UNITED STATES
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CURRENT REPORT
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| Item 7.01 | Regulation FD Disclosure. |
On January 8, 2023, Agios Pharmaceuticals, Inc. (the “Company”) issued a press release outlining its anticipated 2023 milestones and significant value-driving catalysts through 2026, which will be discussed at the Company’s presentation at the 41st Annual J.P. Morgan Healthcare Conference on January 11, 2023. The full text of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference. The slides to be presented by the Company at the 41st Annual J.P. Morgan Healthcare Conference are furnished as Exhibit 99.2 to this Current Report on Form 8-K and are incorporated herein by reference.
The information in this Item 7.01 (including Exhibit 99.1 and Exhibit 99.2) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits.
| Exhibit No. |
Description | |
| 99.1 | Press release dated on January 8, 2023 | |
| 99.2 | Presentation at the 41st Annual J.P. Morgan Healthcare Conference | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| AGIOS PHARMACEUTICALS, INC. | ||||||
| Date: January 9, 2023 | By: | /s/ Brian Goff | ||||
| Brian Goff | ||||||
| Chief Executive Officer | ||||||
Exhibit 99.1
Agios Unveils 2023-2026 Value-driving Catalysts Enabling Company’s Vision to Transform Patient Outcomes in Rare Diseases
– Consistent and compelling clinical data across rare hematological diseases support five ongoing pivotal trials in thalassemia, sickle cell disease and pediatric pyruvate kinase (PK) deficiency –
– Driving toward two additional PYRUKYND® indications, with potential FDA approvals in thalassemia in 2025 and sickle cell disease in 2026 –
– Strong cash position expected to enable completion of ongoing programs and pipeline expansion to cash-flow positivity –
CAMBRIDGE, Mass., January 8, 2023 – Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, today announced its anticipated 2023 milestones and significant value-driving catalysts through 2026 that support the company’s mission to transform patient outcomes in rare diseases. Agios will present at the 41st Annual J.P. Morgan Healthcare Conference on Wednesday, January 11, 2023, at 7:30 a.m. PT, and a live webcast will be available at investor.agios.com.
“Agios is poised for significant growth with the potential for approvals in two additional PYRUKYND® indications by 2026, and is well capitalized to advance its robust existing clinical pipeline and expand its portfolio within our core areas of expertise,” said Brian Goff, chief executive officer at Agios. “As the pioneering leader in PK activation with more than seven years of clinical experience with PYRUKYND®, we have generated an impressive body of consistent and compelling data across rare hematological diseases with shared underlying pathophysiology that further builds confidence in our five ongoing pivotal clinical trials in thalassemia, sickle cell disease and pediatric PK deficiency. Furthermore, we are executing our first rare disease U.S. product launch with PYRUKYND® in adult PK deficiency, providing the first disease-modifying therapy for this patient community that previously had no treatment options and building the capabilities to set us up for success with our expected launches in meaningfully larger patient populations.”
