Spyre Therapeutics Inc (SYRE) 2017 Q4 法說會逐字稿

Greetings, and welcome to the Aeglea Biotherapeutics presentation of key clinical data update and fourth quarter and full year 2017 financial results. (Operator Instructions) As a reminder, this conference is being recorded.

I would now like to turn the conference over to your host, Mr. David Calusdian, from Sharon Merrill Associates. Thank you. You may begin.

Hello, and welcome to Aeglea Biotherapeutics' corporate update and earnings conference call. After management's prepared remarks, they will be available to take your questions.

Before we begin, please note that today's call may include a number of forward-looking statements, including comments on the company's business strategy, strengths and priorities; the timing, plans and success of clinical trials and related data; the timing of announcements and updates relating to clinical trials and related data; the safety, therapeutic benefits and economic value of product candidates; the advancement of technologies and proprietary product candidates; regulatory pathways for development programs; the success of collaborations; the competitive landscape for product candidates; trends with respect to revenues, expenses and cash flows; the company's ability to fund research and development programs; and its ability to manage costs, along with the uses of cash and other matters.

These forward-looking statements are based on assumptions that are subject to risks and uncertainties that could cause the company's actual results to differ significantly from those suggested by these statements. Given these risks and uncertainties, you should not place undue reliance on these forward-looking statements. Please refer to the company's Form 10-K, filed with the Securities and Exchange Commission on March 13, 2018, for some of the important risk factors that could cause its actual results to differ materially from expectations, including any forward-looking statements made on this call. Except as required by law, the company disclaims any obligation to publicly update or revise any forward-looking statements to account for or reflect events or circumstances that occur after this call.

Also, please note that a presentation to accompany this call is available for download on the events and presentations page of the company's IR section of its website at www.aegleabio.com.

I will now turn the call over to Aeglea's Chief Executive Officer, Anthony Quinn. Dr. Quinn, please go ahead.

Thanks, David. Good morning, everyone, and thanks for joining us on the call. With me today are Charles York, our Chief Financial Officer; and Dr. James Wooldridge, our Chief Medical Officer. And Jim will provide an overview of our lead development program, pegzilarginase, including an important update from our arginase-1-deficiency trial, which was presented yesterday at a scientific meeting. Charles will review the fourth quarter and full year financial results and provide an overview of our 2018 financial guidance.

Before they do that, I'd like to review our achievements in 2017. During 2017, the company made significant progress towards our goal of becoming a leading organization that designs, develops and commercializes innovative human enzyme therapeutics for patients with rare genetic disease and cancer. We made substantial progress, particularly in the second half of 2017, in activities related to our lead program, pegzilarginase, which is being investigated in 2 indications: firstly, for the treatment of patients with arginase-1 deficiency, and secondly, as an innovative approach in oncology for the management of arginine-dependent cancers.

In arginase deficiency, we expanded our clinical trial activities to Canada and Europe to ensure timely recruitment of our Phase I/II study. We initiated and completed 8 weeks of once-weekly repeat dosing of 2 arginase-1-deficiency patients who have been previously dosed with single ascending doses of pegzilarginase. These patients transitioned to a long-term extension study in December. And finally, we successfully resolved the dialog with the FDA from earlier in 2017 on the inclusion of pediatric subjects. This allowed us to dose our first pediatric patient in November in the United States.

We completed our dose-escalation study in solid tumors, including identifying a maximally tolerated dose, and we initiated activities for the enrollment of monotherapy expansion arms in 3 tumor types that have a high frequency of vulnerability to arginine depletion. And finally, we've made substantial progress in our preclinical understanding of pegzilarginase use in combination with other oncology treatments. The exciting preclinical data that we generated on pegzilarginase immuno-oncology combinations allowed us to accelerate a clinical combination study with the initiation of an immuno-oncology combination study in a clinical collaboration with Merck of pegzilarginase with pembrolizumab.

We continue to develop our global infrastructure plan, and we've made some strategic hires and partnerships that allow us to accelerate our disease awareness and our patient identification activities as we evolve from primarily a U.S.-based organization.

