Agios Pharmaceuticals : First Quarter 2024 Financial Results Presentation

1. Agios Q1 2024 Earnings Script
2. Operator
3. Good morning and welcome to Agios' first quarter 2024 conference call. At this time, all
4. participants are in listen-only mode. There will be a question and answer session at the end.
5. Please be advised that this call is being recorded at Agios' request. I would now like to turn the
6. call over to Chris Taylor, VP Investor Relations and Corporate Communications for Agios.
7. Chris (introduction)
8. Thank you, Operator. Good morning, everyone, and welcome to Agios' conference call and
9. webcast to discuss first quarter 2024 financial results and recent business highlights. You can
10. access slides for today's call by going to the "Investors" section of our website, agios.com.
11. On today's call, I am joined by:
12. • Our Chief Executive Officer, Brian Goff;
13. • Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development;
14. • Tsveta Milanova, our Chief Commercial Officer;
15. • And Cecilia Jones, Chief Financial Officer.
16. Before we get started, I would like to remind everyone that some of the statements we make on
17. this call will include forward-looking statements. Actual events and results could differ
18. materially from those expressed or implied by any forward-looking statements, as a result of
19. various risks, uncertainties, and other factors, including those set forth in our most recent filings
20. with the SEC and any other future filings that we may make with the SEC.
21. With that, I will turn the call over to Brian.
22. Brian (opening remarks)
23. Good morning, everyone, and thank you for joining us.

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1. Our mission at Agios is to develop and deliver transformative medicines that elevate and extend
2. the lives of patients living with rare diseases, and we're off to a fast start in 2024. Our
3. foundation today leverages mitapivat's novel mechanism of action, which focuses on overall red
4. blood cell health, which has been a key driver for our recent clinical results.
5. On January 3rd, we reported positive data from the Phase 3 ENERGIZE study of our lead PK
6. activator, mitapivat - marketed as PYRUKYND, in patients with non-transfusion-dependent
7. thalassemia. This study met both the primary endpoint of hemoglobin response rate, as well as
8. both key secondary endpoints associated with change from baseline in FACIT-Fatigue Score and
9. hemoglobin concentration, and we look forward to presenting these data at an upcoming
10. medical meeting. As a reminder, non-transfusion-dependent thalassemia accounts for
11. approximately two-thirds of thalassemia in the U.S. and has no FDA-approved treatment option.
12. Despite not requiring regular transfusions it is increasingly understood that these patients
13. experience a significant impact on their quality of life, a wide range of serious morbidities, and
14. an elevated risk of premature death due to chronic hemolysis and ineffective erythropoiesis.
15. Based on these data, our team is actively preparing for a potential launch in thalassemia in the
16. US.
17. Complementing the ENERGIZE study in non-transfusion-dependent thalassemia, we continue to
18. advance the Phase 3 ENERGIZE-T study of mitapivat in transfusion-dependent thalassemia. We
19. expect to report data from this study here in second quarter, a slightly more refined timeframe
20. than previously communicated, and we plan to submit a single regulatory filing encompassing
21. data from both ENERGIZE and ENERGIZE-T to the FDA by the end of the year.
22. In parallel, we look forward to near-term milestones across several additional clinical programs
23. in our pipeline, including completing enrollment in the Phase 3 portion of the RISE UP study of
24. mitapivat in sickle cell disease by the end of this year, and reporting data from 3 additional
25. Phase 3 studies by the end of 2025. Sarah will provide a detailed update on our progress and
26. upcoming milestones across R&D in just a few minutes.
27. Given the consistent, positive data we have generated across the mitapivat development
28. program, and the high unmet need in our target disease areas, we believe mitapivat has the

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1. potential to transform the course of multiple hematologic diseases through improving red blood
2. cell health and become a multi-billion-dollar franchise. To help realize the full commercial
3. potential of mitapivat, and based on the strength of the ENERGIZE data, our commercial
4. organization is laser-focused on building upon the infrastructure established through our
5. current launch in PK deficiency, or PKD, to prepare for potential U.S. launches of mitapivat in
6. thalassemia in 2025 and in sickle cell disease in 2026. Tsveta will provide greater detail on the
7. market opportunity in thalassemia and the team's robust preparation for launch, as well as an
8. update on our current launch in PKD, in just a bit.
9. Finally, as you'll hear from Cecilia, we ended the first quarter with a strong cash position with
10. approximately $714 million in cash and investments on the balance sheet. Importantly, we have
11. the potential to further bolster our cash position in the near term as Servier announced FDA
12. filing acceptance and priority review for a new drug application for vorasidenib for the
13. treatment of certain IDH-mutant diffuse glioma. As you'll recall, as part of the divestiture of
14. Agios' oncology business to Servier, Agios retains rights to a potential $200 million milestone
15. upon FDA approval of vorasidenib and 15% royalties on potential U.S. net sales. If approved,
16. vorasidenib would become a first-in-class targeted therapy for patients with IDH-mutant
17. gliomas, and we look forward to the PDUFA action date of August 20, 2024.
18. With that, I'll turn the call over to Sarah.
19. Sarah
20. Thanks, Brian.
21. As we approach the topline data readout for the Phase 3 ENERGIZE-T study of mitapivat in
22. transfusion-dependentthalassemia, I would like to highlight a few key elements of the mitapivat
23. development program in thalassemia.
24. As a reminder, the Phase 3 program of mitapivat in thalassemia, namely ENERGIZE and
25. ENERGIZE-T,was designed to deliver data across all subpopulations of thalassemia, including
26. alpha and beta thalassemia and populations with different transfusion needs.

