Agios Pharmaceuticals Inc (AGIO) 2022 Q1 法說會逐字稿

Good morning, and welcome to the Agios First Quarter 2022 Conference Call. (Operator Instructions). Please be advised that this call is being recorded at Agios' request. I would now like to turn the call over to Holly Manning, Senior Director of Investor Relations.

Thank you, operator. Good morning, everyone, and welcome to Agios' First Quarter 2022 Conference Call. You can access slides for today's call by going to the Investors section of our website, agios.com.

With me on the call today, with prepared remarks, are Dr. Jackie Fouse, our Chief Executive Officer; Dr. Sarah Gheuens, our Chief Medical Officer; Richa Poddar, our Chief Commercial Officer; Jonathan Biller, our Chief Financial Officer and Head of Corporate Affairs; and Dr. Bruce Car, our Chief Scientific Officer, who will join for Q&A.

Before we get started, I would like to remind everyone that some of the statements we make on this call will include forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC.

With that, I will turn the call over to Jackie.

Thanks, Holly. Good morning, everyone, and thank you for joining our first quarter 2022 results call. The first quarter of 2022 was a milestone moment for Agios as we received U.S. FDA approval for PYRUKYND, a first-in-class PK activator and the first and only approved disease-modifying treatment for adults living with pyruvate kinase deficiency.

From the scientists who first hypothesized the potential utility of PK activation to the chemists who designed our molecule, to the clinical trial coordinators who helped enroll our trials, people across our organization, both past and present, have played a role in this important milestone.

In addition, a tremendous number of people outside our organization were instrumental to this effort. Investigators, patients, caregivers and advocates, all of whom have provided critical insights at every step of the way. Our connection to patients battling this rare and debilitating lifelong hemolytic anemia, along with the promise of what we can deliver to their treatment options is the reason we come to work every day and our connections with patients, health care providers, partners and each other or how we transform this idea into a medicine.

Looking ahead, we are highly motivated to execute the U.S. adult PK deficiency launch to the best of our ability, and we continue to believe PK activation has broad potential beyond PK deficiency. A huge focus for our team this year is executing on our aggressive clinical development plan, spanning thalassemia, sickle cell disease, pediatric PK deficiency and MDS, which Sarah will cover in more detail.

I'm also pleased to share that we recently published our 2022 Environmental, Social and Governance report. In 2020, we published our first ESG report, with the intent of disclosing relevant ESG initiatives and metrics from across the company that are aligned not only with our values and our culture, but also with the United Nations Sustainable Development Goals and the standards for the biotechnology and pharmaceutical industry set by the Sustainability Accounting Standards Board.

Since that time, our ESG program has grown and evolved as we continue to prioritize our commitments to the patients we serve, our employees, our communities and world and business ethics and values. We support and advance a range of ESG initiatives and encourage you to have a look at our report, which is available on our website agios.com under the Corporate Social Responsibility section. A huge thank you to the cross-functional ESG Working Group for bringing this year's report to life.

To wrap up, our commercial team is enthusiastically in the trenches with our U.S. adult PK deficiency launch, and Richard will update you on those details. Our clinical team is actively enrolling thalassemia and sickle cell patients in those pivotal programs, and Sarah will update you on those. And all our other functional teams are working hard to support the achievement of our 2022 corporate objectives and our strategic vision.

With that, I'll now turn it over to Sarah.

Thanks, Jackie. The clinical team has been working extremely hard to execute on our ambitious clinical development plan for 2022. I'll start with pyruvate kinase deficiency, where we are proud to be the first company to create a treatment for this rare lifelong hemolytic anemia. Our marketing authorization applications for PYRUKYND in adult PK deficiency remains under review in the EU, and we remain on track to receive a decision from the EMA by year-end.

