Agios Pharmaceuticals : Q1 2025 webcast presentation 050125 final

Published: 2025-05-01 07:53:05 ET AGIO

Published on 05/01/2025 at 07:53

Q1 2025 Financial Results and Business Update

May 1, 2025

Agios Conference Call Participants

TOPIC

PARTICIPANT

Introduction

Chris Taylor, VP Investor Relations and Corporate Communications

Business Update

Brian Goff, Chief Executive Officer

R&D Update

Sarah Gheuens, M.D., Ph.D., Chief Medical Officer, Head of R&D

Commercial Update

Tsveta Milanova, Chief Commercial Officer

First Quarter 2025 Financial Results

Cecilia Jones, Chief Financial Officer

Q&A

Mr. Goff, Dr. Gheuens, Ms. Milanova, Ms. Jones

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), tebapivat, AG-236 and AG-181; Agios' plans, strategies and expectations for its preclinical, clinical and commercial advancement of its drug development, including PYRUKYND®, tebapivat, AG-

181 and AG-236; the submission of PYRUKYND ® to regulators for approval in alpha-and-beta thalassemia; Agios' strategic vision and goals, including its key

milestones for 2025; and the potential benefits of Agios' strategic plans and focus. The words "anticipate", "expect", "goal", "hope", "milestone", "opportunity", "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 pandemics or other public health emergencies 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 establish and maintain key collaborations; uncertainty regarding any royalty payments related to the sale of its oncology business or any milestone or royalty payments related to its in-licensing of AG-236, and the uncertainty of the timing of any such payments; uncertainty of the results and effectiveness of the use of Agios' cash and cash equivalents; 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.

Business Overview

Brian Goff

Chief Executive Officer

A Rare Blueprint for Success

Multi-Billion-Dollar Market Opportunity with PYRUKYND®

Robust Pipeline, Rich with Near-Term Catalysts

Proven Executional Excellence, Powered by Highly Experienced Team

Strong Financial Position

2025: Breakout Year

2024

Transformative Year

2025

Breakout Year

Progressed pipeline and reached critical clinical and regulatory milestones

Bolstered commercialization expertise

Expanded geographic commercial reach

Strengthened balance sheet

Maximize potential of

PYRUKYND® franchise

Progress and diversify key pipeline programs

Focus capital deployment priorities to sustain growth

Clinical and Regulatory Near-Term Catalysts Offer Potential to Significantly Drive Shareholder Value

2025

LATE

MID-YEAR

EARLY

Pediatric PK Deficiency PYRUKYND®

Phase 3 data readout for ACTIVATE-Kids study

Sickle Cell Disease

Tebapivat

Begin patient enrollment in Phase 2 study

Thalassemia

PYRUKYND®

Potential FDA approval

(PDUFA goal date is September 7, 2025)

Polycythemia Vera

AG-236

File IND application

Sickle Cell Disease PYRUKYND®

Phase 3 data readout for

RISE UP study

Complete patient enrollment in

Phase 2b study

Early: January - April; Mid-Year: May - August; Late: September - December 7

Clinical Overview

Sarah Gheuens, M.D., Ph.D.

Chief Medical Officer, Head of R&D

Advancing Therapies for Rare Diseases with Limited or No Treatment Options

COMPOUND

INDICATION

PRECLINICAL

EARLY-STAGE CLINICAL DEVELOPMENT

LATE-STAGE CLINICAL DEVELOPMENT

REGULATORY SUBMISSION

APPROVAL

PYRUKYND®

First-in-class PK activator

Pyruvate Kinase Deficiency

U.S., EU, GB

ACTIVATE - Kids T

ACTIVATE - Kids

NTDT and TDT

α- and β-Thalassemia

S., EU, KSA, UAE

FDA PDUFA goal date September 7, 2025

Sickle Cell Disease

RISE UP

Tebapivat (AG-946)

Novel PK activator

Lower Risk Myelodysplastic Syndromes

Sickle Cell Disease

AG-181

Phenylalanine hydroxylase (PAH) stabilizer

Phenylketonuria

AG-236

siRNA Targeting TMPRSS6

Polycythemia Vera

of thalassemia patients with no approved therapies in the U.S.

