On February 25, 2021 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and genetically defined diseases, reported business highlights and financial results for the fourth quarter and year ended December 31, 2020 (Press release, Agios Pharmaceuticals, FEB 25, 2021, View Source [SID1234575673]).

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"This past year was a transformative one for Agios," said Jackie Fouse, Ph.D., chief executive officer at Agios. "Despite the extraordinary challenges brought on by the global COVID-19 pandemic and civil and political unrest in the U.S., we remain hopeful for the future of our country and the promise of our industry and more confident than ever in our ability to execute on our plans on behalf of patients. The sale of our oncology business to Servier on attractive terms both allows our oncology portfolio to grow and flourish and facilitates our new laser focus on genetically defined diseases, where we anticipate a catalyst-rich year ahead for mitapivat across our three initial disease indications. In addition to our plans to file for approval for mitapivat in adults with PK deficiency in the U.S. and EU and launching our Phase 3 thalassemia trials later this year, we’re pleased to share our pivotal strategy for mitapivat in sickle cell disease which we believe will enable us to pursue a broad label for patients who desperately need new treatment options."

FOURTH QUARTER 2020 & RECENT HIGHLIGHTS

Entered into definitive agreement to sell commercial, clinical and research-stage oncology portfolio to Servier, an independent global pharmaceutical company, in December.
Achieved TIBSOVO (ivosidenib tablets) net sales of $39.1 million for the quarter and $121.1 million for the year, exceeding the $115 million updated net revenue target and representing a 102% increase in net sales year-over-year.
Announced topline results from two Phase 3 studies of mitapivat in adults with pyruvate kinase (PK) deficiency who were not regularly transfused (ACTIVATE) and who were regularly transfused (ACTIVATE-T ). Both studies achieved statistical significance for their primary endpoint with ACTIVATE demonstrating a clinically meaningful sustained increase in hemoglobin compared to placebo and ACTIVATE-T demonstrating a clinically meaningful reduction in transfusion burden. Statistical significance was also achieved for all pre-specified key secondary endpoints for ACTIVATE demonstrating an improvement compared to placebo, including in patient-reported outcomes (PRO) based on changes from baseline in pyruvate kinase deficiency diary (PKDD) score and pyruvate kinase deficiency impact assessment (PKDIA) score at Week 24. The safety profile was consistent with results from prior studies.
Completed U.S. and EU regulatory interactions on the pivotal development plan for mitapivat in sickle cell disease, resulting in the Phase 2/3 trial design being announced today.
The Phase 2 will randomize 69 patients 1:1:1 to 50 mg mitapivat BID, 100 mg mitapivat BID or matched placebo. The primary endpoint is hemoglobin response defined as ≥1 g/dL change from baseline to Week 12.
The Phase 3 will randomize 198 patients 2:1 to the selected Phase 2 dose of mitapivat or matched placebo. The study includes two primary endpoints: hemoglobin response defined as ≥1 g/dL change from baseline to Week 52 and annualized rate of sickle cell pain crises.
Potential regulatory approval with a broad label based on the operationally seamless Phase 2/3 trial expected by the end of 2026.
Appointed Darrin Miles, previously senior vice president, U.S. commercial and global marketing, to role of chief commercial officer.
Presented final data, including mature overall survival (OS) results, from the Phase 3 ClarIDHy study of TIBSOVO in patients with previously treated isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) in January.
Presented updated Phase 1 data for mitapivat in sickle cell disease at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December.
Launched Anemia ID, a program providing no-cost genetic testing for patients with suspected hereditary anemias, including PK deficiency in November.
ANTICIPATED 2021 KEY MILESTONES

Corporate

Complete sale of oncology portfolio to Servier in a transaction worth up to $2 billion plus royalties, following a shareholder vote on March 25, and execute a meaningful portion of the planned $1.2 billion capital return by year-end.
Genetically Defined Diseases

File for regulatory approval for mitapivat in adults with PK deficiency: submit new drug application (NDA) in the U.S. in the second quarter of 2021 and marketing authorization application (MAA) in the EU in mid-2021.
Initiate two Phase 3 studies of mitapivat, ENERGIZE and ENERGIZE-T, in not regularly transfused and regularly transfused adults with thalassemia in the second half of 2021.
Initiate Phase 2/3 study of mitapivat in sickle cell disease by year-end.
Prioritize new indications for pyruvate kinase R (PKR) and pyruvate kinase M2 (PKM2) activator clinical development by year-end.
Genetically Defined Disease Data Presentations

Submit data from the following clinical studies for presentation at the EHA (Free EHA Whitepaper) Virtual Congress, hosted June 9-17, 2021:
Phase 3 ACTIVATE study of mitapivat in adults with PK deficiency who do not receive regular transfusions
Phase 3 ACTIVATE-T study of mitapivat in adults with PK deficiency who receive regular transfusions
Phase 2 study of mitapivat in adults with α- and β-thalassemia who do not receive regular transfusions
Submit data from ongoing clinical studies of mitapivat in sickle cell disease for presentation at medical meetings throughout 2021.
Present data from the single ascending dose (SAD) and multiple ascending dose (MAD) cohorts of the Phase 1 study of AG-946, the company’s next-generation PKR activator, in healthy volunteers by year-end.
Oncology

Submit supplemental new drug application (sNDA) in the U.S. for TIBSOVO in patients with previously treated IDH1-mutant cholangiocarcinoma in Q1 2021.
Enrollment in the Phase 3 AGILE trial of TIBSOVO in combination with azacitidine in adult patients with previously untreated IDH1-mutant acute myeloid leukemia is expected to complete by year-end.
Enrollment in the relapsed or refractory myelodysplastic syndrome arm of the TIBSOVO Phase 1 study of IDH1-mutant advanced hematologic malignancies is expected to complete by year-end.
Full-year 2021 net product revenue for TIBSOVO is expected to be $160-170 million.
FOURTH QUARTER AND FULL YEAR 2020 FINANCIAL RESULTS

Revenue: Total revenue for the fourth quarter of 2020 was $44.0 million, which includes $2.0 million in collaboration revenue, $39.1 million of net product revenue from sales of TIBSOVO and $2.9 million in royalty revenue from net global sales of IDHIFA under our collaboration agreement with Celgene. This compares to $35.4 million for the fourth quarter of 2019, which included $12.9 million in collaboration revenue, $19.6 million of net product revenue from U.S. sales of TIBSOVO and $3.0 million in royalty revenue from net global sales of IDHIFA. Total revenue for the year ended December 31, 2020 was $203.2 million compared to $117.9 million for the year ended December 31, 2019. The increase in 2020 revenue was primarily driven by a 102% increase in TIBSOVO net product revenue and higher collaboration revenue due to recognition of the remainder of the deferred revenue balance related to the completion of the metabolic immuno-oncology collaboration with Celgene Corporation, a wholly owned subsidiary of Bristol Myers Squibb Company.

Cost of Sales: Cost of sales were $1.0 million for the fourth quarter of 2020 compared to $0.3 million for the fourth quarter of 2019, and $2.8 million for the year ended December 31, 2020 compared to $1.3 million for the year ended December 31, 2019.

Research and Development (R&D) