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ARIAD Pharmaceuticals, Inc. (NASDAQ:ARIA)

Lazard Capital Markets Healthcare Conference

November 14, 2012 1:30 PM ET

Executives

Harvey Berger – M.D, Chairman, and CEO

Analysts

Ryan Martins - Lazard Capital Markets

Ryan Martins - Lazard Capital Markets

I am Ryan Martins, biotech analyst at Lazard. Our next presenting company is Ariad. Ariad actually has a couple of products that are pretty – are quite far long in development. Ponatinib is actually awaiting approval for CML, which should happen in the next few months. And we also have 113, which is currently awaiting initiation of pivotal trial next year. So to give you some more details on the company and the programs, I have with us here, CEO, Harvey Berger.

Harvey Berger

Thanks very much Ryan. It’s a great pleasure to be here this afternoon. We were chatting beforehand, and I’ve been to every one of the Lazard Healthcare conferences, and it’s a real pleasure to have a chance to come back this year. And to share with you the excitement of Ariad, over the last I guess since nine years that they’ve been in these conferences, we’ve certainly made incredible progress over that period of time, we’ve really focused the company virtually exclusively on oncology, and are on the way to building a global, commercial oncology business.

Before I get started, let me just read a reminder that some of the statements in the presentation constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995, and I encourage everyone to read our periodic filings with the SEC and recognize that actual results may differ materially from those expressed or implied by these forward-looking statements.

Well, 2012 coming to an end, is the year in which we’ve taken our science to the next step. We’ve made the clear transition from a discovery and development company in oncology to one now that is building a global commercial organization focused entirely in oncology.

Well there’s been – there’s certainly significant momentum ongoing in Ariad as Ponatinib is under review in the US and EU. Our Phase III EPIC trail to expand the indications of Ponatinib is enrolling patients. We expect completion of enrolment by next year.

A Phase 1/2 trail of Ponatinib is ongoing in Japan. That’s leading the way to Ariad having complete control and ultimate approval of Ponatinib in Japan. Our second oncology – targeted oncology product AP26113 is a clinical proof of concept data presented recently at the European Society of Medical Oncology meeting. And importantly, as I stand here today, we are absolutely ready for commercial of Ponatinib in the US. If we had approval today, we could be out there in ten days or two weeks, commercializing Ponatinib. So we are ready and ready to go.

And we are in the process of building the organization in Europe as well, and I’ll talk more about these in the next couple of minutes.

So Ponatinib starts and ends with patients. It’s all about what we can do for the patient with chronic myeloid leukemia. Initially, with acute lymphoblastic leukemia and then as we’ll discuss briefly, where Ponatinib can lead us.

So we believe this is a potential first-in-class new therapy for chronic myeloid leukemia, a pan-Bcr-Abl inhibitor, a small molecule drug as you see, shown in the illustration on your right, in which Ponatinib nudges down into the crevices of Bcr-Abl and selectively binds to really all of the forms that have been tested of Bcr-Abl, the naturally occurring form that is the cause of the disease, as well as subsequently all of the many resistants, mutations that have cropped up.

It’s clear that although the currently available Bcr-Abl inhibitors have many mutations that have been observed in the clinic, well over 50 for imatinib, 70 each for nilotinib and dasatinib, and we’ve seen none with Ponatinib. So Ponatinib, really this can been distinguished from the other CML drugs that currently are available as it overcomes all the clinical mutations that have been tested.

The paradigm for development and commercialization of new oncology medicines have certainly changed over the last years. We believe Ponatinib will move from the clinic initially to potential approval in the US in under five years. That’s really the hallmark of a targeted therapy in which we nowhere headed before we start the clinical trials, and we are able to move from first-in-man to potentially US approval in a matter of years.

That paradigm I think is going to become increasingly the model of new targeted medicines in cancer; certainly that’s the approach of what we envision for our second product which I will talk about in a few moments, 113.

But let’s start with CML. Even with the availability initially of three and now five different CML medications, there is a significant unmet medical need. Patients without Ponatinib don’t have all of their options met. And we believe Ponatinib will really fit into a major need clinically for patients with chronic myeloid leukemia.

As you look at those patients, really we can think about the disease in the setting of two broad groups; those who are newly diagnosed, that is, those who are treatment naïve and those who are resistant or intolerant to one and more of the available therapies. And there are many patients, who have become and currently are resistant or intolerant to available therapies, and thus really provides us with an opportunity to make a real difference in the lives of CML patients.

At the ASCO meeting about five or six months ago, we presented roughly the nine-month follow-up data for the PACE trial, and I am going to show just a couple of slides about that as background. About 60% of patients in that trial, which is our pivotal registration trial had received at least three prior tyrosine kinase inhibitors, and over 90% had received at least two prior TKIs.

Let’s look at the chronic-phase patients. This is the largest group of patients with CML, with the patients make up most of the prevalent population for CML, those have the disease over a long period of time. In patients who are in chronic phase, the primary endpoint one looks at is MCyR, major cytogenetic response. That’s a marked improvement in the appearance of a bone marrow – aspirates of bone marrow cytogenetic assessment. And overall, over 50% -- 54% of the patients achieved a major cytogenetic response, which is predictive of a long-term beneficial outcome.

