Seeking Alpha
We cover over 5K calls/quarter
Profile| Send Message| ()  

Executives

Glenn Schulman - Director of Investor Relations

Milind S. Deshpande - Chief Scientific Officer and President of Research & Development

David Apelian

Joseph Truitt - Chief Commercial Officer and Senior Vice President of Business Development

Analysts

Brian Corey Abrahams - Wells Fargo Securities, LLC, Research Division

Brian P. Skorney - Robert W. Baird & Co. Incorporated, Research Division

Rachel L. McMinn - BofA Merrill Lynch, Research Division

Edward A. Tenthoff - Piper Jaffray Companies, Research Division

Y. Katherine Xu - William Blair & Company L.L.C., Research Division

Matthew Harrison - UBS Investment Bank, Research Division

Howard Liang - Leerink Swann LLC, Research Division

Liisa A. Bayko - JMP Securities LLC, Research Division

David Ferreiro - Oppenheimer & Co. Inc., Research Division

Imran Babar

Achillion Pharmaceuticals, Inc. (ACHN) Pipeline Update Conference May 30, 2013 12:00 PM ET

Operator

Good morning, ladies and gentlemen and welcome to your Achillion Pipeline Update Conference Call. [Operator Instructions] As a reminder, this conference call may be recorded. I would now like to turn the conference over to Dr. Glenn Schulman, Head of Investor Relations. Sir, you may begin.

Glenn Schulman

Thanks, Sayeed, and good morning, everyone, or good afternoon now. Thanks for joining us today as we provide a brief conference call to review this morning's press release detailing the nomination of ACH-3422 and providing an update on the Achillion pipeline. Hopefully everyone received a copy of this morning's press release. If you have not received this news release or would like to be added to our distribution this, please feel free to call me or e-mail me in the office at (203) 752-5510 after the call. This news release is also available from our website at www.achillion.com.

Today we'll have a brief presentation from the senior management team followed by a Q&A session. Joining me on the call today from Achillion are Dr. Milind Deshpande, our President and CEO; Mary Kay Fenton, Senior Vice President and Chief Financial Officer; Joe Truitt, Senior Vice President of Business Development and Chief Commercial Officer; and Dr. David Apelian, our Executive Vice President and Chief Medical Officer.

Before we begin, I'd like to caution that comments made during this conference call by management will contain forward-looking statements that involve risks and uncertainties regarding the operations and future results of Achillion. I encourage you to review the company's past and future filings with the Securities and Exchange Commission including, without limitation, the company's Forms 10-K and 10-Q, which identify specific factors that may cause actual results or events to materially differ from those described in the forward-looking statements. Furthermore the content of this conference call contains time-sensitive information and accurate only as of the date of the live broadcast today, May 30, 2013. And Achillion undertakes no obligation to revise or update any of the statements to reflect events or circumstances after that date of the conference call.

With all that, I'd like to turn the call over to Dr. Milind Deshpande, President and CEO of Achillion. Milind?

Milind S. Deshpande

Thanks, Glenn, and thanks, everyone, for joining us this afternoon. I want to take a few minutes today to discuss the announcement we made this morning regarding the nomination of a nucleotide inhibitor, ACH-3422. Importantly, I want to discuss how this novel agent provides Achillion with additional optionality that complements our lead combination development program which is sovaprevir, a protease inhibitor and ACH-3102, our second generation NS5A inhibitor. It should be noted that Achillion now is under its control assets from all 3 key classes that are used to cure HCV. We envision that we could combine these 3 classes to optimize the duration and treatment outcomes for all patients with HCV.

Before jumping into the development programs, I would also like to take a second to introduce myself to those I may not have met. I was appointed to the role of President and Chief Executive Officer earlier this week. But I am in no way new to Achillion. I joined Achillion in 2001 as Vice President of Chemistry and rose to the ranks to become most recently the President of Research and Development. During this tenure, I've had the pleasure of working closely with very talented management team which was led by Mike Kishbauch.

Mike led the company towards IPOs and its maturation into the successful organization it is today. I look forward to continuing -- I look forward to advancing the data assets that we have assembled over the last 6 or 7 years in hepatitis C and I'm very pleased to be working with great people that we have assembled at Achillion.

Before reviewing our pipeline, I would also like to take a moment to introduce everyone to Dr. David Apelian. David recently joined Achillion as our Chief Medical Officer. His expertise in hepatology and drug development from his past work at Bristol-Myers Squibb, Schering-Plough and GlobeImmune will be invaluable as we accelerate our development plans and execute on our milestones.

