Idenix Pharmaceuticals (IDIX)

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Idenix Q&A Session by Subject (Earnings Call – Mar 2, 2007)


HCV - Drug Interaction Study and NM283

Question: Okay. And then my last question regarding the drug interaction data. Have you seen any of the data from the first initial time point, the day 36; do you have any sense of the unblinded data, what you might be expecting?

At this point we've left the Company's blinded to this data set and its our intent to leave the study blinded until we get to the critical 36 day PK and 12 week viral load drop for our clinical staff. This is important for the clinical staff because we don't want to bias the results of safety or efficacy when we forward the data in to the FDA. (Mayers)

Question: Can we talk a little bit about the drug drug interaction study. What would the statistical penalty have looked like had you taken a look?

The trial is actually not powered to get a P value at this time. I think the bigger concern was that at the time we would have had to submit an abstract there was a minority of patients who had reached the critical endpoints of the study. And our feeling was that to unblind the study and present preliminary data which could change by the time all the data came in would have been a mistake. And so we felt it was better to get all the data, have a definitive outcome, reach a conclusion with Novartis on the interpretation of the data and then bring it to the market. (Mayers)

Question: Of the total of 130 patients have all completely -- when do we expect the last patient to complete full dosing?

Mid-May. (Mayers)

Question: Can you talk about the nature or remind me of the nature of the discontinuations of the interaction study and was either of them related to NM283?

There is one discontinuation of a patient taking -- we don't know what they were taking because it was a blinded study. But there was one patient who had nausea and vomiting early on during the first week and did discontinue from the study. The other patient had a lack of concentration that was attributed by the clinician to peggylated interferon. So at this point there is potentially one withdrawal out of the 117 patients due to potentially nausea and vomiting from 283. (Mayers)

I think that also what is important is that we have not had any SAE and no grade three or grade four, so very good safety and tolerance in this clinical study so far. (Sommadossi)

What is very clear is that the reduction from 800 milligrams to 200 milligrams has significantly improved the adverse event profile of NM283 with patients having a much better GI tolerability. (Mayers)

Question: And just one other quick question about that study. I know it is powered for PK and PD measure, but I'm sure the viral load reductions are important among the arms. What is different for you guys, are you and Novartis looking for among the NM283 arms versus the interferon ribaviron arms so you'd feel comfortable moving forward into Phase III?

At this point we are still having ongoing discussions with Novartis on the critical endpoints to move forward, so that is as much as I can say. (Mayers)

Question: Just a couple of questions on some of the alternatives on what you might actually find out of this drug interaction study. In the event that I think you've got some form of interaction I am just wondering could you give us a framework of how should we think about the subsequent clinical development plan? And I am just wondering whether this is an either or situation i.e. does it fully interact or does it not interact. Or are there sort of in between scenarios that we should be thinking about and I am just kind of curious as to how should we think about face redesign going from there? Maybe if you can just set out the framework so we can think about it?

I think first of all as we have indicated several times we do not expect any drug drug interaction. I wish that we could report today and move on because I think that the topic has been on the table too long. And that is unfortunately it takes time with clinical development to fully address the question. And it is not an assay in the test tube and within 24 hours you can have an answer. With that said, we do not anticipate and there is no scientific rationale to expect such interaction. (Sommadossi)

I think where we are right now is to try to understand the product profile of 283 and what will be the best development for this product. I think were there is maybe some misunderstanding or difficulties to foresee the future is that basically we are rolling on the forefront of new treatment for hepatitis C. And we are trying to learn how we are going to develop these drugs. I think it's going to be extremely different from the treatments naive standpoint and even the treatment refractory standpoint. (Sommadossi)

As you can see in the abstract of EASL up here on the Website yesterday what we can take in general is that there is going to be more and more combination therapy of investigational drug that are going to be first evaluate in vitro as we have done with Schering-Plough. But you can see that that is going to be actually expanded hopefully into clinical development and with the blessing of the regulatory authorities. And therefore I think that you can expect very likely a new paradigm shift in the development of new hepatitis C drug. (Sommadossi)

So how we are going to design the Phase III study, we don't know yet. We are going to evaluate the 12 week data, we are going to evaluate the '06 data, we are going to -- which is the Phase IIb treatment naive. We are going to basically look everything in terms of the product profile and then take a decision what will be the best development path for an NM283 toward achieving market. (Sommadossi)

Question: And just to make it clear on the ribavirin NM283 interaction study data. Both (indiscernible) week data. Will that be communicated to the street in the form of a press release?

Yes. At this time it is our intention once we submitted to the FDA and reviewed it with our investigators to submit a press release of the top-line data and then to submit several abstracts in the fall to give details of the studies in a scientific forum. (Mayers)

Question: In a scientific forum, not a press release to investors?