Bear in mind that this is a patient population where over 90% of patients have failed at least two prior lines of therapy – two prior tyrosine kinase inhibitors, and almost 60% have failed at least three prior tyrosine kinase inhibitors. And you have 54% reach the primary endpoint. Interestingly in those who were just resistant and intolerant about 49%, but in the group of those who have what’s the called T315I mutation, this is a mutation that’s untreatable with any of the other medicines that are available, 70% of those patients achieved a major cytogenetic response.

And even at this fairly early stage of follow-up, 44% of patients, heavily pre-treated patients had a complete cytogenetic response, which is a many fold reduction in the burden of leukemia in these patients associated with a 30% major molecular response rate. So very striking data overall at about nine months of follow-up.

The updated data that were presented in June show Ponatinib to be well tolerated. The most common adverse events were myelosuppression and thrombocytopenia, and about a third of patients had a variety of constitutional symptoms, none of which were particularly problematic. About 6% of patients had pancreatitis, which was managed well, and was not a major limitation to using the therapy.

When we took these data and filed them with the regulatory agencies this past summer, what we could say then is that we have robust anti-leukemic activity, heavily pretreated population, responses that were seen across the boards in the patients, regardless of whether the status of mutations or the stage of disease from chronic phase all the way up to blast phase disease. These responses appear to be durable, and the safety profile appeared to be quite good for a new treatment in heavily pretreated patients.

And even in patients who had only seen one prior tyrosine kinase inhibitor, an initial response using major cytogenetic response of 86%. So across the whole spectrum of patients in this trial, good results, certainly consistent with a new medicine that can make a real difference in the lives of leukemia patients.

We have moved the Ponatinib program forward with the FDA and the EMA reviewing Ponatinib on priority and accelerated timetables. We are ready to launch. Our team is in place in the US. And we expect to be commercial ready in Europe by July 1 of next year. So the beginning of third quarter of next year.

So we are building a commercial organization that is second to none in my belief, and dedicated and experienced in commercializing oncology and hematology medicines. Part of the future of Ponatinib is the move in to the newly diagnosed patients. This will be based up on the results of the EPIC trial, which is a one-to-one comparison of Ponatinib to Gleevec or Imatinib, with 12 month major molecular response rate as the primary endpoint, and we expect patient enrolment to be completed by the end of next year.

Ponatinib in Japan, another important part of our overall program, we own all the rights of Ponatinib on a global basis, and plan to continue that. In Japan, we have ongoing a Phase 1/2 trial that will include pharmacokinetics, limited safety studies, as well as a run into a phase 2 mini PACE trial, where we will look at resistant/intolerant patients, and then open up the EPIC trial in newly diagnosed patients in Japan.

So for a relatively modest investment, and a clear commitment to global development, we will be able to move Ponatinib forward. We believe to regulatory approval and commercial readiness in Japan as well.

Now, the development plan for Ponatinib extends well beyond CML and has to do with the incremental activities of Ponatinib against other key tyrosine kinases, such as RET, FLT3, KIT, and PDGF; those are targets that are all clinically validated and we will move forward with clinical development in many of those indications as well.

So AP26113 is our second new cancer medicine that we brought into development. It is a dual inhibitor of EGFR and ALK. It is active against the key resistant patients, crizotinib-resistance in ALK and erlotinib-resistance in EGFR based upon the pre-clinical work we are doing. With respect to crizotinib, the initial clinical data are fully supportive of that. Erlotinib and EGFR, those data are still forthcoming, and we have potentially two drugs in one, both in the same cancer type.

So the Phase 1/2 trial has been highly informative. We are nearing the end of the Phase 1 portion of the Phase 1/2 trial in which we’ve been aimed at dose escalation identification of the optimal dose going forward. We will then flip over in the same centers into multiple Phase 2 cohorts, where we will expand out the experience and look at in greater detail both ALK and EGFR positive disease. EGFR positive patients, in those patients, the Phase 2 portion is going to be particularly important. In the ALK groups, we already have such striking information from the Phase 1 portion that those are probably not going to be on the critical path for moving forward.

So, at the ESMO meeting in Vienna in September, we presented the initial clinical data. Let me start with the ALK part of the story. ALK-positive patient response is seen rather strikingly at doses as low as 60 mg and above. The responses were observed in all of the patients who have been assessed in crizotinib-resistant patients. Six of nine had partial responses, but if the patient underwent a radiologic assessment, they had a response. And the longest duration is the time of that data report was about six months. In the crizotinib-naïve patients, that is patients who we were ALK-positive or patients who cannot proceed crizotinib, both of those patients responded to 113, and as well we presented the data on 113 in patients with ALK-positive brain metastasis, which is a very common finding.

The EGFR part of the story is a bit more complicated. You need almost certainly higher doses of 113 to inhibit EGFR, then ALK. We did demonstrate a partial response at 120 mg, with other patients having ongoing stable disease or disease progression. These were very far advanced patients who had failed multiple medicines, erlotinib, bevacizumab, and at least one round of chemotherapy.

