Spyre Therapeutics Inc (SYRE) 2016 Q4 法說會逐字稿

Good day and welcome to the Aeglea Biotherapeutics fourth-quarter and full-year 2016 earnings call. Today's call is being recorded. At this time I would like to turn the conference over to Paul Arndt, Managing Director of LifeSci Advisors. Please go ahead.

Thank you, Matt, and good afternoon, everyone, and thank you for joining us for the Aeglea fourth quarter and fiscal year 2016 financial results conference call. During the course of today's call, we may make a number of forward-looking statements, including comments on our business strategy; strength and priorities; and timing, plans, and success of our clinical trials and related data; the safety, therapeutic benefits, and economic value of our product candidates; the advancement of our technologies and our proprietary product candidates; regulatory pathways for our development programs; the success of our collaborations; the competitive landscape our product candidates; the potential for Arginase I deficiency to be added to the neonatal recommended uniform screening panel; trends with respect to our revenues, expenses, and cash flows; our ability to fund our research and development programs; and our ability to manage our costs, uses of cash, and other matters.

These forward-looking statements are based on assumptions that are subject to risks and uncertainties that could cause our 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 our Form 10-K filed with the Securities and Exchange Commission on March 23, 2017, for some of the important risk factors that could cause actual results to differ materially from expectations, including any forward-looking statements that -- made on this call.

Except as required by law, we disclaim any obligation to publicly update or revise any forward-looking statements to account for or reflect events or circumstances that occur after this call. I will now hand the call over to Dr. David Lowe, Chief Executive Officer of Aeglea.

Good afternoon. Thank you for joining us today. With me here today is our Chief Financial Officer, Mr. Charles York. This is our first clinical update conference call since our IPO last April. A lot has happened since Aeglea became a public company and we had a productive 2016. We made progress in the clinic with three Phase 1 trials for our lead candidate, AEB1102, in Arginase I deficiency, hematological malignancies, and in solid tumors. I want to thank our shareholders for your support and I believe we are well-positioned to advance our clinical programs and build shareholder value in 2017.

Aeglea is a leader in creating and developing novel engineered human enzymes that are designed to degrade or deplete specific amino acids in patients' blood. Our product candidates address two extremes of amino acid metabolism: as enzyme replacement therapy in rare genetic diseases, and targeting tumor metabolism for cancer treatment. In rare diseases, we are working to treat patients with toxic levels of amino acids resulting from a broken metabolic pathway, lowering these levels back down to the normal range. In cancer, we are exploiting a dependence of certain tumors on specific amino acids for survival, which potentially allows us to starve the tumor while avoiding damage to healthy tissues.

There is a lot known about amino acid metabolism and the disease pathways we are targeting across our pipeline of enzyme-based therapeutics. However, amino acids have generally been elusive as drug targets due to the lack of direct product candidates from the human genome. We believe our engineered human enzymes represent a unique and important opportunity in drug development. Working at the intersection of enzyme engineering and clinical need, we focus our research and development to identify product candidates that address unmet medical needs and diseases that are impacted by abnormal amino acid metabolism. We believe our approach has an attractive risk profile due to the well-known biology of the amino acid targets and a blood-based mechanism of action for our enzyme-based drugs. We believe these factors increase the probability of successful drug development in these patient populations that lack adequate treatment options.

The lead product candidate to emerge from our efforts is AEB1102, or Pegzilarginase, which we are developing as enzyme replacement therapy to treat the rare genetic disease Arginase I deficiency and cancer, two critical areas of patient need. Mechanistically, AEB1102 is optimized human Arginase I, an enzyme that degrades or depletes the amino acid arginine in patients' blood. In the case of rare genetic disease, we are looking to utilize AEB1102 as enzyme replacement therapy for patients with Arginase I deficiency, an ultra orphan disorder of the urea cycle.

