- Agios Q1 2024 Earnings Script
- Operator
- Good morning and welcome to Agios' first quarter 2024 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 Chris Taylor, VP Investor Relations and Corporate Communications for Agios.
- Chris (introduction)
- Thank you, Operator. Good morning, everyone, and welcome to Agios' conference call and
- webcast to discuss first quarter 2024 financial results and recent business highlights. You can
- access slides for today's call by going to the "Investors" section of our website, agios.com.
- On today's call, I am joined by:
- • Our Chief Executive Officer, Brian Goff;
- • Dr. Sarah Gheuens, Chief Medical Officer and Head of Research and Development;
- • Tsveta Milanova, our Chief Commercial Officer;
- • And Cecilia Jones, Chief Financial Officer.
- Before we get started, I would like to remind everyone that some of the statements we make on
- this call will include forward-looking statements. Actual events and results could differ
- materially from those expressed or implied by any forward-looking statements, as a result of
- various risks, uncertainties, and other factors, including those set forth in our most recent filings
- with the SEC and any other future filings that we may make with the SEC.
- With that, I will turn the call over to Brian.
- Brian (opening remarks)
- Good morning, everyone, and thank you for joining us.
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- Our mission at Agios is to develop and deliver transformative medicines that elevate and extend
- the lives of patients living with rare diseases, and we're off to a fast start in 2024. Our
- foundation today leverages mitapivat's novel mechanism of action, which focuses on overall red
- blood cell health, which has been a key driver for our recent clinical results.
- On January 3rd, we reported positive data from the Phase 3 ENERGIZE study of our lead PK
- activator, mitapivat - marketed as PYRUKYND, in patients with non-transfusion-dependent
- thalassemia. This study met both the primary endpoint of hemoglobin response rate, as well as
- both key secondary endpoints associated with change from baseline in FACIT-Fatigue Score and
- hemoglobin concentration, and we look forward to presenting these data at an upcoming
- medical meeting. As a reminder, non-transfusion-dependent thalassemia accounts for
- approximately two-thirds of thalassemia in the U.S. and has no FDA-approved treatment option.
- Despite not requiring regular transfusions it is increasingly understood that these patients
- experience a significant impact on their quality of life, a wide range of serious morbidities, and
- an elevated risk of premature death due to chronic hemolysis and ineffective erythropoiesis.
- Based on these data, our team is actively preparing for a potential launch in thalassemia in the
- US.
- Complementing the ENERGIZE study in non-transfusion-dependent thalassemia, we continue to
- advance the Phase 3 ENERGIZE-T study of mitapivat in transfusion-dependent thalassemia. We
- expect to report data from this study here in second quarter, a slightly more refined timeframe
- than previously communicated, and we plan to submit a single regulatory filing encompassing
- data from both ENERGIZE and ENERGIZE-T to the FDA by the end of the year.
- In parallel, we look forward to near-term milestones across several additional clinical programs
- in our pipeline, including completing enrollment in the Phase 3 portion of the RISE UP study of
- mitapivat in sickle cell disease by the end of this year, and reporting data from 3 additional
- Phase 3 studies by the end of 2025. Sarah will provide a detailed update on our progress and
- upcoming milestones across R&D in just a few minutes.
- Given the consistent, positive data we have generated across the mitapivat development
- program, and the high unmet need in our target disease areas, we believe mitapivat has the
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- potential to transform the course of multiple hematologic diseases through improving red blood
- cell health and become a multi-billion-dollar franchise. To help realize the full commercial
- potential of mitapivat, and based on the strength of the ENERGIZE data, our commercial
- organization is laser-focused on building upon the infrastructure established through our
- current launch in PK deficiency, or PKD, to prepare for potential U.S. launches of mitapivat in
- thalassemia in 2025 and in sickle cell disease in 2026. Tsveta will provide greater detail on the
- market opportunity in thalassemia and the team's robust preparation for launch, as well as an
- update on our current launch in PKD, in just a bit.
- Finally, as you'll hear from Cecilia, we ended the first quarter with a strong cash position with
- approximately $714 million in cash and investments on the balance sheet. Importantly, we have
- the potential to further bolster our cash position in the near term as Servier announced FDA
- filing acceptance and priority review for a new drug application for vorasidenib for the
- treatment of certain IDH-mutant diffuse glioma. As you'll recall, as part of the divestiture of
- Agios' oncology business to Servier, Agios retains rights to a potential $200 million milestone
- upon FDA approval of vorasidenib and 15% royalties on potential U.S. net sales. If approved,
- vorasidenib would become a first-in-class targeted therapy for patients with IDH-mutant
- gliomas, and we look forward to the PDUFA action date of August 20, 2024.