In 2018, we've already made solid progress in our clinical trials, and we announced last week that we have dosed the first uveal and the first cutaneous melanoma patient in our monotherapy expansion arms. We're excited that today, we're able to share with you encouraging new repeat-dose data from the Phase I/II clinical trial of pegzilarginase in arginase-1 deficiency and single-ascending-dose data for one pediatric patient with arginase-1 deficiency. This data was presented yesterday at the annual meeting of the Society for Inherited Metabolic Disorders.

I would now like to hand the call over to Jim, who will walk you through the details of the new data.

Thank you, Tony, and good morning, everyone. As you know, our clinical development programs for pegzilarginase are focused on arginase-1 deficiency and cancer. 2018 promises to be a really exciting time to be the CMO at Aeglea, particularly as we present new data from our clinical trials, beginning with this presentation. Today, I'm going to focus primarily on our Phase I/II clinical trial in patients with arginase-1 deficiency. But first, I'd like to walk you through some of the important details of the trial and our 2018 deliverables.

As Tony mentioned, the dosing of our first pediatric patient followed an agreement we reached with FDA that enabled inclusion of pediatric patients in our Phase I/II clinical trial. Trial enrollment is tiered by age, beginning with patients aged 12 to 17, and continuing with patients aged 2 to 11. The trial is designed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects of weekly treatment. We will provide data from pediatric dosing in this trial in Q3. Furthermore, we've given guidance that we will complete the design of our pivotal trial by the end of the year, with plans to start our pivotal study in 2019.

Now let's turn to yesterday's presentation at the annual meeting of the Society for Inherited Metabolic Disorders, which included new data in 3 key areas: first, repeat-dose data from 2 adults after 8 weeks of treatment with pegzilarginase; second, single-ascending-dose data from the first pediatric patient; and third, information regarding new assays and data on guanidino compounds in these patients.

The data from the first 2 adult patients demonstrated that repeated weekly intravenous pegzilarginase for 8 doses resulted in marked and sustained reductions in plasma arginine levels and guanidino compound metabolites of arginine. Moreover, these infusions were well tolerated, and following completion of the repeat-dose phase, these 2 patients transitioned into the long-term open-label extension study.

The first single-ascending dose in the first pediatric patient was well tolerated and resulted in a rapid decrease in arginine into the normal range for 5 days. During the second infusion, the patient experienced an infusion reaction that led to interruption of the infusion and subsequent completion at a slower rate after premedication. Antidrug antibodies were detected in the sample obtained before the second infusion. Further analysis established that the ADA was directed to the peg component of pegzilarginase, and there was evidence of blunting of the expected reduction in plasma arginine after the infusion. The patient transitioned to the repeat-dose part of the trial with premedication and a slower infusion rate. These infusions were well tolerated; however, the patient decided to withdraw consent after 3 doses due to the burden of balancing school and the clinical trial.

Although it's well recognized that patients can develop antidrug antibodies to protein therapeutics, including enzyme replacement therapies, we were surprised to see the infusion reaction, given that we have not observed infusion reactions in the 2 adult patients with arginase-1 deficiency, nor in the more than 60 cancer patients we've treated to date. Furthermore, we have not observed marked or sustained increases in antidrug antibody titers in the adult patients with arginase-1 deficiency or in the oncology patients treated after dosing with pegzilarginase. Low-titer antidrug antibodies were detected at baseline in 1 of the 2 adults with arginase-1 deficiency and 4 of the 48 cancer patients; yet we observed no apparent effect on the presence of low-titer ADA on arginine reduction or the safety profile in these patients.

Another important development was the creation and validation of improved assays for a range of arginine-derived metabolites known as guanidino compounds. Our data demonstrated that baseline GVA, ArgA and NAA were elevated in the 2 adult patients, and that, in addition to arginine, pegzilarginase induced rapid and sustained reductions in plasma guanidino compounds. This is particularly important given the potential contribution of guanidino compounds to the progressive, hyperargininemia-related, neurological abnormalities seen in this patient population.

