate, these amendments resulted in approximately $42 million in license and milestone revenue recorded during the third quarter. Starting with our partnership with Astellas. Beginning in 2020, Astellas will assume full manufacturing responsibilities for linaclotide in Japan including the supply of linaclotide API.

In return, Astellas paid IronWood a $10 million upfront payment recorded in the third quarter. Astellas will also pay Ironwood royalties beginning in the mid-single-digit percent and escalating to the low double-digit percent based on aggregate net sales of LINZESS in the territory.

In 2019, Ironwood continues to expect revenue from Astellas to be approximately $55 million including API sales and the $10 million upfront payment. As a reminder, we will no longer be supplying API to Astellas. And therefore, we'll not record API revenues in 2020 and beyond.

Starting in 2020, we will only be recognizing revenues from royalties from Astellas. In China, AstraZeneca obtained exclusive rights to develop commercialize and manufacture linaclotide. As a result, we will no longer be jointly funding the development and commercialization of linaclotide or sharing in the net profit in China.

In return Ironwood will receive up to $125 million including $35 million in non-contingent payments and up to $90 million in commercial milestone payments.

We recorded approximately $32 million of the $35 million non-contingent milestones as collaboration revenue in the third quarter and will accrete the remaining $3 million as interest income through 2024.

Additionally, Ironwood will receive tiered royalties beginning in the mid-single-digit percent and increasing up to 20% based on aggregate net sales of LINZESS in China. We are excited about the launch of LINZESS in China, which is expected to occur very soon. Product is already available and the AstraZeneca field force has completed training.

Moving to our debt. In an effort to strengthen our capital structure and lower our cash interest expense over the next few years we restructured our debt this past August by issuing $400 million in convertible notes.

With these proceeds we paid off the remaining balance of our 8.375% notes in their entirety and repurchased $215 million of our 2022 convertible notes. We are aware of the potential dilution effect with the convertible instrument and as a result have guided that we expect to settle the remaining principal amount of the 2022 notes in cash.

Additionally, we believe that based on our current cash projections we will have the option to settle our 2024 and 2026 notes in cash as well.

Our new debt structure lowers our expected cash interest payments considerably over the next few years allows us to smooth out the maturities of our debt obligations over time and enables investment behind our core business, while still maintaining strategic and operational flexibility.

Please see our press release for the financial terms of these new converts. Turning finally to our guidance for full year 2019. As Mark mentioned, we are thrilled to be able to raise our 2019 financial guidance.

As a result of our strong performance of the past two quarters we now expect revenues in 2019 to be in the range of $410 million to $420 million and for adjusted EBITDA from continuing operations to be greater than $130 million. This reflects the $42 million in license and milestones recorded during the quarter. Continuing our 2019 guidance.

We also now expect separation expenses to be approximately $30 million restructuring expenses to be approximately $4 million. And as Mark mentioned earlier, we now expect year-over-year LINZESS net sales growth in the mid-single-digit percent. With that, I will turn it back over to Mark for some closing comments before we begin Q&A..

Thanks Gina and thanks to the entire Ironwood team for working so hard to achieve these excellent results. In summary, over the past seven months since the separation Ironwood has demonstrated strong execution against our core priorities. LINZESS demand has continued to show strong growth and we are advancing both 3718 and 7246.

And finally we have taken a number of decisive steps to strengthening our financials improving our operations and growing profits. We believe we are well positioned to continue to advance toward our vision of becoming a leading GI company and look forward to sharing our continued progress with all of you.

With that, I'll turn the call over to the operator and we can begin the Q&A..

Hi. This is Ishmael [ph] on for David. Thank you for taking questions. First given the large population of patients and the demand in refractory GERD can you elaborate on what factors are leading to a slower-than-expected enrollment for 3718? And I have a follow-up after that..

Okay. Thanks Ishmael. I'm going to ask Mike our head of R&D to take that question. Thank you..

Yeah, certainly. So thanks for the question. As Tom mentioned earlier as well as a reminder these are really two big studies with over 1300 patients totally expected to be enrolled. We designed the development program in a rigorous fashion to ensure we enroll appropriate patients in the trial.

That0 includes patients with established gastroesophageal reflux disease and that requires an endoscopy. In addition patients require a Bravo and the Bravo technology needs to be implemented to ensure they have continued acid reflux. Due to this enrollment has been slower than originally expected.

At this time, we continue to target top line data for the end of 2020..

Okay. Great. That's very helpful. And for my follow-up question..

Did you have a second questions?.

Of course. On the abdominal symptoms data you mentioned updates to your marketing and communication. And with the updated guidance of mid-single-digit increases in net sales can you give details around how you may have already seen this data help boost volumes and expectations moving forward? Thank you..

I'll ask Tom to answer that..

Yes. Thanks. I think that it's going to be driven by really two things. Initially, we've been out since June talking to physicians about these additional symptoms which is clearly broadening their view of the appropriate patient.

And combined with the removal of prescription generic MiraLAX, which obviously is boosting sales as far as point of care decisions.

And I think that's really been -- initially our focal point is making sure that physicians are fully aware of these expanded benefits of the drug and looking at a broader set of patients that would be appropriate for LINZESS and they're clearly making those choices. The second piece is certainly on the consumer side.

And this is a two-pronged strategy. First of all, making sure patients are well aware that their symptoms of abdominal discomfort and bloating which often are the most prevalent and problematic symptoms can be relieved.

And obviously educating those patients, who are at point of care, will improve that dialogue between physicians and patients and further enhance LINZESS as a choice. The second piece of that strategy is the broader population of sufferers, who are not actively seeking care but suffering.

And that's in excess of probably 15 million patients, who are suffering from chronic frequent abdominal symptoms associated with constipation and really can get relief. And what we have seen is tremendous promotional response in the DTC effort.

So, by adding those claims to the net add and initially we added it solely focused on the disease portion of the add, we'll be expanding that to make it more visible as we move forward as we get approval and clearance with the FDA.

So we're very, very excited about the opportunity that these new data provide us as far as helping patients and physicians..

Great. Thank you for taking my question..

[Operator Instructions] And your next question comes from the line of Jacob Hughes from Wells Fargo Securities. Go ahead, please. Your line is open..

Hi. Good morning, gentlemen..

Hi. Jacob. On the LINZESS net sales growth guidance increase, what is the assumption there on the price erosion as the mid to high single-digits changed versus prior? And then, I just have one follow-up..

Yeah. I'm going to ask Gina to comment or answer to your question..

Sure. Thank you for the question. As you recall, earlier in this year, we did guide to mid to high single-digit price erosion for 2019 and we were definitely trending towards the higher end of that guidance in the first few quarters of this year.

But, as we have also said a lot of different times throughout these various calls is, that the gross to net does bounce around. And we were able to see a small uptick in price in the third quarter versus Q2 and we're optimistic about where we will be for Q4 as well.

So, as a result, we are still guiding within that range to the mid to high single-digit price erosion for 2019. And maybe just to further clarify, we're optimistic that we'll be able to mitigate the price erosion somewhat in 2020.

We're working right now very closely with Allergan on our forecast for 2020, and we are optimistic that many of the items such as the consolidation competition and the mix of payments that really almost collided in 2018 that had the impact in 2019 that we guided to will be lessened for that price erosion in 2020..

Okay. Understood. And then secondly, I think on the 2Q call, you commented about an active review that you're doing internally.

I think it's more longer-term oriented, but has anything come out of that to date?.

growing LINZESS sales, accelerating our pipeline and delivering on profit. So the bar is high for any sort of business development activity that we pursue. We are getting regular requests and being seen by people that have assets that could be partnered.

And so that's great to hear, but we're going -- and we'll continue to evaluate that to see if there's something that could deliver value to patients and to shareholders. But in the meantime, we're staying focused on our core priorities..

Okay. Thank you very much..

Okay. Thank you..

Your next question comes from the line of Eric Joseph with JPMorgan. Go ahead please. Your line is open..

Hey, guys. Thanks for taking the questions..

Hi, Eric..