- With that, I'll turn the call over to Sarah.
- Sarah
- Thanks, Brian.
- As we approach the topline data readout for the Phase 3 ENERGIZE-T study of mitapivat in
- transfusion-dependentthalassemia, I would like to highlight a few key elements of the mitapivat
- development program in thalassemia.
- As a reminder, the Phase 3 program of mitapivat in thalassemia, namely ENERGIZE and
- ENERGIZE-T,was designed to deliver data across all subpopulations of thalassemia, including
- alpha and beta thalassemia and populations with different transfusion needs.
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- As Brian mentioned, only patients with transfusion dependent Beta thalassemia, which
- represents one-third of U.S. thalassemia patients, have an FDA approved treatment option.
- The other two-thirds of thalassemia patients in the U.S., including all patients with Alpha
- thalassemia and those patients with Beta thalassemia who are non-transfusion-dependent,
- have no approved treatments.
- It is a common misperception that non-transfusion-dependent, or NTD, thalassemia patients are
- less sick - when the reality is that these patients suffer from a poor quality of life, and a high
- rate of serious morbidities - including thrombosis, and premature death. This population, which
- represents approximately two-thirds of total thalassemia patients in the U.S., has a high unmet
- need for any treatment. This unmet need was strongly reinforced through our Phase 3
- ENERGIZE study, by the speed of enrollment, the total number of patients enrolled, and the high
- completion and rollover rates we observed. We were very pleased to announce positive results
- from this study in January, and eagerly await the opportunity to present more complete results
- at an upcoming medical meeting.
- Turning to those results…our goal was to build upon our Phase 2 findings with a more rigorous
- way to measure a hemoglobin response in the phase 3 ENERGIZE trial, which we defined in the
- primary endpoint as an increase of ≥1 g/dL in average hemoglobin concentrations from Week
- 12 through Week 24 compared with baseline, but in a much larger trial. We were excited to be
- able to announce success in this trial, as treatment with 100 mg mitapivat demonstrated a
- highly statistically significant result on the primary endpoint of hemoglobin response rate, with
- 42.3% of patients in the treatment arm achieving a hemoglobin response versus 1.6% of
- patients in the placebo arm. In addition, treatment with mitapivat also resulted in statistically
- significant improvements in both key secondary endpoints, including a change from baseline in
- average FACIT-Fatigue score, an important patient-reported measure of how patients feel. In line
- with its novel mechanism of action that improves overall red blood cell health, mitapivat is the
- first molecule that has shown in a randomized control trial that it does not only improve
- hemoglobin, but actually makes people with thalassemia feel less fatigued.
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- In addition, across the primary and secondary endpoints, all pre-specified subgroup analyses
- favored mitapivat compared to placebo, suggesting that no single subgroup was responsible for
- driving the results, which supports our aim to file for a broad label covering all thalassemia
- subtypes.
- Turning to ENERGIZE-T, let me highlight 3 key reasons why are confident in the outcome of this
- upcoming readout in transfusion-dependent thalassemia.
- • First, it is important to recall that regardless of a patient's transfusion needs, thalassemia
- is a hemolytic anemia. By upregulating PK activity and improving overall red blood cell
- health, mitapivat's novel mechanism of action directly addresses the underlying
- pathobiology of hemolysis in all thalassemia subtypes.
- • Second, this is a similar approach to the one we took for our PKD program. In that case,
- in the Phase 3 ACTIVATE-T study of mitapivat in regularly transfused adults with PKD,
- mitapivat demonstrated a statistically significant and clinically meaningful reduction in
- transfusion burden. These data, together with positive data from the Phase 3 ACTIVATE
- study in patients with PKD who are not regularly transfused, led to FDA approval of
- mitapivat for adults with PKD regardless of transfusion status, and we look forward to
- the potential to do the same in thalassemia.
- • And third, in line with mitapivat's mechanism of action, we have seen consistency in the
- data with improvements in hemolysis and ineffective erythropoiesis in clinical studies
- across 3 hemolytic anemias, namely PKD, sickle cell disease, and non-transfusion-
- dependent thalassemia.
