Arrowhead Pharmaceuticals - Earnings Call - Q1 2015

Transcript

Speaker 0

Ladies and gentlemen, welcome to the Arrowhead Research Fiscal twenty fifteen First Quarter Financial Results Conference Call. Throughout today's recorded presentation, all participants will be in a listen only mode. After the presentations, there will be an opportunity to ask questions. I will now hand the conference call over to Vincent Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead, Vince.

Speaker 1

Thank you. Good afternoon, everyone, and thank you for joining us today to discuss Arrowhead's results for its fiscal twenty fifteen first quarter ended December 3134. With us today from management are President and CEO, Doctor. Christopher Anzalone Chief Operating Officer and Head of R and D, Doctor. Bruce Given and Chief Financial Officer, Ken Myszkowski.

Management will provide a brief overview of the quarter and we'll then open up the to your questions. Before we begin, I would like to remind you that comments made during today's call may contain certain forward looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of Securities Exchange Act of 1934. All statements other than statements of historical fact, including without limitation those with respect to Arrowhead's goals, plans and strategies are forward looking statements. These include, but are not limited to statements regarding the anticipated safety and or efficacy of ARK-five twenty, ARK AAT and our other programs as well as anticipated timing for study enrollment and completion. They represent management's current expectations and are inherently uncertain.

Thus actual results may differ materially. Arrowhead undertakes no duty to update any of the forward looking statements discussed on today's call. You should refer to the discussions under Risk Factors in Arrowhead's Annual Report on Form 10 ks and the company's quarterly reports on Form 10 Q for additional matters to be considered in this regard. With that said, I'd like to turn the call over to Doctor. Christopher Anzalone, President and CEO of the company.

Chris? Thanks, Vince. Good afternoon, everyone, and thank

Speaker 2

you for joining us today. I'd like to break this call into four parts. First, we will talk about the accomplishments of the past quarter. Second, we will discuss regulatory aspects and timing of the ARK-five twenty and ARK AAT clinical programs. Third, we will provide an overview of our financial results for the quarter.

And fourth, we will discuss goals for calendar twenty fifteen. Let's begin with our recent accomplishments. During the first fiscal quarter of twenty fifteen and period since our last call, we achieved several key goals set in 2014. One of the broader goals was to build out our management team to give us deeper expertise internally and enable us to scale our operations and programs. We made great strides toward these ends during the quarter with the appointments of Susan Boynton as Vice President of Global Regulatory Affairs and Patrick O'Brien as General Counsel.

The quality of these executives and the nature of the responsibilities they have assumed are representative of our maturation a company. Our focus is increasingly geared toward clinical programs and the potential shareholder value they may drive. As you know, our two clinical programs are ARK520 and ARK AAT for the treatment of chronic hepatitis B infection and liver disease associated with alpha-one antitrypsin deficiency respectively. We made important progress in both programs last quarter. We presented initial data from the ongoing Phase IIa study of ARC520 in the late breaking poster session at the fourteen American Association for the Study of Liver Disease or AASLD meeting in Boston.

ARK-five twenty showed clear reduction of HBV S antigen after a single dose of one and two mgs per kg. Interestingly, the duration of S antigen knockdown was substantially longer than we expected. As we discussed on our last call, these are important data. We believe that ours is the first report demonstrating S antigen reduction in humans after a single dose. This is something the field has been trying to accomplish for quite some time and the fact that we have done it is encouraging.

This was only the beginning of our Phase IIa single dose escalation study and we have since completed dosing both three and four mgkg cohorts. Cohorts. We are still following the four mg and per kg cohort and both the three and four mg per kg groups are still blinded. The safety profile of ARK-five twenty appears to continue to be very good. We have still not seen any signs of end organ toxicity and no reported AEs have been rated as severe or serious.

We expect to have unblinded data that we can discuss next quarter. We currently have no plans to escalate higher in the single dose Phase IIa study. We have always assumed that ARK-five twenty would be a multiple dose therapy and it is time to understand S antigen reduction kinetics upon repeat dosing. Of course, is a far more clinically relevant endpoint than single dose. RNAi therapeutics rely on loading the risk complex with RNAi triggers and programs all I'm aware of require multiple doses to maximize the loading process.