Given these results, we look forward to assessing the effects of repeated doses of pegzilarginase in additional patients with arginase-1 deficiency. This will provide an opportunity to further evaluate the clinical benefits of longer-term dosing and sustained reduction of plasma arginine beyond what can be achieved with current standard of care.

As for our cancer programs, we recently dosed the first patients in the monotherapy cohort expansions for the Phase I clinical trial in patients with uveal melanoma and cutaneous melanoma. Our objectives are to confirm the safety profile and the Phase II dose, as well as to identify further signals of clinical activity. We also initiated studies in small-cell lung cancer as both monotherapy and in combination with an immune checkpoint inhibitor, and we will provide updates once new information becomes available.

In sum, we recognize there is considerable work ahead, but we are pleased with our results to date and remain on schedule with our development programs in both rare diseases and cancer for 2018.

Thank you, and I'll now turn the call over to Charles.

Thanks, Jim, and hello, everyone. Given the timing of our clinical data presentation at SIMD on arginase-1 deficiency and our annual report, we thought we would take this opportunity to provide a brief update on our Q4 and full year numbers, including an understanding of our cash runway.

Revenues in the fourth quarter of 2017 were $1.5 million, versus $1.2 million in the fourth quarter of 2016. For the full year 2017, we recorded revenues of $5.2 million, compared with $4.6 million in 2016. All revenues were the result of our $19.8-million grant from the Cancer Prevention and Research Institute of Texas, or CPRIT, and those funds are being used to directly support the development of monotherapy and combination clinical trials for pegzilarginase in cancer. The increases in revenue in the fourth quarter and full year 2017 were primarily due to higher qualifying expenditures associated with the clinical trials of pegzilarginase in cancer patients.

Our fourth quarter R&D expense was $5.8 million, versus $4.7 million in the fourth quarter of 2016. For the full year 2017, R&D expenses totaled $22.8 million, versus $18.1 million in 2016. The increases were primarily associated with expanded manufacturing, regulatory, research and clinical development activities as Aeglea completed its Phase I dose-escalation trial in patients with advanced solid tumors. Additionally, the company initiated enrollment in 3 solid-tumor single-agent cohort expansions and a Phase I/II combination trial in patients with small-cell lung cancer.

Fourth quarter 2017 G&A expense was $2.3 million, versus $2 million in the fourth quarter of 2016. For the full year 2017, G&A expense totaled $10.1 million, compared to $8.4 million in 2016. The increases in G&A expense were primarily due to higher personnel, consulting and facility costs.

In the fourth quarter 2017, our net loss was $6.5 million, or $0.39 per share, compared to a net loss of $5.5 million, or $0.41 per share, for the fourth quarter of 2016. For the full years ended December 31, 2017, and 2016, our net losses totaled $27.2 million and $21.7 million respectively.

Now, regarding the balance sheet. We used approximately $7 million in cash to support our operations for the fourth quarter of 2017 and $29 million in cash for the full year 2017. As we continue forward in multiple clinical trials for pegzilarginase in rare genetic disease and cancer, we anticipate our burn will be in the range of $7 million to $10 million per quarter. We believe our year-end cash balance of $50 million, paired with our expected 2018 receipts from CPRIT of approximately $6 million, is sufficient to fund our operations through the third quarter of 2019, and more importantly, through multiple clinical milestones in rare genetic disease and cancer.

In closing, you have heard today about the progress in arginase-1 deficiency with a demonstration of marked and sustained reductions in both arginine levels and related guanidino compounds with repeated once-weekly doses of pegzilarginase. While we recognize the work still ahead, our strong cash position and ownership of worldwide commercial rights strategically position Aeglea to capitalize on our expected 2018 data readouts in both rare genetic disease and cancer. The first quarter has already been busy and productive, and we look forward to building upon today's data in arginase-1 deficiency at the ACMG conference in April 2018.

With that, we will now open the call to questions. Operator, please proceed.