- As a reminder, the primary endpoint of ENERGIZE-T is transfusion reduction response, defined
- as a 50% or greater reduction in transfused red blood cell units with a reduction of equal or
- more than two units of transfused red blood cells in any consecutive 12-week period through
- week 48 compared with baseline. This definition allows patients to achieve a reduction in
- transfusion burden via an increased interval time between transfusions or use of fewer units, or
- both at several timepoints in the trial. In order to standardize as much as possible the standard
- of care in this large global trial, each patient has a specific hemoglobin threshold value that was
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- calculated based on their individual transfusion history prior to enrolling in the trial. Each
- patient's individual hemoglobin threshold value determines the hemoglobin value below which
- they will receive a transfusion in the trial. As the mechanism of action of mitapivat focuses on
- increasing RBC health and decreasing hemolysis, we are hoping to maintain hemoglobin levels
- above this threshold and reduce the need for transfusions.
- We designed this study incorporating learnings from prior studies as well as agency feedback,
- and believe the primary endpoint's dynamic assessment period reflects what matters to
- patients and physicians as well as regulators. In fact, Agios' core philosophy of building deep
- connections with patient communities included seeking input from our patient advisory for the
- construct of these studies.
- We now look forward to the readout of this study in the second quarter and are planning to
- submit a single regulatory filing to the FDA, encompassing data from both ENERGIZE and
- ENERGIZE-Tby the end of this year, seeking a label that covers people living with all subtypesof
- thalassemia.
- Turning to sickle cell disease, enrollment in the Phase 3 portion of the RISE UP study of
- mitapivat continues to progress, and we are on track to complete enrollment by the end of the
- year. We have increasing conviction about the role of mitapivat in sickle cell disease, where we
- believe we have the potential to be both best-in-class and first-in-class. We look forward to
- reporting topline data from this 52-week study next year and believe firmly in mitapivat's
- potential to address the high unmet need in this disease by both improving anemia, making
- patients feel better and reducing sickle cell pain crises.
- We also remain on track to deliver on all milestones across the rest of our advancing pipeline.
- • This quarter, we commenced dosing in the Phase 1 study of AG-181, an oral PAH
- stabilizer, for phenylketonuria, or PKU, a growing patient population with limited
- treatment options. We are excited about the potential to introduce a novel mechanism
- of action for PKU treatment and look forward to providing an update on next steps as
- enrollment progresses.
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- • Based on the data generated in the Phase 2a study of our novel PK activator, AG-946, in
- lower-riskMDS, we plan to increase the doses evaluated in the upcoming Phase 2b
- study, which we expect to initiate in the middle of this year.
- • And in pediatric PKD, we expect to complete enrollment of the Phase 3 ACTIVATE-kids
- study in the middle of this year and we also now expect to report topline data from
- Phase 3 ACTIVATE-kidsT study in mid-2024 as well.
- This is a very exciting time at Agios, and we look forward to providing additional readouts and
- progress as we proceed through the year. In particular, we're looking forward to sharing with
- you the status of submissions for EHA when they are made public in a couple of weeks. With
- that, I will now turn the call over to Tsveta.
- Tsveta
- Thanks, Sarah.
- Today, a diagnosis of thalassemia can be daunting for patients and their families. Regardless of
- the disease subtype, treatment options are limited and the burden of disease - as well as the
- associated cost of care - is significant.
- All forms of thalassemia - including non-transfusion-dependent thalassemia - bring high rates of
- serious morbidities, reduced quality of life, and a heightened risk of premature death.
- There are approximately 6,000 diagnosed adults living with thalassemia in the U.S.,
- approximately 4,000 of whom are non-transfusion-dependent and have no available treatment
- options today. As Sarah mentioned, this patient population was studied in our ENERGIZE clinical
- trial, which demonstrated the benefits of mitapivat in non-transfusion dependent thalassemia
- patients. The remaining 2,000 are transfusion-dependent and have no oral treatment option.
- We are eagerly awaiting the data from our ENERGIZE-T study in the second quarter, which is
- focused on these transfusion dependent patients. Our goal with mitapivat is to transform the
- treatment of thalassemia by becoming the first therapy approved for all subtypes of the
- disease.
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- Galvanized by the positive data from the ENERGIZE study, and the potential for positive data
- from ENERGIZE-T, our commercial organization is actively preparing to address this high unmet
- need with a potential launch in thalassemia next year, beginning with the U.S.
- In addition to the data we are generating through the mitapivat clinical development program,
- we believe there are three key factors that have the potential to support adoption of mitapivat
- among thalassemia patients in the U.S., where we observe more favorable market dynamics vs
- PK Deficiency…
- • First, driven by availability of newborn screening and well-establishedICD-10 codes, the
- diagnosis rate in thalassemia is high, with many patients diagnosed before adulthood.
- • Second, both patients and providers are concentrated in a limited number of centers,
- with approximately 50% of all diagnosed patients treated at fewer than 150 centers in
- the U.S., providing a clear focus for our initial launch.