This is often done with several frequent initial doses referred to as loading doses. Because of the long duration of activity we have seen in ARK520, it's possible that we may achieve this with fewer doses. In December, we met our guidance and submitted an IND application to the FDA to begin Phase 2b multiple dose studies. Throughout the entire ARK-five 20 program, we have operated under very aggressive time schedules and I believe executed well on them. Keep in mind that we went from idea to starting a Phase one study of a novel molecule and a novel delivery system in only approximately eighteen months.

Consistent with this desire to move quickly and increase our lead in the field, we proposed a parallel design for the Phase 2b whereby we would study multiple dose levels simultaneously. On a call in mid January, the FDA requested that we initiate a more traditional ascending dose protocol beginning at one mg per kg. Importantly, no additional studies were required to begin the one mg per kg study. Since that time, we received an official letter from the FDA outlining its requests and it was consistent with the discussions we had. We submitted the amended protocol to the FDA today.

This is a big step for the program and underlying platform. Phase 2a data suggests that one mg per kg is an active dose, so we should generate important data during the first cohort. It is also an important step in building out our safety data set. More broadly, it represents another de risking event for DPCs generally. As we build out our understanding of how DPCs work in humans, we will better able to predict how future candidates including ARG AAT will perform.

This should enable the market to value follow on candidates earlier in their development cycle. This is an important characteristic of RNAi therapeutics. Once we show that a delivery system is well tolerated and active in a given organ system, we believe it is a good assumption that new sequences against different gene targets may follow suit. This is a good start to a program that is addressing a significant unmet medical need. We are approaching a post hepatitis C world and we see hepatitis B as the next great liver challenge.

Because of the complexity of HBV, it is likely that multiple agents will be required to induce a functional cure in at least some populations of the disease. Reducing S antigen levels is thought to be a critical backbone therapy and we have a clear lead in this. We have learned a tremendous amount about the disease and how ARK-five twenty may fit into an effective therapy already. As we see additional data, I believe our lead actually increases. Of course, nobody yet knows if we can achieve a functional cure with ARK-five twenty, but I believe that if there is going to be a breakthrough in HBV over the next two years, it will come from Arrowhead given where we are in the clinic versus our competitors.

As we think about potential combinations, we would like to be the anchor. Big Pharma has clearly increased its focus on HBV and we know that virtually any way one can imagine disrupting virus at different parts of its life cycle are in development. When you combine this with programs at large and small biotech companies and the work being done with immune modulators, the market may begin to feel crowded. However, there is scarcity and potential strategies to reduce S antigen and where there is scarcity there is value. We do not know of any program targeting S antigen reduction that is as far along as ours.

We have demonstrated a very clean safety profile to date. We know that ARK-five 20 is active and RNAi as a mechanism is known to be a reliable way of reducing gene target expression or I'm sorry target gene expression. In addition, remember that ARK520 is designed to knock down the entire HBV genome. So while we often talk about S antigen reduction, we actually hit the virus at multiple points in its life cycle. As such, we believe that ARK520 will be a natural choice for companies to combine their compounds with.

This is good for us. Our strategy is to assess multiple combinations. Because of where we are in the clinic, we have the opportunity to find the best therapies in chronic HBV patients rather than relying on animal models that with the exception of chimps have questionable predictive value. Let's now turn to ArcAAT, our candidate for the treatment of liver disease associated with alpha-one antitrypsin deficiency. Last quarter, we delivered a plenary presentation at AASLD with new preclinical efficacy data on Arc AAT.

This was a prestigious slot and the Arc AAT abstract was highlighted in the AASLD President's press conference as a promising new treatment. Only 11 were chosen for this designation out of a total of 2,106 abstracts. In the presentation, repeat dosing of Arc AAT in primates showed reduction of approximately 90% of serum alpha-one antitrypsin with long duration of effect suggesting that monthly or less frequent dosing may be sufficient for sustained suppression of hepatic AAT production. Late last year, we met our guidance and filed to begin a Phase one clinical trial of ARK AAT. We are on track to begin dosing healthy volunteers in that study by the end of this month.

