Idenix Pharmaceuticals, Inc. Q2 2008 Earnings Call Transcript

Idenix Pharmaceuticals, Inc. (IDIX)

Q2 2008 Earnings Call Transcript

July 28, 2008 8:30 am ET

Executives

Amy Sullivan – IR

Ronald Renaud – CFO and Treasurer.

Douglas Mayers – EVP and Chief Medical Officer.

Jean-Pierre Sommadossi – Founder, CEO, and Chairman.

David Standring – EVP of Biology

Analysts

Howard Liang – Leerink Swann

Melissa [ph] – Caris & Company

Jason Kolbert – SIG

May-Kin Ho - Goldman Sachs

Davis Bu – Goldman Sachs

David Moskowitz – Caris & Company

Howard Liang – Leerink Swann

Vernon Bernardino – Rodman and Renshaw

Presentation

Operator

Good morning. My name is Wanda and I will be your conference operator today. At this time, I would like to welcome everyone to the Idenix Pharmaceuticals second quarter 2008 earnings conference call. All lines have been placed on mute to prevent any background noise. After the speakers remarks, there will be a question and answer session. (Operator instructions). Thank you. Ms. Sullivan you may begin your conference.

Amy Sullivan

Thank you Wanda. Good morning and welcome to Idenix’s conference all to discuss our second quarter financial results. With me today are Jean-Pierre Sommadossi, CEO; Ronald Renaud, CFO; Doug Mayers, Chief Medical Officer; and David Standring, our Executive Vice President of Biology.

Before we begin, I would like to point out that we issued two press releases this morning, one regarding our second quarter financial results and one that provides an update on our HCV discovery program. If you did not receive either of these press releases, you can pull them both from our website at www.idenix.com or call Linay Ampeson [ph] at 617-995-9901 and she can send them here. Also, since we are covering a lot of ground today we are also webcasting a slide show to accompany our call. The webcast link is available on our website as well, as well as linked on our home page under the events heading and again that is www.idenix.com.

Just to review the safe harbor quickly, today's discussion contains estimates and other statements that are forward-looking under the Private Securities Litigation Reform Act of 1995. Such estimates and statements are based on current expectations and assumptions that are subject to risks and uncertainties and involve a number of factors that could cause actual results to differ materially. Additional information concerning these factors is contained in our filings with the SEC, which are available on the investor section of our website. While we may elect to update forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our estimates change. You should not rely on these forward-looking statements as representing our estimates as of any date subsequent to today. I will now turn the call over to Ron.

Ronald Renaud

Thanks a lot, Amy. During the second quarter, we continued to make major progress in our HCV and HIV discovery and development programs. Before I get into the financial results, I want to quickly recap the major events for the company to date in 2008 and provide an agenda for the call, which is on slide 3.

Last quarter, we reported positive data from the ongoing Phase I-2 study of IDX899, our NNRTI drug candidate being developed for the treatment of HIV 1. Doug will review this data with you in more detail. In line with our previous guidance, last month we submitted a US IND for IDX 184, our nucleotide prodrug candidate, for the treatment HCV. JP will review this program in more detail. Additionally, as we announced this morning, we continue to make substantial progress with our HCV discovery effort. Clinical candidates from both our HCV protease inhibitor and non-nucleoside polymerase inhibitor programs are entering IND enabling preclinical studies. David will review these programs with you in more detail today as well. Finally, JP will close with our progress against our corporate milestones, and we will then open the call for Q&A.

Let's move on to the financials on the next slide, slide four. For the second quarter ended June 30, 2008, we reported total revenues of $1.6 million. This compares with total revenues of $19.7 million in the second quarter of 2007. The decrease on the quarter-over-quarter is primarily due to a decline of $11.5 million in reimbursements of research and development costs from Novartis and a decrease of $6.7 million in license fee revenues. You can see the significant impact that the restructuring has had particularly when you look at the decline in SG&A in the second quarter of 2008 as compared to the second quarter of 2007. We reported a net loss of $18.9 million or a loss of $0.34 per basic and diluted share for the second quarter of 2008. This compares to a net loss of $22.9 million or a loss of $0.41 per basic and diluted share for the second quarter of 2007.