In these patients, there's too much arginine in their blood. What is an otherwise normal molecule becomes toxic, resulting in a seriously debilitating, progressive, and ultimately life-threatening disease with neurological and neurocognitive symptoms. In these patients, we want to deplete arginine down to the normal healthy blood concentration. We are essentially replacing the function of a missing or a dysfunctional enzyme. We believe this approach will benefit patients based on published case reports on the clinical benefit of lowering blood arginine. For example, from liver transplant or red blood cell infusion, the two major sources of arginase in our bodies.

Our second program for AEB1102 focuses on cancer. We are exploiting a metabolic dependence on arginine for cancer cell growth, starving the tumor cells of a key amino acid. Our work to date is focused on targeting tumors that depend on arginine for survival and where we have a potential biomarker for our companion diagnostic that allows us to identify tumors that may respond to arginine starvation. We have completed preclinical studies to focus future solid tumor expansion arms on cancers that are arginine dependent, such as melanoma and small cell lung cancer. And in hematology, we have focused the Phase 1 trial on acute myeloid leukemia, or AML, and myelodysplastic syndrome, or MDS, based on our biomarker studies, indications where we believe we have a likelihood of showing clinical benefit.

As we progress further down the cancer path, we are encouraged by preclinical data we have recently presented that builds on the story of engineered human enzymes as a potential therapeutic option for patients. I would like to highlight two key findings from this research. First, we have presented preclinical data at the Society for Immunotherapy of Cancer Conference in November 2016, showing that, contrary to expectation, arginine depletion with AEB1102 is not immunosuppressive when used in combination with the immune checkpoint inhibitors targeting the PD-1 or CTLA-4 pathways.

Rather, our data showed that single agent activity of AEB1102 and immune checkpoint inhibitors was additive or synergistic when these drugs were dosed in combination in models with established tumors. We believe this unanticipated result represents an important therapeutic opportunity at the intersection of tumor metabolism and immuno-oncology and highlights that there are still many unknowns surrounding this important area of tumor biology. As we complete the Phase 1 dose escalation in patients with advanced solid tumors and plan for expansion arms, we are exploring opportunities for combination trials with approved immuno-oncology therapeutics for other existing or emerging standards of care.

Additionally, we presented preclinical data at the Keystone Tumor Metabolism Conference in March of this year that demonstrated AEB1102 does not affect the development of immune memory, where combination therapy with AEB1102 and anti-PD-L1 resulted in tumor cures and immunization against subsequent tumor challenge. We are excited about what we believe to be a great opportunity ahead of us both in rare genetic disease and cancer, where we see the potential for our platform of engineered human enzymes to address clear unmet medical needs.

At this point, I will review the clinical status of AEB1102 in each of these three therapeutic areas that we are now pursuing. In Arginase I deficiency, we are pleased to present top-line data today at the American College of Medical Genetics and Genomics annual clinical genetics meeting which describe the Phase 1 results from two adult patients.

Now let me remind you, Arginase I deficiency is a seriously debilitating, progressive, and ultimately life-threatening disease, where there is no -- where there is currently no approved therapy to treat the root cause of the disease. We are encouraged by the results supporting that AEB1102 is well-tolerated and effective at reducing plasma arginine levels in both patients. Intravenous administration of AEB1102 lowered plasma arginine to lower levels in these patients at low doses and in a dose proportional manner.

Most importantly, the data further demonstrated that one week after dosing, or at 168 hours, plasma arginine levels remained suppressed by 25% and 49% of pre-dose levels in these two patients, suggesting that a once-a-week dosing regimen could be achievable. From a safety perspective, we were very pleased that there were no serious adverse events reported for either patient, no clinically notable trends in vital signs, no clinically significant abnormal laboratory results, and no clinically significant ECG findings.

To provide some further understanding about the trial results, let's look at the two patients in more detail. These two female siblings were in their mid-20s with moderate to severe neurocognitive and neurological deficits, on diet therapy and nitrogen scavengers. This is important because as we've discussed in the past, diet and nitrogen scavengers have not stopped the disease progression primarily, we believe, due to the inability to effectively control arginine levels. In this trial, we saw some evidence of the lack of benefit of current treatment options, where the two siblings both clearly exhibited predose arginine levels well above the upper range of normal and clinical presentation of disease.