Remember that ARK AAT uses the same DPC that is used in ARK-five twenty. This gives us confidence in the ultimate safety profile of the candidate and we are looking forward to understanding activity when targeting an endogenous gene. ARK AAT addresses an important unmet medical need as there are currently no treatments for liver disease associated with alpha-one antitrypsin deficiency. It also represents a relatively straightforward value proposition because liver disease associated with AAT deficiency is a storage disease that should be diminished and possibly reversed by reducing AAT production. The Alpha-one Foundation believes that there may be as many as one hundred thousand people in The U.

S. With the mutation that leads to AATD. Looking deeper into our pipeline, we continue to make important progress on follow on liver candidates. We expect to file an IND or equivalent for our next candidate by the end of calendar twenty fifteen. We have also made good progress on DPC formulations for subcutaneous administration against liver indications as well as IV formulations for extrahepatic targets.

We believe that we will nominate our first subcutaneous candidate or our first extrahepatic candidate by the end of calendar twenty fifteen. In our chemistry, we are always interested in new RNAi trigger technologies. More specifically, we are interested in structures and modifications that could increase gene silencing activity and or provide additional freedom to operate across new targets and indications. Toward those ends, last quarter we acquired an exclusive option to purchase a basket of RNAi technologies and IP. We paid $7,000,000 for this exclusive option and it shows up in our financial statements as other investing activities.

We continue to assess the potential value of these platforms and IP for Arrowhead. With that overview, I would now like to turn the call over to our COO and Head of Development, Doctor. Bruce Given. Bruce?

Speaker 3

Everyone. It was another busy clinical quarter for us and we continue to move forward with our plans. Since our last call, we completed enrolling the three and four mg per kg cohorts in HEPARC-two thousand and one, our Phase IIa study in E negative chronic HBV patients in Hong Kong. Those cohorts remain blinded while the four mg per kg cohort completes follow-up over the next few months. We submitted our IND for ARK-five twenty in December announced in mid January that we had been given in communication with FDA we've been told excuse me in communication with FDA that they were uncomfortable with us progressing from single dose studies directly to a parallel design multi dose study and thus placed the program on partial clinical hold.

We were informed of this during the call at which time FDA asked us to start the program with a more traditional rising multiple dose study beginning at one mg per kg, the starting dose in our single dose They had promised us a letter within thirty days fully detailing their thoughts. We received the FDA letter and it did not contain any surprises relative to what had been communicated on the call regarding the partial hold. As such, we had already written a new protocol which had pretty faithfully captured the main themes. However, the letter also included some recommendations offered regarding non hold ideas that FDA felt would be helpful to the program. We saw these as quite constructive and recognized an opportunity to adjust the new protocol in a couple of aspects that took into account FDA suggestions, while being helpful and cost sparing to the program overall.

This has caused us to make a few tweaks to the prospectively designed study. As such, the protocol has been finalized and the electronic submission went to FDA today. We are submitting the protocol to investigator site IRBs for review in parallel. But let me be clear that we won't start this study until the FDA has blessed the new design. We have previously guided that we expected to submit our global protocols to European and Asian authorities before the January.

However, the additions of the new U. S. Protocol and the way it is being designed has given us the opportunity to reduce the planned size of the core international trials and also to simplify them in some ways that we expect should make them easier and faster to enroll. This has led to a minor delay in their planned submission. The protocols and accompanying documents should be finished this week or next and then will be provided to our CRO for final translation and submission.