There will be a press release in June once we've reached consensus with Novartis and shown the data to our investigators, then we will move to show all the data in a transparent fashion in the fall. (Mayers)

That is right. Basically what we will look to do is just put a press release yes or no and jump into action and present the scientific data with details as Doug indicated in the fall. (Mayers)

Question: Will we get viral load data in the top-line report?

We are not going to discuss today what we are going to issue in the press release. Eugene, what we want to make sure is we are not going to jeopardize any presentation at any scientific meeting but in the same time anything that would be material and as soon as we have it we will communicate to the street. (Sommadossi)


Resistance with Valopicitabine (NM283)

Question: Can you comment on any, have you seen any elements of resistance from the two (indiscernible) trials with valopicitabine?

We have seen resistance developed with valopicitabine with a previously described I think it is 8 282 T mutation. But it is occurring less frequently than has been seen with the other classes of drugs. It is our belief though that the HCV is an RNA virus; it will develop resistance to any single drug if you don't completely suppress viral replication. And that we will ultimately need to be combined with other classes of drugs to achieve a significant breakthrough in curing HCV. (Mayers)

Question: And that data is being presented -- have you presented any of it or are you planning to?

The resistance data has been shown previously for the compound and we are doing right now a number of studies looking at the emergence of resistance in both our treatment naive and treatment experienced trials. Once we have that data analyzed we will present it, yes. (Mayers)


NM283 to FDA

Question: Thanks very much. I'm wondering what if there's a specific time frame from the FDA once you submit the data, is there a regulatory clock that they have to set up a meeting within thirty days for example?

I'm not certain that they have an obligation to respond to us within thirty days. But they will clearly review the data and it is our plan to move forward with discussions with them for an interface two meeting this year. (Mayers)

Question: Okay. Just so I am clear here, you are going to communicate to the street once you've met with the FDA or once you've submitted the data to the FDA?

Our plan is to submit data to the FDA in the end of May on this study. We will then meet with the clinical investigators who conducted the trial and review the data with them. After we've reviewed the data with them and we will then discuss it with the street. So it is our plan probably toward the end of June to issue a press release with the data and then go to a meeting in the fall and probably present several abstracts detailing the information that has resulted from this trial. (Mayers)


503034 plus NM283 study

Question: Can we talk a little bit about the 503034 plus NM283 study, how far is that study gone? When can we expect to hear a little bit more about that?

This is an in vitro study so it was a test tube study in which they combined these two drugs in the replicon system and showed that basically when you combine them together they significantly inhibit the development of drug resistance. We are committed to working with the other companies that produce complementary drugs to 283 to move them into clinical development. But at this time we don't have any clinical trials that are ongoing and we need to have discussions with the FDA to discuss a pathway forward for this type of trial. (Mayers)



NM283 in Combination with Proteases

Question: Is there a thought toward working with other proteases as well?

We are committed to working with other companies that have drugs that will complement our drug, patients with hepatitis C. That is all we can say at this time. (Mayers)


Preclinical HCV program

Question: On your preclinical HCV program, I think the plan is to have another IND candidate; and also you talked about you have programs in each of the major classes. Can you give us an overview or at least you're just encompassing protease inhibitors. Are there other classes that will be the first agent to move forward?

The first candidate that we anticipate to move at IND as I have indicated we are on track to file an IND by the end of this year will be a second generation of nucleoside analog. I have indicated recently that new generation can deliver 10 to 100 times more active metabolized triphosphates at delivered sites. We believe that that should lead to an increased efficacy of nucleoside. We are within a few months to have a proof of concept in chimpanzee infected with genotype 1. This has been actually a good prediction for an NM283 in terms of viral load reductions and we anticipate to submit an abstract on that proof of concept in chimpanzees which is second generation of nucleosides for fall meetings. (Sommadossi)

The other classes entail the non-nucleoside and the PI with different scaffold that are being reporting so far; we are pretty pleased with where we stand today. And as I have indicated I will go over this to having one drug in each class at IND stage by year end 2008. Very likely it will be a non-nucleoside fallout by PI in 2008. (Sommadossi)


HBV - TYZEKA / SEBIVO

Question: I just have some questions regarding SEBIVO. Can you give us some clarity? you said that you expect 20 million in sales for the year and I was wondering is that the 20 million in regulatory milestones that you mentioned in your guidance or is that 20 million end-user sales worldwide or in current markets, can you give us some clarity there?

That 20 million is end-user worldwide sales. It does not include any milestones. (Arkowitz)

Question: Is that in current markets that are approved?

