Arrowhead Pharmaceuticals Inc (ARWR) 2015 Q1 法說會逐字稿

Ladies and gentlemen, welcome to the Arrowhead Research FY15 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.

Thank you. Good afternoon, everyone, and thank you for joining us today to discuss Arrowhead's results for its FY15 first quarter, ended December 31, 2014. With us today for management are President and CEO, Dr. Chris Anzalone; Chief Operating Officer and Head of R&D, Dr. Bruce Given; and Chief Financial Officer, Ken Myszkowski. Management will provide a brief overview of the quarter, and we then open up the call 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 27-A of the Securities Act of 1933, and section 21-E of the 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 not limited to, statements regarding the anticipated safety and/or efficacy of ARC-520, ARC-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-K, 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 Dr. Christopher Anzalone, President and CEO of the Company. Chris?

Thanks, Vince. Good afternoon, everyone, and thank you for joining us today. I'd like to break this call into four parts. First, we will talk about the accomplishments in the past quarter. Second, we will discuss regulatory aspects and timing of the ARC-520 and ARC-AAT clinical programs. Third, we'll provide an overview of our financial results for the quarter. And fourth, we will discuss goals for calendar 2015.

Let us begin with our recent accomplishments. During the first quarter FY15, 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 towards 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 as 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 ARC-520 and ARC-AAT, for the treatment of chronic hepatitis B infection, and liver disease associated with Alpha-1 antitrypsin deficiency, respectively. We made important progress in both programs last quarter. We presented initial data from the ongoing Phase 2a study of ARC-520 in the late breaking poster session at the 2014 American Association for the Study of Liver Disease, or AASLD, meeting in Boston.

ARC-520 showed clear reduction of HBV s-antigen after a single dose of 1 and 2 milligrams per kilogram. 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 2a single dose escalation study, and we have since completed dosing, both 3 and 4 milligrams per kilogram cohorts.

We are still following the [4] milligram per kilogram cohort, and both the 3 and 4 milligram per kilogram groups are still blinded. The safety profile of ARC-520 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 un-blinded data that we can discuss next quarter. We currently have no plans to escalate higher in the single dose Phase 2a study. We have always assumed that ARC-520 would be a multiple dose therapy, and it is time to understand s-antigen reduction kinetics upon repeat dosing.

Of course, this is a far more clinically relevant endpoint than single dose. RNAi therapeutics rely on loading the risk complex with RNAi triggers, and all the programs 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 ARC-520, 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 ARC-520 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 the Phase 1 study of a novel molecule and a novel delivery system, in only approximately 18 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 1 milligram per kilogram. Importantly, no additional studies were required to begin the 1 milligram per kilogram 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 1 milligram per kilogram 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'll be better able to predict how future candidates, including ARC-AAT, will perform.

This should enable the market to value to 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 at 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 ARC-520 may fit into an effective therapy already. And as we see additional data, I believe our lead actually increases. Of course, nobody knows if we can achieve a functional cure with ARC-520. 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 verses 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 the 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 in 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 ARC-520 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 ARC-520 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 ARC-520 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 ARC-AAT, our candidate for the treatment for liver disease associated with Alpha-1 antitrypsin deficiency.

Last quarter, we delivered a plenary presentation at AASLD, with new pre-clinical 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-1 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 1 clinical trial of ARC-AAT. We are on track to begin dosing healthy volunteers in that study by the end of this month. Remember that ARC-AAT uses the same DPC that is used in ARC-520. This gives us confidence in the ultimate safety profile of the candidate, and we are looking forward to understanding the activity when targeting an endogenous gene. ARC-AAT addresses an important unmet medical need, as there are currently no treatments for liver disease associated with Alpha-1 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-1 Foundation believes that there may be as many as 100,000 people in the US 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 2015.

We have also made good progress on DPC formulations for subcutaneous administration against liver indications, as well as IV formulations for extra hepatic targets. We believe that we will nominate our first subcutaneous candidates, or our first extra-hepatic candidates, by the end of calendar 2015. Now 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 required an exclusive option to purchase a basket of RNAi technologies in IP. We paid $7 million 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, Dr. Bruce Given. Bruce?

Thank you, Chris, and good afternoon, 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 3 and 4 milligram per kilogram cohorts in Heparc-2001, our Phase 2a study in E-negative chronic HBV patients in Hong Kong. Those cohorts remain blinded, while the 4 milligram per kilogram cohort completes follow-up over the next few months.

We submitted our IND for ARC-520 in December, and announced in mid-January that we had been given, in communication with FDA -- we have 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 had thus placed the program on partial clinical hold. We were informed of this during a call, at which time FDA asked us to start the program with a more traditional rising multiple-dose study, beginning at 1 milligram per kilogram, the starting dose in our single dose Heparc-2001 study. They had promised us a letter within 30 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 RIBs 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 had previously guided that we expected to submit our global protocols to European and Asian authorities before the end of January. However, the additions of the new US 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 they will be provided to our CRO for final translation and submission. Overall, we do not expect the completion of the core global trials to be delayed, relative to our original 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 2 program.