Overall, we do not expect completion of the core global trials to be delayed relative planning, as long as they meet with regulatory approval in those jurisdictions with normal review times. Once those submissions have been made, we will turn our attention to other studies included in our planned Phase two program. As we have discussed previously, it is simply unknown whether ARK-five twenty plus NUCs as a two drug combination therapy will produce a significant number of seroclearance events. Given how challenging this virus is, it would not be surprising if one or more additional drugs will be necessary to be included in a multi drug cocktail for some or even all patients to reach our goal of producing a substantial number of functional cures. As such, we have been planning to take an open collaboration approach regarding addition of other agents similar to what was done previously in hepatitis C to the great benefit of the patient and treater communities.

This will obviously include already approved agents, but we've also been in positive discussions with companies developing their own drugs for HBV. Over the next two years, there are a large number of agents that will be completing Phase one human testing, some known to the street, some not that will be ready to participate. We believe as do others we speak with that testing their drugs in combination with NUCs and ARK-five twenty is a natural step to take in seeking the earliest path to demonstrating the functional cures that many or most in the field see as the next breakthrough step in HBV therapeutics development. We believe that the next two years will be very exciting in hepatitis B with the best shot in decades of getting to treatments that can actually convert chronic active disease HBV patients into functionally cured non patients off therapy. Because of our leadership position, we think that if this occurs, it is most likely that it will occur in studies including ARK-five twenty as a core component of therapy.

Before I turn the call over to Ken Biszkowski, I'd like to say a few words about ARK AAT. We submitted our application to initiate trials in Australia at the end of last year. I am happy to report that we have received all necessary approvals to proceed with the study and the screening process has begun. We expect to enroll our first subject in that trial this month. In this study, we will treat normal volunteers until we reach a dose that produces modest knockdown of circulating alpha-one antitrypsin levels.

At that time, we will switch to patients as we interrogate higher doses. As such, we expect to understand the depth and duration of knockdown from a single dose in patients from this trial and we hope to have that data this year.

Speaker 4

With that, I'd like to turn the call over to Ken Myszkowski, Arrowhead's Chief Financial Officer. Ken? Thank you, Bruce, good afternoon, everyone. As we reported today, our net loss for the three months ended December 3134 was 22 point $600,000 or $0.41 per share based on 54,700,000.0 weighted average shares outstanding. This compares with a net loss of $10,700,000 or $0.28 per share based on 37,700,000.0 weighted average shares outstanding for the three months ended December 3133.

Total operating expenses for the quarter were $25,300,000 compared with $7,100,000 for the three months ended December 3133. The increase in operating expenses compared to the year ago period are due to costs for research and development, primarily higher drug manufacturing costs, which increased $8,400,000 during the period, mostly related to ARK-five twenty as well as higher clinical trial costs, which increased $4,500,000 Clinical trial costs have increased as we incur start up costs from our CRO related to the planned ARK-five 20 Phase IIb studies. We also incurred costs for our second clinical candidate ARK AAT of about $2,400,000 while ARC AAT clinical costs in the comparable prior period were minimal. Higher G and A costs driven by higher professional services and higher compensation expense, primarily due to increased headcount as compared to the prior year also contributed to higher operating expenses. Net cash used in operating activities for the first three months of fiscal twenty fifteen were $24,200,000 compared with $7,000,000 in the prior year period.

The change in cash used in operations is consistent with our change in operating expenses. Turning to our balance sheet. At December 3134, including our investments in fixed income securities, our cash and investments balance was $145,300,000 compared with $177,300,000 at September 3034. Our common shares outstanding at December 3134 were $54,700,000 consistent with the balance at September 3034. Also at December 3134, there were 18,300 shares of preferred stock outstanding.

These shares are convertible into 4,000,000 shares of common stock. Common shares outstanding including the conversion of our preferred shares would be $58,700,000 With that brief overview, I'll turn the call back to Chris.

Speaker 2

Thanks Ken. We made substantial progress last quarter. As we look at calendar twenty fifteen, there are several key goals we hope to meet. They are: one, complete the Phase IIa single dose study of ARK-five twenty and discuss the three and four mg per kg data. We believe that will happen next quarter two, complete the initial cohort of The U.