Increased Mortality

Lower survival for thalassemia patients, and significantly worse in patients who remain non-regularly transfused compared to regularly transfused patients

~33%

Transfusion dependent (~2K Adults)

~67%

Non-transfusion dependent

(~4K Adults)

Serious Morbidities

High rates of morbidities and frequency of complications increasing as patients age

Poor Quality of Life

Adult patients with NTDT may have similar or worse Healthcare Related QoL compared with patients with TDT

Healthcare Resource Utilization and Cost

A 1g/dL decrease in average Hb levels is associated with increased inpatient, outpatient

and ER visits/costs, Rx costs, and total healthcare costs in patients with NTDT

Sources: Beta-THAL prevalence: HEOR Global THAL Epidemiology SLE (XCENDA, 2021); US: Paramore, et.al; DE: Borchert, et.al; Alpha-THAL prevalence: Agios internal estimates; LEK Analysis | Beta-THAL TD/NTD split: Thuret, et.al., Haematologica 2010; Magnolia TPP MR, April 2020 | Alpha-THAL TD/NTD split; Taher, et.al., Vox Sanguinis, 2015; Magnolia TPP MR, April 2020. Musallam, K, et al.. 2022. Hemasphere 6(12) e806;Thalassemia International Federation, 2023; Musallam, K, et al., 2021. Am J Hematol 97(2) E78-E80; Association of Hemoglobin Levels with Healthcare Resource Utilization and Costs in Non-Transfusion Dependent Alpha and Beta Thalassemia: A Retrospective Observational Study Using Real-World Data (August 1, 2023); Musallam KM et al. Ann Hematol 2021. doi: 10.1007/s00277-020-04370-2; Musallam K., et al. Haematologica. 2021 Sep 1; 106(9): 2489-2492

PYRUKYND® Poised to Be First and Only Approved Therapy Indicated to Treat All Subtypes of Thalassemia

ENERGIZE and ENERGIZE-T Phase 3 Results Presented at EHA 2024 and ASH 2024

Population

Enrolled a total of 452 patients reflective of the real-world thalassemia population

Enrolled adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia

Efficacy

Primary and all key secondary efficacy endpoints were met

Demonstrated significant improvements in hemoglobin and fatigue

Demonstrated significant reductions in transfusion burden

Safety

Overall, incidence of AEs was similar for patients on mitapivat and patients on placebo

During the double-blind periods, there were 4.7% (n=14) of patients on mitapivat and 0.7% (n=1) of patients on placebo with TEAEs leading to treatment discontinuation

During the double-blind periods, two patients on mitapivat experienced events of hepatocellular injury. During the open-label extension period, three patients experienced events of hepatocellular injury after switching from placebo to mitapivat. All events occurred within the first six months of exposure. Liver tests improved following discontinuation of mitapivat

Established a favorable benefit-risk profile for mitapivat in adult patients with non-transfusion-dependent and transfusion-dependent alpha- or

beta-thalassemia

Filed for regulatory approval in the U.S., European Union, Kingdom of Saudi Arabia and United Arab Emirates

FDA accepted PYRUKYND sNDA; PDUFA goal date is September 7, 2025

PYRUKYND® is under investigation for thalassemia and is not approved anywhere for that use.

Sources: Taher AT. ENERGIZE: A global, phase 3 study of mitapivat demonstrating efficacy and safety in adults with alpha- or beta-non-transfusion-dependent thalassemia. Oral presentation presented at: European Hematology Association (EHA) Hybrid Congress; June 2024; Madrid, Spain, and Virtual.

Cappellini MD. ENERGIZE-T: A global, phase 3, double-blind, randomized, placebo-controlled study of mitapivat in adults with transfusion-dependent alpha- or beta thalassemia. Oral presentation presented at: 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 2024; 11

San Diego, CA, and online.

