Q1 2021 Agios Pharmaceuticals Inc Earnings Call

[music].

Good morning, and welcome to address it.

Operator: Good morning, and welcome to Agios' first quarter 2021 conference call. At this time, all participants are in listen-only mode. There will be a question-and-answer session at the end. 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.

First quarter 2021 conference call at this time, all participants are in listen only mode.

A question and answer session at the and please be advised that this call is being recorded and argue that this request.

I would now like to turn the call over to Hollywood in theater work and Investor Relations.

Yeah.

Thank you operator, good morning, everyone and welcome to IGT from first quarter 2021 Conference call you can access line for today's call by going to the investors section.

Holly Manning: Thank you, Operator. Good morning, everyone, and welcome to Agios' first quarter 2021 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 Feltz, our Chief Executive Officer; Dr. Chris Bowden, our Chief Medical Officer; Darren Miles, our Chief Commercial Officer; and Jonathan Biller, our Chief Financial Officer and Head of Legal and Corporate Affairs.

And as our website at <unk> Dot Com with me on the call today with prepared remarks and Dr. Jackie Fouse, Our Chief Executive Officer, Dr. Chris Bowden, Our Chief Medical Officer, Darrin miles, our Chief commercial officer, and Jonathan Biller, Our Chief Financial Officer, and head of legal and corporate Affairs, Dr. Bruce car.

Holly Manning: Dr. Bruce Carr, our Chief Scientific Officer, will join us 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.

Our chief Scientific officer 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 and 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 Jacky.

Jackie Feltz: With that, I will turn the call over to Jackie. Thank you, Holly. Good morning, everyone, and thanks for joining our first quarter 2021 results call. The first three months of this year were extremely productive. We closed the sale of our oncology business, accelerated our late-stage clinical programs for Mitopivat, and prepared for our first regulatory filings and subsequent commercial launch in pyruvate kinase deficiency. Back in December, we announced our strategy to focus on genetically-defined diseases, including accelerating and unlocking the full potential of Mitopivat across its three initial indications in hemolytic anemias, as well as leveraging our overall expertise in PK activation and our other research programs.

Thank you Holly and good morning, everyone and thanks for joining our first quarter 2021 results call.

The first three months of this year were extremely productive we closed the sale of our oncology business and accelerating our late stage clinical programs for many pin that and prepared for our first regulatory filings and subsequent commercial launch and power of a kinase deficiency.

Back in December we announced our strategy to focus on genetically defined diseases, including accelerating and unlocking the full potential of mid a peer that across its three initial indications and hemolytic anemias as well as leveraging our overall expertise and PK activation and our other research programs.

Jackie Feltz: To enable this focus, we also announced the decision to sell our oncology programs to Servier to facilitate and fund this strategy. Since that time, nearly a third of our organization has been actively involved in the important and complex process of ensuring a smooth transition of our assets and people to Servier. The transaction was approved by Agios shareholders on March 25, and on April 1, we announced the closing of the sale.

To enable this focus we also announced the decision to sell our oncology programs to Serbia to facilitate and fund this strategy since that time nearly a third of our organization has been actively involved and the important and complex process of ensuring a smooth transition of our assets and people to serve you.

The transaction was approved by shareholders on March 25th and on April one we announced the closing of the sales.

Jackie Feltz: To each and every oncology employee who helped create truly meaningful, differentiated therapies for patients over the past decade, we are grateful for your impassioned work at Agios and we look forward to watching these programs flourish with Cervier. As we look ahead, Agios is poised for a bright and focused future that will build on the important progress we are making now in Q2. This includes finalizing our global regulatory filings for Mitopivat and pyruvate kinase deficiency, preparing to initiate two phase three trials of Mitopivat and thalassemia, and a phase two, three trial of Mitopivat and sickle cell disease, advancing our patient identification efforts and launch preparations ahead of the potential approval of Mitopivat and PK deficiency next year, and finally, initiating the thoughtful execution of up to $1.2 billion in share repurchases that Jonathan will describe in more detail.

To each and every oncology employee who helped to create truly meaningful differentiated therapies for patients over the past decade, we are grateful for your impassioned work at <unk> and we look forward to watching these programs flourish with Serbia.

As we look ahead and are Joseph is poised for a bright and focus future that will build on the important progress we're making now in Q2.

This includes finalizing our global regulatory filings for <unk> in pyruvate kinase deficiency and preparing to initiate two phase III trials with min and pay that in thalassemia and and phase two three trial and many pay VAT and sickle cell disease advancing our patient identification efforts and launch preparations ahead of the.

Potential approval and made a pivot and PK deficiency next year, and finally, initiating the thoughtful execution of up to $1 $2 billion and share repurchases that Jonathan will describe in more detail.

Jackie Feltz: At the heart of this work is our continued commitment to making a significant difference in the lives of the patients we serve, and I would like to take a moment to recognize some of the important efforts we have been pursuing on behalf of patients in recent months. First, we are excited to announce a collaboration with 23andMe that led to the launch of its very first PK deficiency carrier status report, which is a significant step forward in educating the broader population about PK deficiency.

At the heart of this work is our continued commitment to making a significant difference and the lives of the patients we serve and I would like to take a moment to recognize some of the important efforts we have been pursuing on behalf of patients over recent months.

First we are excited to announce a collaboration with 23 and me that led to the launch of its very first PK deficiency carrier status report, which is a significant step forward and educating the broader population about PK deficiency.

Jackie Feltz: Second, we announced our sponsorship of Citizen Scientist: Unpacking the Science of Sickle Cell Disease, an initiative developed by the Sickle Cell Community Consortium to promote health literacy for sickle cell patients. As part of the Citizen Scientist Initiative, we were also the founding sponsor of a new series of episodes on Cheat Codes, a sickle cell podcast.

Second we announced our sponsorship of citizen scientist Unpacking, the science of sickle cell disease and initiative developed by the sickle cell community consortium to promote health literacy for sickle cell patients within the citizen scientist initiative. We were also the founding sponsor of a new series of epic.

Zones on cheap codes, a sickle cell podcast.

Jackie Feltz: The podcast series brings world-renowned physicians together with patients and caregivers to have real conversations about new sickle cell research emerging from major medical and scientific conversations. The goal is to provide the sickle cell community with access to critical information about better ways to manage their health and innovative new treatments in development. The inaugural episodes focused on the presentations from the 2020 ASH annual meeting and can be accessed by searching for cheat codes wherever you stream your podcast.

The podcast series brings world renowned physicians together with patients and caregivers to have real conversations about new sickle cell research and emerging from major medical and scientific Congresses.

The goal is to provide the sickle cell community with access to critical information about better ways to manage their health and innovative new treatments in development and the.

Inaugural episodes focused on the presentations from the 2020 Ash annual meeting and can be accessed by searching for cheap codes wherever you stream your podcasts and third and honor of rare disease day, we hosted a discussion about thalassemia with Doctor Sujit Chess, who runs the New York comprehensive thalassemia.

Jackie Feltz: And third, in honor of Rare Disease Day, we hosted a discussion about thalassemia with Dr. Sujit Sheth, who runs the New York Comprehensive Thalassemia Center, and his patient, Sam, who's been treated for thalassemia for over 20 years and has a unique perspective on living with the disease. These educational and patient-focused efforts underscore our commitment to making a positive difference in the lives of the people we serve. With that, I will now turn the call over to Chris. Thanks, Jackie.

And his patient Sam who's been treated for thalassemia for over 20 years and has a unique perspective on living with the disease.

These educational and patient focused efforts underscore our commitment to making a positive difference and the lives of the people we serve with that I will now turn the call over to Chris.

Thanks Jackie.