As we have discussed previously, it's simply unknown whether ARC-520 plus nukes, 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 1 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 nukes and ARC-520 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 ARC-520 as a core component of therapy. Before I turn the call over to Ken Myszkowski, I'd like to say a few words about ARC-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-1A trypsin 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.

With that, I'd like to turn the call over to Ken Myszkowski, Arrowhead's Chief Financial Officer. Ken?

Thank you, Bruce, and good afternoon, everyone. As we reported today, our net loss for the three months ended December 31, 2014 was $22.6 million, or $0.41 per share, based on $54.7 million weighted average shares outstanding. This compares with a net loss of $10.7 million, or $0.28 per share, based on 37.7 million weighted average shares outstanding, for the three months ended December 31, 2013. Total operating expenses for the quarter were $25.3 million, compared with $7.1 million for the three months ended December 31, 2013.

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 $8.4 million during the period, mostly related to ARC-520, as well as higher clinical trial costs, which increased $4.5 million. Clinical trial costs have increased, as we incur startup costs from our CRO, related to the planned ARC-520 Phase 2b studies. We also incurred costs for our second clinical candidate, ARC-AAT, of about $2.4 million, while ARC-AAT clinical costs in the comparable prior period were minimal.

Higher G&A cost, driven by our higher professional services and higher compensation expense, primarily due to increased head count, as compared to the prior year, also contributed to higher operating expenses. Net cash used in operating activities for the first three months of FY15 were $24.2 million, compared with $7 million 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 31, 2014, including our investments in fixed income securities, our cash and investments balance was $145.3 million, compared with $177.3 million at September 30, 2014.

Our common shares outstanding at December 31, 2014 were $54.7 million, consistent with the balance at September 30, 2014. Also at December 31, 2014, there were 18,300 shares of preferred stock outstanding. These shares are convertible into 4 million shares of common stock. Common shares outstanding, including the conversion of our preferred shares, would be 58.7 million. With that brief overview, I'll turn the call back to Chris.

Thanks, Ken. We made substantial progress last quarter. As we look at calendar 2015, there are several key goals we hope to meet. They are, one, complete the Phase 2a single-dose study of ARC-520, and discuss the 3 and 4 milligrams per kilogram data. We believe that will happen next quarter. Two, complete the initial cohort of the US Phase 2b study of ARC-520, and escalate to a higher dose as necessary.

Three, fully enroll the initial three-month portion of the Phase 2b studies of ARC-520 in Europe and Asia. Four, begin long-term extension Phase 2b studies of ARC-520 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 ARC-520. Six, begin exploratory studies with ARC-520 at different dosing schedules. Seven, begin dosing the ARC-AAT Phase 1 study of this month.

Eight, complete dosing of healthy volunteers and patients in the ARC-AAT Phase 1 study. Nine, present data from the ARC-AAT Phase 1 study. Ten, launch a multiple dose Phase 2 study of ARC-AAT. 11, file an IND or equivalent for a third clinical candidate. 12, nominate our first subcutaneous administration candidate, or first extra-hepatic candidate. And 13, expand our RNAi chemistry toolbox, to broaden the ways we can achieve freedom to operate in additional indications and targets.

This is indeed an aggressive set of goals for calendar 2015, 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?

(Operator Instructions)

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

Thanks. Just a couple questions on the prepared comments, in relation 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 in to 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.

Thomas, this is Bruce. Some of those were just related to style and format of the way they would 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 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 nukes 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.

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 US study now?

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 the study in the US. So it was just the opportunity to look at the program in its overall goals, and by putting some of the aspects into the US study, we could reduce the size and complexity of the other pieces of the global program.

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? Did the FDA letter contain anything about how long you need to collect data at 1 milligram per kilogram, 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 up through, up to 4 milligrams per kilogram? One, two, three and four? Or can you skip to a higher dose sooner?

It's a rising multiple-dose study. So by definition, you go a dose at a time. That's the mechanism by which you always do rising multiple-dose studies.

I don't think I'm ready yet to talk about the 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 clinicaltrials.gov, and the design will be clearer.

Thanks.

Sure.

Alethia Young, Deutsche Bank. Please go ahead.

Great, thanks for taking my questions. I have a couple of them. In Europe specifically, like how long do you think the delay will be? Do you think you're -- is it weeks? Or is it maybe like a month, from the potential delay to fine tune the stuff that Tom was talking about?