Hi. Just a follow-up on the Phase III recruitment with IW-3718 and your comments around endoscopy. Is it that you're experiencing, I guess greater reluctance on the part of patients to undergo endoscopy compared to expectations or higher than expected failure rates post assessment? And then I have a follow-up..

Mike?.

Yeah. That's a good question. And the answer is actually both. I mean, as enrollment in clinical trials as I'm sure you're aware gets more challenging as patients have to go through more procedures. So the actual execution of going through the procedure does compromise the informed consent for some patients and they decide not to enroll.

And the other side of that in order to pursue an overall GERD or reflux indication, we want a broad spectrum of patients. And -- but we want them to have residual acid exposure as well. So the Bravo technology there is what ensures patients to have adequate acid to ensure they have GERD.

And so they have to pass that test so to speak and have a positive Bravo. And that is one of the other things that actually compromises the ability to enroll patients in the study. So that is correct on both fronts..

Okay.

I guess related to that, are you thinking any differently about the sizing of the additional patient population in your experience? Or this is more just about the patient -- the threshold for patient eligibility in the Phase III trial?.

Tom?.

Thanks Mark. Without question this -- the opportunity has not wavered at all. In fact, I think as we've got into the data and we've learned more about what the role of bile in the disease as well as our effect on -- our ability to improve the mechanics of GERD as well as the symptoms, I think we're even more optimistic with regard to the potential.

And as I mentioned we think there's eight million to 10 million Americans that continue to suffer from really problematic heartburn and regurgitation in spite of taking PPIs.

And I think the most striking piece that we're continuing to see is certainly the importance of heartburn, ongoing heartburn but also regurgitation, which consistently is the more problematic symptom for the majority of these patients. And I think that's where 3718 really stands alone.

There's really nothing that has ever been seen before that really has this magnitude of benefit on regurgitation. And if the Phase III data mirror what we saw in Phase II, I think we feel -- we're very, very encouraged by the commercial opportunity that's in front of us.

But I do recognize we want to make sure that we conduct the study in a very rigorous action and make sure that we have the appropriate patients in there. As Mike said, it's challenging but we want to make sure we absolutely have the right patients to really be able to create the profile of the drug that will enable us to succeed commercially..

I just want to add one qualitative thought. I've had a chance to get out and visit a number of sites investigator sites as have Mike and Tom and other members of the team. And I have to say the enthusiasm for this program is really high. And that's despite -- this is a challenging program for sites to do and it's a big program.

So there's lots of patients being in screen. And I think -- and what they say is that these patients that are coming in are really suffering, they need a new solution and they're excited about the possibilities. These sites -- many of these sites have professional gastroenterologists.

They understand what might be behind the bile and the role it's playing. And so all of that factoring together, I think just reinforces the quantitative numbers that we already know from our previous work that these patients exist and there's really a significant unmet need..

One quick one if I could and I'll hop back in queue. As you contemplate expanding the number of sites, is that going to be similarly within North America? Or do you look to bring on trials outside of the U.S.

and Canada?.

It will stay in North America..

Thanks a lot, guys..

Thanks, Eric..

Your next question comes from the line of Tim Chiang with BTIG. Go ahead please. Your line is open..

Hi, thanks..

Hi, Tim..

Hi, Mark. So just looking at your business model, obviously, you're generating more EBITDA. Now you're focused on profitability. I mean, what sort of focus items do you think you'll really target next year in terms of trying to optimize LINZESS? Obviously pricing trends might improve some. I sort of wanted to get your thoughts on that.

Can you get to positive pricing potentially next year with LINZESS?.

So let me take the second part and I'll let Tom answer the first part. So, again, we believe that we'll see a moderation of price erosion in 2020 from the level that we have today. But we don't say that we're going to see price increase. I think that, in the current environment of healthcare, that wouldn't be a realistic expectation.

But I think we -- as shown by our increase of the guidance for revenue this year, if you have slower erosion with this continued strong growth, then I think we're going to be able to drop more net sales to the bottom line. And we're certainly going to focus on that.

And I'll turn it over to Tom to answer the more specifics about where the levers are for 2020..

one, these additional abdominal symptoms are clearly broadening physician's view of the appropriate patient and they're choosing more patients. I think the other thing that we've also seen is the adherence of the program.