Christopher J. M. Taylor: I'll start with our most advanced genetically-defined disease program, Mitopivak, our first-in-class PKR activator currently being evaluated across three distinct chronic hemolytic anemias. Ayurvedic Kinase Deficiency, Thalassemia, and Sickle Cell Disease In pyruvate kinase deficiency, we reported top-line data from the ACTIVATE and ACTIVATE-T Phase 3 studies, evaluating midipivet in adults with pyruvate kinase deficiency who were not regularly transfused and those who were regularly transfused, respectively. We look forward to sharing data from both studies, including patient-reported outcomes data, at the European Hematology Association Virtual Congress, which is being held June 9 through 7.

Start with our most advanced genetically defined disease program <unk>, our first in class PK activator currently being evaluated across three distinct chronic hemolytic anemias.

Kinase deficiency, thalassemia and sickle cell disease.

In pyruvate kinase deficiency, we reported top line data from the activate and activate T phase III studies evaluating <unk> and adults with pyruvate kinase deficiency.

Not regularly transfused and those who are regularly transfused respectively.

We look forward to sharing data from both studies, including patient reported outcomes data at the European Hematology Association Virtual Congress, which is being held June nine through 17.

These data support the potential for <unk> to be the first disease modifying therapy for PK deficiency and will be the basis for our global regulatory filing and that's currently in process.

Christopher J. M. Taylor: These data support the potential for Mitopivat to be the first disease-modifying therapy for PK deficiency and will be the basis for our global regulatory filing that is currently in process. We are on track to file for regulatory approval in the U.S. this quarter and in the EU mid-year, with potential 2022 regulatory approvals in both geographies.

We are on track to file for regulatory approval and the U S. This quarter and and the EU mid year with potential 2022 regulatory approvals and both geographies.

Christopher J. M. Taylor: Darren will speak to our commercial launch preparations and his... Moving to the phase two study of midipibat and thalassemia, we completed enrollment last year with 20 patients. And in June, we will present data on all patients from the core period of this study at eHeart. Based on the robust proof-of-concept data from this trial, we designed two global placebo-controlled pivotal trials of midipibatin thalassemia, ENERGIZE and ENERGIZE-T, which we unveiled in December. ENERGIZE will evaluate 171 patients randomized 2-to-1 to 100 mg of metipibat, BID, or placebo in both beta and alpha thalassemia patients who are not regularly transfused.

Darrin and we'll speak to our commercial launch preparations and his comments.

Moving to the phase II study of mid of Tibet, and Dallas Femia, We completed enrollment last year with 20 patients and in June we will present data on all patients from the core period of this study at <unk>.

Based on the robust proof of concept data from this trial, we designed to global placebo controlled pivotal trials of mid of Tibet and Scott, Let's see me energized.

Energize and energized T, which we unveiled in December.

Energize will evaluate 171 patients randomized two to one to 100 milligrams of Tibet.

<unk> or placebo and both beta and Alpha thalassemia patients who are not regularly transfused.

The primary endpoint is the percentage of patients with a mean hemoglobin hemoglobin increase of greater than or equal to one gram per deciliter from baseline over a 24 week period.

Christopher J. M. Taylor: The primary endpoint is the percent of patients with a mean hemoglobin increase of greater than or equal to 1 gram per deciliter from baseline over a 24-week core period. ENERGIZE-T will evaluate 240 patients randomized 2-to-1 to 100 mg of metapivib or placebo in both beta and alpha thalassemia patients who are regularly transfused, defined as 6-to-20 RBC units transfused, during the 24 weeks The primary endpoint is the percent of patients with a 50% or greater reduction in transfusion burden in any 12-week rolling period during the 48-week core period. We're in the process of submitting these protocols globally and preparing sites for enrollment.

Energized team will evaluate <unk> 240 patients randomized two to one to 100 milligrams.

At Vib.

Placebo and both data and Alpha thalassemia patients who are regularly transfused defined at 6% to 20 RBC units transfused during the 2012 weeks prior to randomization.

The primary endpoint is the percentage of patients with a 50% or greater reduction and transfusion burden and and and 12 week volume period during the 48 week period.

We are and the process of submitting these protocols globally and preparing sites for enrollment.

Christopher J. M. Taylor: We look forward to initiating both trials by the end of the year. Now, let's turn to sickle cell disease. Last year, Mitopivat was the first PKR activator to demonstrate proof of concept in its disease based on initial data from a study being conducted in collaboration with Dr. Su Lai Tien of the National Institutes of Health. And on our last quarterly results call, we provided an update on regulatory feedback on our pivotal plans and unveiled our Phase 2-3 clinical trial, which we believe minimizes the risk to the approval path for mid-pivot in this challenging disease and maximizes the likelihood of a label with a broad indication.

Look forward to initiating both trials by the end of the year.

Now, let's turn to sickle cell disease.

Last year and made a Pip app was the first PK R activator to demonstrate proof of concept and this disease based on initial data from a study being conducted in collaboration with Dr. Xu Lei Chen of the National Institutes of health.

And on our last quarterly results call. We provided an update on regulatory feedback to our pivotal plan and unveiled our phase III clinical trial, which we believe minimize the risk to the approval path for mid Tibet and this challenging disease and maximizes the likelihood of a label with a broad indication.

The operationally seamless phase two three study of mid pivots and adults with sickle cell disease will include patients for 16 years of age or older have.

Christopher J. M. Taylor: The operationally seamless Phase 2-3 study of mid-PIVF in adults with sickle cell disease will include patients who are 16 years of age or older, have had between 2 to 10 sickle cell crises in the past 12 months, and have hemoglobin within the range of 5.5 to 10.5 grams per deciliter during screening. The Phase II trial will randomize 69 patients 1 to 1 to 1 to 50 mg Metapivat BID, 100 mg Metapivat BID, or matched placebo.

And I've had between 2% to 10 and sickle cell crisis, and the past 12 months and have hemoglobin and the range of five five to 10 and a half grams per deciliter during screening.

The phase II randomized 69 patients one to one to one to 50 milligrams bid for that PID.

100 milligram made up for that.

I'd or matched placebo.

Christopher J. M. Taylor: The primary endpoint is a hemoglobin response defined as a greater than or equal to one gram per deciliter change from baseline to week 12. The data will be used to establish a clear dosing paradigm for the phase 3 portion. Phase 3, which will commence after the Phase 2 analysis, will randomize 198 patients, 2-to-1, to the selected Phase 2 dose of midipivav or matchless. The study will have two primary endpoints.

The primary endpoint and the hemoglobin response defined as greater than or equal to one gram per deciliter change from baseline to week 12.

And the data will be used to establish a clear dosing paradigm for the phase III portion.

The phase III, which will commence after the phase two analysis.

<unk> 198 patients two to one to the selected phase II dose admitted payback or matched placebo.

The study will have two primary endpoints.

Christopher J. M. Taylor: Hemoglobin response defined as greater than or equal to one gram per deciliter change from baseline to week 52 and the annualized rate of sickle cell pain crisis. We are in the process of operationalizing this study and are on track for initiation by the end of the year. In addition, we continue to work with our collaborators at the NIH and the University of Utrecht on their studies of mitotibat and sickle cell disease.

Hemoglobin response defined as greater than or equal to one gram per deciliter change from baseline.

52, and the annualized rate cyclical paying for it.

We are and the process of operationalize it and this study and are on track for initiation by the end of the year.

In addition, we continue to work with our collaborators at the NIH and the University of interest on their studies admitted Tibet and sickle cell.

Disease.

Data from both studies are expected at medical meetings later this year.

Christopher J. M. Taylor: Data from both studies are expected at medical meetings later this year. At the NIH, Dr. Chen has completed enrollment in the core study with 17 patients and continues to enroll patients into the extension study. In support of our hypothesis that midipivet has the potential to be a novel therapy for patients with sickle cell disease, I'm pleased to share that, in collaboration with the investigators from the University Medical Center in the Netherlands, we recently published a manuscript in Blood investigating the ex vivo effect of midipibat on red blood cells from patients with sickle cell disease and healthy controls.

At the NIH, Dr. Chen has completed enrollment and the core study with 17 patients and continues to enroll and to the extension study.

