Ironwood Pharmaceuticals Inc (IRWD) 2010 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Ironwood Pharmaceuticals' second-quarter 2010 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 follow at that time. (Operator Instructions). As a reminder, this conference call is being recorded.

I would now like to introduce your host for today's conference, Ms. Halley Gilbert. Ma'am, you may begin.

Good afternoon and thank you for joining us for our investor update for the second quarter of fiscal year 2010.

Joining me for today's call are Peter Hecht, our Chief Executive Officer; Mark Currie, our Chief Scientific Officer. We will also have Michael Higgins, our Chief Operating Officer; Tom McCourt, our Chief Commercial Officer; and Jim DeTore, our Vice President of Finance, available for the question-and-answer portion of the call.

Today, we will focus on certain updates relating to the ongoing Phase 3 clinical trials assessing the safety and efficacy of our primary drug candidate, Linaclotide, for the treatment of patients with Irritable Bowel Syndrome with constipation, or IBS-C. By now you should have a copy of our press release, which crossed the wire earlier this afternoon. If you need a copy of the press release, you can go to our website at www.Ironwoodpharma.com to find an electronic copy.

Some of the information discussed in today's call, particularly the information related to Linaclotide, is based on information as of today, August 5, 2010, and contains forward-looking statements that involve risks and uncertainties. Actual results may differ materially from those set forth in such statements. We do not undertake any obligation to update any forward-looking statements made during this call or contained in the accompanying slides, as a result of new information, future events, or otherwise.

For a discussion of these risks and uncertainties, you should review the forward-looking statement disclosure in our press release, as well as the risks under the heading Risk Factors in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2010, and any of our future SEC filings.

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

Thank you, Halley, and welcome to all of you who are joining us for this discussion. I'd like to provide a very brief overview of Linaclotide, and then ask Mark to update you on Linaclotide clinical and regulatory matters.

Linaclotide is our GC-C agonist for the treatment of patients with Irritable Bowel Syndrome with constipation and chronic constipation, which we are currently developing and intend to commercialize globally.

The data we've seen to date in a broad development program indicates that Linaclotide offers rapid and sustained improvement of both the abdominal symptoms -- pain, discomfort, and bloating -- and the constipation symptoms that define these chronic GI disorders. Linaclotide was designed here by an Ironwood scientist to act locally at the site of action in the GI tract without detectable systemic exposure at therapeutic doses. We're developing a convenient, once-daily capsule, and we've issued Composition of Matter patents that cover Linaclotide until 2025.

We at Ironwood are enthusiastic and passionate about Linaclotide, as it could present patients and healthcare practitioners with a unique therapy for a major medical need not yet met by existing therapies. We're fortunate to work with high-quality collaborators in the development and commercialization of Linaclotide in certain territories, namely Forest Laboratories in the US, Almirall in Europe, and Astellas Pharma in Japan and certain other Asian countries.

We intend to create a global brand for Linaclotide and, accordingly, we continue to explore Linaclotide's potential opportunity in countries outside of these territories as well.

Mark will now take a few minutes to provide an update on the ongoing Phase 3 IBS-C clinical trials, and then we will do our best to answer questions you may have. With that as backdrop, I'd like to now turn the call over to Mark.

Thanks, Peter. Both of the Phase 3 IBS-C trials are fully enrolled with just over 800 patients in each trial. We and Forest anticipate reporting top-line results from these two trials separately in the fourth quarter of 2010.

Subsequent to each release of the US results' top-line data, we and Almirall will report top-line results on the same day that it's measured against the EU co-primary efficacy endpoint, which evaluate abdominal pain and discomfort, and IBS degree of relief. Pending positive results from these trials as well as sufficient long-term safety and CNC data, we and Forest intend to submit an NDA or IBS-C in chronic constipation in 2011.

We and Forest have decided to amend the protocol for each of our Phase 3 IBS-C trials to add a proposed fourth primary efficacy endpoint. By way of background, the clinical trial designed for each of our Phase 3 IBS-C clinical trials originally included three primary efficacy endpoint; nine out of 12-week abdominal pain and CSBM responders; and nine out of 12-week CSBM responders; and a nine out of 12-week abdominal pain responder.

A nine out of 12-week abdominal pain and CSBM responder is a patient who, for at least nine of the 12 weeks of the treatment period, meets both abdominal pain and CSBM responder criteria. A nine out of 12-week CSBM responder is a patient who, for at least nine of the 12 weeks of the treatment period, has three or more CSBMs per week and an increase of one or more CSBMs per week from baseline. A nine out of 12-week abdominal pain responder is a patient who, for at least nine of the 12 weeks of the treatment period, has at least a 30% average weekly reduction in abdominal pain from baseline.

The FDA issued draft guidance earlier this year on the design of clinical trials for IBS-C, that recommends primary efficacy endpoints assessing abdominal pain and stool frequency. We and Forest are ending the clinical trial protocol with both ongoing Phase 3 IBS-C trials and clinical trials, and have proposed to the FDA to add an additional primary efficacy endpoint that matches the FDA draft guidance.

This additional endpoint is a six out of 12-week abdominal pain and CSBM responder. A six out of 12-week abdominal pain and CSBM responder is a patient who, for at least six of the 12 weeks of the treatment period, may have at least a 30% average weekly reduction in abdominal pain from baseline, and B, has an increase of one or more CSBMs per week from baseline. Adding this endpoint to the clinical trial protocol will ensure that the studies include analyses that conform to the FDA's most current thinking, as reflected in the draft guidance.

We anticipate that the four endpoints will be evaluated sequentially in the following order -- at a [P] less than 0.05 level; nine out of 12-week abdominal pain and CSBM responder; and then a nine out of 12-week CSBM responder; then a nine out of 12-week abdominal pain responder; and then six out of 12-week abdominal pain and CSBM responder.