This 90-day program, Tim, that we launched a year or so ago, which we initiated because we saw a large portion of patients discontinuing therapy in the first 30 days. And they're largely discontinuing because they're not getting adequate pain relief. And we know it takes six to eight weeks to have that.

And once we get them to six weeks, we increase the overall adherence by over 40%.

So what this 90-day program has done, is it enables patients to realize that benefit, it increases overall adherence and it's driving the size of the prescriptions that you're seeing both reflected in the overall demand growth, but also the overall days of -- the annual days of therapy.

So I think, as I look at next year, I think, there's three things. One, we want to continue to expand and motivate patients to come and seek care. We think we can continue to broaden physician's view of the appropriate patients. And I think we're going to continue to try to hang on to these patients for longer periods of time.

So each patient becomes more valuable. I mean to Mark's point, we're being very realistic about what we think is going to happen with price. I think we've done -- we've got everything in place to try to hold the line on price, but there's always unforeseen things that happen.

And I think we just want to make darn sure we're controlling the things that we can control that drive the overall growth and health of the brand..

That's really helpful. I had one follow-up question. It's a financial question for Gina. Obviously, you've reissued new convertible debt at a much lower interest rate. How much cost savings -- is there a way you could quantify that for next year? I mean, obviously, your guidance is around $35 million in net interest expense this year.

I mean, what sort of figure should we expect for next year?.

That's a great question. And one of the areas that I just reiterate and why I thought it was important for us, is that the lower interest rates will provide lower cash payments as opposed to overall interest expense. So maybe, just a couple of comments related to that. I know you asked for 2020, but I'll give you a little bit of color for 2019 as well.

The overall expense in 2019 is about $1 million less but the cash component is about $3 million less for us, just from August to the end of the year. And then for 2020, we will be giving actual guidance in early 2020.

But to give you an indication, the cash component more than doubled for the savings for next year, so probably closer to $7 million savings as opposed to $3 million for this year..

And your next question comes from the line of Boris Peaker with Cowen. Go ahead please. Your line is open..

Great. Just maybe a longer-term question on LINZESS. Several years ago you had a target time line for reaching $1 billion in annual sales, which was then later pulled.

I'm just curious, given kind of the current trajectory and your thoughts on pricing and discounting, do you anticipate at some point reissuing a long-term guidance for LINZESS reaching the blockbuster threshold?.

Yes. So, I think, as we said, we're very excited with the strengthening growth of LINZESS. And, I think, we are certainly aiming to make this $1 billion brand. And plus I think whether we in the future issue guidance on that, but we will continue to discuss and think what investors will need to know to help appropriately value the business.

But at this point, I'm not ready to comment on that other than to say that our ambition remains the same. There's a huge unmet need, a huge number of patients that are not getting LINZESS yet. And so we're aspiring still to deliver on that $1 billion plus ambition..

Great.

And looking at the expansion for LINZESS, just curious for the abdominal pain study that you're doing, what do you need to see in Phase II? What kind of an effect size, do you need to see in order to move it forward into a Phase III program?.

So just to confirm you're talking about 7246?.

Yes..

Okay. I'll turn that over to Mike..

Yes. So it's a good question. And as you know that study, the 7246 study and the 7246 program is initially starting in IBS-D. In IBS-D, we're focusing on the pain benefit in IBS-D. So that is an important nuance because other therapies in IBS-D has focused on the bowel pattern as well as the pain benefit.

So in effect, we're in a new space as a pain therapeutic for GI pain. And so we are targeting a clinically meaningful benefit in that population which we've estimated to be about 30%, because that's consistent with the benefit that you see in IBS-D for the products that had the pain benefit as well as the bowel frequency benefit.

And as a Phase II study again that will be worked on with the FDA as we design the full development program after hopefully a successful Phase II study..

And I think from a commercial perspective what we -- if you look at the existing treatments that are out there, nobody has really achieved that pain only endpoint. I mean VIBERZI is the global endpoint, the composite endpoint with it, but neither XIFAXAN or VIBERZI were able to hit this responder endpoint for pain.