In addition, our team is actively working through start-up activities for 2 pivotal trials in pediatric PK deficiency patients. We expect these trials to initiate in mid-2022. I'm also pleased to share that data from the core period of the ACTIVATE study of PYRUKYND in adults with PK deficiency, who do not receive regular transfusions, were published on April 14, 2022 in the New England Journal of Medicine. This trial and the ACTIVATE-T study in PK deficiency patients, who are regularly transfused, supported the recent U.S. FDA approval of PYRUKYND and continue to generate important data in the extension study about the long-term impact of treatment.

At the EHA meeting in June, we'll share new PRO data from ACTIVATE, data demonstrating the normalization of hemoglobin levels with long-term treatment of PYRUKYND and additional comorbidities and complications data from the PEAK Registry. Beyond PK deficiency, we believe PK activation has the potential to play an important role in the treatment of thalassemia and sickle cell disease. At the end of last year, we initiated our 2 global placebo-controlled pivotal trials of PYRUKYND in thalassemia, ENERGIZE and ENERGIZE-T.

As a reminder, ENERGIZE will evaluate 171 patients randomized 2:1 to 100 milligrams of mitapivat twice daily or placebo in both alpha and beta thalassemia patients who are not regularly transfused. The primary endpoint is hemoglobin response defined as equal or more than 1 gram per deciliter increase in average hemoglobin concentration from week 12 through week 24 compared with baseline.

ENERGIZE-T will evaluate 240 patients randomized 2:1 to 100 milligrams of mitapivat twice daily or placebo in both alpha and beta thalassemia patients who are regularly transfused, defined as 6 to 20 red blood cell units transfused during the 24 weeks prior to randomization.

The primary endpoint is transfusion reduction response, defined as a 50% or greater reduction in transfused red blood cell units, with a reduction of equal or more than 2 units of transfused red blood cells in any consecutive 12-week period through week 48 compared with Phase I.

Last year, we also initiated the Phase II portion of our Phase II/III study in sickle cell disease, RISE UP, which will randomize 69 patients, 1:1:1 to 50-milligram mitapivat twice daily, 100 milligrams mitapivat twice daily or matched placebo. The primary endpoints are hemoglobin response, defined as an equal or more than 1 gram per deciliter increase in average hemoglobin concentration from week 10 through week 12 compared to baseline and the type of adverse events. This data will be used to establish a clear dosing paradigm for the Phase III portion. Our team is focused on continuing global site activation and patient enrollment efforts across all 3 trials.

AG-946 is our novel PKR activator, currently being evaluated in Phase I study. We recently completed the single ascending and multiple ascending dose healthy volunteer cohorts after reaching a maximum tolerated dose. As a result, we have identified the doses that we're moving forward with in the Phase I sickle cell disease cohort as well as the MDS Phase IIa trial. We look forward to sharing updated data from the SAD and MAD cohorts at an upcoming medical meeting.

In addition, we have initiated sites for the sickle cell disease cohort and are on track to enroll the first patient shortly. As a reminder, the purpose of the sickle cell arm is to obtain data in patients with hemolytic anemia. In addition, we are working through operationalizing the 2A part of our AG-946 Phase IIa/IIb study in MDS. The Phase IIa component of the study is an open-label proof-of-concept study of 1 dose level of AG-946 in patients with lower risk myelodysplastic syndrome. The study will enroll 20 patients who will receive AG-946 once daily for the 16-week core period. Patients who complete the core period will be eligible to continue in an extension period.

The primary endpoints for the study are hemoglobin response, defined as an equal or more than 1.5 grams per deciliter increase from baseline in average hemoglobin concentration from week 8 through week 16 and transfusion independence, defined as transfusion-free for equal or more 8 consecutive weeks during the core period in patients with low transfusion burden only. Secondary endpoints include safety, additional measures of anemia, PK and PD biomarkers. We look forward to initiating the trial by the year-end.

I will now turn the call over to Richa, our Chief Commercial Officer.

Thank you, Sarah. I'm pleased to provide the first quarterly PYRUKYND launch update, where we generated net U.S. sales of $832,000 for the first 6 weeks of launch following our approval on February 17. As we've said before, our commercial launch strategy focuses on connecting with the patient and educating the provider to ensure first that patients are accurately diagnosed through efforts like Anemia ID; second, physicians understand the urgency to prescribe and eligible patients to advocate for treatment; and finally, patients connect to myAgios Support Services to optimize these understanding, ensure access and drive long-term medication adherence.