Our discovery efforts have been extraordinarily productive over the last decade resulting in the discovery of a number of proprietary compounds including sovaprevir and ACH-3102. We have always maintained that discovering promising molecules is only part of the equation for success. As part of our mission, the compounds must also demonstrate freedom to operate and patentability. With our past experience with antiviral nucleotides for HIV, we leveraged that expertise to identify potential nucleotides for the treatment of HCV. The result of that effort is ACH-3422, a proprietary uridine nucleotide prodrug. So this morning, we'll go through how ACH-3422 fits in our portfolio strategy which is headlined by ongoing combination trials evaluating sovaprevir and ACH-3102, as well as to discuss our rapid acceleration toward starting theoretical studies with this regimen.

With that brief introduction, I would like to begin our discussion with a review of our portfolio and the profiles of our HCV pipeline. Our lead drugs, sovaprevir and ACH-3102, have already proven themselves in their respective clinical studies with potency, convenience of dosing, improved barriers to resistance, as well as tolerability. We remain committed to advancing these 2 drugs into registrational studies next year as we have a high degree confidence in their ability to cure HCV. However, as I'm sure all of you have seen that no one in HCV drug development is standing still. Companies large and small, continue to invest in promising follow-on compounds that can achieve the goal of both shortening the treatment duration and optimizing treatment outcomes across all types of HCV patients in the world. For Achillion, that is how we envision ACH-3422 fitting in. As a potential next wave candidate that can be leveraged into our existing development program to further enhance treatment and provide consistent and concise treatment duration across patient populations regardless of genotype, liver function, et cetera.

So with that background I would like to turn to the slide that I presume all of you have access to. And I would like to start with Slide 5 which summarizes the target product profile for the 3 drug candidates that we will be talking today. Starting with sovaprevir, which is an NS3 protease inhibitor. In clinical trials we have shown that sovaprevir has excellent activity against genotypes of 1 and 3 and in the replicon assays, we have shown that it can cover other genotypes as well. In the clinical trials that have done with sovaprevir today, we have not seen emergence of resistance and no viral breakthrough was seen on treatment. Based on all the drug interaction studies that have done, we believe that sovaprevir can be effectively used in combination with ACH-3102 and presumably with ACH-3422, which is the new addition to our portfolio. It is also worth noting that sovaprevir is once-daily drug, and it does not require boosting with ritonavir. And again we have demonstrated safety and tolerability for our 12-week treatment duration with sovaprevir.

Moving on to ACH-3102 which is the NS5A inhibitor. Again, based on all the data that we have on hand today, we believe that ACH-3102 is pan-genotypic NS5A inhibitor. In a clinical trial with ACH-3102 and ribavirin, we have shown that it provides a high valued resistance. And we believe that 3102 again will be additive to synergistic with sovaprevir as well as with 3422. In terms of its dosing regimen, 3102 is highly effective as a once-daily drug. And for 3422, which is the nucleotide and NS5A inhibitor, just based on the class of the compound, we believe that 3422 will demonstrate pan-genotypic activity. We also know that nucleotide inhibitors provide a high value to resistance and they can be added effectively to either a protease or an NS5A inhibitor.

So if you move on to Slide 6 which summarizes our current combination development program with sovaprevir and ACH-3102. The first clinical trial which is outlined in this schematic diagram is our 007. This trial is currently ongoing. We are evaluating genotype 1a and 1b patients for 12 weeks in combination with ribavirin. This trial will also evaluate our combination of sovaprevir and 3102 without ribavirin either for 12 weeks or 8 weeks. We anticipate providing preliminary results from this trial starting summer of this year.

Now, aside from the -007 trial, we will also initiate a large Phase IIb trial which is called APOLLO C, and we intend to start this clinical trial towards the end of this year. There are also other clinical trials that we will undertake shortly, and these will be in "special populations", and these will be -- these studies will be conducted in HIV, HCV co-infected patients. Patients that are non-genotype 1, as well as patients that have advanced liver disease.

The next slide shows a schematic diagram of the 007 trial. The enrollment for this trial is going is extremely well. There is high enthusiasm from the investigators in enrolling patients in this trial. The segment 1 outdoor study, which has 2 groups, is currently enrolling. And we anticipate RVR data from segment 1 by end of summer this year. The main objective of this study, as you can imagine, is to determine efficacy as reflected by the RVR end-of-treatment response, as well as sustained viral response. This is a study that is being convicted in the United States, Canada, Australia and New Zealand. And as I just mentioned a moment ago, we anticipate RVR during third quarter, and SVR during fourth quarter of this year.

