Q1 2022 Agios Pharmaceuticals Inc Earnings Call

Okay.

Operator: Ladies and gentlemen, please stand by. Your conference call will begin momentarily. Once again, ladies and gentlemen, please stay on the line. [Music] Good morning and welcome to the IGO's first quarter 2022 conference call. At this time, all participants are in a listen-only mode.

Ladies and gentlemen, please standby your conference call will begin momentarily once again, ladies and gentlemen, please stay on the line.

Yeah.

[music].

Yeah.

Good morning, and welcome to the <unk> first quarter 2022 conference call. At this time, all participants are in a listen only mode.

Operator: There will be a question and answer session at the end. Please be advised that this call is being recorded at Audio's request. I would now like to turn the call over to Holly Manning, Senior Director of Investor Relations. Thank you, operator. Good morning, everyone.

There will be a question and answer session at the end. Please be advised that this call is being recorded August request I would now like to turn the call over to Holly Manning Senior director of Investor Relations.

Holly Manning: And welcome to Agios' first quarter 2022 conference call. You can access slides for today's call by going to the investor section of our website, agios.com. With me on the call today with prepared remarks are Dr. Jackie Faust, our Chief Executive Officer, Dr. Sarah Gheuens, our Chief Medical Officer, Richard Podar, our Chief Commercial Officer, Jonathan Biller, our Chief Financial Officer and Head of Corporate Affairs, and Dr. Bruce Carr, our Chief Scientific Officer, who will join for Q&A.

Thank you operator, good morning, everyone and welcome to <unk> first quarter 2022 conference call you can access slides for today's call by going to the investors section of our website <unk> Dot com.

With me on the call today with prepared remarks, and Dr. Jackie Fouse, our Chief Executive Officer, Dr. Sharon <unk>, our Chief Medical Officer, Richard Allen, Our Chief Commercial Officer, Jonathan <unk>, Chief Financial Officer, and head of corporate Affairs and Dr. Bruce <unk>, Our Chief Scientific officer will join for Q&A.

Holly Manning: 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. However, actual events and results could differ materially from those expressed or implied by any forward-looking statement as a result of various risks, uncertainties, and other factors, including those set forth in our most recent filings with the FCC and any other future filings that we may make with the FCC. With that, I will turn the call over to Jackie.

When 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 or 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.

D C and any other future filings that we may make with the SEC with that I will turn the call over to Jeff.

Jackie Faust: 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 PyroKind, a first-in-class TK activator and the first and only approved 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.

Thanks, Holly and good morning, everyone and thank you for joining our first quarter 2022 results call.

The first quarter of 2022 was a milestone moment for <unk> as we received U S. FDA approval for <unk>, a first in class PK activator in the first and only approved disease modifying treatment for adults living with pyruvate kinase deficiency.

From the scientists to first half half the size of the potential utility of PK activation to the Cumulus two designed our molecule to the clinical trial coordinators, who help to enroll our trials people fall off our organization, both past and present, who played a role in this important milestone. In addition, a tremendous number of people outside of our.

Jackie Faust: 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, debilitating, lifelong hemolytic anemia, along with the promise of what we can deliver in their treatment options, is the reason we come to work every day, and our connections with patients, health care providers, partners, and each other are how we transformed this idea into medicine. Looking ahead, we are highly motivated to implement the U.S.

Organization were instrumental to this effort.

<unk> patients caregivers and advocates all of whom have provided critical insights at every step of the way.

Our connection to patients battling this rare 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.

Jackie Faust: We have launched the 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.

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.

Huge focus for our team this year in 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 Val.

Jackie Faust: 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 pharmaceuticals 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 the 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.

<unk> in our culture, but also with the United Nations Sustainable development goals and the standards for the biotechnology and pharmaceuticals 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 our range of ESG initiatives and encourage you to have a look at our report which is available on our website at <unk> dot com under the corporate social responsibility section.

Jackie Faust: 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 that. 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.

A huge thank you to the cross functional ESG working group for bringing this year's report to live 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 that those pivotal.

Graham 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.

Sarah Gheuens: The clinical team has been working extremely hard to execute on our ambitious clinical development plans 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 application for pyrokines 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 startup activities for two pivotal trials in pediatric PK deficiency patients.

Our clinical team has been working extremely hard to execute on our ambitious clinical development plans 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 application for <unk> in adult PK deficiency remains under review in the EU and we remain on track to receive a decision from the <unk> by year end.

In addition, our team is actively working through startup activities for two pivotal trials in pediatric PK deficiency patients.

Sarah Gheuens: We expect these trials to initiate in mid-2020. I'm also pleased to share that data from the core period of the ACTIVATE study of pyrokines 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 pyrokines and continue to generate important data in the extension study about the long-term impact of treatment.

Thank you Keith drought to initiate in mid 2022.

I'm also pleased to share that data from the core periods of the activate study of pirate kinds 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 FDA approval of <unk> and continue to generate important data in the extension study about the long term impact of treatment.

Sarah Gheuens: At the IHA meeting in June, we'll share new PRO data from ACTIVATE, data demonstrating the normalization of hemoglobin levels with long-term treatment of pyrokines, and additional comorbidities and complications data from the PEAK registry. Beyond TK deficiency, we believe TK activation has the potential to play an important role in the treatment of thalassemia and sickle cell disease.

At the <unk> meeting in June we will share New Bureau data from accuracy data demonstrating the normalization of hemoglobin levels with long term treatment of pirate Cai and additional co morbidities and complications data from the peak registry.

Beyond PK deficiency, we believe CK activation has the potential to play an important role in the treatment of thalassemia and sickle cell disease at.

Sarah Gheuens: At the end of last year, we initiated our two global placebo-controlled physical trials of pyruvines in thalassemia, ENERGYSE and ENERGY-C. As a reminder, ENERGYSE will evaluate 171 patients randomized 2 to 1, to 100 milligrams of metapivas twice daily or placebo in both alpha and beta thalassemia patients who are not regularly transmitted. The primary endpoint is hemoglobin response, defined as an equal or more than one gram per deciliter increase in average hemoglobin concentration from week 12 through week 24 compared with baseline.

At the end of last year, we initiated our two global placebo controlled pivotal trial with pipelines in thalassemia energized and energy.

As a reminder, energize will evaluate 171 patients randomized two to one to 100 milligram of <unk> twice.

Twice daily or placebo in both Alpha and beta thalassemia patients who are not regularly transfused.

Mary endpoint is hemoglobin response defined as equal or more than one gram per deciliter increase in average hemoglobin concentration from week 12 week 24 compared with baseline.

Sarah Gheuens: Energize-T will evaluate 240 patients, randomized 2 to 1, to 100 milligrams of metapifa twice daily or placebo in both alpha and beta thalassemia patients who are regularly transmitted, 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 two units of transfused red blood cells in any consecutive 12-week period through week 48 compared with date.

Henry J D will evaluate <unk> 240 patients randomized two to one to 100 milligrams of Mcafee about twice daily or placebo in both alpha and beta thalassemia patients who are regularly transfused defined 6% to 20 Red blood cell unit transfused during the 24 weeks prior to randomization.

The primary endpoint of transfusion reduction response defined as a 60% or greater reduction in transfusion red blood cell units with a reduction of equal or more than two units of red blood cells in any consecutive 12 week period through week 48 compared with baseline.

Sarah Gheuens: Last year, we also initiated the Phase 2 portion of our Phase 2-3 study in sickle cell disease, RISE-UP, which will randomize 69 patients one-to-one-to-one to 50 mg metapifa twice daily, 100 mg metapifa twice daily, or matched placebo. The primary endpoints are hemoglobin response, defined as an equal or more than one gram per deciliter increase in average hemoglobin concentration from week 10 through week 12, compared to baseline, and the type of adversity.

Last year, we also initiated the phase II portion of our phase III study in sickle cell disease rise up which will randomize 69 patients one to 1% to 1% to 50 milligrams Metopic up twice daily 100 milligram capital twice daily or matching placebo.

Primary endpoints or hemoglobin response defined as an equal or more than one gram per deciliter increase in average hemoglobin concentration from week to week 12, compared to baseline and the type of adverse event.

Sarah Gheuens: This data will be used to establish a clear dosing paradigm for the phase 3 portion. Our team is focused on continuing global site activation and patient enrollment efforts across all three trials. KG946 is our novel PKR activator currently being evaluated in a phase one study.

These 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 three trials.

$89 six is our novel PTR activator currently being evaluated in phase one study. We recently completed the single ascending and multiple ascending dose healthy volunteer cohorts after reaching a maximum tolerated dose.

Sarah Gheuens: 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 1 sickle cell disease cohort, as well as the MDS Phase 2a trial. We look forward to sharing updated data from the SAD and MADD 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 patients shortly. As a reminder, the purpose of the sickle cell arm is to obtain data in patients with hemolytic anemia.

As a result, we have identified the doses that we're moving forward with in the phase one sickle cell disease cohorts 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 cohorts and are on track to enroll the first patient shortly.

As a reminder, the purpose of the sickle cell army to obtain data in patients with the hemolytic anemia.

Richard Podar: In addition, we are working through operationalizing the 2A part of our AG946 Phase 2A-2B study in MDS. The Phase 2A component of the study is an open-label, proof-of-concept study of one dose level of AG946 in patients with lower-risk myelodysplastic syndrome. The study will enroll 20 patients who will receive AG946 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 the average hemoglobin concentration from week 8 through week 16, and transfusion independence, defined as transfusion-free for equal or more than eight consecutive weeks during the four periods in patients with low transfusion burden only.

In addition, we are working through operationalize into two as part of our <unk> $9 six phase III <unk> study in Mds.

The phase II a component of the study is an open label proof of concept study of one dose level of 89 six in patients with lower risk Myelodysplastic syndrome.

He will enrolled 20 patients who will receive $89 six once daily for the 16 week core period.

To complete the core periods will be eligible to continue in an extension periods.

Primary endpoints for this study or a hemoglobin response defined as an equal or more than one five grams per deciliter increase from baseline in average hemoglobin concentration from week eight through week 16, and transfusion independence defined as transfusion free for equal or more eighth consecutive week during the fourth period in <unk>.

Patients with low transfusion burden only.

Richard Podar: 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.

Secondary endpoints include safety additional measures of anemia, PK and PD biomarker.

Look forward to initiating the trial by year end.

I will now turn the call over to Richard <unk>, Our Chief commercial officer.

Richard Podar: I'm pleased to provide the first Quantity Pile Kind launch update, where we generated net US sales of $832,000 for the first six weeks of launch following our approval on February 17th. 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 linear ID. Second, physicians understand the urgency to prescribe, and eligible patients advocate for treatment.