This further adds to our belief that the reduction of blood arginine to the normal range is the most appropriate path for effective treatment of these patients and potentially provides a way of halting the course of the disease. We are quite encouraged by this first evidence of positive pharmacodynamic results from our potential enzyme replacement therapy. This proof of mechanism, together with the encouraging safety profile, provides meaningful proof of concept to continue with our development program. With these results, we believe the use of blood arginine is a primary endpoint in clinical trials linking to clinical stabilization and/or clinical benefit, puts us on a path to a once-weekly IV drug.

Now let's discuss an update on the status of our Phase 1-2 clinical trial for treatment of these patients with Arginase I deficiency. As you know, following completion of dosing of the first two patients in our Phase 1 clinical trial, we submitted a protocol amendment in November 2016 to broaden the scope of our Phase 1 trial into a Phase 1-2 trial. The amended protocol includes dosing of pediatric patients, ages two and older, and weekly repeat dosing in the Phase 2 portion, with the intent to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical response of AEB1102 in patients with this inborn error of metabolism.

In the first quarter of 2017, we received IRB approval for this Phase 1-2 protocol at multiple clinical sites. In March 2017, we received an information request from the FDA which included comments and recommendations on the protocol amendment and a request for supporting documents based on the review of our completed toxicology studies, our dose escalation plan, and supporting information for the inclusion of pediatric patients.

As recommended by the FDA, we replied with supporting information and requested a follow-up meeting. At this time, we believe our Phase 1-2 protocol provides an appropriate path to evaluate the safety and tolerability of AEB1102 in pediatric patients. And pending FDA feedback, we plan to initiate dosing in pediatric patients in the middle of 2017. In the meantime, we intend to continue enrollment of adult patients and plan to dose additional adult patients in the middle of 2017. Top-line data from this trial is expected in the first half of 2018.

Now onto cancer, the other extreme of arginine metabolism. Our Phase 1 dose escalation trial with AEB1102 in patients with advanced solid tumors is ongoing. This trial's key objectives are safety and measuring blood arginine levels following dosing with AEB1102. We are currently enrolling cohort eight at a dose of 0.4 milligrams per kilogram and have seen compelling proof of mechanism of lowering blood arginine in a dose proportional manner. We expect to complete and announce results of this Phase 1 study in the fourth quarter of 2017 or the first quarter of 2018. As you know, this timing is somewhat variable depending on reaching the maximum tolerated dose, or MTD. When the MTD is reached, we plan to initiate single-agent expansion arms in specific solid tumor types and potentially in combination with existing or emerging standards of care, as discussed earlier.

In July 2016, we initiated a Phase 1 clinical trial in patients with the hematological malignancies AML and MDS in the United States and Canada. And so far, the first three cohorts of this trial has shown, as we might expect, based on our advanced solid tumor trial, proof of mechanism with dose proportional lowering of blood arginine. This Phase 1, multicenter, single-arm, open-label, dose-escalation trial is designed to assess the safety and tolerability of AEB1102 as a single agent and determine the recommended Phase 2 dose. We are currently enrolling cohort three at a dose of 0.48 milligrams per kilogram and expect to complete enrollment and announce Phase 1 results in the fourth quarter of 2017 or the first quarter of 2018. Much like the solid tumor trial, this is also a dose escalation and the final timing is dependent upon reaching the MTD, at which point we will initiate an expansion arm for AML and MDS patients.

At this time, I would like to turn it over to our Chief Financial Officer, Charles York, to review our financials.

Thanks, David. Given the alignment and timing of our data presentation at ACMG on Arginase I deficiency and our annual report, we thought we would take this opportunity to build upon the clinical update that David just shared and provide an update on our financials as well, including an understanding of our cash runway.