So with that quick overview of what we currently have in clinical trials, I would like to move on to ACH-3422 which is the NS5B nucleotide polymerase inhibitor. So if we move to Slide 9, the chemical description of 3422 is that it is a nucleotide prodrug of a uridine analog. We have extensively profiled this compound in virology [ph] and we have shown that this compound is specific for inhibition of HCV polymerase. It demonstrates high potency in the replicon assay and 3422 is highly specific for inhibition of HCV. And based on the replicon data that we have to date, we believe that 3422 is a pan-genotypic inhibitor of HCV.

In terms of its pharmacokinetics and metabolism, we see rapid conversion of the prodrug to monophosphate in microsomes as well as in hepatocytes. And the PK profile that we have obtained after single-dose studies suggest that 3422 is a once-daily drug. In terms of safety, we have very recently completed a 14-day animal retoxicity [ph] study. In this study, we attained high exposures of the triphosphate in the liver. And at the high dose, we did not see any significant findings. Aside from these studies, we have also profiled 3422 for its ability to inhibit mitochondrial RNA polymerase, and the results in those assets also are very encouraging. We did not see effective incorporation of ACH-3422 in the mitochondrial assays.

If you look at the activity of 3422 as compared to sofosbuvir or ACH -- GS-7977. In the replicon assay, ACH-3422 is probably about 3 to 5x more potent than sofosbuvir against genotype 1a and 1b and the activity of ACH-3422 is very similar to sofosbuvir in genotype 2. Again as I mentioned, 3422 is a specific drug inhibition of HCV. Looking at the resistance profile, we see a fairly moderate shift in EC 50 in presence of the classic S-282 gene mutation in the NS5B polymerase gene. For our 3422 we see about a 5.74 shift as compared to a 7.64 shift for or sofosbuvir.

In many assays that we have profiled, we see rapid conversion of the prodrug of ACH-3422 to monophosphate. And these assays were done in human liver microsomes as well as in hepatocytes. The conversion of 3422 to corresponding triphosphate is comparable to the conversion that see of sofosbuvir to its corresponding triphosphate. The assays [indiscernible] where we incubate 20 micromolar of each drug, of the drug for a 24-hour period in and human hepatocytes. And for ACH-3422 under the [indiscernible] conditions, we see 5.15 micromolar triphosphate as compared to 5.84 for sofosbuvir. In terms of percent conversion, you see about 26% of 3422 converted to its corresponding triphosphate. While for sofosbuvir, we see 29% conversion of sofosbuvir to its corresponding triphosphate. The activity of ACH-3422 triphosphate, again, it's also very comparable to the activity of sofosbuvir triphosphate, for inhibition of either CGP [ph] as well as UTP [ph] and the IC50 in these assays range anywhere from 1.15 micromolar to about 1.58 micromolar.

We have also profiled ACH-3422 in mutual cytotoxicity and we see about a 304 difference between the EC 50 and the CC 50s that are obtained in the cytotoxicity assays. So if you look at the EC 50 values for 3422 that are obtained in the replicon assay versus the CC 50 values that are obtained in these different cell lines or primary cell cultures.

So that provides a quick overview of ACH-3422. We were very pleased to see that the profile of 3422 is very competitive. And also are very encouraged to see that 3422 did not show or we did not see any significant findings in the toxicity studies that we have completed today. In terms of our capitalization and liquidity, we are very well-funded and we believe that we can progress the combination of sovaprevir and 3102 to our late Phase II trials as well as bringing forward upon the combination of 3422, sovaprevir and 3102.

So I'll wrap up this overview with some comments regarding our HCV development strategy. I believe that we have a portfolio that aims to provide optimal outcomes and treatment duration for all HCV patients. We are moving forward with sovaprevir, ACH-3102 combination for genotype 1. And we expect interim results by third quarter of this year. We are modifying that study to evaluate 8-week as well as 12-week treatment regimens without ribavirin and those ARMS we anticipate to begin sometime this year. We continue to accelerate development program with keen focus on initiating Phase III studies in second half of 2014. And finally regarding the timelines for ACH-3422, the nucleotide NS5B polymerase inhibitor, we anticipate that we will file an IND in first quarter of next year with clinical trials to start shortly thereafter.