Having been in the field for the last couple of months, our conversations with patients, physicians and caregivers continue to underscore the value that we believe PYRUKYND brings to patients living with this disease, and we encourage that we have an opportunity to make a real difference in the lives of these patients with a first-in-class disease modifying therapy. We have gained important insights in the early days of launch to have further reinforce that our commercial loan strategy is effective.

Since our launch in mid-February through the end of the quarter, our team of hemolytic anemia specialists have had more than 1,100 customer interactions, raising awareness of PYRUKYND and educating physicians on how this first-in-class PK activator can be used to benefit the adult patients with PK deficiency. This positive engagement has been successful in driving scripts for those previously identified patients.

Our high-touch patient support program, myAgios, has effectively engaged with patients and physicians to begin disease and drug education as well as navigate reimbursement challenges to ensure access and minimize abandonment.

In addition, a high priority for us is to drive awareness of PYRUKYND among the patient community. So we have been focused on generating awareness through social media pushes, word of mouth, patient webinars, myAgios, and partnerships with patient advocacy groups. These efforts are working as PK deficiency patients have been tremendous self-advocates and proactive patient requests for PYRUKYND have accelerated early prescribing.

In terms of payer dynamics, our national account directors have had dozens of positive interactions with payers to date. As anticipated, these early approvals have been through the medical exception process, while prior authorization and utilization management criteria are being developed across fares.

And finally, turning to Anemia ID, we have continued to see strong interest with more than 3,500 kits ordered with the start of the program. Of the completed tests, which still just represent a portion of the total kits ordered, the PK deficiency positivity rate is in the mid-single-digit percentages and within the range of what we would have expected.

As a reminder, Anemia ID was designed for patients with a general diagnosis of hemolytic anemia of unknown etiology and is not specific to PK deficiency. As previously mentioned, physicians have continued to appreciate the benefit that this program is bringing to their patients, which drives our longer-term strategy to continue to ensure accurate diagnosis, enabling a higher diagnosis rate over time.

We are very encouraged with these early launch successes and the positive experiences we are creating with a broader PK deficiency community. It is important for us to remember, however, that PK deficiency is a rare chronic condition, which is poorly understood. Our efforts around disease education and patient identification continue to be paramount to ensuring longer-term success.

The commercial team is laser-focused on these initiatives despite the ongoing challenges of the pandemic, which have necessitated mostly a virtual engagement. This is challenging in the disease space that requires multiple interactions to both educate a disease to create urgency and also ensure accurate diagnosis. We will have better clarity with respect to the launch trajectory as we work our way through these early quarters.

Based on our work to date, we continue to believe there are approximately 1,500 to 4,000 PK deficiency patients in the U.S. representing a peak revenue potential in the U.S. of $200 million to $225 million. We have built a passionate commercial organization with significant rare disease experience that is fully capable of executing our launch strategy, and we are excited and grateful for the impact we are making on the lives of PK-deficiency patients.

Importantly, what we have seen from this first quarter is that our commercial strategy, our knowledge base and the connections we are making are setting us up for success as we continue to expand the applicability of PYRUKYND to all eligible PKD patients as well as longer term for other genetically-defined diseases. PYRUKYND has the potential to be a global blockbuster therapy with PK deficiency and thalassemia alone.

With that, I'll now turn it over to Jonathan to review first quarter financials.

Thanks, Richa. Our first quarter 2022 financial results can be found in the press release we issued this morning, which I will summarize. More detail will be included in our 10-Q filing later today.

As Richa shared, PYRUKYND revenue for the first quarter was $832,000. Cost of sales for the quarter was $339,000. Turning to operating expenses. Research and development for the first quarter was $70.1 million, an increase of $12.5 million compared to the first quarter of 2021. The year-over-year increase in R&D was driven primarily by start-up costs for the PYRUKYND pivotal studies in thalassemia and sickle cell disease and planned increases in preclinical activities, offset by closeouts of the ACTIVATE and ACTIVATE-T studies.