(Operator Instructions) Our first question comes from the line of Ian Somaiya with BMO.

Let me just start all over again. I feel like I was talking to myself for about 30 seconds. Congratulations on the data. Had a couple of questions for you. I was hoping we could start off with the one patient that did have the -- experienced the ADA. You mentioned that that patient was enrolled in the multi-ascending-dose trial and received 3 doses. Can you just comment on whether the patient was able to achieve arginine levels in line with the first 2 patients while remaining on therapy?

Yes. Ian, this is Jim. So what we observed is reported on the poster in the -- for SIMD, and what you can see is, is that there was a very nice reduction after the first dose but not after the second dose. He -- the data is a little too new, so we don't have data from the multidose for him at this point in time, but we were encouraged by his original dose prior to the development of the event.

Yes. Jim (sic) [Ian], this is Tony. So that's a very important question, because obviously we know that patients who -- with rare diseases who receive protein therapeutics can have antidrug antibodies, and clearly we also know that if you repeatedly dose people, a proportion of those patients induce tolerance. So it is an important question, and obviously, we actually -- that is data that we will be generating moving forward.

Okay. And a second question was on the -- on just efficacy results that go beyond the markers that you spoke to today. Was there any evidence of improvement in symptomatology? Anything -- any anecdotal comments from the clinicians or the patients that you can sort of speak to?

So, Jim (sic) [Ian], what we're obviously talking today about was in our poster today, so -- which is obviously mainly focused on demonstrating something that's really important to start with, is if you give pegzilarginase in a repeated data -- a repeated dose, can you actually maintain arginine improvements? And what we did is, we can sustain arginine depletion with repeated dose. And I think the other thing you'll notice in one of the patients, there was actually a time-dependent improvement in arginine levels over time, in that we were getting better control with repeated dosing. It's still early days; it's only 2 patients. But obviously that's going to be important in understanding that. And then the second thing is, the guanidino compounds is -- just to explain why that's important -- is that -- so arginine can be metabolized to different metabolites. There has been some thinking that some of those metabolites may be important contributing to the hyperargininemia-related neurological effects. What we know from the literature, and there's not a lot of data, but the data that is there in terms of longitudinal data, there are examples with patients with diet where you lower arginine levels but you don't lower the levels of some of these other guanidino compounds. And there's differences between patients. So in one patient, you might lower GVA levels, arginine levels and GVA levels, but you might not lower the NAA levels. Or you may see another patient where you lower the arginine levels but you don't lower the level of another one called GAA. So I think what I'm excited about the data, and I know the team is excited about the data, is in the patients that we've looked at, we see 2 things that are very different. One is, both patients showed consistent reductions in the guanidino compounds that we measured. And the second thing is that the speed of the reduction appears much quicker than has actually been achieved with diet. It looks like with diet, it takes months to lower these levels in the patients that you can lower them. We're actually seeing these reductions within a very short period. So that's kind of where we are. Obviously, that's been the focus of this poster, and obviously, the safety. And the plan is as we move forward with the -- we obviously have another scientific meeting in a few months' -- in a few weeks' time. It's always difficult when you've got scientific meetings close together because we have to present new data at a meeting, so basically, we actually will be providing a little bit more color on some of the clinical indications of the disease in terms of the -- in terms of some of the baseline measures that we're using to assess the neuromotor function in these patients. Jim, have you got anything else you want to add?

Yes. I'd just like to say, Ian, that that's a really important question to us, and the first step was the data we're presenting today to get there. And so that's why we're so excited about seeing these sustained reductions in arginine and the guanidino compounds. So we look forward to presenting our data at ACMG.

Okay. And if I just get one more question in, and I'll get back in queue. Tony, you mentioned as part of your prepared remarks just efforts to identify patients. Can you just provide a little bit more color on what exactly you're doing?