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1. As Brian mentioned, only patients with transfusion dependent Beta thalassemia, which
2. represents one-third of U.S. thalassemia patients, have an FDA approved treatment option.
3. The other two-thirds of thalassemia patients in the U.S., including all patients with Alpha
4. thalassemia and those patients with Beta thalassemia who are non-transfusion-dependent,
5. have no approved treatments.
6. It is a common misperception that non-transfusion-dependent, or NTD, thalassemia patients are
7. less sick - when the reality is that these patients suffer from a poor quality of life, and a high
8. rate of serious morbidities - including thrombosis, and premature death. This population, which
9. represents approximately two-thirds of total thalassemia patients in the U.S., has a high unmet
10. need for any treatment. This unmet need was strongly reinforced through our Phase 3
11. ENERGIZE study, by the speed of enrollment, the total number of patients enrolled, and the high
12. completion and rollover rates we observed. We were very pleased to announce positive results
13. from this study in January, and eagerly await the opportunity to present more complete results
14. at an upcoming medical meeting.
15. Turning to those results…our goal was to build upon our Phase 2 findings with a more rigorous
16. way to measure a hemoglobin response in the phase 3 ENERGIZE trial, which we defined in the
17. primary endpoint as an increase of ≥1 g/dL in average hemoglobin concentrations from Week
18. 12 through Week 24 compared with baseline, but in a much larger trial. We were excited to be
19. able to announce success in this trial, as treatment with 100 mg mitapivat demonstrated a
20. highly statistically significant result on the primary endpoint of hemoglobin response rate, with
21. 42.3% of patients in the treatment arm achieving a hemoglobin response versus 1.6% of
22. patients in the placebo arm. In addition, treatment with mitapivat also resulted in statistically
23. significant improvements in both key secondary endpoints, including a change from baseline in
24. average FACIT-Fatigue score, an important patient-reported measure of how patients feel. In line
25. with its novel mechanism of action that improves overall red blood cell health, mitapivat is the
26. first molecule that has shown in a randomized control trial that it does not only improve
27. hemoglobin, but actually makes people with thalassemia feel less fatigued.

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1. In addition, across the primary and secondary endpoints, all pre-specified subgroup analyses
2. favored mitapivat compared to placebo, suggesting that no single subgroup was responsible for
3. driving the results, which supports our aim to file for a broad label covering all thalassemia
4. subtypes.
5. Turning to ENERGIZE-T, let me highlight 3 key reasons why are confident in the outcome of this
6. upcoming readout in transfusion-dependent thalassemia.
7. • First, it is important to recall that regardless of a patient's transfusion needs, thalassemia
8. is a hemolytic anemia. By upregulating PK activity and improving overall red blood cell
9. health, mitapivat's novel mechanism of action directly addresses the underlying
10. pathobiology of hemolysis in all thalassemia subtypes.
11. • Second, this is a similar approach to the one we took for our PKD program. In that case,
12. in the Phase 3 ACTIVATE-T study of mitapivat in regularly transfused adults with PKD,
13. mitapivat demonstrated a statistically significant and clinically meaningful reduction in
14. transfusion burden. These data, together with positive data from the Phase 3 ACTIVATE
15. study in patients with PKD who are not regularly transfused, led to FDA approval of
16. mitapivat for adults with PKD regardless of transfusion status, and we look forward to
17. the potential to do the same in thalassemia.
18. • And third, in line with mitapivat's mechanism of action, we have seen consistency in the
19. data with improvements in hemolysis and ineffective erythropoiesis in clinical studies
20. across 3 hemolytic anemias, namely PKD, sickle cell disease, and non-transfusion-
21. dependent thalassemia.
22. As a reminder, the primary endpoint of ENERGIZE-T is transfusion reduction response, defined
23. as a 50% or greater reduction in transfused red blood cell units with a reduction of equal or
24. more than two units of transfused red blood cells in any consecutive 12-week period through
25. week 48 compared with baseline. This definition allows patients to achieve a reduction in
26. transfusion burden via an increased interval time between transfusions or use of fewer units, or
27. both at several timepoints in the trial. In order to standardize as much as possible the standard
28. of care in this large global trial, each patient has a specific hemoglobin threshold value that was

