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Idenix Pharmaceuticals (NASDAQ:IDIX)

2012 Deutsche Bank Access BioFEST Conference

December 03, 2012 04:03 PM ET

Executives

Ron Renaud - CEO

Doug Mayers - CMO

Analysts

Alethia Young - Deutsche Bank

Alethia Young

Okay so, it’s Alethia Young here again and I am here with Idenix Pharmaceuticals. I am in the presence of Ron Renaud President, and CEO and Doug Mayers, Chief Medical Officer.

So I guess I want to focus on a couple of things. Why don’t you just kind of give an update on what's going on with the kind of your rolling work with the FDA, what you are seeing, are you on timelines to the year-end submissions for all of that work?

Ron Renaud

Yes, so I'll start and I'll turn it over to Doug to give you a little bit of granularity on that. But if you remember when the clinical hold first started, when we are notified of it back in August, there was a significant amount of work that we had to get done in order to try to understand whether or not we were seeing the same toxicity that Bristol-Myers was seen with their compound. And we received the formal notification from the FDA and a large part of that was work that was already well in progress. So from a preclinical side we had much of it done, on the clinical side, by the time we got the letter we had already started down the path and had received a fair amount of that information.

I can say that now we pretty much have all the information we gathered, it’s been aggregated. What we are waiting for also was to have a series of expert panels but of course we’re a virology company, we’re not cardiac experts. So, we want to have outside cardiac experts take a good hard look at the data, tell us what they thought about it, also wanted to have our KOLs take a look at it. So a lot of that work has been substantially completed and we think we’re well on track to have this meet the timelines to re-file the complete response to be filed before the end of this year.

Doug Mayers

Yes, I think we and BMS talk to each other regularly and they’ve been very open in sharing the data. There is a significant package of clinical, preclinical data they are submitting at the beginning of this month. At the same time we’re submitting our complete response and I think things are very different. In August we had an emerging event, we didn’t have a lot of update, I think we’ve now essentially bought all of our patients in for the echocardiograms; we've done a lot of preclinical work. There is a lot of data for the Agency to look at, we believe in early first quarter, we’ll be able to go down and have a very meaningful discussion about where we go with two methyl-G compounds, what are the requirements for new nucleoside, nucleotides still in the clinic and how do they see us versus BMS and what path is possible to go forward. And at this point, they’ve got the data but we haven't had that filed as yet.

Question-and-Answer Session

Alethia Young - Deutsche Bank

So I guess that brings me to, and I thought it was one of the most interesting people that I kind of had evaluated, how do you see yourselves versus Bristol’s methyl-G compound?

Doug Mayers

I think as you know publicly, they had a number of cardiac and renal events that were serious adverse events in that study that occurred to the seven week time periods. We've now gotten all of our patients through 12 weeks of treatment and have had no cardiac or renal SAEs so clearly we’re different. I think the big issue the comes down to is, they had a pro-drug that was toxic free clinically. It had methyl group it had methanol group. It was clearly very different than our molecule in preclinical work.

On the other hand, they also - we both produced two methyl guanosine in the circulation and they had five to 10 times as much two methyl guanosine as we do with a circulation. And so it really comes down to looking at all the data and deciding was the pro drug what caused the problem and that’s enough that you’re comfortable with moving forward two methyl-G or was it the fact that aggravated on top of a high two methyl-G posed the first problem. And at this point, as I said, we know that we’re very different than they are. I think the data is very compelling clinically and preclinically but how is the Agency approaching this? What sort of requirements are they going to have? I mean there are programs that we can negotiate with them that are reasonable for us to move forward and there are programs that could be quite onerous where it would just not be worth it and we should just move to the two methyl U and move on.

Alethia Young - Deutsche Bank

So maybe can you talk a little bit about what kind of monitoring and different things could be put in place or how that might look?

Doug Mayers

Well I know what we have been recommended by outside experts, but haven't got the concurrence with the Agency yet. So I think early next year, we’ll be able to give you a better sense. Our experts have basically said that they think that we didn’t have a significant signal and that we could do one more test and be done, whether the Agency agrees with that, or feels the need to do longer term monitoring these patients, more consistent with what BMS is doing, I still need to find out.

Ron Renaud

I mean if you think about it right, we outlined what some of the specific questions were from the FDA back in October and one of the things that right out of the gate they asked us to do, even though we didn’t have baseline echocardiogram, was to go and get echocardiograms. We talked about going out and looking at the NT-proBNPs which is an enzyme that looks at ventricular wall stretch and then there is the other cardiac assays and test that you can get done. So we would assume that anything going forward, that would probably be a pretty good part of the picture.

Doug Mayers

So question is we intend to be (inaudible).

Alethia Young - Deutsche Bank

So just meaning how often do they have to come in to be monitored for those and how many are those tests.