That includes expected future approvals as well. (Arkowitz)

Actually, Robyn, as we have indicated now we have been approval, close to be approving all the major markets. (Sommadossi)

Question: In terms of switching gears to SEBIVO in China. Can you just remind us what the economics are for Idenix and how quickly Novartis will be able to launch there?

I can tell you about the economics of that and basically Novartis in China and a number of other territories is this whole party responsible for commercialization. So it's actually a supply price from Idenix to Novartis and then Novartis is providing, doing all the selling and marketing efforts and incurring those expenses and booking the sales. (Arkowitz)

Question: And have you said specifically what that supply price is?

No, we have not. (Arkowitz)

I think the only thing I would really say Novartis are very, very committed to the Chinese market. They've done a lot of premarketing activities and have a very significant sales force and marketing group in place and will be launching shortly. I think the specific dates you would have to contact them. (MacDonald)

Question: And just with China, obviously there is a few other products out there in HBV antivirals. How do you plan to -- it seems like data or sales from those compounds seems to be limited. Is there a particular strategy in place to crack that market given there has been a long and tough market to access?

I'm sorry, Richard. You'll have to talk to the people at Novartis concerning that marketing activity in China. (MacDonald)

Question: And my second question is on TYZEKA, and what is the differentiation that you are using at least on a marketing prospective between (indiscernible)? Thanks.

I think as we said previously focusing on very profound rapid viral load reduction, the six-month predictability which really allows physicians to be able to see which patients if you get PCR detectability of six months you have a very strong prognosis of where you are going to be at one and two years and that is going down very well. And then supporting that with our safety profile, pregnancy category B and then our overall pricingand cost-effectiveness. I think all of that wrapped together gives us a very competitive profile against (inaudible). (MacDonald)

Question: Can you remind us on what the European pricing is going to be for SEBIVO?

We haven't made that available at this time. We will be doing that when we get approval which will hopefully be in the May, June timeframe for the first countries in Europe. (MacDonald)

Question: Could you please provide an update on the bridging study on telbivudine in Japan? And also could you please remind us the milestone payments for Japan approval whether that is comparable to your EU approval milestones? Thanks.

We have not initiated any bridging study in Japan yet. This is a decision for Novartis, as you may know Japan is the only country actually that is slightly different, this is actually a global ICH package that we have. We have not decided with our partner today when we would initiate any bridging studies in Japan to move forward in that country. We actually do not have any specific milestones payments attached to the Japanese approval for SEBIVO. (Sommadossi)

Question: Question on what is your impression thus far with TYZEKA in the U.S. market? And is there anything that you've learned so far with having it available in the U.S. for the last couple of months? I know you mentioned last time we met you mentioned that marketing brochure is awaited, you were waiting to receive a marketing brochure from the FDA. Which will enable your sales force to more effectively differentiate some of the differences of TYZEKA or some of the other drugs that are out there. I was wondering if you could comment on that?

As Guy has indicated we finally received the feedback from DDMAC so we are very pleased about that. And I will let Guy to go in further details. Guy. (Sommadossi)

Obviously for the last few months the field force have only been out there talking to physicians with the package insert. I think first because of the holiday period and everything it did take longer to get DDMAC feedback than we would have anticipated. That put it in perspective as we now have that feedback. It's really not just a sales aid, its really the sales aid and our whole campaign now will be introducing into the U.S. market so the reps will now have all the full tools that we originally envisaged. I really think in terms -- we've learned quite a lot -- we've had some good reactions to the messaging that I talked about earlier. And I think now when we have all of our full promotional campaign out in the field we will be able to see how well we are able to do in the U.S. and be able to look at that probably early in the fall, we will have a good idea of how well we are doing. (MacDonald)


HIV - IDX-899

Question: I have actually two questions. I was wondering when we would see data for IDX-899, can we expect to see some data by the end of the year?

As we mentioned we presented the in vitro preclinical data in a poster at CROI this week. It is our intention once we filed the IND to move into Phase Ia II testing. So we will initially run the dose up in healthy volunteers and then move to HIV infected patients. It is our hope to be able to present data by the end of the year on the activity of the drug at one week in HIV infected patients if everything goes well in the healthy volunteers. (Mayers)


Financials

Question: I have a question regarding the guidance. Does that include the potential milestone payment from Novartis for NM283 for the end of I think it's successful end of Phase II meeting with the FDA, I think that is about 20 to 25 million.

Howard, the guidance of ending 2007 with between 100 and 110 million in cash does not include anything related to NM283 from a license for your milestone payment standpoint. What it does include is as I mentioned is 20 million related to telbivudine regulatory milestones. (Arkowitz)