Thank you Sarah and needs to provide the first quantity pipeline launch update revenue generated net sales of $842000 for the floor.

Please stop launch following approval on February 17th as we've said before our commercial launch strategy focuses on connecting with the patients and educating the provider to ensure.

That patient to accurately diagnose through efforts like anemia I D.

Second physicians understand the urgency to describe an eligible patient advocate for treatment.

Richard Podar: And finally, patients connect to myRGS support services to optimize disease 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 pyrokine brings to patients living with this disease, and we are encouraged that we have an opportunity to make a real difference in the lives of these patients with a first-in-class disease-modifying therapy.

And finally patients connect and myalgia support services to optimize disease understanding ensure access and drive long term medication adherence.

Having been in the field for the last couple of months, all conversations with patients physicians and caregivers continue to underscore the value that Didnt believe incubation.

Thanks to patients living with this disease and yet, but do you have an opportunity to make a difference in the lives of these patients with a first in class disease modifying therapy.

Richard Podar: We have gained important insights from the early days of launch that have further reinforced that our commercial launch strategy has. Since our launch in mid-February through the end of the quarter, our team of hemolytic anemia specialists has had more than 1,100 customer interactions, raising awareness of pyrokines, and educating physicians on how this first-in-class PK activator can be used to benefit their indulged patients with PK deficiency. This positive engagement has been successful in driving scripts for those previously identified. Our high-tech patient support program, myAGIOS, has effectively engaged with patients and physicians to begin disease and drug education, as well as to navigate reimbursement challenges to ensure access and minimize abandonment.

It gained important insights in the early days of launch you have call. It does reinforce that our commercial loan strategies of assets.

Since our launch in mid February through the end of the quarter. Our theme of hemolytic anemia specialists have had more than 1100 customer interactions.

And then as a follow up time and educating physicians on how this Boston plastic yesterday that can be used to benefit patients with PK deficiency.

This positive engagement has been successful in driving scripts for those previously identified teaching.

Our high touch patient support program.

It has affected me engage with patients and physicians to begin to ease in John's education, as well as navigate reimbursement challenges to ensure access and minimize abandonment.

Richard Podar: In addition, a high priority for us is to drive awareness of pyrokines among the patient community, so we have been focused on generating awareness through social media pushes, word of mouth, patient webinars, my audios, and partnerships with patient advocacy groups. These efforts are working, as PK deficiency patients have been tremendous self-advocates, and proactive patient requests for pyrokines have accelerated early prescribing. In terms of pay dynamics, our National Account Directors have had dozens of positive interactions with payers to date.

In addition, a high priority for US is to drive abandoned the pilot sites among the patient community. So we have been focused on generating awareness through social media pushes what is now <unk> my AD yields and partnership with patient advocacy groups. These efforts of wacky PK deficiency patients have been tremendous sense obligate Andrew.

Active patient request for pilot have activated already prescribing.

In terms of payer dynamics and National account directors have had dozens of positive interactions with payers to date.

Richard Podar: As anticipated, these early approvals have been through the medical exception process, while prior authorization and utilization management criteria are being developed across fields. And finally, turning to Anemia ID, we have continued to see strong interest with more than 3,500 kits ordered since 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 anticipated. These all the approvals have been through the medical exception process <unk> authorization.

All translation and utilization management criteria are being developed across the us.

And finally turning to EMEA.

We have continued to see strong interest with more than 2500 kits or that's just the start of the film.

The completed tests with just represented a portion of the duplicate supported the PK deficiency caused the BV is in the mid single digit percentages and within the range of what we would have expected.

As a reminder.

I'd, even designed for patients with a generally diagnosis of hemolytic anemia, ammonia geology, and it's not specific to PK deficiency.

Richard Podar: 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 for the broader PCA deficiency community. It is important for us to remember, however, that TK deficiency is a rare chronic condition that is poorly understood.

Jesse mentioned positions have continued to appreciate the benefit that this program is bringing to the patients with <unk>.

The longer term strategy to continue to ensure accurate diagnosis, enabling a higher diagnosis rates over time.

Yes.

These early launch successes and the positive experiences we are creating with the drawdown PK deficiency community.

It's important for us to remember however that PK deficiency is a rare chronic condition, which is fully understood.

Richard Podar: 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 a disease space that requires multiple interactions to both educate patients on the 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 the early quarter.

So, let's say around disease education, and patient identification continues to be paramount to ensuring long term success.

The commercial team is laser focused on these initiatives. Despite the ongoing challenges of the pandemic, which had said that you did mostly of what's rolling agents. This.

This is challenging in a disease state that it was my phone interactions to both educate on disease defeat urgency and also ensure accurate diagnosis.

We have better clarity with respect to the launch trajectory and we walk away would be for the quarters based on our work to date. We continue to believe the ethanol Timothy 1500 to 4000 <unk> deficiency patients in the U S representing a peak revenue potential in the U S of $200 million to $225 million.

Richard Podar: Based on our work to date, we continue to believe there are approximately 1,500 to 4,000 PCA deficiency patients in the U.S., representing a peak revenue potential in the U.S. of $200 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 P.T. deficiency

Dsos are passionate as promotional optimization is significant red meat experience that is fully capable of executing our launch strategy and the exciting vehicle today and back into making underlies the PK deficiency patients in <unk>.

Richard Podar: 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 pyrokines to all eligible PTD patients, as well as longer term for other genetically defined diseases. Phyrexel has the potential to be a global blockbuster therapy for PK deficiency and thalassemia alone.