Yes. So I mean, obviously, I'm -- this is an area that I'm very familiar with, as you know from my past experience. So look, for all of these rare diseases, physician awareness of the disease is low. We know this in arginase deficiency as well, and what -- the things that tell us that awareness is low is when a patient with quite severe manifestations doesn't get diagnosed having had

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for 6 years. So we know these types of things happen. We know that there's a report from Brazil where there were patients in a -- institutionalized, and they went back and said, I wonder if we've missed arginase-1 deficiency? And they identified, was it 15? 16 patients previously undiagnosed. So the effort is basically reaching out to talk to physicians at key -- particularly at key centers to start with, some of the pediatric hospitals, interact with physicians, go to scientific meetings, generate material to raise awareness. And as I just said, we -- it's important that we do this both in the U.S. and important that we also do this ex-U. S., and we actually have made some early builds to our organization ex-U. S. so that we can actually drive those activities better in Europe.

Our next question comes from the line of Matthew Cross with JonesTrading.

So first, I was wondering if you could clarify on the timing of the ADAs that were detected in the arginase-deficiency and the solid-tumor trials. If I'm understanding correctly, the incidence of these ADAs in the current data that was reported in the arginase-deficiency trial occurred during the initial dose-escalation phase before repeat dosing? And then, could you discuss when the lower ADA titer levels were detected for the handful of cancer patients and the 2 adult arginase-deficient patients?

Yes. Matthew, let me just make sure I understand the first part of your question. I understand the second part.

Sure. Just wanted to clarify that in addition to the adult patients in the arginase-deficiency trial and the levels you saw in some of the cancer patients, when exactly the more severe ADA was detected for this pediatric patient.

Excellent, okay. So thanks, that's helpful. So the ADA in the pediatric patient was detected prior to the second dose. It was not detected prior to the first dose, but the rapidity of the development of the infusion reaction in the ADA leads us to believe that he probably had a preexisting or underlying antibody to peg. With respect to the other patients, the other arginase-1-deficiency patient and 4 cancer patients, they actually had preexisting antibodies to pegzilarginase, primarily the peg component, at baseline. So they did not develop them during the trial. We've only seen the development of one patient who developed mild transient low-titer ADA during the trial, and that was in a cancer patient. And as I mentioned before, when we've looked at the pharmacodynamic and safety impact or -- we did not identify any.

Yes. And let me just add a little bit more color. Obviously this is something I've seen a lot of over the years. Look, antidrug antibodies in rare-disease programs can emerge at any time in your drug development program. Sometimes they emerge late. You've dosed a number of patients -- because it's kind of stochastic. Sometimes it emerges early in your program. The challenge for our -- most companies is when it emerges early in your programs and the only data that you have is 3 or 4 patients with your disease, it's kind of difficult to put it in perspective. So the thing that I think we're at a hugely advantageous situation is that we've actually dosed all of these oncology patients, and in actual fact, that -- the fact that we haven't seen any response like this in the oncology patient, that actually gives me a lot of reassurance that this is not -- obviously, if we had 1 out of 3, that would be a very different thing, thinking about where things are, as opposed to having all this oncology data. And then, the other thing that Jim pointed, which I want to emphasize, is that the early -- some of the -- a small number of patients in the oncology and also one of the adults that had baseline antibodies, these were low-titer antibodies. But for me, the important thing is, in these patients with low-titer antibodies at baseline, we did not see any increase in titer with the actual dosing of the patient. So I think the bottom line at the moment, I mean, I think it's fair to say, I think the -- our thinking is that the pediatric patient is an outlier based on all the other data that we've got. Obviously, to develop drugs in the rare disease space, you have to understand how to manage these patients. And I think the key, the one advantage of sometimes seeing this stuff early is it helps you focus the mind on how to manage an occasional patient like this, because that's obviously what the regulators are expecting as you move through your program. So I hope that provides a little bit of additional color in terms of this one patient.

Yes, absolutely. Appreciate the extra clarification. And then just one more: Looking at the efficacy component following the repeat dosing, it looks as though you may actually be reducing arginine even below the 40-micromolar level that you said is kind of a floor. And I know previously you'd said you could opt to reduce the dose given the consistent level of arginine reduction across doses you've reported previously. So would you consider going to a lower dose and maybe switching to a twice-weekly scheme for the sake of more consistent PK, or what are your current thoughts on the dose and the scheme now that you've seen this data?