Doug Mayers

Right.

Alethia Young - Deutsche Bank

Are any of those tests particularly onerous? Like some people said it wasn't really super onerous any of the tests.

Ron Renaud

I don’t think they are incredibly onerous, but I think you’ve got to put it in the context of okay, if you have a series of clinical trials, HCV clinical trials where you’re looking at three or four or five different direct acting anti-virals that are being tested in any number of scenarios and you want to look at, what are the eligibility criteria to get on those studies, what is the margin, what has to happen on those studies. Even in the clinical trial settings, you want to have a clinical trial that can be competitive from an enrollment perspective with the other one. So again, you don’t want to be having patients coming back for too many more tests than they might have to otherwise on the other studies.

Doug Mayers

At a certain point it becomes a cardiology study where they have to pay the same points.

Alethia Young - Deutsche Bank

Cardio clinical trials.

Doug Mayers

Right and that’s not where we want to be.

Alethia Young - Deutsche Bank

Definitely, so I guess that brings me to kind of something I find interesting which is your uridine program, can you tell us a little bit, when we’ll know something about it, kind of the screening and the work that you’ve done there to get to those time periods?

Ron Renaud

Yes, again, the next nuke that we have going into the clinic, we've detailed as a uridine analogue and this comes out of, we've been working on nukes for quite some time but when I came into this feedback over a little over two years ago, we made a decision at that point to really go back and focus on nucleosides and nucleotide pro drug in earnest. And what I mean in earnest that is to try to understand exactly what makes a good nucleotide pro drug in HCV. So you have the pro drug component, you have the sugar component and you have the base part of it.

And so we looked at tweaking all three of those in a number of different ways which gave us, as you can imagine hundreds and now thousands of different permutations. So we’ve synthesized somewhere in the order of about 2,000 to 2,100 novel nucleotide pro drugs and while we’re doing that, we've also set up a screening cascade for ourselves that, it presents a very high hurdle. It incorporates safety, pre-clinical safety, pre-clinical toxicity and also we want to have some level of confidence in the preclinical potency.

And so when we get to the end of that, we end up with somewhere in the order of 10, 20 novel nucleotide pro drugs that we like a lot, U happens to be one of, 368 was initially one of the compounds to come out of that which is the G that’s currently on hold but the U was the one that was right after that and I think what we’re happy about is as we were working to bring 368, file the IND and bring that to the clinic, the U wasn't that far behind. So when this clinical hold situation happened, we were already ready to embark on the IND enabling study. So that’s a compound we’re super excited about and should be in the clinic the first half of next year.

Doug Mayers

So the bottom line is basically with the discussions with the agency we think, sometime in the first half of the year, we will either have a G and the U going or U going forward that we think will be very competitive and we’re ready to match it up with our NS5A toward the end of the year in an all-oral, pan-genotypic three months study of our own internal compound.

Alethia Young - Deutsche Bank

When’s the filing on the U again, potentially?

Doug Mayers

First half.

Alethia Young - Deutsche Bank

And so kind of walk us through the mindset of like if we went back in time and there was no clinical hold and you had to the Ds and you had the U kind of, how would you see pathways differ effectively?

Ron Renaud

They probably wouldn’t, remember our intention was that, we had filed the IND for 368, so we were working under an assumption that potentially maybe that this time period we would be talking about the data from the genotype 1 as a portion of that proof of concept study. We were also planning to initiate the 719, 184 combination study at this point. The additional novel nucleotide pro drug were always part of the equation. If you remember, we kept talking and we continue to talk about bringing more nuke forward that were going to be non-[D] [ph] compound and ones that could potentially enable us to have a through nuke-nuke strategy so to have novel sugar approaches, ones that conferred different resistance profile that we could truly put together and have a real nuke-nuke strategy. That was always going to be part of our 2013 game plan, it just takes on more importance now with the (inaudible) on clinical hold.

Alethia Young - Deutsche Bank

Sounded a little underappreciated to me but talk a little bit about what is Novartis kind of breakup of the relationship has done for you strategically.

Ron Renaud

It’s a great question and unfortunately, the same week that we announced the Novartis relationship had changed was right when the Bristol-Myers announced the first patient issue with 094. So we haven't had much of a chance to talk about this but Novartis has been in a relationship that goes back to May of 2003 and historically they had rights to every compound in our pipeline. They have had the first right of refusal for everything in the pipeline after proof of concept. And so as we think through our decisions to develop certain drugs and move down certain pathways that had always had to be a consideration, knowing whether or not they were going to opt in or not opt in was something that weighed heavily on our minds but more on the minds of investors. And so when they didn’t exercise their options on 184, that was more of a decision that was based on, back in 2003, proof of concept studies were much longer and upfront payments were much lower for direct acting antivirals in HCV. We were asking Novartis to make a decision then on a compound where we had three days of proof of concept data, not 14 or 28 like they had back in 2003. And you had a mean NPV of HCV direct acting antivirals largely driven by the frenzy around telaprevir of $6.5 billion, and so the original agreement goes up from payments were driven off from market models. So everything is flip flop. It was really a business decision, but in everybody else’s minds it was it must be something wrong with 184 and that was back in 2009.