And support of our hypothesis that made up for that has the potential to be a novel therapy for patients with sickle cell disease, I am pleased to share that and collaboration with the investigators from the University Medical Center and the Netherlands.

And we recently published a manuscript and blood investigating the ex vivo effect admitted Tibet and Greg.

And blood cells from patients with sickle cell disease and healthy controls.

Red blood cells isolated from patients with sickle cell disease should reduce pyruvate kinase activity compared to controls.

Christopher J. M. Taylor: Red blood cells isolated from patients with sickle cell disease showed reduced pyruvate kinase activity compared to controls due to decreased stability of PKR. Treatment of Isolated Sickle Cell Red Blood Cells with Mitokinat Restored Pyruvate Kinase Activity Leading to a Reduction in 2,3-DPG and Cell Sickling Behavior This publication is important because, first, it suggests that compromised red blood cell metabolism may contribute to the complex pathophysiology of sickle cell disease.

Due to decreased stability of PK.

Treatment and isolated sickle cell red blood cells with mid pivot and restored pyruvate kinase activity, leading to a reduction and <unk> and cell signaling behavior.

Location is important because first and suggests that compromise red blood cell metabolism.

Contribute to the complex pathophysiology sickle cell disease and.

Christopher J. M. Taylor: And second, it provides mechanistic support for midipiven as a potential novel therapy for sickle cell disease. Beyond Mitopivak, we're also advancing our next generation PKR activator, AG946, through a phase one healthy volunteer study. The trial began enrolling last fall, and we expect to submit data from it for presentation at a medical meeting by the end of the year. Our analysis of the totality of the AG946 healthy volunteer data will inform next steps for the clinical development of this molecule. With that, I'll turn it over to Darren to discuss our commercial activities. Thank you, Chris.

Second it provides and mechanistic support for <unk> and the potential novel therapy for sickle cell disease.

Beyond that and Pip that we're also advancing our next generation PK R. Activator AG 946 gross.

Phase one healthy volunteer study.

The trial began enrolling last fall and.

And we expect to submit data from it for presentation at a medical meeting by the end of the year.

Our analysis of the top of the of the AG 946 healthy volunteer data will inform next steps for the clinical development of this molecule.

With that I'll turn it over to Darren to discuss our commercial activities.

Thank you Chris.

Darren Miles: Today, I'll first briefly review Tubesilver performance for Q1, which is the last period for which Agios is accountable for sales of the product. I'll then summarize our progress on cross-functional launch preparedness in anticipation of the potential approval of MediPivot in 2022. Tips of the Net Sales in Q1 reached $37 million, largely driven by market increases in utilization across newly diagnosed and relapsed refractory AML, partially offset by higher expenses related to Q1 Part D coverage gap seasonality and increased volume moving through Z40B. Carrington made a pivot at launch readiness.

Good day I'll first briefly review each of similar performance for Q1, which is the last period for which I'll just accountable for sales for the product.

And then summarize our progress on cross functional launch preparedness and anticipation for potential approval of medical and.

And 2022.

Net sales in Q1 reached $27 million, largely driven by market increases and utilization across and we diagnosed and relapsed refractory AML, partially offset by higher expenses related to Q1 part D coverage GAAP seasonality and increased volume moving through Q4.

Institutions.

Turning to mobile for that launch readiness for chemo progress and the number of pumps, including PK deficiency patient education physician and patient profiles.

Darren Miles: The team made progress on a number of fronts, including PK deficiency, patient education, physician and patient profiling, and the ongoing field team build. In November, we announced the launch of the Anemia ID program, a partnership with Perkin-Elmer to offer free genetic testing to help patients and physicians reach a definitive diagnosis for patients with suspected hereditary anemia.

And the ongoing fields and bills.

November.

Moms the launch of <unk>.

And B program, a partnership with Perkin element also free genetic testing to help patients and physicians, which a definitive diagnosis for patients with suspected went until you need it.

Darren Miles: The program has been well received and is increasingly utilized to help patients with their diagnosis by simplifying the testing requirements intended for reaching a definitive diagnosis of a patient's hemolytic anemia. The program also provides AGIOS with de-identified patient-level information, which adds meaningfully to our understanding of the PK deficiency patient profile. Our experience with this program highlights the magnitude of unmet need in the community and the deepening sense of urgency to improve the diagnosis of patients with hemolytic anemias like PK-DFY.

The program has been well received and is increasingly utilize to help patients with their diagnosis by simplifying the testing requirements attendant with reaching a definitive diagnosis of a patient's hemolytic anemia and <unk>.

Program also provides odds yields would be identified patient level information, which adds meaningfully to our understanding of the PK deficiency patient profile.

Our experience with this program and highlights the magnitude of unmet need and the community and to deepen and sense of urgency to improve the diagnosis for patients with hemolytic anemias like PK deficiency.

And as Jackie mentioned and March 23, and knee added and PK deficiency carrier status report to the library and genetic insights and tools.

Members, who were either carriers or homozygous for the <unk> 46, W variant and the PTA enlarging the most common southern European PK or variance are invited to receive customized report with more information regarding google's from developing PK deficiency and additional resources.

Darren Miles: As Jackie mentioned, in March, 23andMe added a new PK deficiency carrier status report to their library of genetic insights and tools. Members who are either carriers or homozygous for the R486W variant in the PKLR gene, the most common Southern European PKR variant, are invited to receive the customized report with more information regarding their risk of developing PK deficiency, and additional resources. The report includes a summary of the signs and symptoms of PK deficiency and other relevant clinical and genetic information.

We reported includes some signs and symptoms of PK deficiency, and other relevant clinical and genetic information.

We expect and a number of patients who are carriers will seek and genetic counseling for more robust testing potentially through in EMEA.

And although mechanisms, resulting and a definitive diagnosis.

We've also made good progress and extending our ability to provide important information about <unk> decision to patients with questions and we intend to launch and robust PK deficiency patient education program by the end of the quarter administered and existing infrastructure geospatial support.

The program will invite patients to optics and routine communications with print and stuff related to information about their disease.

Darren Miles: We expect that a number of patients who are carriers will seek genetic counseling for more robust testing, potentially through anemia ID and other mechanisms resulting in a definitive diagnosis. We've also made good progress in expanding our ability to provide important information about PK deficiency to patients. We intend to launch a robust PK-deficiency patient education program by the end of the quarter, administered through existing Agios Pharmaceuticals.

The launch of the expanded patient education program coincides with the expected completion of the build of our customer facing field organization before the end of Q2.

Modest sales fuel team will include hemolytic anemia specialists and skilled clinical edge teams.

These rules are essential for accelerating our understanding of physicians treating PK deficiency. The profiles of the patients we are treating and our disease education efforts via virtual and increasingly face to face interactions as we head into the second half of the year.

These efforts along with the anticipated approval of the PK deficiency specific ICD 10 code by the end of the year will substantially accelerate our understanding of the number and profile of patients being diagnosed with PK deficiency today.

Darren Miles: The program will invite patients to opt into routine communications with trained staff related to information about their disease. The launch of the Expanded Patient Education Program coincides with the expected completion of the build of our customer-facing field organization before the end of the year. The modest-sized field team will include hemolytic anemia specialists and skilled clinical educators.

Overall launch preparedness is on track and we're pleased with progress to date.

I'll now turn it over to Jonathan to cover Q1 financials.

Thanks, Darrin, our first quarter 2021 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 Jackie mentioned the sale of the oncology business. The survey closed on March 31, and as a result for first quarter results related to our oncology business can be found and the discontinued operations note to our financial statements.

Darren Miles: These roles are essential for accelerating our understanding of physicians treating PK deficiency, the profiles of the patients they are treating, and our disease education efforts via virtual and increasingly face-to-face interactions as we head into the second half of the year. These efforts, along with the anticipated approval of a PK, ICD-10 code by the end of the year, will substantially accelerate our understanding of the number and profile of patients being diagnosed with PKD. Overall, launch preparedness is on track, and we are pleased with progress. I'll now turn it over to Jonathan to cover Q1. Thanks, Darren.