Now, in terms of our 2008 financial guidance, we ended the first quarter with $80.6 million of cash, cash equivalents and marketable securities. While our cash burn rate increased slightly from the first quarter to second quarter, we do remain on track from a budget perspective and continue to expect till in 2008 with approximately $50 million of cash, cash equivalents and marketable securities, assuming no milestone payments, license fees, reimbursement for development programs, and financing activities during 2008. Any licensing fees from IDX899 would be incremental to our year-end cash guidance. Our anticipated use of cash for the remainder of this year is comprised of expenditures related to the funding of our HCV discovery and development programs, G&A expenses, Capex, and working capital. And with that I'll now turn the call over to Doug.

Douglas Mayers

Thank you, Ron. On slide 6, I will quickly review the data for the IDX899 that was presented at the HIV drug resistance meeting in Spain in June. The new IDX899 data displayed here are from the 400 and 200-milligram per day cohorts in the Phase I-2 proof of concept study in HIV 1 infected patients. To remind everyone of the study design, this was a single-center, sequential-cohort, double-blind, placebo-controlled study. There are ten patients in each cohort, randomized eight to IDX899 and two to placebo for seven days of treatment. We have now completed the evaluation of the 800, 400, and 200-milligram per day cohorts and as you can see on this slide, the viral load reductions for each cohort have come in at approximately 1.8 logs. We are very pleased with these results and based on the viral load reductions achieved with the 200-milligram per day dose greater than 1.5 logs we have amended the study the evaluate the 100-milligram per day cohort which is now ongoing.

Moving now to slide 7, as you can see on the left side of the slide, the pharmacokinetics of 899 observed in this study show no clear relationship between dose, drug levels, and antiviral activity in these patients. Of note, every patient in this study achieved a one log or greater reduction in viral load which compares quite favorably against other NNRTIs, currently in development. On the right side of the slide you can see that the 12 levels of IDX899 remain well above the EC 90 against wild type viruses for all doses. This is consistent with the lack of PK/PD relationship and produces a good antiviral response. These plasma drug levels were measured just prior to the administration of the last dose of IDX899 on day seven.

On slide 8, you can see the adverse events that have been reported in this study. To date IDX899 has been well tolerated with no treatment emergent SAEs or premature discontinuations, no discernible patterns of adverse events between treatment groups, no grade 3 or grade 4 laboratory abnormalities during studied drug treatment period, and laboratory profiles are similar between IDX899 groups and placebo. Additionally, no patients in this study have reported any vivid dreams.

On slide 9, most of you have probably seen this slide from us before, but we will show it to you again as with each additional cohort completed, we continue to be very pleased with the performance of IDX899 as a once daily, low-dose drug candidate for treatment of HIV 1. The antiviral response seen at seven days for IDX899 is comparable to the most pronounced viral load reductions reported for each class of agents used to treat HIV-infected patients.

The next step is the IDX899 program as outlined on slide 10 or to complete the ongoing evaluation of the 100-milligram per day cohort. We will have this data from the cohort by the end of this quarter. Additionally, we plan to announce a partnership for the program by the end of the year. I will now turn the call over to JP.

Jean-Pierre Sommadossi

Thank you, Doug. Moving on to our nucleoside-nucleotide program on slide 12, IDX 184 is a once daily IDX is a once daily, oral nucleotide prodrug candidate based on our proprietary liver- targeting technology. As reported on EASL in late April, the compound has showed positive preclinical data both in in vitro and in vivo with the demonstration of high levels of active nucleoside triphosphate present at the liver site. Please note that this drug is also fully active against all HCV genotype 1 through 4. The efficiency of our liver targeting technology is fully demonstrated on slide 13, indeed after oral administrations to monkeys. IDX 184 appeared only transiently in the portal circulation, which is the green line and is rapidly and efficiently extracted by the liver by more than 95%. Almost no unchanged IDX 184 which is the red line or is nucleoside metabolite which the blue line appearing in the systemic circulation. Of note, the level of circulating nucleosides is about 364 log than that measured after administration of an equivalent dose of a nucleoside prodrug of the first generation such as valopicitabine or NM283. We believe that this PK profile may helpfully lead to a very improved efficacy safety ratio for these kinds of drug.

As you can see now in the slide 14, in HCV genotype 1 infected chimpanzee, once-daily oral administration of 10 milligram per kilo per day of IDX184 produced a mean viral load reduction of about 2.3 log after only four days of dosing. These data is supportive of once-daily low milligram dosing of this drug in med.