Recent Highlights
| • | Adult PK Deficiency: Received marketing authorization for PYRUKYND® in adults with PK deficiency in the EU and Great Britain |
| • | Thalassemia: Enrolled approximately half of patients in the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND® in not regularly transfused and regularly transfused adults with thalassemia, respectively |
| • | Sickle Cell Disease: Closed screening in the Phase 2 portion of the RISE UP study of PYRUKYND® in adults with sickle cell disease in December and expect to complete enrollment in January |
| • | Data Presentations: Presented broad set of clinical and translational data at the 64th American Society of Hematology (ASH) Annual Meeting & Exposition, including long-term PYRUKYND® data in adults with non-transfusion-dependent thalassemia and in adults with PK deficiency |
| • | Leadership: Appointed Tsveta Milanova to the role of chief commercial officer, bringing two decades of experience in rare disease commercial strategy and global market access |
Anticipated 2023 Milestones
| • | Thalassemia: Complete enrollment of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND® by mid-year |
| • | Pediatric PK Deficiency: Enroll at least half of patients in the Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies of PYRUKYND® by year-end |
| • | Sickle Cell Disease: Announce data readout from Phase 2 portion of RISE UP study of PYRUKUND® and go/no-go to Phase 3 decision by mid-year |
| • | Lower-risk Myelodysplastic Syndromes (LR-MDS): Complete enrollment of Phase 2a study of novel PK activator AG-946 by year-end |
| • | Earlier-stage Pipeline: File investigational new drug (IND) application for PAH stabilizer for the treatment of phenylketonuria (PKU) by year-end |
Agios 2026 Vision
By 2026, Agios’ vision is to establish a classical hematology franchise with PYRUKYND® approvals across PK deficiency, thalassemia and sickle cell disease; expand its portfolio by advancing AG-946 and the preclinical pipeline as well as through disciplined business development aligned with the company’s core therapeutic focus areas and capabilities; and achieve cash-flow positivity. Agios provided a roadmap of additional significant potential catalysts between 2024 and 2026 to enable the realization of this vision, as follows:
2024
| • | Data readout from Phase 3 ENERGIZE study of PYRUKYND® in adults with non-transfusion-dependent thalassemia (first half of 2024) |
| • | Data readout from Phase 3 ENERGIZE-T study of PYRUKYND® in adults with transfusion-dependent thalassemia (second half of 2024) |
| • | Data readout from Phase 2a study of AG-946 in LR-MDS |
2025
| • | Potential FDA approval for PYRUKYND® in thalassemia |
| • | Data readout from Phase 3 portion of RISE UP study of PYRUKYND® in sickle cell disease, pending go/no-go decision in 2023 |
| • | Data readouts from Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies of PYRUKYND® in pediatric PK deficiency |
2026
| • | Potential FDA approval for PYRUKYND® in sickle cell disease |
| • | Potential FDA approval for PYRUKYND® in pediatric PK deficiency |
| • | Achieve cash-flow positivity |
Presentation at 41st Annual J.P. Morgan Healthcare Conference
Agios will webcast its corporate presentation from the 41st Annual J.P. Morgan Healthcare Conference on Wednesday, January 11 at 7:30 a.m. PT. A live webcast of the presentation can be accessed under “Events & Presentations” in the Investors section of the company’s website at agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation.
About Agios
Agios is a biopharmaceutical company that is fueled by connections. The Agios team cultivates strong bonds with patient communities, healthcare professionals, partners and colleagues to discover, develop and deliver therapies for rare diseases. In the U.S., Agios markets a first-in-class pyruvate kinase (PK) activator for adults with PK deficiency, the first disease-modifying therapy for this rare, lifelong, debilitating hemolytic anemia. Building on the company’s leadership in the field of cellular metabolism, Agios is advancing a robust clinical pipeline of investigational medicines with programs in alpha- and beta-thalassemia, sickle cell disease, pediatric PK deficiency and MDS-associated anemia. In addition to its clinical pipeline, Agios has multiple investigational therapies in preclinical development and deep scientific expertise in classical hematology. For more information, please visit the company’s website at www.agios.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of PYRUKYND® (mitapivat), AG-946 and its PAH stabilizer; Agios’ plans, strategies and expectations for its preclinical, clinical and commercial advancement of its drug development, including PYRUKYND®, AG-946 and its PAH stabilizer; Agios’ strategic vision and goals, including its key milestones for 2023 and potential catalysts through 2026; and the potential benefits of Agios’ strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios’ product candidates will successfully continue. There can be no guarantee that any positive developments in Agios’ business will result in stock price appreciation. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation: risks and uncertainties related to the impact of the COVID-19 pandemic to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S.
FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios’ ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios’ ability to maintain key collaborations; the failure of Agios to receive milestone or royalty payments related to the sale of its oncology business, the uncertainty of the timing of any receipt of any such payments, and the uncertainty of the results and effectiveness of the use of proceeds from the transaction with Servier; and general economic and market conditions. These and other risks are described in greater detail under the caption “Risk Factors” included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
Contacts
Investors:
Adam Bero, Ph.D.
Kendall Investor Relations
abero@kendallir.com
Media:
Jessica Rennekamp
Senior Director, Corporate Communications
Jessica.Rennekamp@agios.com
Fueled by Connections to Transform Rare Diseases Brian Goff, Chief Executive Officer January 11, 2023 Exhibit 99.2
Forward-looking statements This presentation and various remarks we make during this presentation contain forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of PYRUKYND® (mitapivat), AG-946 and its PAH stabilizer; Agios’ plans, strategies and expectations for its preclinical, clinical and commercial advancement of its drug development, including PYRUKYND®, AG-946 and its PAH stabilizer; Agios’ strategic vision and goals, including its key milestones for 2023 and potential catalysts through 2026; and the potential benefits of Agios’ strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios’ product candidates will successfully continue. There can be no guarantee that any positive developments in Agios’ business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this presentation and various remarks we make during this presentation could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation: risks and uncertainties related to the impact of the COVID-19 pandemic to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios’ ability to maintain key collaborations; the failure of Agios to receive milestone or royalty payments related to the sale of its oncology business, the uncertainty of the timing of any receipt of any such payments, and the uncertainty of the results and effectiveness of the use of proceeds from the transaction with Servier; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this presentation and various remarks we make during this presentation speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
Track record of success in discovering, developing and commercializing therapies Unmatched expertise in cellular metabolism The Leader in Pyruvate Kinase (PK) Activation DEVELOPED APPROVED THERAPIES IN ONCOLOGY 2017 & 2018 FIRST PYRUKYND® APPROVAL ADULTS WITH PYRUVATE KINASE (PK) DEFICIENCY 2022 RARE DISEASE FOCUS: POTENTIAL APPROVALS IN THALASSEMIA AND SICKLE CELL DISEASE By 2026
Leader in pyruvate kinase (PK) activation poised for significant growth Compelling and consistent data across connected diseases Robust clinical data set supports potential of PK activation to transform patient function, quality of life, and long-term outcomes Meaningful commercial opportunities on the horizon First rare disease launch building capabilities to maximize anticipated franchise expansion Potential for two additional PYRUKYND® indications by 2026 Well capitalized to advance and expand Strong cash position expected to support completion of ongoing programs and disciplined portfolio expansion
Pediatric PK Deficiency No approved therapy for pediatric PK deficiency patients Our goal: Deliver the first approved therapy for pediatric PK deficiency Thalassemia No approved therapy for ~60% of thalassemia patients Our goal: Deliver the first therapy approved for all thalassemia subtypes Sickle Cell Disease No novel oral therapy improves anemia and reduces sickle cell pain crises Our goal: Deliver a novel oral therapy that improves anemia and reduces VOCs Lower-Risk MDS No oral therapy addresses ineffective erythropoiesis Our goal: Deliver the first oral therapy that addresses ineffective erythropoiesis Focused on expanding from PK deficiency to other diseases with shared pathophysiology, limited treatment options, and profound unmet needs PYRUKYND® is approved in the U.S., EU, and Great Britain for adult PK deficiency and is under investigation for pediatric PK deficiency, thalassemia, and sickle cell disease. AG-946 is under investigation for LR-MDS.