S. Phase 2b study of ARK-five twenty and escalate to a higher dose as necessary. Three, fully enroll the initial three month portion of the Phase 2b studies of ARK-five twenty in Europe and Asia. Four, begin long term extension Phase 2b studies of ARK-five twenty in Europe and Asia. These are designed to go out as long as nine months immediately after the three month lead in studies.

Five, begin exploratory combination studies for ARK-five twenty. Six, begin exploratory studies with ARK-five twenty at different dosing schedules seven, begin dosing the ARK AAT Phase I study this month eight, complete dosing of healthy volunteers and patients in the ARK AAT Phase I study nine, present data from the ARK AAT Phase one study 10, launch a multiple dose Phase two study of ARK AAT 11, file an IND or equivalent for a third clinical candidate 12, nominate our first subcutaneous administration candidate or first extrahepatic candidate and 13, expand our RNAi chemistry toolbox to broaden the way we can achieve freedom to operate in additional indications and targets. This is indeed an aggressive set of goals for calendar twenty fifteen, but we believe it is achievable. Watch our progress and monitor how we do against these. We commit to do our best to create value by achieving these goals and to communicate our progress regularly.

With that, I'd like to turn the call over to questions. Operator? Thank

Speaker 0

And our first question comes from Thomas Wei of Jefferies. Please go ahead.

Speaker 5

Thanks. Just a couple of questions on the prepared comments in relation to this to the FDA letter. Could you be a little bit more specific on what some of these other suggestions were from the agency that you've incorporated into the protocol? It sounds like it's very helpful stuff, but I'm having a hard time figuring out what the nature of those suggestions might be.

Speaker 3

Thomas, this is Bruce. Some of those were just related to style and format of the way they'd like to receive some of the data that we know has been traditionally asked for in these HBV development programs. But they also had a couple of specific suggestions that related for instance to how we might look at the potential impact on the PK of tenofovir and entecavir, which as you know are the NUCs that we are dosing along with. So it was some of those sorts of things, but they were things that we actually found valuable and caused us to make a few changes in the protocol. Nothing earth shattering, but helpful.

And by dealing with some of those now, we think actually money saving and time saving for the program down the road.

Speaker 5

How does that reduce the size of the international studies? Is it just that you were going to lead in with some drug interaction component that you no longer need to do because you're doing it in The U. S. Study now?

Speaker 3

Yes. Some of it relates to those sorts of things aspects that we were able to take out of that study or numbers that we were able to reduce since we were doing this study in The U. S. So it was just it was an all the opportunity to look at the program in its overall goals and by putting some of the aspects into The U. S.

Study, we could reduce the size and complexity of the other pieces of the global program.

Speaker 5

That's helpful. And just in the protocol that you have submitted, can you share with us a little bit more detail on the designs that we can map out the potential timing of this? Is did the FDA letter contain anything about how long you need to collect data at one mg per kg before you can move on to the next dose? And are you going to be moving through each of these doses sequentially all the way through up to four mgs per kg one, two, three and four? Or can you kind of skip to a higher dose sooner?

Speaker 3

Well, it's a rising multiple dose study. So by definition, you go a dose at a time. That's the mechanism by which you guys do rising multiple dose studies. I don't think I'm ready yet to talk about final design because until the FDA gives their final blessing and we're sure we're on exactly the same page, I don't want to speak for them and get out ahead of it. So once they have approved the trial, it will eventually show up in trials.gov and the design will be clear.

Speaker 0

Thanks. Sure. Our next question comes from Alethia Young from Deutsche Bank. Please go ahead.

Speaker 6

Hey, great. Thanks for taking my question. I have a couple of them. Just in Europe specifically like how long do you kind of think the delay will be? Do you think you're kind of is it weeks or is it maybe like a month from the potential delay to kind of fine tune the stuff that Tom was talking about?

Speaker 3

I think it's going to be probably a month or less. And as I said, I don't think it actually delays the program because we've actually made the studies have been simpler and made them smaller. So I think net net the program actually should stick to its original time timelines. But relative to what our plan had been for submission, it's probably going to cost us I think hopefully inside of a month, but somewhere around a month, Alethia.