Selling, general and administrative expenses were $31.5 million for the first quarter, representing a $2 million decrease over the first quarter of 2021. The decrease in SG&A expense was primarily due to lower workforce-related spend. TIBSOVO royalty revenue, which is recorded under royalty income from gain on sale of oncology business on our income statement, was $2.7 million. We ended the quarter with cash, cash equivalents and marketable securities of approximately $1.2 billion.

With this cash balance, we expect to be able to execute our current operating plan through major catalysts and to cash flow positivity without the need to raise additional equity. In the current environment, we are grateful for our strong balance sheet, but also mindful to maintain this advantage and ensure the capital necessary to execute on our promising clinical programs and retain flexibility for business development.

Consequently, as we begin our annual long-range planning process, a process we kick off in the early spring of each year, we continue to be laser focused on capital allocation to only our highest priority as well as continuing to proactively manage our expense base.

With that, operator, please open the line for questions.

(Operator Instructions) Our first question comes from Anupam Rama with JPMorgan.

What are you seeing on the reimbursement front for PYRUKYND? And what are you seeing in terms of time to script written to getting on to therapy? And then what's the phenotype of the initial patients going on therapy in terms of severity, transfusion dependence and other things like that?

Thanks for the question, Anupam. So in terms of reimbursement, early conversations with the payers have been very positive. And from a reimbursement standpoint, as expected, majority of the approvals have been through the medical exception process. We expect that to continue in the second quarter as well, until the payable policies are developed. So overall, I would say, on track and doing exactly as we expected. Payer policies are still being developed across the board. So it's really too early to comment on the specifics of the prior authorization, utilization management criteria, but we should have details on that in the next few quarters. So stay tuned for more updates on that front.

In terms of your question around patient types, very reminiscent of what we would expect, again, of the overall adult PKD patient populations. We are not seeing that there is a high utilization in a specific kind of PKD patient, what we are seeing as expected. Given the paucity of treatment options and the huge unmet medical need and this being the first approved therapy, we are getting used across a variety of different types of patients in both the not regularly transfused patients, the regulatory transfused patients, patients that are young, patients that are old, patients that have various different types of symptoms. So very representative of the overall patient population.

Our next question comes from Marc Frahm with Cowen & Company.

Congrats on the early launch. Just -- was there any impact from stocking in the quarter? Or is this the $800,000 really true demand in the few weeks that you had in the quarter post approval? And then kind of looking more broadly over the last 3 months, did you see an initial bolus of demand kind of coming through in terms of start forms? Or have the start forms really kind of steadily built through the past 3 or so months since approval?

Yes. So I'll address your second question. Since -- so in terms of the overall dynamics, no bolus, it is as we expected. When patients are showing up, if they have appointments with the physicians, they're getting on therapy. We're working through, they're getting connected to the myAgios Patient Support program and then navigating through the access portion of it. So very, very consistent with our early expectations. So no like, oh, everyone's clamoring to get to the drug very similar to what we expected, just given the nature of the disease. And you'll continue to see the ongoing impact of the pandemic, and knowing that this is a rare chronic condition, you still see prioritization happening in terms of not -- physicians are not actively calling the patients or waiting for the appointment. The staff to be constantly educating on disease and getting both patients and physicians aware about the disease as well as the availability of the therapy. So that's been very consistent with our early expectations.

With regards to your questions around the $832,000, that is represented as we do book sales based on orders that we get from our distribution partners. So there is going to be fluctuations, again, first quarter, early quarter, right? So once we have better sense of like overall how the dynamics will play out, we should be able to give you better guidance. But for now, that is representative of the -- it's a mix, right? You take some time to get scripts on and then get [approval] as well. But this is booked based on the orders from distribution partners.

Okay. Very helpful. And then just on 964, you said MTD was found. Remind us what are the adverse event findings that supported the determination of a maximally tolerated dose?