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1. calculated based on their individual transfusion history prior to enrolling in the trial. Each
2. patient's individual hemoglobin threshold value determines the hemoglobin value below which
3. they will receive a transfusion in the trial. As the mechanism of action of mitapivat focuses on
4. increasing RBC health and decreasing hemolysis, we are hoping to maintain hemoglobin levels
5. above this threshold and reduce the need for transfusions.
6. We designed this study incorporating learnings from prior studies as well as agency feedback,
7. and believe the primary endpoint's dynamic assessment period reflects what matters to
8. patients and physicians as well as regulators. In fact, Agios' core philosophy of building deep
9. connections with patient communities included seeking input from our patient advisory for the
10. construct of these studies.
11. We now look forward to the readout of this study in the second quarter and are planning to
12. submit a single regulatory filing to the FDA, encompassing data from both ENERGIZE and
13. ENERGIZE-Tby the end of this year, seeking a label that covers people living with all subtypesof
14. thalassemia.
15. Turning to sickle cell disease, enrollment in the Phase 3 portion of the RISE UP study of
16. mitapivat continues to progress, and we are on track to complete enrollment by the end of the
17. year. We have increasing conviction about the role of mitapivat in sickle cell disease, where we
18. believe we have the potential to be both best-in-class and first-in-class. We look forward to
19. reporting topline data from this 52-week study next year and believe firmly in mitapivat's
20. potential to address the high unmet need in this disease by both improving anemia, making
21. patients feel better and reducing sickle cell pain crises.
22. We also remain on track to deliver on all milestones across the rest of our advancing pipeline.
23. • This quarter, we commenced dosing in the Phase 1 study of AG-181, an oral PAH
24. stabilizer, for phenylketonuria, or PKU, a growing patient population with limited
25. treatment options. We are excited about the potential to introduce a novel mechanism
26. of action for PKU treatment and look forward to providing an update on next steps as
27. enrollment progresses.

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1. • Based on the data generated in the Phase 2a study of our novel PK activator, AG-946, in
2. lower-riskMDS, we plan to increase the doses evaluated in the upcoming Phase 2b
3. study, which we expect to initiate in the middle of this year.
4. • And in pediatric PKD, we expect to complete enrollment of the Phase 3 ACTIVATE-kids
5. study in the middle of this year and we also now expect to report topline data from
6. Phase 3 ACTIVATE-kidsT study in mid-2024 as well.
7. This is a very exciting time at Agios, and we look forward to providing additional readouts and
8. progress as we proceed through the year. In particular, we're looking forward to sharing with
9. you the status of submissions for EHA when they are made public in a couple of weeks. With
10. that, I will now turn the call over to Tsveta.
11. Tsveta
12. Thanks, Sarah.
13. Today, a diagnosis of thalassemia can be daunting for patients and their families. Regardless of
14. the disease subtype, treatment options are limited and the burden of disease - as well as the
15. associated cost of care - is significant.
16. All forms of thalassemia - including non-transfusion-dependent thalassemia - bring high rates of
17. serious morbidities, reduced quality of life, and a heightened risk of premature death.
18. There are approximately 6,000 diagnosed adults living with thalassemia in the U.S.,
19. approximately 4,000 of whom are non-transfusion-dependent and have no available treatment
20. options today. As Sarah mentioned, this patient population was studied in our ENERGIZE clinical
21. trial, which demonstrated the benefits of mitapivat in non-transfusion dependent thalassemia
22. patients. The remaining 2,000 are transfusion-dependent and have no oral treatment option.
23. We are eagerly awaiting the data from our ENERGIZE-T study in the second quarter, which is
24. focused on these transfusion dependent patients. Our goal with mitapivat is to transform the
25. treatment of thalassemia by becoming the first therapy approved for all subtypes of the
26. disease.