Now as Ron indicated in detail on slide 15, we have initiated a first-in-man study of IDX184. The recent FDA comment on new HCV anti-virals entering clinical development will need to be evaluated first in a single dose escalation study in a healthy volunteer then followed by a short duration we anticipate a three-day monotherapy study in HCV infected patients, and actually genotype 1 treatment naïve HCV infected patients.

Therefore our first-in-man study for IDX184 is a double-blind placebo-controlled single-dose escalation study to evaluate the safety and pharmacokinetic activity of IDX184 in healthy volunteers. The study will evaluate six single rising doses of IDX184 ranging from five to 100 milligram once per day. Each cohort of the study will evaluate eight volunteers, randomized six to IDX184 and two to placebo.

We are pleased to report that we have already completed dosing of the 5 milligram cohort, which occurred in eventually. The study will be followed by a Phase I/Phase II short duration, as I said, and we anticipate about three-day monotherapy proof-of-concept study in treatment naïve HCV genotype 1 infected patients planned to begin this fall.

I will now turn the call over to David for a review of our HCV discovery program.

David Standring

Thank you, JP. Following our presentation at EASL, we have continued to progress our HCV protease inhibitor discovery program. Today I’m pleased to provide more details on our two lead macrocyclic protease inhibitor clinical candidates, IDX136 and IDX316, which we are now scaling up production.

Both of these drug candidates are based on our selected preferred scaffold B and will develop through SAR or structure activity relationship approaches that were aided by high resolution co-crystal structures with the HCV protease. Our effort has laid to potent and selective antiviral activity against the HCV protease with favorable characteristics required for this class of drug.

We’ve summarized these characteristics on slide 17 and I will review them in more detail in the next few slides. On slide 18, you can see that IDX136 and IDX316 have demonstrated single nanomolar potency against HCV genotype 1a and 1b purified HCV protease enzymes. They also have nanomolar potency against the HCV replicon with EC50s of 4 to 10 nanomolar respectively. And additionally, both compounds have low cytotoxicity with CC50s of 35 to greater than 100 micromolar, meaning that they have good selective indices.

On slide 19, as you can see, our microcyclic protease inhibitors also are highly selective, binding tightly to the HCV protease while demonstrating no activity against eight human cellular proteases.

On slide 20, you can see that both drug candidates appear to have a differentiated resistance profile when compared to other protease inhibitors currently in development. Not surprisingly, IDX136 shows loss of activity against HCV replicons carrying the D168A mutation, the signature resistance mutation from microcyclic PIs. However, IDX136 remains active against HCV replicons carrying A156S mutants. These are resistant to linear PIs and also to R155Q mutant replicons that are resistant to the other macrocyclic PIs. We are currently evaluating the resistance profile of IDX316, but we expect it to be in line with that of IDX136, as these compounds are both based on the same scaffold and have reasonably similar structures.

As you can see on slide 21, favorable plasma drug exposure of IDX316 from IDX136 in non-human primates combined with higher liver drug concentrations for both drugs suggest the potential for once or twice-daily dosing for these compounds

Now on slide 22, I’m delighted to share with you for the first time some details of our non-nucleoside polymerase inhibitor discovery. We have advanced this program much faster than we had anticipated and recently selected our lead clinical candidate IDX375.

Now let’s review our IDX375 preclinical data on slide 23. This compound targets the palm non-nucleoside pocket of the HCV polymerase and exhibits promising potency and selectivity. IDX375 has demonstrated single nanomolar in vitro potency against HCV genotype 1b replicon, EC50 approximately two nanomolar, and also against the HCV genotype 1b polymerase with similar activity observed against genotype 1a.

In preclinical in vitro studies, IDX375 did not inhibit human cellular DNA polymerases alpha, beta and gamma, as shown by the IC50 of greater than 100 micromolar, demonstrating selectivity for the HCV 1a and 1b polymerases. Consistent with these data, IDX375 has a high selectivity index of greater than 33,000. As you can see on slide 24, favorable plasma drug exposure levels in monkeys combined with good oral bioavailability 30% and a higher liver concentration suggest the potential for once-daily dosing for IDX375.

Idenix is now initiating IND-enabling pharmacology and toxicology studies for IDX375. I will now turn the call back to JP.