- • And third, our clinical trial sites in the U.S. are in some of the main centers of excellence,
- so many treating physicians will have first-hand experience with mitapivat
- Given these data and mitapivat's target product profile, we believe we are well-positioned to
- provide a potential foundational treatment option for patients with thalassemia regardless of
- subtype, and our team is focused on 4 core areas of U.S. launch preparation.
- • First, we are conducting extensive market research and claims data analysis to further
- deepen our market understanding and refine our HCP targeting.
- • Second, we are rolling out a disease education campaign in the coming weeks designed
- for both patients and clinicians, highlighting the long-term complications and burden of
- disease across all thalassemia subtypes. A key focus of this effort is to increase the
- urgency to monitor and treat non-transfusion-dependent patients by increasing
- awareness of the risk of long-term morbidities and premature death, driven by chronic
- hemolysis and ineffective erythropoiesis.
- • Third, we are executing a disciplined expansion of our commercial and medical teams in
- order to right-size the organization for a successful launch in this larger, but still rare
- market.
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- • And fourth, our market access team is already engaging with payers on disease state
- education. I'm proud that our team has obtained broad market access for PYRUKYND in
- PKD, and we look forward to the same strong outcome in thalassemia.
- In addition to the U.S., we aim to maximize the potential of markets outside of the US through
- coordinated regulatory filings, which we intend to pursue with one or more partners. These
- markets include the Gulf region, which is home to approximately 70,000 thalassemia patients
- some of the leading treatment centers in our clinical trials.
- Let me now provide an update on the current launch of PYRUKYND in PKD.
- In the first quarter of 2024, we generated $8.2 million in net PYRUKYND revenue compared to
- $7.1 million in the fourth quarter of 2023.
- A total of 188 patients have completed a prescription enrollment form, including 10 in the first
- quarter of 2024, a 6% increase versus the prior quarter.
- This has translated into net 120 patients on therapy, a 10% increase versus the prior quarter.
- Patients on therapy continue to stem from a growing and diverse prescriber base of 162
- physicians and represent a broad demographic and disease manifestation range that is
- consistent with the adult PKD population.
- We continue to be encouraged by the persistency of patients on treatment and remain focused
- on efficiently identifying providers likely to treat patients with PKD.
- We believe the capabilities we continue to strengthen through the current launch, including
- efficient targeting analytics, patient and HCP awareness and education, and patient access, will
- provide a firm foundation from which to maximize potential future U.S. launches of mitapivat in
- thalassemia in 2025 and in sickle cell disease in 2026.
- Above all, Agios is once again incredibly proud to be pioneering a potential new therapy for
- these two underserved patient populations.
- With that, I'll turn the call over to Cecilia.
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- Cecilia
- Thanks, Tsveta.
- Our first quarter 2024 financial results can be found in the press release we issued this morning
- and more detail will be included in our 10-Q, which will be filed later today.
- Let me now take a moment to provide some context and highlight a few key points.
- First quarter 2024 net PYRUKYND revenue was $8.2 million dollars, an increase of $2.6 million
- dollars compared to the first quarter of 2023.
- Consistent with other rare disease launches, gross to net has been - and is expected to be - in
- the 10% to 20% range on an annual basis.
- Cost of sales for the quarter was $0.6 million dollars.
- R&D expenses were $68.6 million dollars for the first quarter, an increase of $1.3 million dollars
- compared to the first quarter of 2023. This increase was primarily driven by progression of our
- pipeline. SG&A expenses were $31.0 million dollars for the first quarter, an increase of $2.6
- million dollars compared to the prior year quarter. This was primarily driven by an increase in
- commercial-relatedactivities as we prepare for the potential approval of PYRUKYND® in
- thalassemia.
- As a reminder, as part of the divestiture of our oncology business to Servier, we retain rights to a
- potential $200 million milestone upon FDA approval of vorasidenib and 15% royalties on
- potential U.S. net sales.
- We ended the quarter with cash, cash equivalents, and marketable securities of approximately
- $714.3 million dollars. We expect that this balance, together with anticipated product revenue,
- interest income and the potential vorasidenib milestone, will enable the company to fund our
- operating expenses and capital expenditures through several value-creating milestones and at
- least into 2026.
- This guidance does not include cash inflows that could extend our runway beyond 2026,
- including the potential royalties or royalty monetization from vorasidenib, commercializing
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Agios Pharmaceuticals Inc. published this content on 02 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 02 May 2024 13:52:44 UTC.