In the fourth quarter of 2016, our net loss was $5.5 million, or $0.41 per share, compared to a net loss of $4 million, or $6.36 per share, for the fourth quarter of 2015, which was prior to IPO. For the full years ended December 31, 2016 and 2015, our net losses were $21.7 million and $11.3 million, respectively. Revenues in the fourth quarter of 2016 were $1.2 million versus $1.6 million in the fourth quarter of 2015. For the full year 2016, we recorded revenues of $4.6 million compared to $6.1 million in 2015.

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 support the development of AEB1102 in cancer. The decline in revenue for the fourth-quarter and full-year 2016 was primarily due to the timing of qualifying expenditures associated with the clinical trials of AEB1102.

Our fourth-quarter 2016 R&D expense was $4.7 million versus $4.0 million in the fourth quarter of 2015. For the full-year 2016, R&D expenses totaled $18.1 million versus $11.5 million in 2015. The increases were primarily due to expanded preclinical and clinical activity for AEB1102, including the treatment of two patients with Arginase I deficiency in our Phase 1 study, the continuation of our Phase 1 trial in patients with advanced solid tumors, and the launch of our Phase 1 clinical trial of AEB1102 in patients with the hematological malignancies AML and MDS.

Fourth-quarter 2016 G&A expense was $2 million versus $1.6 million in the fourth quarter 2015. For the full-year 2016, G&A expense totaled $8.4 million compared to $5.9 million for 2015. The increases in G&A expense were primarily due to additional legal, insurance, and personnel costs associated with being a public company.

We used approximately $6.1 million in cash to support our operations for the fourth quarter of 2016 and ended 2016 with a cash balance of $63.5 million, which we believe is sufficient to fund our operations through the first quarter of 2019. And in addition to the funds received from CPRIT during 2016, we anticipate that we will receive an additional $10.2 million in grant funds from CPRIT in 2017 and 2018. And we expect our cash burn will increase this year to a range of $7 million to $9 million per quarter as we continue and expand our clinical testing of our lead product candidate, AEB1102.

With that, let me turn it back over to David for closing remarks.

Thanks, Charles. In 2016, Aeglea made significant strides in advancing our lead program, AEB1102, in multiple indications. In 2017, we look forward to our presentation on newborn screening for Arginase I deficiency tomorrow at ACMG and to receiving FDA feedback on our protocol amendment for the Phase 1-2 trial in patients with Arginase I deficiency. In the meantime, we are working diligently to establish site readiness at our clinical trial sites with IRB approvals, with the expectation to enroll both pediatric and adult patients in the middle of 2017. We anticipate reporting an update on this program at an appropriate time in an academic peer-reviewed form later this year.

In cancer, we are continuing to enroll our Phase 1 clinical trial in patients with advanced solid tumors and we expect to complete and subsequently report results of this study late this year or in the first quarter of 2018. We also anticipate completing enrollment in our ongoing Phase 1 AML/MDS trial and reporting those results in the fourth quarter of 2017 or early in 2018.

Finally, I am pleased that we continue to expand our AEB1102 program as we present additional preclinical data on AEB1102 at the upcoming AACR meeting next month which we believe builds on the emerging story of the intersection of immuno-oncology and tumor metabolism. In closing, I would like to add my welcome to Dr. Suzanne Bruhn, who joined our Board of Directors last month. Suzanne is a talented executive with substantial experience in the development of treatments for rare genetic diseases and cancer. We greatly appreciate her advice and counsel and look forward to her contributions to our Company's future success.

That concludes our prepared remarks. Now I would like to open the call to your questions.

(Operator Instructions) Chad Messer, Needham and Company.

Just in Arginase I deficiency, that 40 micromolar threshold, can you talk a little bit about what the line of evidence justifying that is? Is that something we are really confident is the right level to target for ultimate clinical benefit? Or is that something you will have to continue to look at as you go through Phase 1-2?