I will first address and continuing operations for the business research and development for the first quarter was $57 7 million.

And increase of $2 3 million compared to the first quarter of 2020.

And modest year over year increase and R&D was driven primarily by startup costs associated with the phase III studies and minute to that in thalassemia and sickle cell disease.

Selling general and administrative expenses for continuing operations were $33 1 million for the first quarter, representing a one 5 million increase over first quarter 2020.

Jonathan Biller: Our first quarter 2021 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 Jackie mentioned, the sale of the oncology business to Servier closed on March 31st, and as a result, the first quarter results related to our oncology business can be found in the discontinued operations note to our financial statement. I will first address our continuing operations for the business.

The increase in SG&A expense was primarily due to certain onetime workforce and expenses.

And for our discontinued operations total revenue for the first quarter was $41 4 million.

Which included $37 million of net sales of <unk>.

Also included in discontinued operations is $52 million of operating expenses that were primarily attributable to professional fees and workforce expenses directly related to the <unk> transaction.

We ended the quarter with cash cash equivalents in marketable securities of $2 4 billion.

Jonathan Biller: Research and development for the first quarter was $57.7 million, an increase of $2.3 million compared to the first quarter of 2020. The modest year-over-year increase in R&D was driven primarily by startup costs associated with the Phase III studies of minipivet and thalassemia and sickle. Selling general and administrative expenses for continuing operations were $33.1 million for the first quarter, representing a $1.5 million increase over the first quarter of 2020. The increase in SG&A expense was primarily due to certain one-time work. For our discontinued operations, total revenue for the first quarter was $41.4 million, which included $37 million of net sales of Tipsovo. Also included in discontinued operations, is $50.2 million of operating expenses that were primarily attributable to professional fees and workforce expenses directly related to the survey agency.

We expect that this cash balance together with anticipated interest income future product sales and mitigate that and royalties on chip Soma will fund our current operating plan through major catalysts and to cash flow positivity and without the need to raise additional equity.

As previously disclosed our board of directors authorized the repurchase of up to $1 $2 billion of our outstanding shares using the proceeds from the sale of the oncology business and earlier. This month, we closed the repurchase of approximately seven 1 million shares of <unk> common stock held by BMS and and.

Affiliates for an aggregate purchase price of $344 5 million or.

For $48 38 per share. In addition, we have put in place and <unk>. One plan designed to efficiently repurchase a meaningful portion of the remaining shares by year end.

As is customary and he will report on repurchases made pursuant to these plans and any open market and privately negotiated repurchases and our future quarterly earnings reports.

Jonathan Biller: We ended the quarter with cash, cash equivalents, and marketable securities of $2.4 billion. We expect that this cash ballot, together with anticipated, Future product sales of Minipivat and royalties on Tipsobo will fund our current operating plan through major catalysts, and to cash flow positivity without the need to raise additional As previously disclosed, our Board of Directors authorized the repurchase of up to $1.2 billion of our outstanding shares using the proceeds from the sale of the Oncology, And earlier this month, we closed the repurchase of the approximately 7.1 million shares of Agios common stock held by BMS and its affiliates for an aggregate purchase price, $344.5 million or $48.38 per share.

With that operator, please open the line for questions.

Thank you to ask a question you will need to press star one of your telephone to withdraw your question press the pound key.

Please stand by while we compile the Q&A losses there.

Our first question comes from the Lithia Young with Cantor Your line is open.

For and congrats and welcome progress.

I just wanted to talk a little bit about maybe potential pipeline.

And our indication expansion for both net of part of that and potentially nine for effects just from that.

How youre thinking about some of the potential new indications that you might be moving forward with based on what you know about the biology here.

Hey, Alethia, it's Chris Bowden here.

Yes, we are we think about pyruvate kinase and.

Two ways at this point is the PK or part of it and.

Jonathan Biller: In addition, we have put in place a 10B51 plan designed to efficiently repurchase a meaningful portion of the remaining shares by year end. As is customary, we will report on repurchases made pursuant to that plan, and any open market or privately negotiated, and our future quarterly earnings. With that said, operator, please open the line for questions. Thank you. To ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Malithia Young of Cantor, Maryland.

And I.

And I spoke and my and Youre familiar with the.

And the advanced stage program for we're going after registrations and pyruvate kinase deficiency thalassemia and sickle cell disease.

A couple of other.

Indications that we are thinking about.

Where we can approach pyruvate kinase from activating wild type and a number of them include there's a number of them, including hereditary script type tenants.

We have some interest and Myelodysplastic syndrome, the anemia Myelodysplastic syndrome could can potentially be addressed for the activation of wild type PK R again, addressing and improving the red cell health.

Operator: I just wanted to talk a little bit about maybe potential pipeline or indication expansion for both MetaPIVOT and potentially 946, just kind of how you're thinking about some of the potential new indications that you might be moving forward with based on what you know about the biology here.

And then you have.

We have been talking about the potential for activating PK and two.

Christopher J. M. Taylor: Hey, I believe he is. Chris Bowden here. I love you.

Opening up a number of doors and some other indications.

Christopher J. M. Taylor: You know, we think about pyruvate kinase in two ways at this point. There's the PKR part of it, and, you know, I spoke in my — and you're familiar with the advanced stage programs where we're going after registrations for pyruvate kinase deficiency, thalassemia, and sickle cell disease. There's a couple of other indications that we are thinking about, where we can approach pyruvate kinase from the activating wild type, and a number of them include there's a number of them, including hereditary sclerocytosis. We have some interest in myelodysplastic syndrome.

Why don't I stop at that point, and let Bruce car who's on the call with US today talk a little bit about pecan too and we're looking forward to the.

The second half of the year and opening that up a little more research David Bruce why don't you provide a little more color. Please.

Yes, thanks, very much Chris and so.

Just by analogy.

<unk> of.

And PK deficiency, and red cells, and it's relatively dispersion and many different hemolytic anemias.

When one looks at and tissues that express to pay and soon.

Christopher J. M. Taylor: The anemia of myelodysplastic syndrome could, can potentially be addressed through the activation of wild-type PKR. Again, you know, addressing and improving red cell health. And then we have been talking about the potential for activating PKM2 as opening up a number of doors and some other indications. Why don't I stop at that point and let Bruce Carr, who's on the call with us today, talk a little bit about PKM2. And we're looking forward to the second half of the year and opening that up a little more at Research Day. But Bruce, why don't you provide a little more color, please? Yeah, thanks very much, Chris.

Each generation of ATP and function is abnormal and and many disease states as well so since early last year and things.

Setting the tissue distribution, and the and Baltimore as Teekay, and Sue and a variety of different disease processes.

Based on that day.

And identified several lots of indications from Teekay, and so and they really they're really quite broad depending on the.

The price.

And just it's expressed in the brain and the retina and regenerating muscle and many other tissues and at that low with being conducting appropriate non.

Non clinical models to evaluate.

Net canceled for the disease indications and we're actually just starting to get some very promising data and in recent months, suggesting the indications that we could possibly go into many of which would of course with glass on partnering well outside of that ethylene metrology expertise and we hope to we haven't talked about the indications.

Bruce Carr: So just by analogy, PKR is deficient, of course, in PK deficiency in red cells, and it's relatively deficient in many different hemolytic anemias. When one looks at the tissues that express PKM2, its generation of ATP and function are abnormal in many disease states as well. So since early last year, we've been studying the tissue distribution and the involvement of PKM2 in a variety of different disease processes. Based on that work, we then identified several likely indications for PKM2, and they're really quite broad, depending on the place it's expressed. It's expressed in the brain, in the retina, in regenerating muscle, and many other tissues in the gut wall.

At some time later in the third quarter.

And in R&D day.

But the work you've done very well and for now and some of these indications are actually yielding.

Non clinical results for the.