Speaker 6

Okay. And then just talking a little bit about I think just kind of segueing on Tom's question. I mean, is it just really like the critical mass of the work that you need to be done is more around PK, but there's nothing really particularly like else that's there that is important to this design? So that's the biggest feedback the FDA gave was PK. Does that

Speaker 3

make No. I mean, the FDA mean, there that he asked for an example. So I sort of gave you an example. That was kind of an example. But way Alethia we try to look at this is we kind of start with the end in mind.

So we're thinking at the end of Phase two what is the sort of data package necessary to be convincing to regulators that you're ready to go into Phase three. And there are a lot of aspects of that. I mean, obviously, one of the things we absolutely want to show is the ability to produce seroclearance. I mean, that's the cornerstone of this program. And I think frankly the cornerstone of all HBV programs going forward.

But in addition to that, there's also sort of a critical mass of safety data, PK data and other things that go into a Phase two program that regulators get their hands around and feel they sort of have clarity. So coming from it at that angle, when the FDA basically changed our approach in The U. S. That allowed us to continue to look at the overall Phase II. And if you took out the pieces that are now being done in The U.

S. In a study that we really hadn't planned that allowed alterations in the remainder of the program. That's what I'm trying to sort of indicate here.

Speaker 6

Okay. And just two more. So one, I know you made some comments around perhaps other kind of assets and being strategic in the space, but just wanted to see if you guys could give a little bit more color on like do you think this is something that we should expect to be a 2015 or a 2016 event for potential other non exclusive collaborations?

Speaker 2

So you're talking about the combination studies? Sure.

Speaker 3

Expect to

Speaker 2

launch several combination studies this year absolutely.

Speaker 6

But I guess with some of the more novel stuff, so maybe not NUC or interferon, but some of the other stuff out in the space, like would you expect that would be kind of something that could happen this year? Is it something more next year?

Speaker 3

Yes. Alethia, would say that there are a few things that can probably be ready this year. Several that we're aware of are probably more 2016 just because they need to get through their own Phase 1s.

Speaker 6

Yes. That makes sense. And then last question just on your cash guidance. Can you remind us what it was and kind of give us a way of how to think about maybe the potential spend for R and D over this year?

Speaker 2

Right. So what have always said publicly is that we burn around $2,500,000 a month to cover our internal R and D and corporate costs etcetera and then layer on top of that clinical costs. Now it's difficult to forecast those clinical costs because that's necessarily bumpy. That's going to be a bit volatile. And also it's going to be influenced by how many Phase 2b studies or cohorts that we do when we're looking at these combination studies and how long those go out.

And that's difficult to forecast at this point. And so my hope is that as we get into that we can better forecast what that is. At this point it's a bit difficult. And so I would just say look our core spend on internal R and D and corporate cost is pretty stable at that $2,500,000 or thereabouts per month. And then you can imagine what the clinical cost will generally cost on top of that.

Speaker 6

Okay. But basically kind of think about maybe more a couple of quarters away like maybe the last two quarters being more loaded than your cost if you're starting AAT and like Phase 2b studies?

Speaker 2

Again, it's hard to say because for instance this last quarter we spent a lot of money on manufacturing that will take us potentially through most of Phase 2b for ARK-five 20 and an awful lot of ARC AAT that might even get us into Phase two for ARC AAT. So it's the timing of that is really variable.

Speaker 6

Great. Thanks for taking my question.

Speaker 0

Sure. Our next question comes from Michael Yee of RBC Capital Markets. Please go ahead.

Speaker 7

Thanks and congrats on all the progress so far. A couple of quick ones. Just so I understand it better, the design of the Phase 2b study was always sort of a two mg and four mg multiple dose study and then following these patients out a long while. Can you make clear to me that that hasn't really changed at all OUS? But in The U.

S. You have amended the protocol and still plan to start at the low dose and are waiting for FDA to sign off on that before you start that. So these are two geographies are in different tracks. Can you just clarify how U. S.

Versus U. S. And how the design of the studies might differ?