Sure. So we -- as expected, in a Phase I, we basically push up the dose as far as we can go, and we did identify a dose-limiting toxicity under the form of thrombocytopenia, which was not associated with any other clinical adverse event and which was very monitorable and manageable because everything returned back to baseline when drug was discontinued. And so we also were able on that data to actually identify the doses because we had already reached the pharmacodynamic effects we wanted to observe. So we were able to determine a safe dose for sickle cell disease patients and MDS patients that did not have these events. And so we're very excited about it. The operationalizing components of both the sickle cell disease component of the Phase I and MDS are well on track.

Our next question comes from Greg Harrison with Bank of America.

Are you able to talk about how many patients have started PYRUKYND therapy? And what can we expect to see throughout the early launch in terms of metrics like patient starts, discontinuations, duration of therapy and things like that?

Yes. So we are not giving specifics yet, Greg, on the patients that have started. It's still very, very early days of launch, right, and it is a rare chronic condition. So what we want to do is in order for us to be able to help you model appropriately, want to look at the trends over time and give you a better sense once we have a sense of what those trends look like.

Right now, as we said before, most of the approvals through the payer process through the medical exception process, so that is taking a while because we want to make sure that accurate payer policies can develop and patients have access longer term. So our strategy is working, we're seeing that, and we are continuing to have positive interactions that is enthusiasm as anticipated from the patient community and from the physician community for this therapy. So stay tuned for more updates in future quarters. Still too early to tell.

It's Jackie. I was just going to -- I mean, we're seeing a nice, steady flow and things going the way that we expected that they would go just as Richa said. So scripts are being written. We're actually already seeing refills. So this, I think, shows a nice dynamic because we're only in the second full -- well, moving into the third full month of the launch. And I'd also just remind everybody that we're using 1 specialty pharmacy. So this is not a situation where you've got like some kind of massive distribution network that you're filling a pipeline for. So I want that just to be clear. And sorry, I didn't mean to interrupt you.

Yes. That's helpful. The other question I had was whether you've -- I know it's very early, but if there's been any noticeable increase in disease awareness. And what do you expect to be the impact on diagnosis rates as people become more aware that there's a treatment available?

So I would say on the disease awareness front, it is trending in the right direction. We'll have updates as we collect data over time because as you know, it's only been a first partial quarter of launch. With regards to diagnosis rate, that's something that takes a few years to track, right? So you would not expect us to provide updates on that necessarily on a quarterly basis. One thing I will say about that is our efforts around Anemia ID are particularly important. And the reason why we keep -- we are very encouraged by the interest we see in that program because that is the one avenue we have available to us to really help both with our efforts around these education, but also to ensure accurate diagnosis, which will enable longer-term improvement in the diagnosis rate. So that we continue to see steady growth and set interest. So that's exciting for us, and that will continue to remain a focus.

Our next question comes from Mark Breidenbach with Oppenheimer.

Congrats on the launch. Just a quick -- a couple of quick ones for me. Can we kind of expect cost of sales as a percentage of revenue to kind of come down a little bit in future quarters? I guess I'm wondering where you're seeing that might stabilize to. And just with respect to SG&A for the quarter, which was pretty flat versus the previous quarter, does that kind of imply that all the commercial infrastructure and all the hirings that need to be done to support PYRUKYND's launch have been completed at this point.

Mark, it's Jonathan. I'll take your questions in order. So cost of goods, yes, you'll see that as volumes go up, you'll see cost of goods come down because we have the fixed costs that become more leverageable as demand picks up and the launch progresses. So that number will come down. And it's a small molecule. So you'll see ultimately similar to like what we had with TIBSOVO for you, you should see very healthy gross margins.