I would now like to turn the call over to the Operator to open up the lines for questions.

(Operator Instructions). Geoffrey Meacham, JPMorgan.

Thanks for taking the question. Just to go over the new endpoint, was this simply based on harmony with FDA guidelines? Or was this based on any new data that you have or discontinuation trends, et cetera, that are ongoing in the study?

Yes, Geoff. It's exactly as you indicated at the beginning. It's to align ourselves with the latest thinking so that we would have the latest think -- thoughts of the FDA around the guidance in our data analysis.

And the follow-up is that -- does this change -- what are the statistical implications of the new endpoint? It sounds like it's obviously a lower bar, but it is also lower on the tiering, in terms of the primary endpoint hierarchy.

Yes, so utilizing the Phase 2B data and projecting that forward, it has almost no impact on the powers. We're still way above 90% in power.

For each of the four endpoints.

Okay. Thanks.

[Thomas Pugh], Morgan Stanley.

Thanks for taking the question. Can you clarify the statistical analysis a little bit? You said there was going to be 0.05 applied to each of the endpoints in the order that you listed sequentially? Is that --?

Correct. It's done in a hierarchical manner. We would pass through the combined nine out of 12-week pain CSBM responder first; then going down, passing that, go to the CSBM responder for nine out of 12 weeks; the pain responder for nine out of 12 weeks; and then pass through there into the six out of 12 weeks combined pain CSBM responder.

And each one of those is [P] of 0.05?

That's correct.

So if you miss on the first one, what is that -- how's that [then] tied to the following analyses?

Yes. So if you miss on the first one, you would not proceed to the subsequent analysis.

Okay. And then the press release says that -- it seems to indicate that this is proposed to the FDA. So the FDA hasn't signed off on this, I guess?

Yes, so we've amended the protocol and will be sending in, with the statistical analysis plan, our proposal to get feedback on adding this endpoint.

When do you think you would hear back from the FDA on this?

Again, for us, it will be combining the statistical analysis plans, give that feedback to the FDA that we're planning to add this endpoint in as a primary. And obviously, we would be then hoping to hear back feedback, but we wouldn't know exactly when that date would be.

Okay. And then when you get the feedback, would you be releasing that as a press release? Or would it be some kind of announcement?

No, we wouldn't be issuing a press release on that.

Okay. Thank you very much.

Ian Sanderson, Cowen and Company.

Thanks for taking the question. My understanding was that in the two pivotal trials, only one had a composite endpoint. The other actually has the composite plus the two separate endpoints of CSBM and abdominal pain. Will the now -- well, can you explain to me how you're going to look at the data in those two separate -- one not having that composite in -- or not having the two separate endpoints? Will the two separate endpoints now be added to both trials?

We haven't changed the endpoints for either of the trials. They're exactly the same as far as the first three. We've always had a composite as the first level of the analysis, and that's the combined nine out of 12-week CSBM pain responder. That's in both -- that's always been for both trials. And then, again, the only thing we've done is we haven't changed, though we've added the more recent guidance from the FDA.

Okay. And the more recent guidance, just to make sure I have this correct -- it will be kind of tacked on as the final two endpoints in the order of analysis, is that correct?

Ian, Peter. Let me make sure I'm clarifying it, because if I understood your question right, the implication was that, originally, the two trials had different endpoints.

Yes.

That's not correct. I'm sorry if we confused you with that. (multiple speakers) The two trials have identical statistical analysis packages. The primary endpoint for both trials have always involved three primary endpoints (multiple speakers) -- the combined pain and constipation nine out of 12-week; the CSBM, nine out of 12-week; and the pain, nine out of 12-weeks. Those three primaries have always been the primary endpoints for most trials -- at 12 weeks.

Okay. Thank you.

And in both trials, we are now adding a fourth endpoint, which is the six out of 12-week endpoint that conforms and matches the FDA's recent guidance.

Great. Okay. That helps a lot. Thank you.

Yes. Sorry for the confusion.

Rachel McMinn, Bank of America.

This is [Marcia Chapman] for Rachel. Can you please talk about the progress on the stability testing and if there are any special requests that are important for an oral peptide from a regulatory perspective? Thank you.

This is Michael. So we continue -- as we've discussed in the past, we've put registration badges up on stability. We need to get to 12 months in order to submit the NDA in the middle of next year. That is progressing and we don't have any additional updates at this time.

John Newman, Oppenheimer.

Thanks for taking the question. I just wondered if you could give us a sense as to the statistical analysis plan, in terms of the type of analysis that's going to be done here? Are you going to be looking at the data based on an intent-to-treat analysis? Are you going to be using anything like last observation carried forward? And also, does your protocol allow for any kind of pooling of the nine out of 12-week endpoints? Thanks.

Just for clarification before Mark answers the question, when you ask about pooling, are you talking about pooling between the two independent trials?

Yes.

So, it's certainly designed for intent-to-treat population and we do not use last observation carryforwards. Relative to pooled analysis, each of the trials will be initially analyzed separately, but certainly, we have set up procedures to ultimately be able to pool the studies and do further analysis on the pooled studies.

Okay. Great. Thank you.

Geoff Meacham, JPMorgan.

Thanks for the follow-up. Just a real quick -- does the new statistical analysis -- what impact, if any, does it have on the -- on secondary endpoints? And are those tiered as well?

The secondaries are tiered. It has minimal impact on those, other than obviously passing through the now-added fourth endpoint to get to those secondaries.

Got you. Do you have the tiering off the top of your head, just what the -- for the secondaries?

No, I don't, Geoff.

Okay. Thanks.

(Operator Instructions). I'm not showing any further questions at this time. Would you like to continue with any closing remarks?

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may now disconnect. Thank you and have a great day.