ADDITIONAL OPPORTUNITIES FOR THE FRANCHISE WITH NOVEL PK ACTIVATOR AG-946 PK deficiency Approved for adults in the U.S. and EU Thalassemia Potential U.S. approval in 2025 Sickle cell disease Potential U.S. approval in 2026 PK activation franchise positioned for meaningful expansion, with near-term opportunity in thalassemia 3-8K patients in the U.S./EU5 18-23K patients in the U.S./EU5 120-135K patients in the U.S./EU5 75-80K patients in the U.S./EU5 Source: Agios internal estimates Lower-risk myelodysplastic syndrome Orphan patient populations High unmet need Focused prescriber pool Differentiated product profile PYRUKYND® is the first and only disease-modifying treatment approved for adults with PK deficiency Potential for two additional PYRUKYND® indications by 2026
RESEARCH EARLY-STAGE CLINICAL DEVELOPMENT LATE-STAGE CLINICAL DEVELOPMENT REGULATORY SUBMISSION APPROVAL Pyruvate Kinase Deficiency α- and β-Thalassemia ACTIVATE Kids ACTIVATE KidsT ENERGIZE ENERGIZE-T Sickle Cell Disease* Myelodysplastic Syndrome (MDS) Healthy Volunteers / Sickle Cell Disease Phenylketonuria (PKU) RISE UP PHASE 2 PHASE 1 PYRUKYND® First-in-class PK activator AG-946 Novel PK activator Phenylalanine hydroxylate (PAH) stabilizer US, EU, GB Building a diverse pipeline leveraging our expertise in cellular metabolism *In addition to RISE UP, two investigator-sponsored trials are ongoing with the NIH and University of Utrecht.
Compelling and consistent data across connected diseases PK activation may address a range of hemolytic and acquired anemias underpinned by shared pathophysiology
Energy imbalance in red blood cells can lead to severe hematological disease Insufficient ATP production Leads to red blood cell metabolic stress, anemia, and reduced patient quality of life Energy supply Energy demand Healthy Red Blood Cell ATP production meets demand PK Deficiency Other Anemias Thalassemia, Sickle Cell Disease, Lower-Risk MDS
Chronic Hemolysis Destruction of red blood cells Ineffective Erythropoiesis Decreased output of red blood cells Disease areas share common pathophysiology and severely impact quality of life ANEMIA TRANSFUSION BURDEN IRON OVERLOAD REDUCED BONE MINERAL DENSITY LONG-TERM ORGAN DAMAGE Significant near and long-term clinical consequences of chronic hemolysis and ineffective erythropoiesis… CHRONIC FATIGUE, SUSCEPTIBILITY TO ILLNESS CHALLENGES WITH BASIC SOCIAL, SCHOOL / WORK ACTIVITIES IMPACT ON EMOTIONAL AND MENTAL HEALTH PAIN AND FRACTURES ECONOMIC BURDEN ..that lead to major implications for patient quality of life and how they feel and function. PK Deficiency Sickle Cell Disease Thalassemia MDS Associated Anemia Red Blood Cell Metabolic Stress
Phase 3 ENERGIZE and ENERGIZE-T studies Phase 2 long-term extension study Phase 3 long-term extension study Phase 2/3 RISE UP study Investigator-sponsored trials Consistency of clinical data to date supports potential of PYRUKYND® to address unmet patient needs across hemolytic anemias 1. Al-Samkari et al. N Engl J Med 2022; 386:1432-1442; 2. Glenthoj et al. The Lancet Haematology, 2022, Vol 9, e724 - e732; 3. Van Beers et al. ASH 2021: Abstract 757; 4. Al-Samakri et al. ASH 2021. Abstract 924; 5. Kuo et al. ASH 2022: Abstract 506; 6. Van Beers et al. ASH 2022: Abstract 1021; 7. Grace et al. ASH 2022: Abstract 2328; 8. Kuo KHM et al. Lancet 2022; 400:10351; 9. Kuo KHM et al. ASH 2021: Abstract 576; 10. Kuo KHM et al. ASH 2022: Abstract 1030; 11. Van Dijk MJ et al. Am J Hematol. 2022;97:E226; 12. Xu JZ et al. Blood. 2022;140:2053; 13. Van Dijk MJ et al. EHA 2022: Abstract P1501. Thalassemia (Wild-type PK enzyme) Data through Phase 2 Adult PK Deficiency (Mutant PK enzyme) Approved in the U.S., EU and Great Britain Sickle Cell Disease (Wild-type PK enzyme) Data through Phase 1 and ISTs Hemoglobin improvement Hemolysis improvement Erythropoiesis improvement Transfusion reduction PRO improvements Sickling reduction ONGOING STUDY ONGOING STUDIES ONGOING STUDIES