And we understand it translatable, we're not sure yet, but a lot of promise and many additional indications for PK and too.

Thank you very much.

Thank you. Our next question comes from Mohit Bansal with Citigroup. Your line is open.

Great. Thanks for taking my question and congrats on the progress a couple of questions from my side.

Bruce Carr: We've been conducting appropriate non-clinical models to evaluate the potential for these disease indications, and we're actually just starting to get some very promising data in recent months suggesting the indications that we could possibly go into, many of which would, of course, require partnering well outside of our hematology expertise. We hope to be able to talk about these indications perhaps sometime later in the third quarter at an R&D day. But the work is going very well at the moment, and some of these indications are actually yielding spectacular non-clinical results, to the extent we understand they're translatable. We're not sure yet, but a lot of promise for many additional indications for PKM2.

One is.

Regarding the pricing and it may sound like a broken record and for that lawsuit and the past is low.

But given you would be launching and an ultra rare indications like PK D. How are you thinking about pricing right now because more.

And there are indications like sickle cell is still not.

Probably like 40 years of age.

After the <unk> indication and I'll pause here.

Hey, Mike This is John low book and liquid at all and happy.

Happy to address any questions on price and now I won't tell you the place and that we're thinking about that.

I can give you some indications and how we're thinking about it right. So as you acknowledged it is and ultra ultra orphan indication, we're going to price and a way that reflects the clinical value and particularly now that we've seen the both of the phase III studies.

Operator: Thank you very much.

But what price in a way.

Operator: Thank you. Our next question comes from Mohit Bansal. Thanks for taking my question and congratulations on the progress. A couple of questions from my side.

And so it reflects the clinical value for this patient population.

Share in the past.

R R.

Our takeaway from.

Operator: One is regarding pricing, and I may sound like a broken record because I've asked it in the past as well, but given you would be launching in an ultra-rare indication like PKD, how are you thinking about pricing right now? Because more of a rare indication like sickle cell is still probably not like four years after the PKD indication. And that is possible. Emily, this is Darren. No broken record at all.

Engagements with the payer community.

Is that we believe that that price oil should also extends to policymakers.

Going to sickle cell you have a different payer mix a different mix of patient population and middle and associated.

Payer mix change as well so there is the potential that we would adjust price for.

For the sickle cell markets, but right now we think the <unk>.

Price that we launch.

Darren Miles: I'm happy to address any questions on pricing. Now, I won't tell you the price that we're thinking about, but I can give you some indications of how we're thinking about it, right? As you acknowledged, it is an ultra-orphan indication.

For.

For Pte.

Carryover well into and to sell and then we'll revisit that as we go into <unk>.

Super High and it actually sorry.

And just add one thing Mohit, it's Jackie.

As Darren alluded to I think we'll also price for sickle cell based on the totality of the clinical data from the pivotal program for <unk> for sickle cell. So we'll need to see what that yields in terms of both the.

Darren Miles: We're going to price in a way that reflects clinical value, particularly now that we've seen both of the Phase III studies, but we'll price in a way that reflects clinical value for this patient population. As we've shared in the past, our takeaway from engagements with the payer community is that we believe that that pricing should also extend to phallocenia. Going to sickle cell, you have a different payer mix, a different mix of patient population, and associated payer mix change as well.

Both of the endpoints that we have built into that program.

Very helpful. Thank you for this sector and David and one more question if I may.

Probably for Jackie again.

So given that I mean.

Strong balance sheet and even if you like.

Darren Miles: So there's the potential that we would adjust prices for the sickle cell market. But right now, we think the price that we launch at for PKB will carry over well into FAO, and then we'll revisit it as we go. Super-hybrid, actually. Thank you. Sorry. I just want to add one thing. Hi Mohit, it's Jackie. As Darren alluded to, I think that we'll also price for sickle cell based on the totality of the clinical data from the Pivotal program for sickle cells. So we'll need to...

And the buyback plan and leave a lot of cash on hand.

So when you look at your pipeline and cash it had do you think you could look at the external opportunities as Benno you think you have enough on your plate right now, but the preclinical and clinical.

Programs right now.

So I think one of the things that's.

And most exciting about where we are as we start the next chapter and our RJ goes live.

It is the number of things that we have and the pop line and some of the opportunities that Bruce alluded to where I think the.

We're going to see.

Start to see support for those and where we might be able to go with him, including also the indications that Chris highlighted for potentially mid to pay that non for six where you can move quite quickly and to the clinic. So we have a ton of things that we wholly own that we know the chemical.

Jackie Feltz: to see what that, you know, yields in terms of both the, both the...

Jackie Feltz: Both of the endpoints that we have built into that program. Very helpful. Thank you for this, Jackie and Darren. And one more question, if I may, probably for Jackie again.

<unk> matter, very well and the biology and everything else. So those are our top priorities for the moment and that being said, we do keep our eyes on other things that are out there and we don't want to miss anything that might be.

Jackie Feltz: So given that, I mean, your strong balance sheet, and even if you, like, even with the buyback plan, it'll leave a lot of cash on hand. So when you look at your pipeline and cash at hand, do you think you could look at the external opportunities as well, or you think you have enough on your plate right now with the preclinical and clinical programs? So I think one of the things that's, Most exciting about where we are as we start the next chapter in our Agios life is the number of things that we have in the pipeline and some of the opportunities that Bruce alluded to where I think that, We're going to, you know, start to see support for those and where we might be able to go with them, including also the indications that Chris highlighted for potentially midopivatin 946, where you could move quite quickly into the clinic.

Complementary irrelevant for us and we always do that and we will continue to do that.

No.

It's not out of the realm of possibility that we might do something on the early side, because that's kind of been what's been and our sweet spot, but we have a ton of things that we think are pretty cool going on right. Now that are really what we've got the team focused on things got it. Thank you Jack you really appreciate it.

Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.

Okay.

The question and thanks for the update just a question for Jonathan just on.

The share repurchase and.

And how quickly I think and doing that.

If you've got a kind of a.

And in line by year end.

Share count and.

And when that.

Repurchase thoughts.

Sure. Thanks, Thanks for the question so.

As we've talked about we have you made a nice start with our share repurchase program.

Jackie Feltz: So, we have a ton of things that we wholly own, and we know the chemical matter very well, and the biology and everything else. So, those are our top priorities for the moment. That being said, we do keep our eyes on other things that are out there, and we don't want to miss anything that might be complementary or relevant for us. We always do that and will continue to do so.

Successfully negotiating and repurchase of the 10% stake that Bristol owned.

We think we got that and attractive price.

And around that same time, we put in plan.

<unk> plans to be repurchasing and the market through <unk> one plans.

And I think we've disclosed that.

And at plan, that's in place with by up to $600 million and the timing of that depends and we have algorithms and other things in place. So it depends on stock price movements and things like that but we would expect that by the end of the year, we would have and in combination with the Bristol stake have exceeded half.

Jackie Feltz: So, you know, it's not out of the realm of possibility that we might do something on the early side because that's kind of been what's been in our sweet spot. But we have a ton of things that we think are pretty cool going on right now that are really what we've got the team focused on. Thank you.

Operator: Thank you, Jackie; I really appreciate it. Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.

Or more of the purchases that repurchases that we intend to make it be exact amount and it's hard to predict because it does depend to some extent on the volatility.

Operator: Thanks for taking the questions. Thanks for the update. Just a question for Jonathan on the share repurchase and kind of how quickly you're thinking about doing that. If you've got a kind of a...

We'll see and our stock price and macro volatility as well.

Great. Thank you and then just a quick question for you Chris.

Jonathan Biller: I'd go in line by year end share count and purchase stuff. Sure. Thanks for the question. So, you know, as we've talked about, we have made a nice start with our share repurchase program, successfully negotiating the repurchase of the 10% stake that Bristol owned. You know, we think we got it at an attractive price.

Chris I would be around where it was 23 and me.

Peak efficiency curious does that do you think thats going to help and how is that literally kind of better understanding around.