And that's where we see a huge unmet medical need first in IBS-C -- IBS-D but certainly having a drug that we know can relieve pain has really no effect on bowel habit and appears to be quite safe. The utility beyond IBS-C is really quite significant. And that's the work that we're currently doing as we see data come out of this IBS-D study.

Now the challenge is where do we go next, because this is a very, very large opportunity for us. It creates a whole new area for growth for linaclotide..

So just to confirm the target is 30% improvement on a pain score? Just making sure, I understand your response..

It's 30% improvement in responder end point. 30% improvement per patient responding in the study..

Got you. Okay, great. Thanks for taking my question..

Thanks, Boris..

[Operator Instructions] Your next question comes from the line of Ram Selvaraju with H.C. Wainwright. Go ahead please. Your line is open..

Hi. Thanks so much for taking my question..

Hi, Ram..

Hi. Thanks so much. I wanted to ask specifically about the givosiran partnership with Alnylam.

I would -- it would be helpful if you could perhaps give us maybe some background on the givosiran market opportunity just recap the partnership metrics and how that relationship is going to work? And also maybe give us an idea of what the pricing situation would be for that product? And what the prescriber overlap is likely to be relative to what your sales force is currently doing? And if you could also confirm that the PDUFA date is in fact February 4, 2020? And then I had one follow-up.

Thanks..

So -- yes. So it's just a couple of things. There are a couple of questions in there for example like the PDUFA date and pricing. We're going to defer those to Alnylam. That's the scope of their responsibility.

I'll let Tom talk a little bit about sort of the market opportunity and why we see such an exciting sort of synergy with the work that we're doing. And then Gina will recap the -- what we've shared around the details of the partnership..

Yes. Thanks, Mark. This is a rare disease. I mean, it's an extremely debilitating disease. And the reason why this is attractive to us and why Alnylam saw the value of us getting involved in the partnership is the primary symptom that these people suffer from is really severe intractable abdominal pain.

And most people don't even think about acute hepatic porphyria as an option as far as the underlying cause. So -- and almost all of these patients are seen by gastroenterologists multiple times in their patient journey.

So there was a clear opportunity for us to play a role educating our current customers on certainly the disease which we're actively doing right now as well as the drug gets approved the benefits of the drug. So our role primarily is to identify patients.

Now the challenge here with any orphan disease or rare diseases is where are those patients and how do we identify them. So we're working very closely with Alnylam to do that. So there's a pretty broad range of estimates of the overall prevalence of the disease. And it's really quite unknown.

And I think for us we see an opportunity to help our customers improve care for a very, very debilitating disease. It also creates the opportunity for us to learn about how to market in rare disease or orphan diseases as we look at future opportunities for the company. So I think we're very excited about the opportunity.

The collaboration with Alnylam is going very, very well. The response that we've already heard in the field is extremely encouraging with our existing customers. We got not only the engagement but the belief that they probably do have symptoms or patients there that they just haven't properly evaluated.

So as we move forward, obviously we'll learn a lot more in the next year or two with regard to the overall commercial opportunity, but I'll turn it over to Gina to talk more specifically about kind of our financial arrangement..

Sure. And actually you'll be able to see -- we are expecting to file our 10-Q later today and you'll be able to see a bit more detail as well. But until that time just to share a few things with you. One just the contract term is August 2019 through December 2022 and that includes about $9.5 million of total fixed payments.

So that's part of our contract consideration and then there's also royalties in addition to that. And to give you a little bit of insight about what we expect to recognize on a quarterly basis this is our first quarter with the co-promote. It was a partial quarter and we recognized approximately $700,000 of revenue this quarter..

Okay. Great. And then just one follow-up which is not related to Givosiran.

Can you just give us a sense of when you expect plecanatide generics to enter the market? And if you are anticipating the introduction of generics for that product significantly ahead of generics for linaclotide? And if that is the case approximately how far in advance of the introduction of linaclotide generics you expect the availability of plecanatide generics? Thank you.

.