So with that, I'll hand it back to Glenn.

Glenn Schulman

Sure. Operator, we're ready to open up for the Q&A.

Question-and-Answer Session

Operator

[Operator Instructions] Your first question comes from Brian Abrahams from Wells Fargo.

Brian Corey Abrahams - Wells Fargo Securities, LLC, Research Division

Appreciate all the detail on the news profile. The FDA's obviously has been a bit cautious in terms of the potential development path for nukes, given some of the history. Can you talk about maybe some of the detox work that you've done that might help, if at all, might help address that and allow you to move more quickly through the clinic and into combinations with sovaprevir and 3102. And maybe just talk a little bit about how you envision the early clinical path. I know we're still a year away from the clinic but be interested to hear your views if you got any feedback on that thing.

Milind S. Deshpande

Sure. So the short answer is we have not received any feedback. This still compound is still -- we have just completed the [indiscernible]. But Brian, the question that you ask is, is very relevant. The bio part progressing nucleoside inhibitors into development has certainly shifted. So in our preclinical studies, we will do a very thorough evaluation of cardiac toxicity, liver toxicity as well as establish safety margins as compared to what we think the clinical exposures are going to be. So we are very aware that the development path for nucleosides can be slow if the preclinical tox is not done correctly. And as I said, we'll pay very close attention to cardiac toxicity, liver toxicity as well as making sure that we established high safety margins.

Brian Corey Abrahams - Wells Fargo Securities, LLC, Research Division

Have you have had the chance to do any sort of studies in the nonhuman primates and perhaps echoes?

Milind S. Deshpande

So those studies will start -- we will be starting those studies shortly. So we are going to look at monkeys as our second task [ph] species and we will do echocardiography as well as other monitoring in our nonclinical studies.

Brian Corey Abrahams - Wells Fargo Securities, LLC, Research Division

One more quick question, I'll hop back in the queue. Can you talk a little bit more about the prodrug technology that this uses and how similar or different it is to other drugs that have entered the clinic?

Milind S. Deshpande

All I can say is that there is precedent for this type of prodrug that we are using with ACH-3422. The attributes that we see for this prodrug are very rapid absorption to the drug. We see a high conversion of the monophosphate into the triphosphate. And again, the half-life of the prodrug itself in microsomes is fairly short.

Operator

Our next question comes from Brian Skorney from Robert Baird.

Brian P. Skorney - Robert W. Baird & Co. Incorporated, Research Division

I guess, just a couple of quick questions on the nuke that you're proposing to move into the clinic. I guess, we've kind of talked about the complexity around IT for the nucleotides in hep C. And I'm just wondering what your thoughts are around the [indiscernible] nuke space. And at the recent USPTO determinations regarding some of the broader patents around the structure had given you increased confidence to move forward without fear of the significant legal repercussion here?

Milind S. Deshpande

So let me briefly describe what we have done. So as I mentioned, we are looking at a uridine analog. And the novelty for chemical composition comes from modification of the sugar mobility [ph], as well as the base. So we believe that we have scrubbed the IP landscape quite thoroughly. And at this time, I'm comfortable moving this compound into development.

Brian P. Skorney - Robert W. Baird & Co. Incorporated, Research Division

And I guess this is a follow-up to some of the cytotox questions. Have you actually seen -- I was trying to look for it but I couldn't find any of the cytotox data from 938, the pharma side nuke that was discontinued for liver tox. Because I believe the CC 50 is for 7851 across the same cell lines you're describing, exceed 100 micromolar but CC 50s and some liver cells seem a much lower for 3422.

Milind S. Deshpande

Let me just pull up the data. So again, looking at the [indiscernible] toxicity data that we have so far, the lowest CC 50 that we have is 13.6 micromolar [ph] and we have G2 [ph] cell line. And that gives us a 304 margin as compared to the EC 50 values.

Brian P. Skorney - Robert W. Baird & Co. Incorporated, Research Division

But I guess my question is you're making a bit of a comparison to 7977 and at least the [indiscernible] doesn't have any margin in terms of threshold for liver tox. So I'm just wondering if you've see any data on 938 because it might be a little hard to determine how much triphosphate exposure you'll get.

Milind S. Deshpande

So we are generating the data for 7977 as well as 938 [ph] in our own hands for the cytotoxicity assays and we will have a direct comparison of 3422 with these 2 compounds. At this time, I don't have that data.