Okay. So obviously this is a relatively small amount of data at the moment in terms of the repeat dose. We'll be building that picture with our additional patients and as we dose more in the long term. We'll be doing -- obviously we will be modeling the information to look both at the dose and the dose scheduling for moving into the pivotal study. Based on what we can see at the moment, we -- as a -- we don't believe that we will need to dose more frequently than once a week if -- and again, the clearest thing to (inaudible) plan at the moment is if -- do we need to do it once a week or -- but it's not going to be more than that. Jim, do you have anything you want to add?

No, that summarizes it well, Tony. Thanks.

Our next question comes from the line of Chad Messer with Needham & Company.

I mean, so I guess that the 2 things I'm taking away from here is, we're trying to home in on the dosage schedule. We've got a little bit of data for that. And then we have, and I think you characterized it as a little bit of a surprise and hopefully an outlier on an infusion reaction. I guess my question for you is this: Is the protocol you're running through now, is that going to be adequate to answer both of those questions, in your opinion, or are there maybe some course adjustments, different doses, different monitoring or anything, that needs to be tweaked as we go along here?

Okay. No, that's a good question. So we have some elements of the protocols that we've got that allows us actually to do some additional dose changes within individuals moving forward so that we can improve our understanding of the dose-response relationship. So basically -- look. Basically what we have at the moment is, and we've given guidance to this, is we believe that we will have repeat adult and pediatric data by the third quarter, and we will have -- is that we'll have the information generated that will allow us to design our pivotal study by the end of the year and obviously initiate our pivotal study in 2019. So it's -- I think that speaks to our confidence that we actually will -- we will be generating the information that we need to design a solid pivotal study.

(Operator Instructions) Our next question comes from the line of Jeff Hung with UBS.

The pre-dose values for Patient 2 were consistently above the normal range, but the 7-day profiles after Dose 1 and Dose 8 suggest they were largely in the range. Are there any differences between the 2 patients that you can use to determine which types of patients might result in more consistent arginine levels within the normal range, or does it even matter that patients might be above the range for 1 to 2 days per week given that they -- where they were at baseline?

Okay. So let me have a stab at that, and then I'll get Jim to add to it. So those are some good questions. So look, as with any drug, you will see some variability in terms of the effects, so that's obviously why we actually need to take the data we've got, we need to build on that data, we need to model that data so that we can understand that. Obviously, just to give you an example of the types of things that we obviously are very aware of and we need to look at very carefully, is that obviously if we give the drug to a patient and it makes them feel better, they actually might start eating a little bit more, okay? So that actually mean -- would mean that you're making them better, they start eating a little bit more protein and their arginine level goes up. So those are the types of things that we need to be acutely aware of as we move forward with the program and analyzing those things and actually building a picture of the selection of the dose for our pivotal study. So that -- does that help? Have I missed -- did I miss one aspect of what you asked? Jim, do you want to . . .

So one of the things that I was thinking of -- thinking to add based on your question is, just pointing out the fact that if you look at the single-ascending-dose slide that was in our deck, that points out some data from the literature that shows what is commonly achieved with dietary protein restriction alone, and that's the red box at the top. And you see very high levels of arginine even with best therapy. In fact, the range is 256 to 799 micromolar with a mean of 479 micromolar, and that was based on 19 patients. And what I think is really striking is the ability for pegzilarginase to go beyond that into the normal range. So when you ask questions about, do -- are we concerned about perhaps being above the normal range, the reality is, is that therapy has never really been able to approach this as consistently as we have seen with this particular study. And in fact, the guidelines recommend that the target arginine levels should be less than 200 micromolar. And so we're really encouraged by the fact that these patients are really spending a significant amount of time not only in the normal range but essentially all the time under the 200-micromolar mark. So hopefully that helps add a little color as well.