<unk>, what we have seen from this first quarter is that our commercial strategy and policy and the connections. We are making are setting us up for success as we continue to expand the applicability of <unk> to all eligible <unk> patients as well as longer term other genetically defined diseases.

For example, with a potential to be a global blockbuster penalty with PK deficiency, and thalassemia alone with that I'll now turn it over to Jonathan to the new first quarter financials.

Jonathan Biller: 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 10-2 filing later today. As Richard shared, Pyrotime revenue for the first quarter was $832,000. Cost of sales for the quarter was $330,000.

Thanks, Richa, our first quarter 2022 financial results can be found in the press release, we issued this morning, which I'll summarize.

More detail will be included in our 10-Q filing later today.

As Richard shared private client revenue for the first quarter was $832000.

Cost of sales for the quarter was 339.

Jonathan Biller: Turning to operating, 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 startup costs for the pyrokine pivotal studies in thalassemia and sickle cell, and Planned Increases in Preclinical Activity. Offset by closeouts of the Activate and Activate Season. Selling General and Administrative, $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 costs. Kip Sobo, Royal, which is recorded under royalties.

Turning to operating expenses research and development for the first quarter was $70 1 million, an increase of $12 5 million compared.

Compared to the first quarter of 2021.

The year over year increase in R&D was driven primarily by startup costs for the pilot and pivotal studies in thalassemia sickle cell disease and planned increases in preclinical activity offset by Closeouts of the activate and activate T study.

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.

<unk> royalty revenue, which is recorded under royalty income from gain on sale of oncology business on our income statement was $2 $7 million.

Operator: Again, on sale of oncology, our income statement was $2.7 million, and 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 achieve 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 a promising clinical program and Retain Flexibility for Businesses. Consequently, as we begin our annual long-range planning... We continue to be laser focused on capital allocation to only our highest priority, as well as continuing to proactively manage our. With that, Operator, please open the line.

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 free 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.

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.

Yeah.

Richard Podar: Ladies and gentlemen, if you have a question or a comment at this time, please press the star, then the one key on your touchtone telephone. If your question has been answered or you wish to move yourself from the queue, please press the pound. Our first question comes from Andupan Ramu with J.P. Hey guys, thanks for taking the question. What are you seeing on the reimbursement front for pyrokine? And what are you seeing in terms of time from 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 so much.

Ladies and gentlemen, a question or a comment at this time. Please press. The Star then the one key on your Touchtone telephone. If your question is banana sort of if you will.

We're seeing with yourself from the queue. Please press the balance sheet. Our first question comes from <unk> Rama with JP Morgan.

Hey, guys. Thanks for taking the question.

What are you seeing on the reimbursement front for powered kind and what are you seeing in terms of time to script written to getting.

Onto 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, so much.

Richard Podar: Thanks for the question, Anupam. So, in terms of reimbursement, our conversations with the payers have been very positive. And from a reimbursement standpoint, as expected, a majority of the approvals have been through the medical exception process.

Thanks for the question on the Com. So in terms of reimbursement already conversations with the payers have been very positive.

Positive and from a reimbursement standpoint as expected a majority of your growth have been through the medical exception process, we expect that sometimes meal in the second quarter as well in terms of the payer policies that developed so overall I would say on track and doing.

Richard Podar: We expect that to continue in the second quarter as well until the payroll policies are developed. So, overall, I would say it's on track and going 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 and utilization management criteria, but we should have details of that in the next few quarters.

Exactly as we expected.

Our payer policies are still being developed across the board.

Can you comment on the specifics of the prior authorization and utilization management and psychiatric Nishu have details on that in the next few quarters. So stay tuned for more updates on that front.

Richard Podar: 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 of a specific kind of PKD patient.

Thomas your question around patient types very reminiscent of what you would expect again of the overall adult PKU patients foundations. We are not seeing that that is a high utilization any specific kind of PPD patient, what you're seeing as expected given the paucity of treatment options and the huge unmet medical need.

Richard Podar: What we are seeing, as expected, given the paucity of treatment options and the huge unmet mathematical need, and this being the first approved therapy, is that it is being used across a variety of different types of patients. So, both the not regularly transfused patients, the regularly transfused patients, patients that are young, patients that are old, patients that have various different types of symptoms. So, very representative of the overall population.

The vast approved therapy of Youre getting used across a variety of different types of patients are going to knock transfused patients.

Transfused patients.

Patients are young patients or patients that have very different types of symptom survey very representative of the overall patient population.

Richard Podar: Thanks so much for taking our questions. Our next question comes from Mark Fromm with Cowan & Co. Thanks for taking my question and congrats on the early launch. Was there any impact from stocking in the quarter?

Thanks, so much for taking my questions.

Our next question comes from Mark <unk> with Cowen and company.

Richard Podar: Is this, you know, the 800,000 really, you know, true demand in the, you know, few weeks that you had in the quarter post approval, and then kind of looking more broadly over the last three 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 over the past three or so months? Yes, I'll address your second question, Tessa. So in terms of the overall dynamics, no bullets.

Hi, Thanks for taking my questions and congrats on the early launch.

Just was there any impact from stocking in the quarter or is this the 800000 really true demand in the few weeks that you had in the quarter post approval and then looking more broadly over the last three months did.

Do you see an initial bolus of demand coming through in terms of start forms or have the start forms really kind of steadily built through the through the past three or so months since approval.

Yeah. So I'll address your second question first.