Operator

Our next question comes from Rachel McMinn from Bank of America.

Rachel L. McMinn - BofA Merrill Lynch, Research Division

I guess, my question after is, just given the complexity of the space, do you have other nucleoside candidates or nucleotide candidates that you will be bringing behind this program? I just want to get a sense of the conviction level in the company of how important a nuke is to achieving your long-term goals?

Milind S. Deshpande

Rachel, so there is robust discovery effort ongoing around the nucleoside program. Obviously, we have identified certain chemical modifications that we believe will give us the intellectual property. And so, we are continuing our chemistry efforts to fortify our IP. So in that process, we are looking at additional analogues of 3422.

Rachel L. McMinn - BofA Merrill Lynch, Research Division

Okay, great. And then just while we have you, I know it's not the topic of the day, but is there anything you can say more about the safety profile of 3102 in terms of numbers of patients you have out to 12 weeks? Just given the very long half-life, I want to get a little as much clarity as you guys have on the progress of that compound on safety.

Milind S. Deshpande

So, we have 12-week data in the -- from the ongoing study which is 3102 plus ribavirin. We have those 8 patients in that study for 12 weeks. And the drug was safe and [indiscernible].

Rachel L. McMinn - BofA Merrill Lynch, Research Division

Okay. So that's all the data they have now and it's not until the -007 study gets more mature that you'd have a more robust safety package?

Milind S. Deshpande

That's correct. Yes.

Operator

And our next question comes from Ted Tenthoff from Piper Jaffray.

Edward A. Tenthoff - Piper Jaffray Companies, Research Division

And pulling the rabbit out of the hat here with the nuke, I don't know how you kind of kept it secret from everybody. I appreciate the IP insight. Maybe kind of taking this back, I guess, the biggest question really is on safety. And obviously we're going to have to wait until we see this in man to really understand the safety profile. But can you talk to us about, mechanistically with respect to what your understanding is both around the prior Pharmasett, the Idenix and Inhibitex compound, and sort of where this might fit in, might be different. I think it's more similar to the vertex compound, if that's right. But maybe you can just tell us a little bit more about structure and some of the competitive mechanisms?

Milind S. Deshpande

So the difference between the structure of 3422 and either the Inhibitex compound is -- and the main difference is in the base. The [indiscernible] Inhibitex compound was [indiscernible] analog and what we are looking at with 3422 is a uridine analog. There are certain advantages of using a uridine monophosphate prodrug and we have seen these advantages with a compound like 7977. But also in the profiling assays that we have done. What we see is that there Is a clear difference with 3422 triphosphate being used as a substrate for mitochondrial RNA polymerase. At 1/100 of the concentration of 3422 triphosphate, UTP [ph] can compete out 3422. So what this indicates is that 3422 triphosphate is not really a good substrate for mitochondrial RNA polymerase. And many of the toxicity issues that arise with nucleosides are related to mitochondrial toxicity and incorporation of these nucleoside analogues into mitochondrial polymerase. So that's another important assay that we have looked at. As I mentioned earlier, moving forward, we will be looking at the safety very, very carefully. We will monitor echoes. We will look at other markers of cardiac toxicity as well as liver toxicity which have really been the main issues with other nucleoside analogs that have been progressed for treatment of HCV.

Operator

Our next question comes from Katherine Xu from William Blair.

Y. Katherine Xu - William Blair & Company L.L.C., Research Division

A few questions. So, well, my congratulations as well to Milind and David to your new positions. A few questions. So are you saying that -- I'm just curious, is this new nuke, is it not a 2 level base [ph] nuke, can you at least say that?

Milind S. Deshpande

No. We are not commenting on that, Katherine. All we are saying is that the modifications that we have made are in the uridine portion of the molecule, as well as in the sugar portion of the molecule.

Y. Katherine Xu - William Blair & Company L.L.C., Research Division

Okay. And then you think that the IP so far looks like it's pretty clear I know that you have you're pretty confident about that?

Milind S. Deshpande

That's our assessment at this time.

Y. Katherine Xu - William Blair & Company L.L.C., Research Division

And then if you monitor the echo in monkeys frequently, do you think going forward in humans the FDA would in monitoring in humans?

Milind S. Deshpande

That remains to be seen. Obviously, we will have a dialogue with the FDA as to how we want to proceed with the clinical trials for 3422. But I'll ask my colleague, David, to comment on it on his thoughts.