Jean-Pierre Sommadossi

Thank you, David. Our expertise and focus on anti-viral discovery and development has enabled us, as I’m sure you can appreciate, to efficiently execute our HIV and HCV programs. Thanks for the superb effort of our discovery team we have now a comprehensive pipeline including two drug candidates from each of the major classes of direct-acting HCV antivirals with IDX184 entering clinical studies.

By next summer we plan to be in the clinic with at least one drug candidate from each of these three programs that we have reviewed in detail during this conference call. We continue to execute our corporate milestones, as detailed during this call and more summarized on slide 27.

On the note, I would like to end our formal remarks and open the floor to Q&A. Operator, are there any questions?

Question-and-Answer Session

Operator

(Operator instructions) Your first question comes from the line of Howard Liang with Leerink Swann.

Howard Liang – Leerink Swann

Hi, thanks very much. Good morning.

Jean-Pierre Sommadossi

Good morning.

Howard Liang – Leerink Swann

Good morning. My first question is, I think you mentioned FDA now has made a decision basically only allowing compounds to go through healthy volunteers first. Can you talk about – is that the only reason why you are not starting trials in patients directly?

Jean-Pierre Sommadossi

Doug will address that question since he had direct interaction with the FDA officials.

Douglas Mayers

Yes. I mean, from now on, essentially all of our compounds will have to go through a single rising dose study in healthy volunteers and then to a three-day proof-of-concept. The reason for this being that other companies have seen drug resistance at day four with their classes of anti-virals for Hepatitis C. So that’s the new paradigm you will be seeing of all the companies.

Howard Liang – Leerink Swann

Okay. And I have a question regarding the dose that you are using in the healthy volunteer study only going up to 100 milligrams. What is the human equivalent dose of 10 mg/kg, which I think is the dose that you use in the chimpanzee study?

Jean-Pierre Sommadossi

That’s correct. The reason that we use – it’s about 400 to 500 milligram, and the reason we use a 10 milligram per kilo of IDX184 was to compare historically with NM283 where we’ve got about 0.7 log for a week with 10 milligram per kilo. And in the same time if you recall the presentation in EASL, we had also IDX102. So what we wanted to do in chimpanzee was to compare those historical studies since we have a limited number of chimpanzees. Now what I would like to emphasize in terms of the dose and how we evaluated the dose in men based on the proprietary liver targeting technology, it’s important to pinpoint that 100 milligram per day corresponds to about 2 to 3 gram per day of any third generation nucleoside. Therefore we believe that we will have sufficient potency at this dose envelope.

Howard Liang – Leerink Swann

Okay. But it sounds like you could go higher if you wanted. I remember I think you had presented a--?

Jean-Pierre Sommadossi

Absolutely. If – let’s say that we grow – we have a very large safety margin. So if we like the data, absolutely we can go.

Howard Liang – Leerink Swann

Okay. All right. And then the -- and you mentioned that the next study will be a three-day study, would you be doing a 14-day study or is that going to be I guess only three days?

Jean-Pierre Sommadossi

I’m going to let Doug to address that.

Douglas Mayers

Basically because of resistance concerns, the FDA is limiting monotherapy studies to three days. So after that, we’ll move in to a combinational but at this point, the exact nature of that study hasn’t been determined.

Howard Liang – Leerink Swann

Okay, great. And the last question for me is on the protease inhibitors. Have you worked out the scale-up yet?

Jean-Pierre Sommadossi

I’m sorry?

Howard Liang – Leerink Swann

Have you worked out the scaling up of the production of the microcycles?

Jean-Pierre Sommadossi

David?

David Standring

We are current scaling up the compounds to do more detailed PK and also toxicology studies, and potentially even proof of concept.

Howard Liang – Leerink Swann

Okay, great. Thanks very much.

Jean-Pierre Sommadossi

Thank you.

Operator

Your next question comes from the line of David Moskowitz with Caris.

Melissa – Caris & Company

Hi, this is Melissa [ph] on behalf of David. You have mentioned about a partnership with 899 by year-end. Can you provide any more details on the profile or the kind of partnership terms that you would – given within what you can discuss that you would like to have or you are expecting?

Jean-Pierre Sommadossi

Ron?

Ronald Renaud

Yes. It’s a good question. As we said in the past, it’s not really a good proxy for partnership or licensing deal in the HIV arena. Most of them have benefited at the internal pharmaceutical development level. So there is not really a good roadmap for that. And we’ll let you know when we get the deal done.