AEs: Adverse events; TEAEs: Treatment-emergent adverse events; sNDA: supplemental New Drug Application; PDUFA: Prescription Drug User Fee Act

OUR OPPORTUNITY

120-135K patients

in the U.S./EU5*

~150K patients

in GCC*

>3M patients

Worldwide*

Increased Mortality

30-year reduction in life expectancy; 48 years median survival in patients with severe sickle cell disease

Serious Morbidities

Associated with high rates of morbidities, including anemia, increased risk of

infection, acute chest syndrome, and stroke

Poor Quality of Life

Significantly disrupts various aspects of life, including fatigue, emotional and financial well-being

Healthcare Resource Utilization and Cost

Economic burden driven by frequent hospitalizations, ER visits, outpatient visits, and

prolonged hospital stays

*Prevalence figures

Sources: Agios internal estimates. Faro EZ, et al. Am J Prev Med. 2016;51(suppl 1):S48-S54. National Academies of Sciences, Engineering, and Medicine. Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action. 2020. The National Academies Press. https://doi.org/10.17226/25632. Huo J, et al. Value in Health. 2018;21(suppl 2):S108. 2. Lee S, et al. Int J Gen Med. 2020:13:361-377.

EU: European Union; GCC: Gulf Cooperation Council; ER: Emergency Room

PYRUKYND® Offers Best-in-Class Opportunity in Sickle Cell Disease with Potential to Improve Anemia, Reduce VOCs and Improve How Patients Feel and Function

Phase 3 RISE UP study topline readout in late 2025; Potential U.S. launch in 2026

STUDY POPULATION

Sickle cell disease patients 16 years of age or older

200+ patients enrolled worldwide (trial enrollment completed in October 2024)

STUDY

DESIGN

52-week double blind period followed by 216-week open label extension 2:1 randomization (100 mg mitapivat or placebo, BID)

TWO PRIMARY ENDPOINTS*

Hb response defined as a ≥1.0 g/dL increase in average Hb concentration from Week 24 through Week 52 compared with baseline

Annualized rate of SCPCs

SECONDARY ENDPOINTS

Additional clinical efficacy measures related to anemia, hemolysis, erythropoiesis, patient-reported fatigue and pain, annualized frequency of hospitalizations for SCPCs and 6MWT

*Powering details in appendix

PYRUKYND® is under investigation for sickle cell disease and is not approved anywhere for that use.

Source: Andemariam B. Study design of the phase 3 portion of RISE UP: A phase 2/3, randomized, double-blind, placebo-controlled study of mitapivat in patients with sickle cell disease. Poster presentation presented at: 2024 European Hematology Association (EHA) Hybrid Congress; June 2024; Madrid, 13

Spain, and Virtual.

VOCs: Vaso-occlusive crisis; BID: Twice daily; Hb: Hemoglobin; SCPCs: sickle cell pain crises; 6MWT: 6 minute walking test

Tebapivat Provides High-Growth Potential with Best- and First-in-Class Opportunities in Areas of Critical Medical Need

Lower-Risk MDS

Potential first oral therapy for lower-risk MDS-associated anemia

~75K-80K

patients in U.S./EU5

MEDICAL NEED

PREVALENCE

No oral therapy addresses ineffective erythropoiesis; accounts for ~70% of all MDS cases

STATUS

Phase 2b study ongoing, with patient enrollment completion expected in

late 2025

Sickle Cell Disease

Expand addressable

patient population

~120-135K

patients in U.S./EU5

Multiple innovative

therapies

that demonstrate clinically meaningful benefits

Phase 1 study complete; Phase 2 patient enrollment to be

initiated in mid-2025

Sources: Agios internal estimates. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. 14

MDS: Myelodysplastic syndromes; EU: European Union

Phase 2 Study of Tebapivat in Sickle Cell Disease

Phase 2

Primary endpoint:

Status

Patient enrollment expected to

commence mid-2025

Key inclusion criteria

≥ 16 years of age

Hemoglobin 5.5-10.5 g/dL

If taking hydroxyurea, dose

stable for 90 days

Key Exclusion Criteria

>10 SCPCs in the 12 months prior to consent

Receiving regularly scheduled RBC transfusion therapy

Secondary endpoints: Safety, changes in hemoglobin, additional measures of hemolysis, erythropoiesis; PROs: PROMIS Fatigue, PROMIS Pain, ASCQ-Me