David Apelian

I really think it's going to be based on the data we get together in the preclinical program to make the case for the IND. And then, as Milind said, we would kind of have a constructive with the agency to make sure it satisfies their concern [ph].

Y. Katherine Xu - William Blair & Company L.L.C., Research Division

For raprivir [ph], have you gathered more information on the geo type 3 activity?

Milind S. Deshpande

There was a few trials. We did one study where sovaprevir was dosed as a BID agent in genotype 3 and in 3 out of 6 patients, we saw more than 3 log drop and 3 patients had a log drop which was around 2.5 logs. So the -- I believe that mean maximum change units in remain that study was 2.7 logs. That's all the data we have for sovaprevir and genotype 3.

Y. Katherine Xu - William Blair & Company L.L.C., Research Division

Do you have any thoughts on sovaprevir plus 3102 without the pan-genotypic? I guess genotype 3 is kind of the weakest.

Milind S. Deshpande

Yes it is. And we will try that experiment. Based on the replicon data that we have for ACH-3102, I think it is an experiment certainty we're doing. But genotype 3 has provided many surprises to everybody in the field. So I think unless we do the experiment, I would hesitate to speculate on the outcome.

Operator

Our next question comes from Matthew Harrison from UBS.

Matthew Harrison - UBS Investment Bank, Research Division

I have 2. So I guess the first question is, and some people have asked questions around this, but do we know what the safety bar is with the FDA or what kind of safety data you need to generate for the IND given sort of their recent set of concerns and have they made that clear to everybody or is there some guessing involved in that? And then the second question is around the prodrug structure. Anything you can say -- I know you don't want to tell us what it is. But anything can say about the precedent of the structure and the safety of the structure?

Milind S. Deshpande

What was the last part, Matt?

Matthew Harrison - UBS Investment Bank, Research Division

It was around the safety of the prodrug structure. I know some people positive but some of the different structures of the pro drug is part of the issue. So I'm just wondering, given the precedent you said, it was for the pro drug structure. What can you can say about safety?

Milind S. Deshpande

Yes. So to your first question, has FDA provided any guidance in terms of how or what their expectations are to carry a nuke into clinical studies or what nonclinical studies need to be done. I'm not aware of any guidance that the FDA has provided. What we will be doing is putting together a very robust package for safety. One of the key things, again, is going to be to establish high safety margins as compared to what you think the clinical exposures are going to be. And as far as our thinking is concerned at this stage, I think if we have all the boxes checked for the IND-enabling studies, with high safety margin established in the toxicity studies, I think we should be able to initiate our clinical studies. And again, I'll ask David to comment on this.

David Apelian

Well, I think it's an excellent question and, in this particular case, it's an emerging concern with this class of agent. There are ways to engage the agency pre the IND filing to make sure that what we're proposing is acceptable to them. So we would take every advantage of the dialogue with them to make sure that there are no surprises.

Matthew Harrison - UBS Investment Bank, Research Division

Okay. And then just to be clear, you haven't had that kind of dialogue, yet, though?

Milind S. Deshpande

No, we have not. And to your next question regarding the nature of the prodrug. I don't believe that the chemical structure of the prodrug after cleavage would impart any toxicity. We have seen other prodrugs which had an [indiscernible] and there was speculation whether that [indiscernible] causes toxicity after cleavage. And all I can say is that we don't have that chemical structure.

Operator

Our next question comes from Howard Liang from Leerink Swann.

Howard Liang - Leerink Swann LLC, Research Division

My, I guess, first question is on the 14-day animal tox study. Can you tell us what species or whether there was more than one species that was seen?

Milind S. Deshpande

The study was done in a rat. We evaluated a lower dose and a high dose of ACH-3422. And it was a fairly thorough toxicity study where we looked at clinical chemistries, hematology and full histopathology.

Howard Liang - Leerink Swann LLC, Research Division

I don't know if you're ready to tell us what dose that you had given?

Milind S. Deshpande

Yes. The high dose was 250 milligrams per kilogram per day.

Howard Liang - Leerink Swann LLC, Research Division

Okay, great. And you mentioned that the prodrug technology for this compound had been used, employed previously. Can you say that the sugar modification had also been employed before?

Milind S. Deshpande

No.

Howard Liang - Leerink Swann LLC, Research Division

Okay. And then the last question is on the -- whether the modification to -- I think when you said that you're proposing a modification to -007 [indiscernible], can you talk about the rationale?