And on SG&A, yes, I mean, we've been -- we worked hard last year, and we're still working to make sure that we have the right cost base to run our business efficiently and allocate our capital to the highest priorities, which are the launch, and we're very excited about clinical development across thalassemia, sickle cell and MDS. And Richa has had her team on board really by about the middle of last year. And so that is the run rate you'll see. And I think overall, on OpEx, generally, you should see pretty consistent numbers through this year. You're not going to be seeing numbers going up. It will be -- there's always a little bit of fluctuation quarter-to-quarter, but it should be pretty flat or maybe even some quarters could even come down a little bit. So it's a very good indication, I think, of what you can kind of model going forward.

Our next question comes from Salveen Richter with Goldman Sachs.

This is Matt on for Salveen. Could you please provide some color on where you stand getting patients enrolled in the Phase II portion of RISE UP, ENERGIZE and ENERGIZE-T? And then separately, when can we expect or look forward to any clinical catalysts from Agios or its academic collaborators this year?

Sure. So well, for both our ENERGIZE, ENERGIZE-T and RISE UP studies, we are very happy that we've enrolled the first patients and that we're focused on really global site activation and enrolling patients in those trials. We don't provide specifics on each enrollment number as we go along, but we are on track to meet our milestones as we had outlined before, and so are very excited about the work that's going on there.

And then second part of the question? Can you repeat the second part of the question, please?

It's about the data catalyst.

Data catalyst, yes. So right now, the execution piece is ongoing. So the Phase III ENERGIZE and ENERGIZE-T are blinded and will -- there's no interim plan. So there's no immediate data catalysts coming from there. A big one for us is going to be the Phase II study of RISE UP, which is for next year. And then at EHA, of course, we have multiple data presentations outlining data from across our programs that we're super excited about, and those abstracts will drop next week actually. So we're very excited about that.

Our next question comes from Andrew Berens with SVB Securities.

Can you hear me now?

Yes.

Congrats. I was just wondering a few on the launch. Do you know how many scripts were written that generated the $800,000 in sales? And then I wanted to get some color on the addressable market that you highlighted in the prepared remarks. I think you said up to 4,000 patients in the U.S. And in the past, you've talked about a registry of identified patients that are around 1,100 to 1,200 patients. So are these 4,000 patients, have they been identified? Or is it a hypothetical calculated prevalence?

And then one on 946. How low did the platelets go at maximum tolerated dose? And do you know the etiology of the thrombocytopenia? I don't think we've seen it with any of the other PKR drugs that I'm aware of. And is it off target or on target?

Okay. So with regards to your question around scripts, we're not providing specifics on that. The $832,000 was the sales to the distributors. That being said, over time, they will translate the reason why they have those sales is because there is patient demand and those are translating over time into patient scripts. So once we have better sense of the overall trends, we would provide information on that on an ongoing basis. So stay tuned for more updates on that as we learn more. But there's some inventory dynamics, again, obviously, too early to say, but as Jackie also pointed out, we only have one distributor, so you don't have like massive (inaudible) inventory that are happening. So it is reflective overall of patient demand. It will just take time for us to sort of see that going through. But now spoke to me, it's not from an accounting standpoint, but based on the sales to distribute. So that's your first question.

The second question on the overall prevalence in PK deficiencies. As we've mentioned in previous calls, overall because it is a rare disease, it's poorly understood, not well characterized and a chronic condition, we've had to work with thought leaders, with a broader patient community to really help us understand what the theoretical prevalence might be in this disease. And we've taken and triangulated data from a lot of different sources, which gives us confidence that the peak potential for pyruvate kinase deficiency is in that range of 1,500 to 4,000. But the purposes of the (inaudible), we should consider the midpoint of that rating, somewhere in that 3,000. And we feel pretty good about that number from a theoretical prevalence standpoint. That doesn't mean we've identified those many patients. We've said that the diagnosis rate is about 30% at this point and our efforts both prelaunch and they continue and will continue forever in this disease space have been focused on improving disease familiarity and also driving up that diagnosis rate through efforts like Anemia ID.

And as we've said in the past as well, we believe that it's -- there's a like number of patients in Europe also. So I think it's -- or let's talk about 3,000 to 8,000 between the U.S. and Europe and about half and half in each geography, with 3,000 in the U.S., as Richa said, being kind of at the midpoint of that range, but only 30%...