In terms of the overall dynamic snowball as it is as we expected.

Richard Podar: It is as we expected. When patients show up, if they have appointments with their physicians, they're getting on therapy, we're working through, they're getting connected to the myRGS patient support program, and then navigating through the access portion of it. So, very, very consistent with our early expectations.

When patients are showing up if they have appointments with their possessions and getting on therapy and walking through and they're getting connected to my address patient support program and then navigating to the access a portion of that so a very very consistent in my talk on the expectation. So no like Oh everyone's clamoring to get to get to the drugs based on weather.

Richard Podar: So, like, oh, everyone's clamoring to get to the drug, very similar to what we expected, just given the nature of the. And you'll continue to see the ongoing impacts of the pandemic, and knowing that this is a rare, chronic condition, you still see prioritization happening in terms of not, you know, physicians are not actively calling their patients and waiting for appointments and stuff. So we are constantly educating people about the 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 all the expectations.

What would be expected just given the nature of the disease and you'll continue to see the ongoing impacts of the pandemic and knowing that this is a rare chronic condition you still see privatization happening in subjects not physicians are not can be calling that patients are waiting for the appointment to the stuff that we are constantly educating disease are getting onboard.

<unk> acquisitions.

About one just the diseases.

So that's been very consistent with not only the expectation.

Richard Podar: With regard to your questions around the 832,000, that is representative; we do book sales based on the orders that we get from our distribution partners. So there will be fluctuations again, first quarter, early quarter, right? So once we have a 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 whole picture. It's a mix, right? You take some time to get scripts on and then get approval as well. This is booked based on orders from distribution. Okay, thanks, very helpful. And then, just on 964, you said MPD was found.

With regards to your question.

800000 could cause of that is represented we do book sales based on.

Or does that we get from our distribution partners.

There is going to be fluctuations again first quarter or the quarter right. So once we have that perfect.

Dynamics will play out we should be able to give you better guidance, but for now that is right.

If it makes you take some time to get a.

Scripts gone and that get corporate as well.

This is based on.

I guess from our distribution partners.

Okay. Thanks very helpful. And then just on 96 four.

MPD within minutes.

Sarah Gheuens: Remind us, what are the adverse event findings that supported the determination of a? of a maximally tolerated dose? Sure. So we basically push up the dose as far as we can go in phase one. And we did identify a dose-limiting toxicity in the form of thrombocytopenia, which was not associated with any other clinical adverse event and which was very monitorable and manageable because everything, you know, returned back to baseline when the drug was discontinued. And so we also were able, based on that data, to actually identify the doses because we had already reached the pharmacodynamic effects we wanted to observe.

What are the adverse event findings.

That supported the determination of the.

That's a maximally tolerated dose.

Sure.

As expected in our phase one 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, which was very monitor both and manageable because everything.

And can it return 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 have observed so we were able to determine.

Sarah Gheuens: So we were able to determine, you know, 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 components of phase one and MDS are well on track.

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 operational arriving components of both the sickle cell disease component of the phase one in Mds are well on track.

Okay. Thank you.

Richard Podar: Thank you. The next question comes from Greg Harrison with Bank of America. Good morning, thanks for taking our question. Are you able to talk about how many patients have started pyrokine therapy and what we can expect to see throughout the early launch in terms of metrics like patient stars, discontinuations, duration of therapy, and things like that? So, we are not giving specifics yet, Greg, on the patients that have started. It's still in the very, very early days of launch, right, and it is a rare frontotemporal disorder.

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

Good morning, Thanks, Thanks for taking our question.

Are you able to talk about how many patients have started <unk> therapy, and what can we expect to see throughout the early launch in terms of metrics like patient starts continuations duration of therapy and things like that.

Yeah. So we are not giving specifics yet Greg.

Ah patients that have started it still 30 day on E D.

Entre and dessert chronic condition. So what we wanted to do with in order for us to be able to help you model appropriately wanted to look at the trends over time.

Richard Podar: So, what we want to do is, in order for us to be able to help you model appropriately, we 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've said before, most of the approvals through the peer process are through the medical exception process, so that is taking a while because we want to make sure that accurate peer policies get developed and patients have access longer term. So our strategy is working.

And give you a better sense once we have a sense of what those trends look like.

Right now as we've said before most of the approval process through the medical exception process or that it's taking a while because we want to make sure that that's correct payer policies get developed and you should have access to all the time charter.

Richard Podar: We are seeing that, and we are continuing to have positive interactions. There 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. It's still too early to tell.

Strategy is working and we are continuing our positive interactions and enthusiasm has anticipated from the patient community and from the physician community for this therapy.

Keep tuned for more updates in future quarters.

Wanting to Dol.

Got it.

Yeah.

Sorry, sorry, it's Jackie I'm, 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 Richard said, so scripts are being written we're actually already seeing refills. So this I think shows a nice.

Jackie Faust: I was just gonna, I mean, we're seeing a nice, steady flow and things going the way that we expected that they would go, just as Rich has said. So scripts are being written. We're actually already seeing refills.

Jackie Faust: So this, I think, shows a nice dynamic because we're only, what, in the second full month of the launch. And I'd also just remind everybody that we're using one 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. Thanks, that's helpful.

Dynamic because we're only one in the second full are moving into the third full month of.

The launch and I'd also just remind everybody that we are using one specialty pharmacy. So this is not a situation where you've got like some kind of massive distribution network that you are filling our pipeline for someone that.