Hi Chad, thanks for your question. That's actually a topic of conversation that we have on a regular basis and touches on a variety of topics. For our clinical trial, that range was one that was provided to us by the FDA based on data from Framingham. But if you look at the testing in the newborn screening among the states, the normal range varies from lab to lab. So I think there is some more work that needs to be done to perhaps standardize the range that is being used. But for now 42 as the lower limit of normal is what we use. Other testing labs we now used 20 to 120. In the literature, you will even find 1 to 40 as a range, for example. So I think where we stand with our standardization and we are comfortable with the range that we are in and we will continue to work on further harmonization.

Great, thanks. And then maybe just one on the financials. It seems you have extended out a little bit your expected cash runway. Great. Just wondering if there's any particular changes in assumptions that are driving that or if it's just a recalculation as time goes on.

Hey, Chad, thanks. Thanks for the question. From our perspective, it's really just making sure that we have an appropriate runway to ensure the clinical activities that we need to get done and making sure that we meet milestones. I don't perceive any change in ultimate direction of 1102 as a result of increasing our timeline, just a true understanding of where we want to be in the future.

All right, great. Thanks for taking my questions.

Jim Birchenough, Wells Fargo Securities.

Hi. Thanks for taking my call. This is Yanan in for Jim. So could you talk a little more about the FDA information request regarding the amendment of the protocol? Any additional color there?

Hi, Yanan. Thanks for your question. Sure, I would be happy to address that. So the FDA requested additional information about the description of the toxicology studies and wanted to understand further background on the safety of AEB1102. And we have provided them with that information and are awaiting any additional feedback from them.

Got it, thank you. And also a question regarding the lower -- the threshold. So I'm wondering, is there are any safety concerns for reaching a level below the lower limit of normal 40 micromolar or some other threshold in the literature? Is there any particular concern in being below that threshold for an extended amount of time?

Well, that's a question that I think is best answered by looking at the data from the cancer trials, where we have treated now -- dosed over 40 patients. And we know from that work that patients can tolerate levels of arginine below the limit of detection, which is 1 micromolar, for extended periods of time. And by that I mean several days. So -- and that is consistent with work in the literature using other approaches for arginine depletion as well. So I think we do have a -- I think a very good window as we think about the dynamic range of arginine that we can work with and the therapeutic index.

Got it, that's very helpful. And also, can you talk about the variability of baseline arginine levels in the general patient population and whether that is -- remains conducive to selecting one dose for all patients?

Well, for Arginase I deficiency, we know from the literature that the blood levels of arginine can vary quite a bit from several times the upper limit of normal, which it could be several hundred micromolar up to 1,000 micromolar. So our clinical trial design takes that into account, with the Phase 1 portion as a single ascending dose study to, in an inter-patient manner, really determine the most effective -- or what is the effective dose to bring the arginine down to the lower range.

And so we are starting at a very low dose, 0.015 milligrams per kilogram, and then gradually increasing. And you see then the dose effects of that in the two patients that we presented today. And how there was a different dose that proportionately brought the arginine down into the normal range for the two patients, given how they -- even though they were sisters, their arginine levels were quite different. And so the sister with the higher blood arginine that required the next higher dose to bring her arginine level down to the normal range compared to the other sister.

So I think we are looking at really understanding the dose proportionality on an individual patient basis that will allow us to understand the dosing for any given individual.

Would that be the strategy going into commercially? Or do you have to eventually select one dose, or it could be a patient-dependent dosing?

I think that really remains to be determined from our clinical experience with these patients and how the lowering of blood arginine maps to the trends in stabilization or trends in improvement and clinical signs and symptoms.

Got it. And last question. In a future clinical study plan, is there a plan to look at whether diet restrictions and nitrogen scavengers could be removed as part of the benefit for 1102?

Well, I think that's definitely -- those are both topics of conversation that we have internally and I think are best considered in the context of an extension arm where patients are on therapy after the Phase 2. But that -- the design and scope of those trials remains to be determined as we continue with our development program.