Milind S. Deshpande

Yes. So these are the modifications. Just to clarify, these are the modifications to the -007 trial, is that correct?

Howard Liang - Leerink Swann LLC, Research Division

Yes.

Milind S. Deshpande

Yes. So we are amending the protocol as we speak to add 1 arm for 12 weeks without ribavirin. And we are also adding an 8 recon [ph] without ribavirin. Obviously, the 8 recon [ph] will be triggered after evaluating the data from the 12-week arm.

Howard Liang - Leerink Swann LLC, Research Division

Okay. Then this will be for both genotype 1b and 1a patients?

Milind S. Deshpande

That's correct. That's the intent. And again, we might have to sequence the studies, but the intent is to evaluate that in 1a as well as 1b.

Operator

Our next question comes from the Liisa Bayko from JMP Securities.

Liisa A. Bayko - JMP Securities LLC, Research Division

I just want to step back and understand sort of the strategic decision to move into the nuke area. Obviously, it's a highly competitive space and there have been some -- the safety hurdle is high. You have a protease NS5A that is fairly far along, they're already in combination together. And I think the suggestion there is that, that may be sufficient to drive very high cure rates and in a pan-genotypic fashion. So I'm just trying to understand sort of, does this decision to move into the nucleotide area say anything about your conviction level on the kind of notion of high cure rates with your existing clinical development-stage candidates in combination? Or really, what do we make of your decision now to go into the sort of therapeutic class? What's your intention?

Milind S. Deshpande

So the short answer to your question, Liisa, is that our conviction has not changed. In terms of the competitive landscape and how we see 3422 feeding into our portfolio. I'll ask Joe to comment on it.

Joseph Truitt

Hi, Liisa. So we kind of see things rolling out with protease NS5A combination. We believe that wave will allow us to treat most of the patient types that we've identified previously, the genotype 1a, 1b, naive, experienced, and start to address the cirrhotic populations. But what we believe the nucleoside will do for our portfolio is actually take us another step forward, which is to optimize the treatment across all patient types, all genotypes, all different stages of liver disease. Look for a standardization at a base case of 12 weeks and optimally at 8 weeks which we believe would then give us a significant competitive advantage. Because we think the evolution of this treatment market will move towards triple DAA combinations, optimized for both duration and patient types. So that's where we think things are going and that should be the final wave of development in HCV. But that's how we kind of see it. So we took the opportunity to get the nucleoside out of our own labs and we think it puts us really in an optimal strategic position.

Liisa A. Bayko - JMP Securities LLC, Research Division

Okay, that's great. And then just on genotype 3, that's been a tough one to tackle for some of the other compounds. Can you maybe talk about your activity for 3422 against genotype 3?

Milind S. Deshpande

I don't have the data as yet, Liisa. And as soon as we are comfortable with the data that we generate in genotype 3, we'll communicate that.

Operator

[Operator Instructions] Our next question comes from David Ferreiro from Oppenheimer.

David Ferreiro - Oppenheimer & Co. Inc., Research Division

Most of them have actually been answered. But maybe longer term, can you, as best you can, estimate when you'd expect 3422 to actually make it to a Phase III trial and everything goes according to plan? And then also speculate what you think the FDA would like to see as a comparator at that time thinking forward? And then big picture in enrolling a Phase III, if there are numerous short durational or oral cures in the market, do you think it's going to be difficult to actually fill that clinical trial?

Joseph Truitt

So David, this is Joe. So just to map out the plan. So we plan on filing the IND in about 6 months. From there, we would roll right into a proof of concept trial for 3422, and that would most likely be a 7-day proof of concept. And ideally, what we'd like to do at that point is merge 3422 into our protease NS5A combination and then move that through a proof of concept, what you will call maybe a Phase IIa. And then aggressively move that into the much larger Phase IIb, Phase III kind of studies. Under the current timelines, again, looking at a pretty aggressive push here, we would have this combination as triple into Phase III in 2015. And then hope to be on the market sometime in 2017 with the triple.

So that's kind of the scope of the development plan. As far as what the FDA will require, I'll probably pass it over to David Apelian to give some commentary. But the last piece about enrolling patients into the clinical trials, as of right now, our experience has been very positive. That patients seem to be anxious to get into these interferon-free HCV trials. Can't always project exactly what the future would be but it doesn't look like the population is going away anytime soon. So I would imagine that, that would remain a high level of interest, especially if you bring forward something novel and something that is advancing the treatment. But, David, do you want to comment on comparator arms?