Melissa – Caris & Company

Thanks, Ron.

Operator

Your next question comes from the line of Jason Kolbert of SIG.

Jason Kolbert – SIG

Hi. Congratulations on what’s really developing as an exciting platform. I just want to ask a question about the macrocyclics and what you are expecting in terms of efficacy ultimately beyond genotype 1?

Jean-Pierre Sommadossi

David?

David Standring

Yes. We think that basically these molecules will be efficacious against genotypes 1a and 1b. Efficacy will fall off against genotype 2 and even further against genotype 3, for example. So we are really positioning these compounds for use against genotype 1a and 1b.

Jason Kolbert – SIG

And given the breadth of your platform, can you just give us some idea of what you are strategizing in terms of combination therapy going forward?

Jean-Pierre Sommadossi

Well, first, Jason, what we anticipate – and again, this is really in the crystal ball. It’s clear that IDX184, as we indicated, one of the major attributes of IDX184 is that it is active against all genotype at essentially the same potency. And that will be obviously very important in terms of being part of combination therapy. And at the same time, as you know, we were I believe one of the first, maybe the first to report the complementarity in terms of resistance and synergy and additivity with protease inhibitors. So we anticipate that the first combination in the clinic maybe IDX184 with one of our PIs. But it’s clear that -- we don’t know and this is why we are very excited about 375. We think that we are at the conjunction where we were with HIV maybe 15 years ago and then you are asking basically what will be ultimately the cocktail. I don’t see that anyone will have foreseen that in terms of which combination it would be. So we believe that we have – by have a very comprehensive pipeline with all three classes, then also we can combine obviously potentially even the shelf class with the non-nucleoside. And in terms of timing, what we foresee is, as soon as we will have about a month’s of Phase II data in each class, we potentially can combine those drugs and we will make sure to have obviously toxicology studies in terms of those potential combinations.

Jason Kolbert – SIG

Thank you so much.

Jean-Pierre Sommadossi

You’re welcome.

Operator

Your next question comes from the line of May-Kin Ho with Goldman Sachs.

May-Kin Ho - Goldman Sachs

Hello?

Jean-Pierre Sommadossi

Yes, good morning, May-Kin.

May-Kin Ho - Goldman Sachs

How are you?

Jean-Pierre Sommadossi

Great.

May-Kin Ho - Goldman Sachs

My question is on 899, you mentioned that you were looking for partnership by year-end. What are the things that you are looking for in this partnership?

Jean-Pierre Sommadossi

Ron?

Ronald Renaud

May-Kin, it’s interesting. We are at pretty advanced discussions with two different groups on that thing. And what’s interesting is, each group has a different set of needs. So I think we’re probably going to stay away from trying to (inaudible) exactly what our needs are and we’ll kind of take each one on a one-by-one basis and figure out what’s right for the partner and what’s right for Idenix.

May-Kin Ho - Goldman Sachs

But what is right of Idenix?

Ronald Renaud

Maximizing the value and making sure that the product ends up in the hands of someone who is going to best leverage what we think are the good qualities of an NNRTI.

Amy Sullivan

May-Kin.

Ronald Renaud

Hello?

Jean-Pierre Sommadossi

Hello?

Amy Sullivan

Wanda, can we see if there are any more questions please?

Operator

(Operator instructions) Your next question comes from the line of Davis Bu with Goldman Sachs.

Jean-Pierre Sommadossi

Hello?

Davis Bu – Goldman Sachs

Yes. I just – can you remind us what the partnership arrangements with Novartis and what their options are at this point?

Jean-Pierre Sommadossi

Sure. Ron?

Ronald Renaud

Yes. So it’s – they haven’t changed the same as what we’ve had for about five years. And that is that Novartis has the first right of refusal on other products that we develop. And what basically happens is when we complete the proof of concept stage, which is essentially the first demonstration of efficacy and safety, we would then give Novartis a notice and then there is a time period which they get back to us and make a decision on their desire to either opt in or not.

Davis Bu – Goldman Sachs

And if they opt in, what are their responsibilities in terms of the R&D and so forth?

Ronald Renaud

Once they opt in, there is obviously some payment terms that are associated with that, that we’ve not disclosed, but they then become responsible for the expenses related to R&D associated with some of the programs.