So as far as -- I really, can't comment on plecanatide and their IP status. But obviously when I look at where we are in the marketplace they have a minimal presence in the marketplace. I think we've demonstrated that linaclotide has a very, very strong brand profile.

And the reason that it continues to perform so well is obviously the overall satisfaction that we're seeing from both patients and physicians as well as what we've been able to do with payers. So certainly we know we have IP into 2030. We're going to continue to raise the bar with regard to the clinical profile.

As far as plecanatide's IP I really can't comment on.

But I think we as the market leader have to continue to stay the course to grow this market as fast as we can, continue to differentiate the brand and expand the clinical utility of what we have with linaclotide, which we've already started to do both with regard to additional symptoms the dosage formulation, the life cycle management plan and the overall strength of the product.

And that's really what we got to stay focused on..

Thank you very much..

Your next question comes from the line of Patrick Trucchio with Berenberg Capital. Go ahead, please. Your line is open..

Hi, Patrick..

Good morning. Hi. So just a follow-up question on MD-7246 and a follow-up on LINZESS. Just first on LINZESS. So the commercial margin this quarter increased to 70% on the collaboration. Can you tell us what is driving….

Patrick, we lost you.

Are you still there?.

Yes. I'm still..

Yes. So you're asking about what's driving the improvement in the brand margin -- commercial margin. Is that correct? Because you broke up, at the end..

Yeah. Sorry. So the commercial margin for LINZESS increased to 70% this quarter. I'm just wondering, what's driving that improvement. And what could drive further improvement in the fourth quarter and in 2020? And then, if there's a peak margin, we should expect over the long-term..

Yeah. Tom, go ahead..

Yeah. I mean, I think, what we've seen, over the last several years is, the level of investment has been pretty steady, while revenues continue to grow, which is really what's driving the overall margin. And we see that continuing. That being said, we're going to continue to invest in the brand. I mean this is a huge market.

The brand is doing extremely well. We still see this as a growth brand. I think we're going to continue to invest in the brand. I think if we do see opportunities to accelerate growth which we see some opportunities already that we're taking a look at to say -- knowing that we have IP to 2030.

And we got a long way to go this is still about driving demand. And with that, I think, we believe we will continue to see growth healthy growth in the margin, and profitability of the brand..

So this -- so the program is moving fast at IBS-D.

Can you discuss the potential for additional indications? So I'm wondering, as you evaluate those additional indications this compound would you be able to move immediately into Phase III studies? Or should we also anticipate Phase II studies in those additional indications?.

Mike?.

Yeah. It's a good question. So as you're alluding to we're starting with IBS-D. And again we have the Phase II study, in IBS-D. The Phase II study by itself is a fairly robust. Phase II in terms of the size and duration of therapy. So we do expect to be able to go as quick as we can to Phase III in that program.

But to address your question directly, in parallel we have active considerations for additional indications. We have a broad dose range being explored in Phase II and IBS-D. So we'll need to look at that closely, and the applicability of that dose finding for the other indications we're pursuing.

But currently we don't necessarily anticipate that to repeat Phase II. At this stage, we do think some of our proposed secondary indications will not require that. But we need to work out that further. And clearly have to have discussions with the FDA to get clarity on that in order to make -- to move forward with other development programs..

And we're currently working closely with Allergan to identify other proof-of-concept studies. Pending a positive outcome, with the current Phase II program, that would broaden the clinical utility, possibly in other forms of IBS as well as other chronic GI pain disorders.

Such as, organic diseases or more organic diseases, such as, chronic pain related to inflammatory bowel -- excuse inflammatory bowel disease and Diverticular disease, to really establish that -- this drug as a Non-opioid intestinal analgesics if that could have broad application across multiple GI conditions..

And there are no further questions at this time. I'd like to turn the call back over to our presenters..

So, I just want to thank everybody for their time and continued interest in Ironwood. And of course, I want to recognize the team again. And our entire company for the great results they achieved here in Q3. We still have plenty of work to do ahead to unlock value for patients and to shareholders. And we'll be very focused on doing that.

Thanks, everyone..

This concludes today's conference. We do thank you for your participation. You may now disconnect..