Yes, Jim, that's actually -- that's very helpful. Thanks for that. So yes, so just -- so once again, I think as Jim's highlighted, that slide is really important. The red box showing what current standard of care achieves, the green box showing the normal range, and that we're able to drive things into the normal range. We do know that there are occasional patients that really are obsessed and very strict about their diet where you can lower their arginine levels and you see some improvement in the neurological manifestations. So I think the point you make is, you don't -- you can see improvements of neurological manifestations by reducing arginine levels, albeit not particularly well with diet. But what we're talking about is we're actually talking about a really transformational change in the ability to lower arginine levels because we're not talking about lowering them slightly less than that red box, we're talking about driving them into the normal range. So that's basically why we actually are confident based on -- and we've talked a lot about this previously -- based on the -- there's a lot of orthogonal data out there that actually gives us the confidence of reducing arginine levels, is actually going to be accompanied by clinical benefit. And as we said, we're in a very different position. And that's actually why we're excited about the guanidino data, and I mentioned it earlier, so just let me just remind you, is that the -- with arginine-restricted diet, guanidino levels decrease very slowly or may not decrease at all in some patients. Okay? So there's an inconsistency. There's an inconsistency in terms of the diet effect and neurological manifestations in terms of lowering arginine levels and the effects on guanidinos. Why we're excited is not only are we seeing a consistent effect on arginine levels driving them to the normal range, but when you look beyond arginine, we are actually seeing this consistent effect on the guanidino compounds, which is very -- appears very different than the data that's out there about the effects of diet. So that's actually why we're excited, because this is the, obviously, the foundation (inaudible) we move into, obviously, additional data that we'll be presenting as we move out to the next meeting.

Great. That's very helpful. And then speaking of additional data, I guess, you mentioned that the first pediatric patient received 3 repeat doses. So will you ultimately show that data? Like the 7-day profiles for at least those 3 doses?

Yes, absolutely.

And then, I guess, for the data at ACMG in April, will there be additional patients, or is it more additional analyses of the patients from yesterday's posters?

So the data, obviously there's always a lag between submitting data to meetings. So the focus of the data will be on the patients that we've described today. So obviously our focus today is about the arginine and the guanidinos. As we move to the ACMG, we will have additional information on baseline assessments. So one of the things that's important during drug development in a rare disease is an understanding of how useful standardized assessments are in measuring disease severity. So obviously we've incorporated a number of baseline assessments into our Phase I/II study to assess the effect of arginase-1 deficiency on a broad range of disease manifestations, and these include assessments of neurologic motor function which measure mobility and balance at baseline, and these have never been used in arginase-1 deficiency patients before. So we look forward to sharing that information, and obviously, the dosing period is still relatively short, but we'll be sharing some additional information about these important assessments of clinical activity. Jim, anything to add?

No, that was great, Tony.

Great. And the last one, I guess, for the data readout in 3Q, how many additional patients can we expect? Do you think that you'll have the data from the full 10 patients by then?

So basically we believe that we'll have data from a sufficient body of patients to design a pivotal. So we think we need about 6 to 8 patients to do that, so that's kind of what we need. Obviously, the reason why we actually have gone ex-U. S. is obviously so that we can recruit that study in a more timely way. The other advantage of going ex-U. S. is obviously, that allows Jim and his team to build relationships with the European key opinion leaders and the regulators, which will put us in a good position for our pivotal study, so.

Thank you. Dr. Quinn, there are no further questions at this time. I'll turn the floor back to you for any final comments.

That's great, thank you very much. So listen, in closing, I'd like to remind everyone that 2018 is poised to be a data-rich and transformational year for Aeglea because we anticipate that we're going to have multiple clinical data reads-out for pegzilarginase, beginning with the ACMG conference in April.

In addition to driving our lead program to clinic, we're going to continue to invest in research and in building our team, and with the goal of bringing forward and accelerating the development of additional enzyme-based therapeutics that have the potential to transform the lives of patients with rare genetic diseases and cancer.

I'd like to thank you all for joining us this morning, and even though it's snowing, I hope you guys all have a good day. Thanks very much.

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.