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1. Galvanized by the positive data from the ENERGIZE study, and the potential for positive data
2. from ENERGIZE-T, our commercial organization is actively preparing to address this high unmet
3. need with a potential launch in thalassemia next year, beginning with the U.S.
4. In addition to the data we are generating through the mitapivat clinical development program,
5. we believe there are three key factors that have the potential to support adoption of mitapivat
6. among thalassemia patients in the U.S., where we observe more favorable market dynamics vs
7. PK Deficiency…
8. • First, driven by availability of newborn screening and well-establishedICD-10 codes, the
9. diagnosis rate in thalassemia is high, with many patients diagnosed before adulthood.
10. • Second, both patients and providers are concentrated in a limited number of centers,
11. with approximately 50% of all diagnosed patients treated at fewer than 150 centers in
12. the U.S., providing a clear focus for our initial launch.
13. • And third, our clinical trial sites in the U.S. are in some of the main centers of excellence,
14. so many treating physicians will have first-hand experience with mitapivat
15. Given these data and mitapivat's target product profile, we believe we are well-positioned to
16. provide a potential foundational treatment option for patients with thalassemia regardless of
17. subtype, and our team is focused on 4 core areas of U.S. launch preparation.
18. • First, we are conducting extensive market research and claims data analysis to further
19. deepen our market understanding and refine our HCP targeting.
20. • Second, we are rolling out a disease education campaign in the coming weeks designed
21. for both patients and clinicians, highlighting the long-term complications and burden of
22. disease across all thalassemia subtypes. A key focus of this effort is to increase the
23. urgency to monitor and treat non-transfusion-dependent patients by increasing
24. awareness of the risk of long-term morbidities and premature death, driven by chronic
25. hemolysis and ineffective erythropoiesis.
26. • Third, we are executing a disciplined expansion of our commercial and medical teams in
27. order to right-size the organization for a successful launch in this larger, but still rare
28. market.

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1. • And fourth, our market access team is already engaging with payers on disease state
2. education. I'm proud that our team has obtained broad market access for PYRUKYND in
3. PKD, and we look forward to the same strong outcome in thalassemia.
4. In addition to the U.S., we aim to maximize the potential of markets outside of the US through
5. coordinated regulatory filings, which we intend to pursue with one or more partners. These
6. markets include the Gulf region, which is home to approximately 70,000 thalassemia patients
7. some of the leading treatment centers in our clinical trials.
8. Let me now provide an update on the current launch of PYRUKYND in PKD.
9. In the first quarter of 2024, we generated $8.2 million in net PYRUKYND revenue compared to
10. $7.1 million in the fourth quarter of 2023.
11. A total of 188 patients have completed a prescription enrollment form, including 10 in the first
12. quarter of 2024, a 6% increase versus the prior quarter.
13. This has translated into net 120 patients on therapy, a 10% increase versus the prior quarter.
14. Patients on therapy continue to stem from a growing and diverse prescriber base of 162
15. physicians and represent a broad demographic and disease manifestation range that is
16. consistent with the adult PKD population.
17. We continue to be encouraged by the persistency of patients on treatment and remain focused
18. on efficiently identifying providers likely to treat patients with PKD.
19. We believe the capabilities we continue to strengthen through the current launch, including
20. efficient targeting analytics, patient and HCP awareness and education, and patient access, will
21. provide a firm foundation from which to maximize potential future U.S. launches of mitapivat in
22. thalassemia in 2025 and in sickle cell disease in 2026.
23. Above all, Agios is once again incredibly proud to be pioneering a potential new therapy for
24. these two underserved patient populations.
25. With that, I'll turn the call over to Cecilia.

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1. Cecilia
2. Thanks, Tsveta.
3. Our first quarter 2024 financial results can be found in the press release we issued this morning
4. and more detail will be included in our 10-Q, which will be filed later today.
5. Let me now take a moment to provide some context and highlight a few key points.
6. First quarter 2024 net PYRUKYND revenue was $8.2 million dollars, an increase of $2.6 million
7. dollars compared to the first quarter of 2023.
8. Consistent with other rare disease launches, gross to net has been - and is expected to be - in
9. the 10% to 20% range on an annual basis.
10. Cost of sales for the quarter was $0.6 million dollars.
11. R&D expenses were $68.6 million dollars for the first quarter, an increase of $1.3 million dollars
12. compared to the first quarter of 2023. This increase was primarily driven by progression of our
13. pipeline. SG&A expenses were $31.0 million dollars for the first quarter, an increase of $2.6
14. million dollars compared to the prior year quarter. This was primarily driven by an increase in
15. commercial-relatedactivities as we prepare for the potential approval of PYRUKYND® in
16. thalassemia.
17. As a reminder, as part of the divestiture of our oncology business to Servier, we retain rights to a
18. potential $200 million milestone upon FDA approval of vorasidenib and 15% royalties on
19. potential U.S. net sales.
20. We ended the quarter with cash, cash equivalents, and marketable securities of approximately
21. $714.3 million dollars. We expect that this balance, together with anticipated product revenue,
22. interest income and the potential vorasidenib milestone, will enable the company to fund our
23. operating expenses and capital expenditures through several value-creating milestones and at
24. least into 2026.
25. This guidance does not include cash inflows that could extend our runway beyond 2026,
26. including the potential royalties or royalty monetization from vorasidenib, commercializing

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