Got it. Thank you so much for the answers.

(Operator Instructions) Jeff Hung, UBS.

How generalizable are the [ACMT] Phase 1 data, given that both patients were female siblings?

Hi, Jeff, thanks for the question. At this point, there is no reason for us to expect that there is a -- any sort of dimorphism in the penetrance of arginase deficiency between the sexes.

Okay. And then the plasma arginine level at predose (technical difficulty) for each subsequent dosing seems to decline, so the plasma arginine levels do not appear to return to baseline. How confident are you on the differential effect of dosing every two weeks in that trial versus the increased dose?

Well, this is a data set that then goes into our modeling for the subsequent study, the Phase 2 with the repeat dosing every week. And we need to really learn from that dose escalation experience on what the dose for the -- repeat dosing will be. As there might be expected to be a, say, accumulation of the pharmacodynamic effect over time. That will remain to be determined with our trial.

Okay. And then the last question around that 40 micromolar level. The patient stopped after a different number of doses. So then in the commercial setting, would you expect patients to require regular monitoring of plasma arginine levels to determine if they need to hold off on treatment until the levels return to above that 40 micromolar?

That all remains to be determined as we continue with our development program.

Okay, thank you.

Ian Somaiya, BMO Capital.

Thank you and congratulations, David and Charles, on the encouraging results. I have a couple questions. One maybe just housekeeping. The plan for this study was to enroll up to 10 patients, obviously, and evaluate up to seven doses. Do you feel comfortable in the -- where you are ending up on the dose standpoint? I guess you have already made a decision on the dose schedule.

Hi Ian, thanks for the question. Yes, we are comfortable with the doses that we have achieved for these two patients. And the design of the Phase 1 as a single ascending dose study, effectively a dose titration on a per patient basis, I think really provides us with confidence going forward into the Phase 2 portion for each patient and the dose that they will receive. Does that help?

No, it does, it does. And just from the FDA standpoint, are the questions related to evaluating 1102 in younger patients? So are we just looking at what -- and I guess a different type of -- different level of safety. A bit of caution on the safety side, or are there uniqueness in terms of the analysis that they've asked of you? It would just be good to know what the line of thinking is, the line of questioning is coming from the FDA.

So, the FDA is really interested in understanding in more detail the risk/benefit of dosing children. And so we have provided them with the appropriate background information on the prevalent population and the severity of the disease.

Okay. And just given the -- at least the safety data from these two patients as well as the data you have generated in the cancer setting, and as you mentioned the higher doses, do you feel like there is potential for delay from the timelines that you have laid out?

I have no way of predicting how the FDA is going to respond, Ian. But we are confident in our approach. And in fact we have IRB approval for the protocol at a couple of sites. So I think that by independent review, at least, the risk/benefit has been evaluated. And so we are looking forward to moving ahead with the trial as we get the FDA feedback.

Okay. And I know you mentioned that the goal of the next round of studies -- set of studies will be to link blood arginine to clinical benefit. And just given the variability in the presentation of the disease, just curious what endpoints you would look at when we think about the younger patients versus the two older patients that you have data from in the part one?

Thanks for the question, Ian. That is really an important topic that we've spent quite a bit of time studying and coming to a conclusion on. The trial design is available on clinicaltrials.gov, for those of you that are interested. We are really focusing on really three domains, principally neurological and neurocognitive together with biochemical endpoints, for example, such as liver function and so forth.

For the neurological, we are looking at seizures, for example. Abnormal muscular tone, spasticity as measured by specific spasticity scales in addition to walk tests, for example. And then also evaluating neurocognitive function with a variety of tools that test executive function and other elements. And clearly these have to be tailored to -- in an age-appropriate manner -- to the patients in question. And whether, for example, is speech function appropriate to measure in a two-year-old as opposed to a 12-year-old, for example. So there is some nuance there as well, but I think with the range of endpoints that we have, as we line those up against our natural history study, I think we will be in a good position to understand, we hope, the clinical impact of arginase in lowering arginine in these patients.