Davis Bu – Goldman Sachs

But they are not until then?

Jean-Pierre Sommadossi

Exactly.

Davis Bu – Goldman Sachs

Right. Okay. Thank you.

Operator

You do have a follow-up question from the line of David Moskowitz with Caris & Company.

David Moskowitz – Caris & Company

Good morning. Real quick, on the two protease inhibitors 136 and 316, do you guys plan to choose one of those protease inhibitors? And the other question on that is, when will the – when can we expect the proof-of-concept studies to begin with those products? Thanks.

Jean-Pierre Sommadossi

We are right now moving with both PIs. We anticipated there was no surprises to potentially go and file INDs for both products since one is probably a b.i.d. and one is a once-a-day. In the same time, we expect to potentially order some differentiation between the two compounds. So, we anticipate to have INDs within the first half of 2009 and we will probably go to a proof of concept at least with those compounds and thereafter we will decide how to move either one in phase 2.

David Moskowitz – Caris & Company

JP, thanks for that, and would you also remind us which one is the once daily which once is the twice daily?

Jean-Pierre Sommadossi

136 is the twice a day that is what the PK suggest and the 316 suggest once a day. Now, we will like to put a caveat as well. The data that we obtained was in monkeys and actually we have another animal species. This is without any specific formulation. So, it is clear that this is as really as you guessed, just putting a compound in an animal without any formulation work. So, we probably even go with once a day with some formulation, with 136. But the characteristic of the compound and this is actually 136 as you have seen since we have now full data set with 316 was the first one and we have modified some of those characteristic of 136 to achieve 316 to be more stable with metabolism and that is why we have longer half life for 316.

David Moskowitz – Caris & Company

Thanks, just one final question on 184, do you think we would see data by the AASLD meeting later this year?

Jean-Pierre Sommadossi

Again, we will let you know. But, we are not going to promise anything at this stage.

David Moskowitz – Caris & Company

Is it possible that we will see data at that point?

Ronald Renaud

Again, we are not going to promise anything at this stage. We will talk in the next earning call.

David Moskowitz – Caris & Company

All right, thanks very much.

Ronald Renaud

Thank you.

Operator

Your next question, comes from the line of Howard Liang with Leerink Swann.

Howard Liang – Leerink Swann

Thanks for taking the follow up. So, 184, can you talk about what toxicology data you have, and how long in what species?

Jean-Pierre Sommadossi

Yes, sure. Well, we have right now monkeys and rats, and we have completed toxicology studies necessary to support the IND and enter human clinical studies. So, we have two weeks as we have always done tox in two species. Any other questions.

Howard Liang – Leerink Swann

How do you know it is once a day, I think you mentioned that in the press release?

Jean-Pierre Sommadossi

The half life of the triphosphate is 17 hours, Howard. So, it is clear that we have only a once a day drug and actually we have seen in chimp also, it looks very good. So, from that standpoint we are very confident of being a once a day drug.

Howard Liang – Leerink Swann

Okay, and I just have a follow up on the rationale of the dose selection for phase 1, I know, you said you think there is more than enough coverage, but why you are not testing the equivalent dose that you use in chimpanzees, which I think is 400 to 500 milligrams.

Jean-Pierre Sommadossi

Well, again, let’s go where we stand in term of the dose escalation and then after we will see what we get. We feel pretty confident that we are going to be basically around 2 logs by day 5. If you look any nucleoside today in the clinic after 4 days, I doubt that you will have 2 log or more within 4 days. So, again, I hate to – and I know, David has a pretty strong opinion about that to have a direct comparison between the chimpanzee and also the man situation. Doug, do you want to comment as well.

Douglas Mayers

Yes, the other issue is that, quite frankly, since this is a liver targeted drug of very low milligrams, we may not see any drug in the serum or plasma that we can measure and so the only really good measurement of exposure we have with this drug is going to be viral load reduction. So, we feel it is most appropriate to get into HCV infected patients where we can then look at viral load reductions to demonstrate drug exposure.

Howard Liang – Leerink Swann

Well, that exactly is the reason for my question. So, why not in the phase 1 A portion go up to, let us say, 500 milligrams so that you can do that dosing in the patients. I guess, if you found out that 100 is not enough, will it be too late?