So these were just things that kept weighing in and so as we thought about having partnership discussions, we now had 184 that wasn't part of the Novartis equation anymore but we had new compounds that were and potential partners that had a long term vision of a combination strategy and made those discussions impossible if you wanted to have 184 as part of it, because you had to wait for the Novartis option to get [access] [ph].

So I think I think it was a good collaboration, it was the right collaboration for the time but getting it unwound has been a terrific weight off of our shoulders and has allowed us to have many discussions that we haven't been able to have otherwise. For example, now we can have this, that week we started having discussions around our NS5A, around 719. We wouldn’t have been able to have that discussion until we got through fully through the proof of concept which in the 90 day clock after that. So we’d be in that clock probably right around now.

Alethia Young - Deutsche Bank

So the opt in was 90 - proof of concept and then another three months after that.

Ron Renaud

Yes, we had a certain timeframe, I think we had a 30 or 45 days to give them a data package and then they had 90 days to give it back to us.

Alethia Young - Deutsche Bank

Yes, easily six months, running around.

Ron Renaud

Yes, it just ended up being a protracted time period whereas now we’re waist deep in these discussions on collaborating 719, collaborating with another direct acting anti-viral on 719. We’ll be able to accelerate that much better than we could have otherwise.

Alethia Young - Deutsche Bank

So I guess, do you think fair to characterize over the next 12 months probably you’ll see more drugs possibly in the clinic than you would have with this agreement in place?

Ron Renaud

I think we’ll have the ability to move more quickly and more strategically than where we have, you know drug development is still fraught with the risk of drug development. So I hope we have more, I am not sure that whether with Novartis was part of the mix or not that has any bearing on it, I think that has the bearing in terms of have we done our discovery efforts over the last few years.

Doug Mayers

I think it lets us do more creative - earlier and more create combination studies than we could have done…

Ron Renaud

That’s true.

Alethia Young - Deutsche Bank

That could be important which brings me to my next idea, I mean discussion point which is the NS5A which I think the NS5A is going to be one of the most interesting evolutions over the next 12 months. So you guys have an interesting one, so why don’t you tell us a little bit about it and what makes it so interesting and then also the kind of what you thought with Gilead data, what did you make of that and where you think the class is going.

Doug Mayers

I think the NS5A is interesting because they have very low drug-drug interaction potential, they are easily combined so that with coming clear with the PI for example is a lot of drug-drug interaction for the other medication to 50 year old patients are taking. A nuke NS5A will be very attractive because it will potentially fix those combination like Gilead is doing; there also is very low interaction potential to the other drug. More recently, because of the Abbot data, I think a lot of people have been onerous to looking at a 5A. ours is unique in that its pan-genotypic and we showed in the clinic the fact against genotypes 1 through 4 with a little bit of an issue even if we had two weeks to talk about. But what would basically allow us to do is to combine currently with the (inaudible) in genotype 1 and 4 is probably in fairness we get our nukes up to do pan-genotypic studies which most companies can’t do. And so I think the thing we’re really unique is because we do nukes, our nukes are pan-genotypic both the (inaudible). Our NS5A is pan-genotypic and so right now, what there is an interest in is doing 2 and 3 drug combination of other data through NS5A. so that’s what you’ll see us doing early next year is putting together one class plus NS5A plus riba, two classes plus NS5A with or without riba and you know potentially do interesting populations. So for example (inaudible) receptor failures where no one is really going so far or to go after genotypes 2,3 type (inaudible) failure where no one has gone so far.

So I think it gives us the opportunity to do some very innovative studies and it has raised the interest of the outside potential collaborators to work with us, that gives us the three month data then to go after our own nuke NS5A strategy and if the two nuke strategy works in 2014, you can see us doing a nuke-nuke strategy and making it (inaudible) HPV and a nuke-nuke NS5A strategy which would give us the AAA equivalent HPV with a pan-genotypic combo. So I think if we can execute well through 2013, we can have some very interesting creative studies in ’14.

Alethia Young - Deutsche Bank

So what are the kind of to lack of your failures, what that market side looked like and the 2, 3 failures that been out there.