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 -- the studies have been simpler, and made them smaller. So I think net/net, the program actually should stick to its original timelines. But [relative] to do what our plan had been for submission, it is probably going to cost us, I think, hopefully inside of a month, but somewhere around a month, Alethia.

Okay. And then just talking a little bit about -- segueing on Tom's question. Is it just really the critical mass of the work that you needed to be done is more around PK, but there's nothing really particularly [elf] that's there, that is important to this design? So that's the biggest feedback the FDA gave was PK, to some degree?

No, no. The FDA -- he asked for an example, so I gave an example. That was an example. But the way, Alethia, we try to look at this is, we start with the end in mind. So we're thinking, at the end of Phase 2, what is the sort of data package that's going to be necessary to be convincing to regulators that you're ready to go into Phase 3? And there are a lot of aspects to that. Obviously, one of the things we absolutely want to show is the ability to produce seroclearance. That is 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 a clinical mass of safety data, PK data, and other things that go into a Phase 2 program, that regulators can get their hands around, and feel they have clarity. So coming from it at that angle, when the FDA basically changed our approach in the US, that allowed us to continue to look at the overall Phase 2. And if you took out the pieces that are now being done in the US, in a study that we really haven't planned, that allowed alterations in the remainder of the program. And that's what I'm trying to indicate here.

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

So you're talking about the combination studies? Sure, yes. I expect to launch several combination studies this year, absolutely.

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

Alethia, I 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 1's.

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

Right. So what we have always said publicly is that we burn around $2.5 million a month to cover our internal R&D and corporate costs, et cetera. 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. But at this point, it's a bit difficult. And so I would just say, look, our core spend on internal R&D and corporate costs is pretty stable at that $2.5 million, or thereabouts, per month. And then you can imagine what the clinical cost will generally cost, on top of that.

Okay, but basically, think about maybe more -- couple quarters away? Like maybe the last two quarters being more lower than the costs, if you're starting AAT and Phase 2b studies?

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 ARC-520, and an awful lot of ARC-AAT, that might even get us into Phase 2 for ARC-AAT. So it's -- the timing of that is really variable.

Great. Thanks for taking my questions.

Sure.

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

Thanks, and congrats on the progress so far. A couple quick ones. Just so I understand it better, the design of the phase 2b study was always a 2 milligram and 4 milligram multiple-dose study, and then following these patients out a while.

Can you make clear to me, that hasn't really changed at all, OUS? But in the US, 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 OUS verses US? And how the design of the studies might differ?

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

We're planning, in phase 2, 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 ARC-520 plus nukes, in the core international studies. So that has still not changed. That is still the approach that we expect to be taking in those studies.

But are you going to be starting at 2, 3 and 4 milligrams, outside the US? And in the US, you're going to start at the low doses?

The US, we are definitely starting at 1 milligram per kilogram, because that's where the FDA asked us to start. I think the doses in internationally, I'm not really prepared to talk about it 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 in the public sphere, I feel the same way with the 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.

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

No. It would be that -- submissioned. (multiple speakers) We expect to get those all submitted. But the international regulatory authorities don't operate under a 30-day clock the way the US does. So in general, those approval processes take more along the lines of two to three months.

Okay. So to come full circle, a few months, then, to start, at least, for OUS and US. What's your best estimate on starting there? Realizing there's a 30-day clock or whatnot, and then hopefully, they come to agreement. So what are we thinking for US? Thanks.

Yes, it is 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 are going ahead and submitting to the IRBs now. So realistically, it's quite possible that we could be up and running in the US this quarter, but that's not guidance. That's just a question of what is possible. But ultimately, that the timeline is going to be determined by the reviews.

Okay. Thank you, guys.

You bet.

(Operator Instructions)

Our next question comes from Ted Tenthoff, Piper. Please go ahead.

Great, thank you. So I missed a little bit of the beginning of the call. So just to confirm, when should we get data from the 3 milligram and 4 milligram per kilogram 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 a $7 million option fee? If you could answer those two questions, that'd be helpful. Thanks.

Sure. Thanks, Ted. So 3 and 4 milligram per kilogram groups are now -- look, 3 milligrams per kilogram is complete. 4 milligrams per kilogram, we have finished dosing, and we are still following those patients out. Both are still blinded. I think that we will have data that we can then talk about some time in the second quarter -- second calendar quarter.

Okay.

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

Okay. And just to be clear on the 3 milligram and 4 milligram per kilogram. I know we talked about this in San Francisco, but just to be clear, it is unlikely those will be at [esol avian], correct?

Yes, that's right. Unfortunately, the late breaker deadline is just a bit too tight for this. Because again, 4 milligrams per kilogram is all dosed, but we are still following them out, and they are still blinded. And so we are not quite going to make that. But we will have a complete data set for both of those in the second quarter. And so we should be able to talk about it at that point.

Great, that's helpful. Thanks.

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

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

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