Jean-Pierre Sommadossi

Again, we basically go up with very rationale approach Howard. We know that these doses correspond to 2 to 3 gram of third generation nucleoside. So, we believe that we will have definitely sufficient potency, and so let’s get the data and thereafter, as --, you know, if the same situation as 899 but in reverse. Basically, we went at a higher dose with 899 and now we are going down, and here basically with 184 we can go up. We have a very long safety margin. So, we can go up. So, that is not an issue, and we can do at any time. So, let’s gather the data and then after we will see.

Howard Liang – Leerink Swann

Okay, then just lastly on 899. Can you talk about what data – sort of nature of data you will be presenting at the Mexico AIDS meeting?

Jean-Pierre Sommadossi

Doug?

Douglas Mayers

At the Mexico AIDS meeting, we are going to present the complete data set of all the PK/PD and viral load for the 800 to 200 milligram cohorts. We are going to wait until we have a complete data set in 100 milligrams to present that data set.

Howard Liang – Leerink Swann

When will the 100 data be available?

Douglas Mayers

The 100 milligram data will be available by the end of the third quarter.

Howard Liang – Leerink Swann

Okay, thanks so much.

Operator

Your next question comes from the line of Vernon Bernardino with Rodman and Renshaw.

Vernon Bernardino – Rodman and Renshaw

Hi, thanks for taking my question. Regarding 184, can you briefly describe the liver targeting technology, in particular, how the efficient hepatic extraction is achieved as well as what toxicities have you seen so far and what is the main route of metabolism for the countdown?

Jean-Pierre Sommadossi

Okay. Once the -- let me start by the end of the question. What limiting toxicity, well, as we expected with a liver targeted compound hepatotoxicity, but I have to emphasize, so without any lactic acidosis was the dose limiting toxicity at very high dose of IDX 184 in all species, and that is not surprising. In term of the metabolism, we have at least 3 or 4 routes of metabolism, one being cytochrome P-450 3A, three of those being NADPH dependent, but non- cytochrome P-450 and those three of four different routes lead to the intercellular formation of IDX 184 nucleoside monophosphate which then is activated to the active triphosphate metabolite targeting the HCV polymerase. That is in term of the extraction. This is -- as we see it and if you can have a more detail questions regarding your targeting questions, may be we can address it.

Vernon Bernardino – Rodman and Renshaw

Okay, thank you.

Operator

You do have a follow up question from the line of May-Kin Ho with Goldman Sachs.

Jean-Pierre Sommadossi

Hi, May-Kin.

May-Kin Ho – Goldman Sachs

Hi, I am sorry I was cut off.

Jean-Pierre Sommadossi

It is all right.

May-Kin Ho – Goldman Sachs

I was going to ask about the manufacturing 184, is it a simple manufacturing?

Jean-Pierre Sommadossi

Well, explaining that today May-Kin is not a PI manufacturing. So, clearly it is easier. We already synthesize several kilos, but we basically, you know, basically it is a little bit more difficult than a nucleoside obviously, because you have the liver targeting approach, but it is slightly more than challenging than the regular nucleoside prodrug, but nothing exceptional. As I have said, we already kilos of it and this is internally, we have synthesized all for detox. We have contracted out for the GMP (inaudible). We transfer the technology, it works very well. So, we believe that we have no issues there.

May-Kin Ho – Goldman Sachs

And then in terms of 136 versus 316, any difference in manufacturing?

Jean-Pierre Sommadossi

Yes, there is some. It is the same scaffold but there is some difference definitely -- but in terms of the number step for example, in terms of the challenge, in term of those PI, you know, any MI (inaudible) is going to be challenging. So, to tell you we stopped when we were at the milligram, we still (inaudible) but we have less steps, some PI as you know have as many as five (inaudible) centers, we have only about just 2 (inaudible). So, you know, it is what it is in term of the PIs.

May-Kin Ho – Goldman Sachs

Okay, thank you.

Jean-Pierre Sommadossi

You are welcome.

Operator

(Operator instructions) At this time, there are no further questions. Sullivan, are there any closing remarks?

Amy Sullivan

Okay. I just want to thank everyone for their time today and their interest in Idenix. If you have any additional questions, please feel free to call. Thank you.

Operator

Thank you. This concludes the Idenix Pharmaceuticals second quarter 2008 conference all. You may now disconnect.

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