Doug Mayers

The significant percentage of patients getting toll-like receptorvire (ph) because remember the high-need patients for patients that back really wanted to treat for those who had cirrhosis and advancing disease, who got peg and riba and they don’t get a good response rate, the numbers are 15, 20% in that population and SCR and if they don’t respond they have toll-like resistance. So we think if there is going to be a reasonably large market of people who tried toll-like receptorvire (ph) and either had a side effect and couldn’t take it or failed on it, they are at very high needs, whereas if you can get a combination that had drugs, had activity outside of the (inaudible) you have to go in and give them a sense of hope and actually have a high-need population.

Ron Renaud

It’s been an area I think where sponsors have been the most reluctant to go. I think in some cases if you have a (inaudible) to go back into that pre-condition population but we talked to the KOLs and we do the market research, these are some of the areas that have the greatest needs and when we sit down and try to think strategically, how to move quickly, that’s the feedback. So it seems like a reasonable quick path forward for us.

Alethia Young - Deutsche Bank

One is, the genotype 2 activity worry any of your collaborators like the kind of slight resistance we've seen there or talk about characterize those conversations for us, the plus end of it.

Doug Mayers

For most collaborators we’re talking they only have genotype 1, 4 active drug so it doesn’t impact them that much. For the ones who have genotype 2, 3 active, we've got a very good response which is basically we’re going to genotype everyone. If you have genotype 2, we’re going to do a point mutation assay for L31 or M31, if you have an M31 we’ll exclude you for the study and remember the ones who didn’t have a M31 got a full well response. And so basically we’ll clean up the patients who would not get a good response and then everyone else will say genotype 1, the 2s, that are L31, 3, 4, 5 and 6, we can put all the genotypes and our studies beyond that.

Ron Renaud

I think Doug makes an important point though and that is for the folks we’re talking of the potential collaborators, there is very few that actually have the ability to give us another genotype 2 or genotype 3 compound on the other side of NS5A. so it actually as we think about it here today, it’s more of a concern for us in that it’s a concern, we’re really not really that worried about as we think about as pan-genotypic approach will do that permutation assay and we’ll make sure we exclude those patients out of these assays.

Alethia Young - Deutsche Bank

Last question is, what would you say for the common bearing which is, there is any developing of any of these drugs because Gilead and Abbott and Bristol may have this whole thing locked down. Just talk a little bit about potential populations of some of the stuff you’ve seen there.

Ron Renaud

I'll give the big picture view on that and that is there hasn’t been a therapeutic area where the first major entrant has come in, taken over the whole space, at least it’s rare as I am sure there is somebody in this audience or somebody who will text me up afterwards and say it happened in these three different places but it’s rare to see a therapeutic area where somebody comes in first with an overall regime and owns the whole place. And I think if you look at some of the good data sets out there, you look at the Gilead data set, you look at the Abbott data set, Abbot has, I think if you take the regimes out of it, you just look at the data, I think Abbot does some very impressive data. Its robust data. It looks at a pretty broad class of patients; it seems to be a very durable data set. But I think when you step back and you look at (inaudible) boosted, you look at there is a lot of drugs there; I think at the very base case it presents an opportunity.

I think on the Gilead data, again, 7977 is a great drug. I mean it seems to be working just about everywhere they put it but there are opportunities when you look at data sets, when you look at the genotype 2, 3 data, it’s clear to us that there are some hurdles that are not going to be insurmountable in terms of the SCR rates and getting to better SCR rates with genotypes 2, 3. I think as we continue to see some of that data work through in the more difficult to treat patient populations for cirrhotic and some of the pre-treated patients. I think opportunities will continue to arise. I think the (inaudible) always want to have more than one opt-in and again, if we can continue to stay focused on having a low dosage, pan-genotypic approach to this, I think that gives us an opportunity to be incredibly disruptive when we get to market.

Doug Mayers

And I think you know the other issue that is beginning to emerge at the doctor is drug-drug interaction because it’s not a young population. They have a lot conmeds, (inaudible) obviously makes that more complicated; even the PI toll-like receptovoire (ph) has become an issue. If we can get nuke NS5A or a nuke-nuke strategy where the interactive potential is very low, you basically don’t have to worry about those other medications. That we think will be very competitive. And as you look beyond the US and Europe at this market, New York and Europe is going to start to tail off in the mid-2020s. The cost of goods for nuke-nuke combination fill will be very low. So you’ll be able to then have a very competitive strategy to move into the brick countries and the rest of the world where 90% of the hepatitis C patient population lives. So that we think, we can be competitive because we can go down the low 1 milligram once a day, one pill like A triplets provider type of strategy and then we can then be very competitive when you move into a market where you’re going to have a more competitive pricing.

Alethia Young - Deutsche Bank

Awesome, so I really appreciate you guys joining us today and best of luck for that.

Doug Mayers

Thank you.

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Source: Idenix Pharmaceuticals' CEO Presents at 2012 Deutsche Bank Access BioFEST Conference (Transcript)
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