David Apelian

Sure. Difficult to speculate on that, as you can imagine, because standard of care is not something that the agency necessarily will declare. The trading community will move in that direction when there are enough options out there and there enough data. But you can imagine in a good case scenario where the PI NS5A doublet for Achillion gets down ahead of it. And this gives them the piggyback or a combination to optimize further. It offers some interesting opportunities. But it's really is difficult to speculate when there's going to be multiple emerging or oral combinations in that year or 2 preceding how the agency's perspective on comparator groups will evolve. So that's something obviously we have to be in a good dialogue with them about as things develop.

Operator

And our next question comes from Imran Babar from Cowen.

Imran Babar

Most of my questions have been answered. But I had one other kind of tangled question. You mentioned that there was an EC 50 shift in the [indiscernible] of the [indiscernible] mutation. Have you guys looked at any other mutations that would be of interest?

Milind S. Deshpande

That work is ongoing. So we are trying to generate resistant variants with 3422. But it has been difficult to generate resistant variants. So what was done in this case was not really generate the 282-resistant in presence of 3102. The 282, the resistant was generated in NS5B polymerase. And then we just tested the compound for it's activity against that mutation.

Unknown Analyst

Okay, thanks. That's helpful. And one of the questions, we talked earlier about structure and I'm just curious with respect to sofosbuvir, what specifically in the structure do you think accounts for the lower EC 50s that you were able to see?

Milind S. Deshpande

Several reasons, and that work is ongoing. One of the things could be is that in -- with sofosbuvir, after the prodrug [indiscernible] is cleaved into the monophosphate, there is a pathway where the monophosphate is clear to some extent into the nucleoside and that becomes a dead end for the compound in the sense that it can't be converted to a triphosphate. So we are looking into the details of that to see if we minimize the hydrolysis of the monophosphate to the nucleoside.

Operator

I would now like to hand the conference back over to Dr. Glenn Schulman.

Glenn Schulman

Thanks, Sayeed. I think, Milind, you have a couple of closing comments for us?

Milind S. Deshpande

Yes. I would like to thank everybody for joining the conference call. We are very excited about the potential of our advanced clinical candidates of sovaprevir and 3102. As well as bolstering the portfolio of the denomination of ACH-3422. We look forward to providing additional updates during the summer on our clinical studies as well as the SVR4 results we expect to announce during the fourth quarter around the time of AASLD. Thanks, everyone, and have a great day.

Operator

Ladies and gentlemen, thank you for participating in today's conference. This concludes our program. You may all disconnect, and have a wonderful day.

Copyright policy: All transcripts on this site are the copyright of Seeking Alpha. However, we view them as an important resource for bloggers and journalists, and are excited to contribute to the democratization of financial information on the Internet. (Until now investors have had to pay thousands of dollars in subscription fees for transcripts.) So our reproduction policy is as follows: You may quote up to 400 words of any transcript on the condition that you attribute the transcript to Seeking Alpha and either link to the original transcript or to www.SeekingAlpha.com. All other use is prohibited.

THE INFORMATION CONTAINED HERE IS A TEXTUAL REPRESENTATION OF THE APPLICABLE COMPANY'S CONFERENCE CALL, CONFERENCE PRESENTATION OR OTHER AUDIO PRESENTATION, AND WHILE EFFORTS ARE MADE TO PROVIDE AN ACCURATE TRANSCRIPTION, THERE MAY BE MATERIAL ERRORS, OMISSIONS, OR INACCURACIES IN THE REPORTING OF THE SUBSTANCE OF THE AUDIO PRESENTATIONS. IN NO WAY DOES SEEKING ALPHA ASSUME ANY RESPONSIBILITY FOR ANY INVESTMENT OR OTHER DECISIONS MADE BASED UPON THE INFORMATION PROVIDED ON THIS WEB SITE OR IN ANY TRANSCRIPT. USERS ARE ADVISED TO REVIEW THE APPLICABLE COMPANY'S AUDIO PRESENTATION ITSELF AND THE APPLICABLE COMPANY'S SEC FILINGS BEFORE MAKING ANY INVESTMENT OR OTHER DECISIONS.

If you have any additional questions about our online transcripts, please contact us at: transcripts@seekingalpha.com. Thank you!

Source: Achillion Pharmaceuticals' Management Hosts Pipeline Update Conference (Transcript)
This Transcript
All Transcripts