The incidence and prevalence of P. J D.

And I think Darrin, it's the best place for answer that and you want to jump in there and her.

Sure happy happy too so.

Jonathan Biller: And around that same time, we put in place plans, our own plans to be repurchasing in the market through 10b51 plans. And I think we've disclosed, you know, the current plan that's in place would buy up to $600 million, and the timing of that, you know, depends on whether we have algorithms and other things in place. So it depends on stock price movements and things like that. But we would expect that by the end of the year, you know, we would have, in combination with the Bristol stake, exceeded half, or more of the repurchases that we intend to make. The exact amount is hard to predict because it depends to some extent on the volatility that we'll see in our stock price and macro volatility as well.

So I think it adds meaningfully to our understanding of.

The overall patients patient profile.

It's important to note that that the tweaking and meet chip looks at one very interest in important bearing interest what's most commonly.

For two and the and the literature, but if you if you recall, we've got upwards of 300 and.

Patients are so for.

D.

So it's important and it's giving us some very meaningful and sites.

Based on the population and.

And then taking the planes and when these losses.

Certainly we won't be sufficient right. So we continue looking at multiple sources to be able to help us better understand the true too.

Operator: Great, thank you. And then just a quick question for Jackie or Chris, maybe, around the work with 23andMe on PTSD. [inaudible] both the incidence and prevalence of PKD. Yeah, I think Darren's the best person to answer that. Do you want to jump in, Darren, or not?

<unk> and sub disease, but what we've seen thus far is very encouraging and at least in the mall and you need.

Dataset.

And the fact that those patients, who then are carriers or or homozygous for the for the 46th mutation.

Right.

And are getting direct intervention to help them understand and what they should do based on that and.

Darren Miles: Yeah, sure, happy to. So, yes, I think it adds meaningfully to our understanding of the overall patient's patient profile. It's important to note that the 23andMe chip looks at one variant. It's an important variant. It's what's most commonly referred to in the literature.

And then we created additional mechanisms for channels around those patients to help them to be able to pursue additional genetic testing.

Potentially food and EMEA and.

And then eventually.

And once we launch the the the the.

And the modules PK.

Darren Miles: But if you recall, we've got upwards of 300 mutations or so for PKD. So while important, and it's giving us some very meaningful insights based on the population that has taken the 23andMe test, certainly it wouldn't be sufficient, right? So we continue; we're looking at multiple sources to be able to help us to better understand the true prevalence of the disease. But what we've seen thus far is very encouraging, at least in the 23andMe data set.

Oh, the kinase deficiency patient support program by the end of the quarter potentially those patients will then opt into.

Our patient support program, which will then allow them to be able to to get time.

Finally.

Yeah.

For information about their disease after approval access to access to better.

And for them.

Great. Okay. Thanks, rich thanks for taking the questions.

Cool.

Thank you and our next question comes from Omnicom Rama with Jpmorgan. Your line is open.

Yeah.

Good morning, guys. This is Kathryn and Macau for earnings.

Darren Miles: And the fact that those patients who are then carriers or are homozygous for the 486 mutation or variant are getting direct information to help them understand, then, what they should do based on that. And then we've created additional mechanisms or channels around those patients to help them to be able to pursue additional genetic testing, potentially through anemia ID. And then eventually, once we launch Myalgios PK, part of a kinase deficiency patient support program by the end of the quarter, potentially those patients will then opt into our patient support program, which will then allow them to be able to get timely information about their disease and then, after approval, access to medication.

Thanks for taking our question.

And just one from US can you remind us and is there are any additional key analyses.

And June.

We should be looking at specifically around just alasania or <unk> programs. Thanks, so much.

Yes, Hi, Catharine, it's Chris Bowden here.

I think that the for.

Pyruvate kinase deficiency. This is the first time that we're net.

And that the results from the pivotal studies activate and activate T will be presented.

So I think that.

The key analyses are multiple there is of course for primary endpoints and safety I think one really important component of activate its a randomized trial so it'll.

Operator: Great. Okay. Thank you so much. Thanks for taking the question. Thank you. Our next question comes from Anupam Rama with J.P. Morgan. Your line is open.

And that'll be the first time, we'll be able to see.

Resolve the safety results submitted pair that against.

Operator: Good morning, guys. This is Tessa on the call for Anupam.

Placebo control and we're both patients and clinicians are blinded.

Operator: All for Anupam. Thanks for taking our question. Just one from us. Can you remind us if there are any additional key analyses at EHA in June that we should be looking at specifically around the Thalassemia or PPAD programs? Thanks so much.

Give us a much better and I would say balanced view of what the safety profile looks like over a substantial dosing period of course for patient reported outcomes as well and a placebo controlled trial are very important.

Christopher J. M. Taylor: Yeah, hi Catherine, it's Chris Bowden here. I think that, for part of a kinase deficiency, this is the first time that the results from the pivotal studies, Activate and Activate T, will be presented. So, I think that the key analyses are multiple. There are, of course, the primary endpoints. There's the safety.

So there will be multiple components of that that will be important for.

<unk> seen the build on the previous data that we showed to see.

And how durable that those hemoglobin responses were quite will be very important because this is another program that we're taking forward into phase III and since we see may depend that as a drug and that continues to demonstrate with its safety profile.

Christopher J. M. Taylor: I think one really important component of ACTIVATE is that it's a randomized trial. So, it'll be the first time we'll be able to see the results, the safety results of Mitopibat against a placebo-controlled trial where both patients and clinicians are blinded. So, that would give a much better, and I would say balanced, view of what the safety profile looks like over a substantial dosing period. Of course, patient-reported outcomes, as well, in a placebo-controlled trial are very important.

And it can be given prolonged periods of time and say its share.

<unk> with chronic dosing.

Durability of responses are very important as well.

<unk>.

Are the key components and.

And there will also be additional data around long term safety with meta payback and as well as other descriptions and the disease burden and pyruvate kinase deficiency.

Christopher J. M. Taylor: So, there will be multiple components of that that will be important. For thalassemia, building on the previous data that we showed to see how durable those hemoglobin responses look like will be very important because this is another program that we're taking forward into phase three. And since we see metapivat as a drug that continues to demonstrate with its safety profile that it can be given for long periods of time, it's compatible with chronic dosing, the durability of responses is very important as well.

So there will be many analyses and the overall I think the overall picture will be extensive that will present glut and made a pip out across those two diseases.

Great great. Thanks, so much for taking our questions.

Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. Your line is open.

Okay.

Mark Your line is open please check your mute button.

And sorry can you hear next from Michael Schmidt.

Hi can you hear me.

Yes, Yes go ahead.

Sorry about that.

Thanks for taking the question sorry about the complication.

Christopher J. M. Taylor: I think those are the key components, and there will also be additional data around long-term safety with metapivat as well as other descriptions of the disease burden of pyruvate kinase deficiency. So there will be many analyses, and the overall picture will be extensive that we will present on imidapibat across those two diseases.

Just on.

On the upcoming Readouts from your academic collaborators working and sickle cell disease.

And I'm wondering if the NIH readout will include results from the extension study or will it more likely focus on the core study period and.

Operator: Great. Thanks so much for taking our questions. Thank you. Our next question comes from Mark Breidenbach.

And also what can we reasonably expect in terms of number of efficacy evaluable patients from the <unk> study and could you remind us of the main differences between the indirect and NIH trials and in terms of study design and thanks for taking the question.

Operator: Thank you. Our next question comes from Mark Breidenbach with Oppenheimer.

Operator: Your line is open. Thank you very much. Mark, your line is open. Please check your mute button.

Yes.

The I'll take the back part first the and.

Operator: Sorry, can you hear me? Hi, can you hear me?

NIH study.

As you start it's an eight week dosing period that ranges with continuous dosing period with the dose escalation built in starting at five milligrams to 20 to 50 to 100, and then Theres a taper and then patients are eligible to go into an extension study.