Emerging Long-term Data Thalassemia (Wild-type PK enzyme) Data through Phase 2 Adult PK Deficiency (Mutant PK enzyme) Approved in the U.S., EU and Great Britain Sickle Cell Disease (Wild-type PK enzyme) Data through Phase 1 and ISTs Consistency of clinical data to date supports potential of PYRUKYND® to address unmet patient needs across hemolytic anemias Hemoglobin improvement Hemolysis improvement Erythropoiesis improvement PRO improvements Sickling reduction Transfusion reduction Bone health stabilization Iron overload reduction Length of exposure OVER 7 YEARS OVER 4.5 YEARS OVER 2 YEARS 1. Al-Samkari et al. N Engl J Med 2022; 386:1432-1442; 2. Glenthoj et al. The Lancet Haematology, 2022, Vol 9, e724 - e732; 3. Van Beers et al. ASH 2021: Abstract 757; 4. Al-Samakri et al. ASH 2021. Abstract 924; 5. Kuo et al. ASH 2022: Abstract 506; 6. Van Beers et al. ASH 2022: Abstract 1021; 7. Grace et al. ASH 2022: Abstract 2328; 8. Kuo KHM et al. Lancet 2022; 400:10351; 9. Kuo KHM et al. ASH 2021: Abstract 576; 10. Kuo KHM et al. ASH 2022: Abstract 1030; 11. Van Dijk MJ et al. Am J Hematol. 2022;97:E226; 12. Xu JZ et al. Blood. 2022;140:2053; 13. Van Dijk MJ et al. EHA 2022: Abstract P1501.
Meaningful commercial opportunities on the horizon FDA approval and launch of PYRUKYND in PK deficiency builds capabilities to maximize potential product expansion
Optimizing Patient & Provider Journey PYRUKYND® launch in PK deficiency building commercial capabilities to support potential expansion in meaningfully larger patient populations Therapy Onboarding Access & Adherence Diagnostic Efficiency Awareness & Education Coverage support, free product eligibility, copay program Free genetic testing to help confirm diagnosis of hereditary anemias PK deficiency patient identification via claims-based targeting Activate physicians to prescribe and eligible patients to advocate for treatment Drive awareness and urgency to manage PK deficiency among providers and patients
High unmet need across patient segments and geographies ~18-23K Patients in U.S./EU5 Significant opportunity outside U.S./EU5 Thalassemia: no approved therapies for ~60% of patients Beta-THAL prevalence: HEOR Global THAL Epidemiology SLE (XCENDA, 2021); US: Paramore, et.al; DE: Borchert, et.al; IT: Italian Society of Thal & Hemoglobinopathies Patient Registry, Jan 2021, Angelucci, et.al, 2017; FR: French registry for thal (Thuret, et.al.); ES: Cela, et.al.; UK Registry for Hemoglobinopathies, 2020; Alpha-THAL prevalence: Agios internal estimates; LEK Analysis | Beta-THAL TD/NTD split (60% / 40%): Thuret, et.al., Haematologica 2010; Magnolia TPP MR, April 2020 | Alpha-THAL TD/NTD split (5% / 95%): Taher, et.al., Vox Sanguinis, 2015; Magnolia TPP MR, April 2020. PYRUKYND® is under investigation for thalassemia and is not approved anywhere for that use. PYRUKYND® Address full range of thalassemia patients Chronic therapy Oral Improved Hb and reduced transfusion burden Improved ineffective erythropoiesis Safety profile consistent with prior clinical experience TARGET PROFILE ~30% ALPHA-THALASSEMIA NON-TRANSFUSION DEPENDENT ~40% BETA-THALASSEMIA TRANSFUSION DEPENDENT ~28% BETA-THALASSEMIA NON-TRANSFUSION DEPENDENT ~2% ALPHA-THALASSEMIA TRANSFUSION DEPENDENT NO AVAILABLE THERAPIES 60%