Hb response, defined as ≥ 1.0 g/dL increase in hemoglobin concentration from Week 10 through Week 12 compared with baseline

Tebapivat

Placebo

Tebapivat (dose randomization)

Extension Period

Placebo (n=8)

2.5mg QD

Extension Period

2.5mg QD (n=16)

N=56

Dose ranging study with concurrent placebo control

Randomization

Tebapivat

5mg QD

Extension Period

5mg QD (n=16)

7.5mg QD

Extension Period

7.5mg QD (n=16)

Core Period: 12 Weeks

OLE: 1 Year

Hb= hemoglobin; OLE=open label extension; PKa=pyruvate kinase activator; ASCQ-Me= Adult Sickle Cell Quality of Life Measurement Information System;

PRO=patient reported outcome; SCPC=sickle cell pain crisis; RBC=red blood cells 15

Phase 2b Open-Label Study of Tebapivat in Lower-Risk MDS

N=60

Completion of enrollment in one cohort triggers the opening of enrollment in the next cohort

Phase 2b

Primary endpoint:

Secondary endpoints: safety, change in hemoglobin, TI for 12 weeks, additional measures of anemia, PK and PD biomarkers

Transfusion independence, defined as transfusion-free for ≥8 consecutive weeks during the Core Period

10mg QD

Core Period

Tebapivat Treatment Period

10mg QD

Extension Period

15mg QD

Core Period

Tebapivat Treatment Period

15mg QD

Extension Period

20mg QD

Core Period

Tebapivat Treatment Period

20mg QD

Extension Period

Status

Completion of enrollment expected in late-2025

Key inclusion criteria

≥ 18 years of age

Lower-risk MDS (risk score: ≤3.5) according to IPSS-R classification (WHO classification; Arber et al, 2016)

Transfusion dependent, with LTB or HTB according to revised IWG 2018 criteria

An Hb concentration <10.0 g/dL

Up to 2 prior therapies, including ESAs and/or luspatercept

Key exclusion criteria

Known history or AML or secondary MDS

Prior exposure to a PK activator, IDH inhibitors, IST, stem cell transplant

Currently receiving imetelstat, lenalidomide, HMAs allowed after

QD = once daily; TI = transfusion independence

HTB = high transfusion burden; LTB = low transfusion burden; IWG = International Working Group; AML = Acute myeloid leukemia

Core Period: 24 Weeks

Extension Period: 156 Weeks

sufficient washout period

Early-Stage Pipeline Offers Opportunity for Advancement

PREVALENCE

MEDICAL NEED

STATUS

Phenylketonuria

AG-181

~35-40k patients

in U.S./EU5

Left untreated can cause range of neurocognitive issues and decrease in IQ; limited treatment options

Phase 1 study in healthy volunteers progressing to MAD in mid-2025

Polycythemia Vera

AG-236

~100k patients in U.S.

Risk of thrombosis, CV events, enlarged spleen and death; Phlebotomy is standard of care

IND application filing in mid-2025

Sources: Agios internal estimates. van Wegberg et al. Orphanet Journal of Rare Diseases (2017) 12:162. Spivak JL. Myeloproliferative Neoplasms: Challenging Dogma. J Clin Med. 2024;13(22):6957. doi:10.3390/jcm13226957. 17

Commercial Overview

Tsveta Milanova

Chief Commercial Officer

PYRUKYND® Expansion into Larger Patient Populations Provides Multi-Billion-Dollar Market Opportunity

18-23K patients

in the U.S./EU5*

~70K patients in GCC*

>1M patients worldwide*

120-135K patients

in the U.S./EU5*

~150K patients

in GCC*

>3M patients

worldwide*

3-8K patients

in the U.S./EU5*

PK Deficiency 2022

Approved for adults in the U.S., EU and Great Britain

Thalassemia 2025

Potential U.S. approval

Sickle Cell Disease 2026

Potential U.S. approval

O U R G O A L

Deliver the first approved therapy for pediatric PK deficiency

O U R G O A L

Deliver the first therapy approved for all thalassemia subtypes

O U R G O A L

Deliver a novel oral therapy that improves anemia

and reduces VOCs

PYRUKYND® is approved in the U.S. for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency and in the Europe Union and in Great Britian for the treatment of PK deficiency in adult patients. It is under investigation for pediatric PK deficiency, thalassemia, and sickle cell disease.