Just to be just to be clear and sorry, I didn't mean to interrupt you.

Jackie Faust: The other question I had was whether there's been any noticeable increase in disease awareness, and what do you expect the impact on diagnosis rates to be as people become more aware that there's a treatment available? So, I would say on the disease awareness front, it's trending in the right direction.

Yeah. Thanks, that's helpful.

The other the other question I had was whether you.

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 is a treatment available.

So I would say on the disease awareness front, it's trending in the right direction, we have updates as we collect data over.

Jackie Faust: We'll have updates as we collect data over time because, as you know, it's only been the first partial quarter of the launch. With regard to diagnosis rates, that's something that takes years to track, right? So, you would not expect us to provide updates on that necessarily on a quarterly basis.

Time, because as you know, it's only been a partial quarter. After you launch, but you got to diagnosis rate that's something that you.

Take the U S should track rates. So you would not expect us to provide an update on that necessarily on a quarterly basis. The one thing I will say about that is our efforts around in EMEA IV are particularly important and the reason why we keep we.

Jackie Faust: The one thing I will say about that is our efforts around anemia ID are particularly important and the reason why 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 disease education but also to ensure accurate diagnosis, which will enable longer-term improvement in the diagnosis rate. So, we've continued to see steady growth and steady interest, so that's exciting for us.

We are very encouraged by the interest we see in that program because that is the one avenue, we have available to us should really help with our efforts around disease education, but also to ensure accurate diagnosis, which will enable longer term.

<unk> mentioned the diagnosis rates, so that we continue to see steady.

Debbie grow up.

Net interest so that's exciting for us.

We continue to remain a focus.

Great. Thanks again.

Jackie Faust: And that will continue to remain a focus. Great, thanks again. Our next question comes from Mark Breidenbach with Oppenheimer. Hey, good morning, guys. Thanks for taking their questions and congratulations on the launch. Just a quick couple of quick ones for me.

Our next question comes from Mark Breidenbach with Oppenheimer.

Jackie Faust: 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 think that might stabilize to. And just with respect to SG&A for the quarter, which is pretty flat versus the previous quarter, does that kind of imply that all the commercial infrastructure and all the hiring that need to be done to support launch have to have been completed at this point? Thanks for taking the question. Hi, I'm Marlon Strachan.

Hey, good morning, guys. Thanks for taking the questions and congrats.

On the launch.

Just a quick couple of quick ones for me.

Can we kind of expect cost of sales.

The percentage of our revenue.

Come down a little bit in future quarters, So I guess im wondering where youre seeing that.

Stabilize too and just with respect to.

SG&A for the quarter, which was pretty flat.

Versus the previous quarter. So is that kind of imply that all of the commercial infrastructure and all of that.

Our hirings that needs to be done to support pilot launch.

Been completed at this point, thanks for taking the questions.

Hi, Mark its John .

Jonathan Biller: I'll take your questions in order. So, cost of goods, yes, you'll see that as volumes go up, you'll see the cost of goods come down because we have the fixed costs that, you know, become more leverageable as demand picks up and the launch progresses, so that number will come down. And, you know, it's a small molecule, so you'll see, ultimately, similar to what we had. And on SG&A, yes, I mean, 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 what we're very excited about, clinical development across thalassemia, sickle cell And Rich had her team on board really by about the middle of last year.

I will take your questions in order so cost of goods, yes, youll see that as volumes go up you will see cost of goods come down because we have the fixed costs that.

<unk> got more leverage.

Yes.

Demand picks up as the launch progresses, so that number will come down.

It's a small molecule so youll see ultimately similar to like what we had with.

Chip.

For you and you should see very healthy gross margins and.

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 trying to launch it in.

Very excited about clinical development across thalassemia sickle cell in Mds as mentioned Patrick team.

Or really by about the middle of last year, and so that is good run rate Youll see and I think I think overall on Opex generally you should see pretty consistent numbers through this year, we're not you're not going to be seeing numbers going up but it'll be there's always a little bit of fluctuation quarter to quarter, but it should be pretty flat.

Jonathan Biller: 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. 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.

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.

Jonathan Biller: So it's a very good indication, I think, of what you can kind of model going forward. Thank you so much. Our next question comes from Salveen Richter with Goldman Sachs. Hi, thanks. This is Matt on behalf of Salveen.

Thank you so much.

Our next question comes from from Celgene Richter with Goldman Sachs.

Sarah Gheuens: Could you please provide some color on where you stand getting patients enrolled in the phase two 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 academic collaborators this year? Thanks a lot.

Alright. Thanks, this is Matt on for Celgene.

Could you. Please provide some color on where you stand in getting patients enrolled in the phase II portion of rice up under Jive N enjoys T. And then separately when can we expect and look forward to any clinical catalysts from <unk> academic collaborators. This year. Thanks a lot.

Sarah Gheuens: Sure. So, well, for both our ENERGIZE, ENERGIZE-T, and RISE-UP studies, we're 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, you know, each enrollment number as we go along, but we are on track to meet our milestones as we had outlined before and are very excited about the work that's going on there. Um, and then, So right now, the execution piece is ongoing, so you know, the phase 3 energizer and energize P are blinded, and there's no interim plan, so there's no immediate data catalyst coming from there.

Sure so well for both our energizing our Jive N rise of studies, we are very happy that we've enrolled the first patients and they were focused on really global site activation and enrolling patients in those trials, we don't provide specifics on each.