Operator: Yes. Yes, go ahead. Sorry about that.

Operator: Thanks for taking the question. Sorry about the complication. Just on the upcoming readouts from your academic collaborators working in sickle cell disease, I'm wondering if the NIH readout will include results from the extension study, or will it more likely focus on the core study period? And also, what can we reasonably expect in terms of the number of efficacy of valuable patients from the Utrecht study? And could you remind us of the main differences between the Utrecht and NIH trials in terms of study design?

And the <unk> study and enrolling up to 10 patients.

And they started 20 then they go to 15, and then go from 100 and they stay on with chronic dosing.

So I think those are the major differences over all the patient populations from and eligible.

While eligibility.

Operator: Thanks for taking the question. Well, I'll take the back part first. The NIH study, when you start, it's an eight-week dosing period that ranges with an eight-week continuous dosing period with a dose escalation build-in starting at five milligrams to 20 to 50 to 100.

Criteria are.

Roughly comparable.

So now your question around what will be presented.

By the NIH.

Still up and the air and I think that depends on where it will really depend on how many patients come into the extension and how much follow up they have at the time of when they perform their data cut.

In order to prepare for whatever meeting and Theyre going to submit this too and just remind you. This is an investigator sponsored studies for a whole D.

Christopher J. M. Taylor: And then there's a taper, and then patients are eligible to go into an extension study. The UTREX study is enrolling up to 10 patients, and they start at 20, then they go to 50, then they go to 100, and they stay on with chronic dosing. So I think those are the major differences.

And are the primary decision maker on those issues, we collaborate with them and things are going really well, but at this point they haven't.

And they're not and if they haven't really gotten around to thinking through that.

Christopher J. M. Taylor: Overall, the patient populations from the trial eligibility criteria are roughly comparable. So, now, your question around what will be presented by the NIH is still up in the air, and I think that depends on – it will really depend on how many patients come into the extension, and how much follow-up they have at the time of when they perform their data cut in order to prepare for whatever meeting they're going to submit this to.

Level of detail in terms of overall evaluable patients from the <unk> study the way that protocol is written is that they are going to be looking for at least 10.

Up to 10 I should say.

Okay got it and very quickly on the pellet premium I'm wondering if you can tell us what the planned distribution is between European versus U S clinical sites and energize trials.

Christopher J. M. Taylor: I'll just remind you this is an investigator-sponsored study, so they hold the IND and are the primary decision-maker on those issues. We collaborate with them, and things are going really well, but at this point, they haven't really gotten around to thinking through that level of detail. In terms of overall valuable patients from the UTREX study, the way that protocol is written is that they're going to be looking for at least 10. Up to 10, I should say. Okay, I got it.

And to what extent is COVID-19, creating an obstacle for opening clinical sites, especially in Europe right now.

So we will be able to provide a slight lift.

And we will do that and the trials and progress type session or something like that.

Information will be forthcoming at.

At this point, we're not running into any turbulence with activating the study and getting it up and running with.

Christopher J. M. Taylor: And very quickly on thalassemia, I'm wondering if you can tell us what the planned distribution is between European versus US clinical sites in energized trials, and to what extent is COVID creating an obstacle for opening clinical sites, especially in Europe right now? So we will be able to provide a site list, and we'll do that in the Trials in Progress type session or something like that, so that information will be forthcoming.

With regards to the pandemic.

However, that's something that we really keep our close high on because things can change.

Rapidly, but no problems as of this juncture I'm knocking on my desk wood here.

Alright sounds good thanks for taking my questions.

Yes.

Okay.

Thank you. Our next question comes from Michael Schmidt with Guggenheim Securities. Your line is open.

Dr. Kelsey on for Michael Thanks for taking our questions and we got a couple on mid tier that and PK D.

Christopher J. M. Taylor: At this point, we're not running into any turbulence with activating the study and getting it up and running with regard to the pandemic. However, you know, that's something that we really keep our close eye on because things can change very rapidly, but no problems as of this juncture. I'm knocking on my desk wood here.

And now that we're almost I guess that about a year out from launch I guess, how are you thinking about the speed of uptake and how maybe the.

Education efforts might accelerate this and then have you been able to get any initial feedback from physicians on the data. So far maybe just that presented and the top line press releases.

Christopher J. M. Taylor: All right, sounds good. Thanks for taking the questions. Thank you. Our next question comes from Michael Schmidt with Guggenheim Security. Hi Kelsey, I'm from Michael.

Got you Dan here.

No.

Yes, so about a year out from from approval and so we've been building and expanding.

Operator: Thanks for taking our questions. We had a couple on Medipivet and PKD. I guess now that we're almost, I guess about a year out from launch, how are you thinking about the speed of uptake and how maybe the education efforts might accelerate this? And then have you been able to get any initial feedback from physicians on the data so far? Maybe just that presented in the top line of such releases? Thanks.

Expanding the team in order to be able to.

And get a lead on and I'll go ahead.

All of the profiling and Pete.

And profiling and position profiling efforts right, which ultimately will help with help with uptake post post approval. So as I mentioned.

<unk> sales team, we expect them to be trained and went out and the field.

By the end of by the end of the quarter. So.

And we've also added and added some.

Clinical educators will also engage with practices to help them with an understanding and increasing overall awareness and understanding of the disease. That's on top of the expanded patient finding efforts all of which will help us to ensure that we are.

Darren Miles: Got you, they're in here. So the Yeah, so we're about a year out from approval. And so we've been building and expanding the team in order to be able to get a lead on, or get ahead on all of the profiling and patient profiling, physician profiling efforts, right? Which ultimately will help with uptake post-approval. So as I mentioned, we've hired the full sales team.

We've got a.

Good and understanding of the overall market, including <unk>.

Number of potential diagnose patients by the time, we get through approval and we will continue those efforts through approval and.

When it comes to uptake and post approval.

Obviously those patients that are identified for those physicians who have patients.

Darren Miles: We expect them to be trained and then out in the field by the end of the quarter. So we've also added in some clinical educators. We'll also engage with practices to help them understand, increasing overall awareness and understanding of the disease. That's on top of the expanded patient recruitment efforts. All of which will help us to ensure that we've got a good understanding of the overall market, including the number of potentially diagnosed patients. By the time we get through approval, then we'll continue those efforts through approval.

And that are identified will low.

We'll be a top of the list in terms of promotional efforts by the by the team.

The key regulator on uptake is going to be obviously physician inclination to prescribe, but also payor Payor management right and so but it will take a few months for policies to be written so that that.

It is important but doesn't necessarily have to be an obstacle for adoption and just may require positions before.

Appears fully adopted a policy of craft and policy too.

Darren Miles: When it comes to uptake post-approval, obviously, those patients that are identified or those physicians who have patients that are identified will be at the top of the list in terms of promotional efforts by the FDA. The key regulator on uptake is going to be, obviously, physician inclination to prescribe but also payer management. And so it'll take a few months for policies to be written. So that is important, but it doesn't necessarily have to be an obstacle for adoption.

To seek.

And to get involved in terms of helping patients to be able to get access, but that's that's not unusual that's customary and and all approvals and.

In terms of early physician response to the dataset.

We've been working with them.

And none of my data to be able to get some physician and payer reaction to the overall profile which has been.

Which has been quite encouraging for us.

It's mostly consistent with what we need.

Darren Miles: It just may require physicians, before a payer's fully adopted a policy or crafted a policy to seek, to get involved in terms of helping patients to be able to get access. But that's not unusual. That's customary in all of them.

What we've seen or heard from the community and we're using just the target profile data.

But actually given the given what.

And what we've seen in terms of responses mobile profile.

Of the patient population as well as the PRA low quality of life data.

And actually is even more encouraging.

Darren Miles: In terms of early physician response to the data set, we've been looking at... Anonymous Data to be able to get some physician and payer reactions to the overall profile, which has been quite encouraging for us. It's mostly consistent with what we've seen or heard from the community when we were using just the target profile data, but it's given what we've seen in terms of responses, the overall profile of the patient population, as well as PRO quality of life data.