Speaker 3

Yes, Michael. This is Bruce again. Our plan is still to seek approval for parallel design ex U. S. We still believe that it's likely to take somewhat long term therapy, I guess, is the way to think of it to get HBV to functional cure.

We're planning in Phase II to start off with three months of dosing, but somewhere fairly soon here this spring we will have our nine month tox data in primates. It's necessary for us to ask for an extension. And our planning has been to dose patients for a full year with ARK-five twenty plus NUCs in the sort of core international studies. So that has still not changed. That's still the approach that we expect to be taking in those studies.

Speaker 7

Are you going to be starting at two, three and four migs outside The U. S. And in The U. S.

Speaker 3

You're going to start at low doses? Well, The U. S. We're definitely starting at one mg per kg because that's where the FDA asked us to start. I think the doses internationally, I'm not really prepared to talk about at this point only because we've got to be working with the international regulatory authorities.

And just as I really don't want to be negotiating with the FDA sort of in the public sphere, I feel the same way with international authorities that we'll see where this winds up. But our feeling is that we have a pretty good chance that they'll go along with the parallel design that we're proposing. But I don't want to necessarily forecast where those doses are going to wind up at this point.

Speaker 7

Okay. And that as you just said to another question may start within a month or so?

Speaker 3

No. It wouldn't be that submission.

Speaker 2

We expect

Speaker 3

to get those all submitted. But the international regulatory authorities don't operate under a thirty day clock the way The U. S. Does. So in general, those approval process take more along the lines of two to three months.

Speaker 7

Okay. So to come full circle, a few months then to start at least for OUS and U. S, what's your best estimate on starting there realizing there's a thirty day clock or whatnot and then hopefully they come to agreement. So what are we thinking for U. S?

Thanks.

Speaker 3

Yes. It's always a little hard to predict because I can't necessarily predict regulatory cycles. But we are submitting the protocols and the paperwork to the IRBs in parallel with the submission to the FDA because we think we have a design that they'll be okay with. So we're going ahead and submitting to the IRBs now. So realistically, it's quite possible that we could be up and running in The U.

S. This quarter, but that's not guidance. That's just a question of what is possible. But ultimately, the time line is going to be determined by the reviews.

Speaker 7

Okay. Thank you, guys.

Speaker 3

You bet.

Speaker 0

Bet. And our next question comes from Ted Tenthoff of Piper. Please go ahead.

Speaker 8

Great. Thank you. So I missed a little bit at the beginning of the call. So just to confirm, when should we get data from the three mg and four mg per kg cohorts from the HK study? And then secondly, can you give us a little bit more detail about these RNAi assets that you are reviewing for which you paid like a $7,000,000 option fee?

If you could answer those two questions that would be helpful. Thanks.

Speaker 2

Sure. Thanks, Ted. So three and four mg per kg groups are now well three mg per kg is complete. Four mg per kg we have finished dosing and we're still following those patients out. Both are still blinded.

I think that we will have data that we can then talk about sometime in the second quarter second calendar quarter.

Speaker 8

Okay.

Speaker 2

Regarding RNAi trigger IPs and modifications and such, there's not much else I can tell you about that at this point.

Speaker 8

Okay. And just to be clear on the three mg and four mg per kg. I know we talked about this in San Francisco, but just to be clear, it's unlikely those will be at EASL AVN, correct?

Speaker 2

That's right. Unfortunately, the late breaker deadline is just a bit too tight for this because again four mgkg is all dosed, but we are still following them out and they're still blinded. And so we're not quite going to make that. But we will have a complete data set for both of those in the second quarter and so should we be able to talk about it at that point.

Speaker 8

Great. That's helpful. Thanks, guys.

Speaker 2

You're welcome.

Speaker 0

There are no more questions at this time. I'll now turn it back to Chris Anzalone for closing remarks.

Speaker 2

Thank you all for your attention and we look forward to seeing you soon.

Speaker 0

Ladies and gentlemen, this does conclude today's conference. Thank you for your attendance. You may now disconnect. Everyone have a great day.