Each enrollment number as we go along but we are on track to meet our milestones as we had outlined before and so we're very excited about the work that's going on there.

And then.

Second part of the question.

And your second part of the question can you repeat the second part was on a plane starts data all the data catalysts, Jeff. So right now the execution piece is ongoing so the phase III energized and energize, our blindness and it will there's no interim plant. So there is no no immediate data catalysts coming from there are big.

Sarah Gheuens: The big one for us is going to be the phase 2 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 program that we're super excited about, and those abstracts will drop next week. We're very excited about that.

One for us is going to be the phase two study of horizon.

For next year and then at Ehealth of course, we have multiple data presentations.

Finding data from across our programs that we're super excited about and those abstracts will drop.

Drop next week actually so we're very excited about that.

Okay.

Great. Thank you.

Sarah Gheuens: Great, thank you. Our next question comes from Andrew Burns with SBB Security. Andrew, your line is open, you can ask your question. Can you hear me now? You're coming through loud and clear. Can you guys hear me?

Our next question comes from Andrew Burns with SBB Securities.

Andrew Your line is open you can ask your question.

Can you hear me now.

Okay.

Come through luck guys hear me.

Great Congrats.

Operator: Great. Congratulations, and thanks for taking the question. 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 your prepared remarks. I think you said up to 4,000 patients in the U.S. 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.

Congrats and thanks for taking the question I was just wondering a few on the launch do you know how many scripts were written that generated the 800000 in sales and then.

I wanted to get some color on the addressable market that you highlighted in the prepared remarks, I think you set up for 4000 patients in the U S and the.

Past, you've talked about a registry of identified patients that are around 11 under the 200 patients.

These 4000 patients have they been identified or is it a hypothetical calculated prevalence.

And then one on 946.

Richard Podar: How low did the platelets go at the 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?

How long did the platelets go.

Well tolerated dose and do you know.

The etiology of the thrombocytopenia I don't think we've seen it with any of the other features of our drugs that I'm aware of.

Is it off target or on targets.

Okay. So with regard to your question around scripts youre not providing specifics on the.

Richard Podar: So with regard to your question around scripts, you're not providing specifics on that. The 832,000 were the sales to the distributors. That being said, over time, they will translate.

822000 was the ceiling to their distributors that in fact over time. They will translate the reason why we have those sales is because there is patient demand and does that translate over time to a patient scripts. So once we have better sense of the overall trends, we will provide information on that on an ongoing basis.

Richard Podar: The reason why they have those sales is because there is patient demand, and that is translating over time into patient scripts. So once we have a better sense of the overall trends, we will 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 massive swings in inventory that are happening.

So stay tuned for more updates on that.

Actually no one one but that's the kind of inventory dynamic again, obviously at two.

Why do you do see but Jack you want to point it out.

One distributor so you won't have that massive swings in inventory that harmony.

Richard Podar: So it is reflective overall of patient demand. It'll just take time for us to sort of see that pull through, but now it's booked based on, from an accounting standpoint, but based on sales to distributors. So that's your first question.

So it is a flexible where a patient demand. It will just take time for us to set up.

See that flowing through.

But now it's booked based on from an accounting standpoint book based on lithium.

So that's your first question the second question on the overall.

Richard Podar: The second question around the overall prevalence of 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 the 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.

Prevalence in PK deficiency says we've mentioned in previous.

Cause overall is because it is a rare disease.

Understood.

<unk> and.

Anna chronic condition, we have to work with thought leaders with a broader patient community because what he has such understand what the theoretical prevalence might be in this disease and we've taken an 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 1500 to 4000, but the purpose is.

Richard Podar: For the purposes of the U.S., we usually say we should consider the midpoint of that range, somewhere in that 3,000, and we feel pretty good about that number from a theoretical prevalence standpoint. But that doesn't mean we've identified those many patients. We've said before that the diagnosis rate is about 30% at this point, and our efforts both pre-launch, and they continue, and will continue forever in this disease phase, have been focused on improving disease familiarity and also driving up that diagnosis rate.

Last week, we usually see peak, we should consider that midpoint of that range somewhere in that two Thompson.

And we feel pretty good about that number from a theoretical covenant standpoint that doesn't mean, we've identified those many patients <unk> said before that the diagnosis rate is about 20% at this point in our efforts.

Both prelaunch and they continue on with continue forever in this disease space have been focused on improving disease familiarity and also driving up that diagnosis rate to athletes like on EBIT.

Richard Podar: And we've said in the past as well, there, we believe that there are a similar number of patients in Europe also. So I think I heard us talk about 3,000 to 8,000 between the U.S. and Europe, and about half and half in each geography.

And that's what we've said in the past as well.

We believe that.

There is a like number of patients in Europe also so I think it's.

Let's talk about 3000 to 8000 between the U S in Europe and about now it's about half and half in each geography.

Richard Podar: With 3,000 in the U.S., it's interesting being kind of at the midpoint of that, but only 30% of them died today. And what would be the phenotype of these patients? Are they patients that are getting transfusions? What is the cutoff that you're using? So to cut off, this is basically everyone, right?

With 3000 in the U S. As Richard said, they can kind of at the midpoint of that.

But only 30 okay.

Okay.

And what would be the phenotype because these patients are they patients that are getting transfusions.

What is the cutoff that you're using.

So they'll cut off this is basically everyone raised everyone's that'd be busy he has highly kind of deficiency Beecher and I'll work with the board at PK deficiency community.