Okay. And if you'd just allow me, I have two more questions. Just given the safety profile that we have observed to date, just curious how much efficacy data the FDA wants to see in the pediatric population to consider approval. And from an endpoint standpoint, what matters most to them? Have you gotten any feedback in that regard?

We have not.

Okay, okay.

But our operating assumption is that normalization of blood arginine would be the primary endpoint and we need to link that to trends in stabilization or trends in improvement in clinical signs and symptoms. And as you look at sort of a basic symptom complex of, say, seizures, spasticity, and neurocognitive decline, if you see anyone of those or a combination of two of those symptoms in children emerge. And then before they are 10 years old, you will see all three. And so, you could imagine how a child that is having seizures -- if we can show that we have obviated or reduced the frequency of those seizures, for example, or hyperammonemic crisis, might be really meaningful clinically in linking that back to control of arginine.

Right. And the last question related to the guidance, as you think about your plans to potentially evaluate 1102 in combination with potentially checkpoint inhibitors [for the] IO drug. The guidance implies that you are likely going to do some sort of an agreement, data sharing agreement, get access to the commercial drug, the IO drug. Is that -- am I reading into it correctly? And would you just give a sense for timing of that study and if there is likely to be a partnership, what the timing of that could be?

Thanks for that question on the cancer programming. And we certainly have a strong aspiration that we would enter into some sort of an agreement with a company that has an improved IO therapy, and we are working to go down that path. And at this point I can't make any predictions on the timing there, but my aspiration is that when we complete the dose escalation in patients with late stage solid tumors, that we are in a position to progress down that path.

Okay. Thank you very much and congratulations again.

Jerry Isaacson, LifeSci.

Fortunately it looks like the other analysts covered most of my questions pretty thoroughly, but I do have a couple things. First of all, Charles, I just wanted to confirm that you said that this was a call that was coincidental with results and you don't plan to do any quarterly call going forward?

Hey, Jerry. Yes, that is correct. Our anticipation here going forward was to do these around clinical updates, not necessarily around our timing of earnings. This one just happened to work out well and thought it would be a good time to reset everyone for the status of where the Company currently is.

Got it, thanks. And then just one other thing. David, I wanted to talk a little bit about the poster that you will be presenting tomorrow. And I know -- I'm sure you can't get into the exact details, but maybe you could talk about the strategies and problems -- opportunities you see with this postnatal testing.

Thanks, Jerry, for that question. Yes, happy to discuss that. The abstract has been presented, and what we know -- what I can tell you is that, unlike many rare genetic diseases, arginine has been recommended on the secondary panel for newborn screening. And because it's an amino acid and readily detected, it is actually part of the primary panel in over 30 states. However, due to the variation in metabolism of newborns, the raw data or the raw level of arginine varies quite a bit. And so the data -- it really isn't used, and how it is handled from state to state varies considerably. So we have looked at every state, including the District of Columbia, and what their standard and practice is here. And it's different in every state.

And so what we did is we took the lead from a publication that came out several years ago in California and New York where we were able to access the legacy testing data. We were able to show that, instead of using raw arginine levels, you actually use a ratio of arginine to another amino acid that you rapidly -- or dramatically improve the sensitivity and specificity of the test. So I think we are really in good shape to -- as we look to taking our product candidate potentially to approval, to really line that up with having effective newborn screening in place by that time.

Yes, that actually was what I was thinking. As I imagine the availability of a therapeutic to treat the disease would certainly encourage people to do more thorough screening.

Agreed.

Okay. Good enough. Thanks, guys. I appreciate it.

That's all the time we have budgeted for today's call. I will now hand the call back over to David Lowe for final comments.

Thank you, all, for your participation and support today. Really appreciate it, and we look forward to providing updates throughout 2017.

Once again, this does conclude today's conference call. Thank you all for your participation.