And many respects and what we've what we've heard before so.

I think all and all.

And in good shape moving up to the approval and then.

Are you able to raise awareness and enthusiasm for what.

And what was driving me to pick up once we get through.

Great. That's super helpful. Thank you so much.

Okay.

Thank you. Our next question comes from solving Richter with Goldman Sachs. Your line is open.

Great. Thank you for taking our question and this is Elizabeth Arden and first of all being and regarding the anemia program. Just wondering how many indications that may open up for you and then are you thinking of pursuing similar programs to the 23 and me.

Darren Miles: It actually is even more encouraging in many respects than what we've heard before. So I think, all in all, we're in good shape leading up to the approval and being able to raise overall awareness and enthusiasm for prescribing Medi-Pid once we get through.

Sales for other rare indications and potentially expanding for other variance of PK day. Thank you.

Great.

So darn hill eligible for foresee for email I E.

Operator: Great. That was super helpful. Thank you so much.

As well as.

'twenty three and neither both focused on helping us.

Operator: Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Great, thank you for taking our question. This is Elizabeth on behalf of Salveen.

And prove our understanding of T D specifically so.

In the Meanwhile, the panel that is used can help a physician to identify any number.

Hemolytic anemias.

And what we're focused on.

Darren Miles: Regarding the Anemia ID program, you know, just wondering how many indications that might open up for you, and then are you thinking of pursuing similar programs to the 23andMe initiative for other rare indications and potentially expanding to other variants of PKD? Thank you. So, this is Darren Hale. I'll address this first. For Anemia ID, as well as 23andMe, they're both focused on helping us to improve our understanding of. Although in Anemia ID, the panel that is used can help a physician to identify any number of hemolytic anemias, what we are focused on are those data associated with primary kinase. Now, we haven't yet discussed how those programs may be helpful as we look ahead to the expanded indications for MediPivot.

Those data associated with.

Part of your tenants sufficiency.

And seeing with 'twenty through 'twenty, three and now we haven't yet discussed how those programs may be helpful. As we look ahead to the expanded indications for me to that.

And given what we've observed.

With the programs this fall and stuff like Inc.

And what we're having.

With P. D. I would say those are probably viable options for us.

For the additional indications as well.

Thank you.

Okay.

Our next question comes from Marc Frahm with Cowen and company. Your line is open.

Hi, David This is there any because if it goes for mark for <unk>.

Taking my question.

And I have a follow up question to your earlier comments regarding the <unk> data that went from center.

Operator: But given what we've observed with the programs thus far, and the success I know we're having with PKD, I would say that those are probably viable options for us for the additional indications as well. Thank you. Thank you. Thank you. Our next question is from Mark Fram with Kellman & Company. Your line is open. Hi Divya, this is Daniel Rodriguez speaking for Mark.

In terms of.

And with their data and it would be and large enough to be.

And with a long enough follow up to start capturing the day impact being proof and hemoglobin level.

And then second question regarding de Energize trials, how long do you expect enrollment to take and shall we expect both trials will be on a similar top line or is one likely to take less time to complete.

Operator: Thank you for taking my question. I have a follow-up question to your earlier comments regarding the thalassemia data that were presented at IHA. In terms of, you know, would the data set be large enough to be with a long enough follow-up to start capturing the impacts of the improved hemoglobin level?

Besides the fact that day that they have the frame and.

And for enrollment.

And yes, it's Chris here. Thank you for your question.

We our initial.

Operator: And then a second question regarding the ENERGIZE trials. How long do you expect enrollment to take, and should we expect both trials to be on a similar timeline, or is one likely to take less time to complete, besides the fact that they have different ends or start dates? Yes, it's Chris here.

Presentation of the data Dr. Clos.

The second quote game and E.

Last year.

And I think illustrated what we.

And.

Defined as proof of clinical concept, where we saw the majority of patients having a greater than one gram per deciliter increase so I think one of the important finding and this presentation is now.

Christopher J. M. Taylor: Thank you for your question. This was our initial presentation of the data, Dr. Kuo, that Dr. Kuo gave at EHA last year. I think this illustrates what we and defined as proof of clinical concept where we saw the majority of patients having a greater than one gram per deciliter increase. So I think one of the important findings in this presentation is now, a year later, with Twenty patients accrued with longer-term follow-up. The durability of those responses and their safety will be a very important part of that presentation.

A year later.

And.

20 patients accrued with longer term follow up the durability of those responses and safety will be a very important part of that.

The presentation.

And with regards to the timelines.

Christopher J. M. Taylor: Now with regard to the, I'm sorry, the timelines for accrual of one trial versus the other. It's too early for us to guide you to that, but I can refer you to the slide that we presented today, where our first goal, our most immediate goal, is initiating both of these studies in the second half of this year, and we're very much on track to do so with anticipated approvals in the 2025 timeframe.

The timelines of accrual of one trial versus the other.

Too early for us to guide to that but I can refer you to the slide.

And that we presented today, where our first go arm and most immediate goal is initiating both of these studies and the second half of this year and we're very much on track to do so.

With anticipated approvals into 2025 timeframe that we'll be able to provide more details as things go along.

Christopher J. M. Taylor: So we'll be able to provide more details as things go along. And right now, we're just entering into the second stage of the operations. That is, we're beyond the beginning of the beginning, and now we're getting into IRBs, dealing with sites, and all that. So, it's too early for us to guide you through one trial finishing the timing of one versus the other. We very much set our timelines based on detailed feasibility and then, of course, track things along the way. And if we see important movements in either direction, things going faster or slower, then it's our job to talk about that once we're very confident of it and what the implications are.

And right now we're just entering into the what I call. The second stage of the operations that we're beyond the beginning at the beginning and now we're getting into.

IRB and dealing with price and all of that so it's too early for us to guide to one trial, finishing the timing of one versus the other we very much and set our timelines based on detailed feasibility and then of course track things along the way and if we see important movements in either direction and things going faster or slower than its hard.

Our job too.

Talk about that once we are very confident of it and what day.

The implications are but right now and what we.

Christopher J. M. Taylor: Right now, we're very encouraged by how we're tracking in terms of starting the studies and sticking with our anticipated approval guidance of 2025. Thank you. Thank you. Thank you, Michael. Thank you. And I'm currently showing no further questions at this time.

We're very encouraged by how we're tracking in terms of starting the studies and sticking with our anticipated approval guidance for 2025.

Alright. Thank you. Thank you for taking my call.

Thank you and I'm currently showing no further questions at this time I'd like to turn the call back over to Jacky sounds for closing remarks.

Jackie Feltz: I'll turn the call back over to Jackie Sells for closing remarks. Thank you, operator. I'm very excited about the progress we've made so far this year, including the transition of our oncology business to Cervier. We look forward to making a meaningful difference in the lives of patients with diseases that lie within our focus areas as we move into our future as a transformed AGIOS, starting with PK deficiency. To close, I would like to thank my Agios colleagues for their dedication and passion for making a difference for patients. I also want to thank all of the patients, caregivers, and physicians who participate in our clinical trials. Without them, we could not do what we do.

Thank you operator, I'm very excited about the progress we've made so far this year, including the transition of our oncology business to therapy.

We look forward and making a meaningful difference and the lives of patients with diseases that line within our focus areas as we move into our future as a transformed <unk>.

Darting with PK deficiency.

To close I would like to thank my <unk> colleagues for their dedication and passion for making a difference for patients and I also want to thank all of the patients caregivers and physicians, who participate and our clinical trials.

Out them, we could not do what we do and thank all of you for joining us today take care.

Operator: And thank all of you for joining us today. Take care. This concludes today's conference call. Thank you for participating. You may now disconnect.

This concludes today's conference call. Thank you for participating you may now disconnect.

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Operator: BF-WATCH TV 2021

And then.

And then.

Sure.

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