*Prevalence figures.

Source: Agios internal estimates

Commercial Expertise and Capabilities in Place to Deliver Strong U.S. Launch; PDUFA Goal Date September 7, 2025

Disease State

Education

Patient and HCP targeted education on unmet need via digital and personal channels

Synergistic omni-channel approach

Commercial

Presence

Right sized customer-facing teams

Focused targeting and HCP profiling

Market

Access

Payer education on Thalassemia

Strong value proposition for payers

Initial PYRUKYND® U.S. Launch will Focus on Addressing ~65% of Thalassemia Patient Population

Initial Launch Focus for PYRUKYND

Expanded Launch Focus

for PYRUKYND

Younger Transfused Patient on Iron Chelators*

Older Patient with Kidney Disease and/or Diabetes

Hb<10 g/dL Patient with Anemia and Fatigue

Hb>10 g/dL Patient with Anemia

Co-morbid Sickle Cell Disease Patient

~ 65%

of diagnosed thalassemia patients; Based on higher frequency of visits

~ 35%

of diagnosed thalassemia patients

*Patients aged 18 years and older

Source: U.S. EHR Data Analysis 21

Agios Market Research Identified Top Clinical Characteristics Healthcare Providers Will Consider When Prescribing PYRUKYND

Top Clinical Patient Characteristics HCPs Will Consider When Prescribing PYRUKYND

Hb Fe

Transfusion Burden

Fatigue Iron

Overload

Source: US THAL Demand Study (N=97 Heme/Oncs); Agios internal data, 2024

PYRUKYND® has Potential to Transform the Thalassemia Treatment Landscape

PYRUKYND® Q1 2025 Performance Metrics Highlight Continued Progress

$8.7M net sales of PYRUKYND®

compared with $10.7M in Q4 2024 and $8.2M in Q1 2024

136 patients on PYRUKYND®,

which includes new prescriptions and those continuing treatment

234 unique patients completed PYRUKYND® prescription enrollment forms, including 11 in Q1, a 5% increase over Q4 2024

Unique prescriber base of

202 physicians, diversified across the country

Financial Overview

Cecilia Jones

Chief Financial Officer

First Quarter 2025 Financial Results

Statement of Operations

Three Months Ended 3/31/25

Three Months Ended 3/31/24

PYRUKYND® Net Revenue

$8.7M

$8.2M

Cost of Sales

$1.1M

$0.6M

Research & Development Expense

$72.7M

$68.6M

Selling, General & Administrative Expense

$41.5M

$31.0M

Net Loss

($89.3M)

($81.5M)

Balance Sheet

3/31/25

12/31/24

Cash, Cash Equivalents and Marketable Securities

$1.4B

$1.5B

Closing Remarks

Brian Goff

Chief Executive Officer

Clinical and Regulatory Near-Term Catalysts Offer Potential to Significantly Drive Shareholder Value

2025

LATE

MID-YEAR

EARLY

Pediatric PK Deficiency PYRUKYND®

Phase 3 data readout for

ACTIVATE-Kids study

Sickle Cell Disease Tebapivat

Begin patient enrollment in

Phase 2 study

Thalassemia PYRUKYND®

Potential FDA approval

(PDUFA goal date is September 7, 2025)

Polycythemia Vera AG-236

File IND application

Sickle Cell Disease PYRUKYND®

Phase 3 data readout for RISE UP study

Complete patient enrollment in Phase 2b study

Early: January - April; Mid-Year: May - August; Late: September - December 28

Delivering Significant Value Through Strategic Capital Allocation

$1.4B Cash, Cash Equivalents and Marketable Securities*

Maximize

PYRUKYND®

Thalassemia

and Sickle Cell Disease Potential Launches

Advance

Early- and Mid-Stage Clinical Pipeline

Expand

Pipeline with Internal and External Opportunities

Thank You!

Disclaimer

Agios Pharmaceuticals Inc. published this content on May 01, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 01, 2025 at 11:52 UTC.