Richard Podar: Everyone that we believe has thyroid kinase deficiency based on our work with the broader PK deficiency community. Within that, you have about 80% of patients that are adults. 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.

Within that you.

You have about 80% of patients that are not so there's no reason for us to believe that the adult <unk> patient population is different than your average.

Population is.

The United States is being represented on that so that they get 80% of adults, which is where we have a 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.

Richard Podar: So that split is 80% adults, 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 PKD deficiency population. But for now, we have an approval, and what the commercial team is focused on is the adult PKD deficiency, which is representative of that 80%. So overall, 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.

Is the adult PK deficiency, which is represented by 80%.

So overall.

That's the theoretical prevalent that focuses around disease education and driving awareness of the approval.

Those activities are ongoing right now.

Sarah Gheuens: And then in regards to your questions around 946, so... You know, it's a phase one study that we really pushed up the dose. So, the event that we observed was a dose that we're not planning to use. So, in regards to what is a 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 pyrokines, for instance. And so, you will not see that reflected in our label.

Okay, and then in regards to it.

Questions around 94 six so.

It's a phase one study that we really pushed up the door. So the event that we observed was that a dog that we're not planning to use them. So in regards to what is possible hypothesis, we've been thinking about that but then because with these are doses that we're not going to use we are not going to further explore that especially because of the event is.

Very manageable 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 private bank for instance.

You will not see that reflected in our label and in regards to nine for success as mentioned the doses that we've selected are lower than the dose. That's what this was observed and we're on track to initiate those studies.

Sarah Gheuens: And in regards to 946, as mentioned, the doses that we selected are lower than the doses at which this was observed, and we're on track to initiate those studies. Okay, thanks for answering all the questions and congrats again on the early launch. Our next question comes from Danielle Brill with Raymond J. Hey guys, this is Alex on behalf of Danielle.

Okay, great. Thanks for answering all the questions.

Brad for grant on the early launch.

Yeah.

Our next question comes from Danielle Brill with Raymond James.

Hey, guys. This is Alex on for Danielle Thanks for taking my question.

Operator: Thanks for taking our question. Question on anemia ID, and you said the 3,500 kits. Have all of those kits been filled? Are those just ordered, or has it actually been processed?

A question on EMEA.

3500 kits have all of those kits Ben.

Build are those just ordered or.

Actually been processed.

Richard Podar: 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 details on 946. Can you reveal the maximum tolerated dose in the healthyies and or the doses chosen for the SED cohort? Thanks.

And do you have the type of information available to say, how many of those identified patients in and the hit rate.

Prescription written started treatment.

And then a detail on 94 six can you reveal the maximum tolerated dose and the healthy.

Or the doses chosen for the cohort.

Richard Podar: Yeah, so with regard to anemia ID, as we've mentioned, there are 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 the mid-single limit 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 there's nothing unexpected there either

Yeah, so with regards to EMEA.

As we've mentioned, it's Tony you guys conduct it did but only a portal completed so physicians maybe ordering decades.

Knowing that they have patients that will come to that practice in the future. So not all of them had been competing.

We also said in not.

On the office about mixed signals in terms.

The positivity rate, which again is better than our expectations because we have.

No knowing that it is designed for hemolytic anemia on 92 on an as yet 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 not nothing unexpected.

That you're dark what we are encouraged about is sports at the value of the physician fee. This has for that patient.

Sarah Gheuens: What we are encouraged about is both the value physicians see 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 the physician that has the patient, then the physician has to call the patient in, the patient has to be willing to go in, and all of that.

And the fact that we are continuing to see strong interest in the program and utilization.

I think the direct conversion off.

In EMEA I D patients out into like a script that process takes a little bit of time, where you can find the patient they have to find where to pick up with the physician.

And that has the patient and the physician have to call the patient and the.

The patient has to be willing to go in and all of that so we've been following that and keeping track of all the patients we found through the program and ensuring that we're connecting to the physicians knowing that they may have found the patient.

Sarah Gheuens: So we've been following that and keeping track of all the patients we found through the program and ensuring that they're connecting to the physicians, knowing that they may have found the patient. And then those conversations usually result in a script, but you can't just direct them. It takes time before that happens. And in regards to your question regarding the dose assessment, we will, you know, disclose all of the details around our healthy volunteers if they have an upcoming medical meeting.

And then those conversations.

You either don't result in his script, but you cant just direct it takes time before that.

Sure.

And then in regards to your question regarding the dose that we will disclose all of the details around our healthy volunteer study at an upcoming medical meeting.

Sarah Gheuens: What I can tell you about the dose selected for sickle cell disease and MDS is that, you know, 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.

I can't tell you around the dose selected for sickle cell disease, and Mds is that for sickle cell disease. A protocol was already written for MBS actually as well and we did not change any of our dose selection criteria based on the offense observed.

Sarah Gheuens: Okay, great. Thank you. And I'm not showing any further quest time.

Okay, great. Thank you.

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

Jackie Faust: I'd like to turn the call over to Jackie for any questions. 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.

Thank you operator, and thank you everyone for the questions. This morning as always I would also like to thank my <unk> colleagues for their dedication and passion for making a difference for patients.

So I 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 are connections across all of our stakeholders and our collective efforts together fuel ongoing innovation and impact for people with genetically defined diseases.

Jackie Faust: 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... [music]

Thank you for joining us. This morning, you may now disconnect.

Yeah.

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

Yeah.

[music].