So the key here, we will be moving into the Phase 2 cohort where we will be in a position to really refine the patient population, and evaluate patients who have just become erlotinib or EGFR resistant. It will have, as well, genomic information from tumor profiling that will confirm a genetic abnormality of those patients. And that will be an important part of the ongoing study.

So in summary, we’ve dose escalated to 300 mg a day, single once a day oral dosing. With ALK, I believe we have compelling clinical proof of concept. With the EGFR, we have promising additional opportunity and emerging evidence of clinical activity. And this represents, and what I am very excited about, another internally discovered area, cancer medicine that came out of the same discovery group that brought us Ponatinib.

So with 113 we have this potential for the same type of paradigm, that is the ability to move quickly from Phase 1/2 which began towards the end of third quarter of last year, and is now, will move to Phase 2 cohort this year and next year, and potential pivotal trial beginning next year, with ultimate potential marketing approval in 2015-2016 timeframe.

So with that, let me sum up and say where are we today. We brought the company forward through a narrow – a major transformation internally, as we have built a strong commercial organization initially in the US, moving as well into Europe and into Japan. We are close to approval for Ponatinib in the US. We will believe Europe will follow soon thereafter. 113, our second new cancer medicine discovered internally is moving through clinical development towards pivotal trials next year and we are excited about the ability of the organization to continue to move forward and to build a fully integrated oncology business.

Our vision is to transform the lives of cancer patients with breakthrough medicines. I believe we have made great inroads and headway in achieving that vision, certainly in CML and ALL and hopefully as well in lung cancer. Thank you.

Ryan Martins - Lazard Capital Markets

Thanks Harvey. And maybe if we can start out just talking about with the Ponatinib launch, for your plans. Are you going to target just the big academic centers first and then maybe reach out to the community centers, just do give us some perspective on how you plan to go through the launch and the initial phases

Harvey Berger

Well I think the way we’ll target physicians will be really by their – the patterns by which they write prescription. That information is readily available. We won’t limit ourselves at all to the academic centers. Clearly the academic centers take care of a large percentage of the resistant/intolerant population. So certainly it’d be an important part of our focus. But we will target as well the major oncology practices and groups that may not be in the academic setting, but represents a critically important part of the overall physician mix that care of patients with CML.

Ryan Martins - Lazard Capital Markets

In terms of the label, you could potentially get a label which could be for use off any approved TKI. How do you see physicians using this, especially if it’s a patient that’s just failed Gleevac for example. Is that the way you see this drug being used? Or that may be something that may come over time?

Harvey Berger

Well, it’s in part determined by what our ultimate label turns out to be, and it’s in part determined by how physicians interpret the clinical data as they get published and presented more. There’s nothing based on the PACE trial that would prohibit someone or discourage some physician from using Ponatinib in any patients who is resistant or intolerant because all of those patients were included in the PACE trial, whether they had one, two or more tyrosine kinase inhibitors, or whether they failed Imatinib or one of the second generation tyrosine kinase inhibitors.

So it’s going to be a balance between what the final label provides us with and physicians’ interpretation of the clinical results. But certainly the PACE data as presented thus far as ASCO would support the use of Ponatinib in the resistant intolerant patients.

Ryan Martins - Lazard Capital Markets

And I think Novartis recently, in their early day, talked about initiating a couple of trials looking at treatment-free remission, complete molecular responses. Are you looking at complete molecular responses in the EPIC trial?

Harvey Berger

Sure, it’s one of the secondary endpoints of the trial, primary endpoint is working on major molecular response. But the 4.5 flog (ph) reduction that you see with a complete molecular response certainly is one of the secondary endpoints that we will monitor in that trial.

Ryan Martins - Lazard Capital Markets

Okay. And just moving on to 113, you just recently signed I think a collaboration with Foundation Medicine. Maybe you can talk about how the chemo (ph) profiling there is going to help in terms of enrolling patients into the trial?

Harvey Berger

So that’s how enrolment and understanding the patient – really understanding the genetic makeup of the patients that are enrolled. Enrolment will be based on having ALK – having been ALK-positive, which is a commercially available test, for having mutations in ALK, for which sequencing studies can clearly delineate that and the same sort of things apply for EGFR.

But the Foundation Medicine collaboration is to really understand those patients and look for signatures – genomic signatures from those patients. It could be predictive or help us understand how to better treat those patients.

Ryan Martins - Lazard Capital Markets

And maybe one on the ALK-positive trial that you are initiating. In terms of future development plan, are you considering maybe combinations of 113 with maybe like a HSP90 or some other – any of the drugs that you may want to use as a combination.

Harvey Berger

I mean so far the results for the ALK-inhibitor is such that aren’t clear that a combination is going to get you any better results. On the other hand there is no reason why in the future, you couldn’t combine 113 with various different drugs, whether it’s HSP90 inhibitor or other things. So I mean I think those opportunities are open for the future as they are for all oncology products. But I think right now the focus is on 113 as a standalone treatment.

Ryan Martins - Lazard Capital Markets

Okay. Thank you.

Harvey Berger

Great. Thank you very much.

Question-and-Answer Session

[No Q&A session for this event]

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