And what would be the phenotype of these patients? Are there patients that are getting transfusions? What is the cutoff that you're using?

So the cut off, this is basically everyone, right? Everyone where we believe has pyruvate kinase deficiency based on our work with the broader PK deficiency community. Within that, you have about 80% of patients that are adult. So there's no reason for us to believe that the adult PKD patient population is different than your average population in the United States. It's very representative of that. So that split is 80% adult, which is where we have our label. As you may have heard from us before, we are evaluating and planning on initiating studies in the pediatric population, which will enable us to address the entirety of the PK deficiency population. But for now, we have an approval and what the commercial team is focused on is the adult PK deficiency, which is representative of that 80%.

So overall, just -- that's the theoretical prevalence that focuses around disease education and driving awareness of the approval of therapy. So both of those activities are ongoing right now.

And then in regards to your questions around 946. So it's a Phase I study that we really pushed up the dose. So the event that we observed was at a dose that we're not planning to use. So in regards to what is possible hypothesis, we've been thinking about that. But then because these are doses that we're not going to use, we are not going to further explore that, especially because the event is very monitorable and manageable and physicians that are actually working on the diseases that we're exploring are comfortable managing things like this as well. So we have not observed thrombocytopenia in the context of PYRUKYND for instance. And so you will not see that reflected in our label. And in regards to 946, as mentioned, the dose that we selected are lower than the dose as with this was observed, and we're on track to initiate those studies.

Next question comes from Danielle Brill with Raymond James.

This is Alex, on for Danielle. Question on Anemia ID. And you said that 3,500 kits. Have all of those kits been filled? Like are those just ordered or it's actually been processed? And do you have the type of information available to say how many of those identified patients in the hit rate have had a prescription written, started treatment? And then a detail on 946. Can you reveal the maximum tolerated dose in the healthy and/or the doses chosen for the [SAD] cohort?

Yes. So with regards Anemia ID, as we mentioned, it's 3,500 kits ordered, but only a quarter completed. So physicians may be ordering the kits knowing that they have patients that will come to their practice in the future. So not all of them have been completed. And as we also said in our remarks, it's about mid-single digits in terms of the positivity rate, which again is well within our expectations because we have -- knowing that Anemia ID is designed for hemolytic anemia of unknown etiology, and it's not specific to PK deficiency, we were expecting the range to be in that sort of mid-single-digit range. So it's nothing unexpected there either.

What we are encouraged about is both the value [proficiency] this has for their patients and the fact that we are continuing to see strong interest in the program and utilization. In terms of like the direct conversion of the Anemia ID patient found into like a script, that process takes a little bit of time, right? You find the patient, then you have to find where the physician that has the patient and the physician has to call the patient in, the patient has to be willing to go in and all of that. So we've been following that and keeping draft of all the patients we found through the program and ensuring that we are connecting to the physicians, knowing that they may have found a patient. And then those conversations usually result in a script, but you can't just direct. It takes time before that happens.

And in regards to your question regarding the dose (inaudible), we will disclose all of the details around our healthy volunteer study at an upcoming medical meeting. What I can tell you around the dose selected for sickle cell disease and MDS is that for sickle cell disease, the protocol was already written and for MDS actually as well, and we did not change any of our dose selection criteria based on the events observed.

And I'm not showing any further question time. I'd like to turn the call over to Jackie for any closing remarks.

Thank you, operator, and thank you, everyone, for the questions this morning. As always, I would also like to thank my Agios colleagues for their dedication and passion for making a difference for patients. I also would like to thank all patients, caregivers and physicians who partner with us in so many ways and especially those participating in our clinical trials across all indications. Our connections across all of our stakeholders and our collective efforts together fuel ongoing innovation and impact for people with genetically-defined diseases.

Thank you for joining us this morning. You may now disconnect.

Ladies and gentlemen, this concludes today's presentation. You may now disconnect, and have a wonderful day.