PYRUKYND® Chronic Therapy Oral Improved hemolytic anemia Improvement in sickle cell pain crises (vaso-occlusive crises; VOCs) QoL data Safety profile consistent with prior clinical experience TARGET PROFILE Sickle Cell Disease: no novel oral therapy improves anemia and reduces sickle cell pain crises PYRUKYND® is under investigation for sickle cell disease and is not approved anywhere for that use. Estimated 120-135K patients across the U.S. & EU5 Significant opportunity outside of U.S./EU Deliver a novel oral therapy that improves anemia, reduces VOCs and is supported by the largest body of clinical evidence Innovative seamless Phase 2/3 trial RISE UP developed with community input Global approach to clinical development Connections with SCD patient and physician communities Global Reach PYRUKYND® Opportunity Critical Success Factors
Well capitalized to advance and expand Long-term growth and value creation fueled by accomplished leadership team and strong balance sheet
Focused on rare diseases rooted in cellular metabolism Strong cash position expected to support portfolio advancement and expansion PYRUKYND® First and only disease-modifying treatment for adults with PK deficiency Potential for two additional indications by 2026 AG-946 Potential to be first oral therapy to address the underlying cause of ineffective erythropoiesis in MDS LEAD RESEARCH PROGRAM PAH stabilizer for the treatment of PKU ~15-20K patients in the U.S.; ~20K in the EU5 Target to file IND by year-end 2023 DISCIPLINED BD STRATEGY Prioritize opportunities based on: Rare disease focus Transformative for patients Identified regulatory pathway Potential to de-risk early Clear path to value creation CLINICAL-STAGE PIPELINE EARLIER-STAGE PIPELINE BUSINESS DEVELOPMENT Deliver transformative therapeutics for patient communities with profound unmet need *PAH: phenylalanine hydroxylate; PKU: Phenylketonuria
2023 and Beyond Clinical development strategy driving toward broader commercial opportunities
Clinical and regulatory milestones targeted in 2023 lay the foundation for transformational data readouts Build commercial capabilities to efficiently launch additional indications and evaluate business development opportunities to expand pipeline Thalassemia PYRUKYND® Pediatric PK Deficiency PYRUKYND® Sickle Cell Disease PYRUKYND® Lower-Risk MDS AG-946 (Novel PK Activator) Complete enrollment of Phase 2a study (year-end) Complete enrollment of Phase 3 ENERGIZE and ENERGIZE-T studies (mid-year) Phase 2 RISE UP data readout & go/no-go to Phase 3 decision (mid-year) Enroll at least half of patients in the Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies (year-end) Earlier-stage Pipeline File IND for PAH stabilizer for the treatment of PKU (year-end)
Potential for two additional PYRUKYND® indications by 2026 Thalassemia PYRUKYND® Pediatric PK Deficiency PYRUKYND® Sickle Cell Disease PYRUKYND® Lower-Risk MDS AG-946 (Novel PK Activator) Phase 3 ACTIVATE-kids and ACTIVATE-kidsT readouts Phase 3 ENERGIZE (1H) and ENERGIZE-T (2H) readouts Potential approval Potential approval Potential approval Phase 2a readout 2024 2025 2026 Potential Phase 3 RISE UP readout* *Pending Go/NoGo decision in 2023
Differentiated Capabilities & Cross-functional Connectivity Hematology franchise spanning 3 hemolytic anemias Expanded portfolio aligned with our core expertise Cash flow positive 2026 VISION Driven to transform patient outcomes in rare diseases
Q&A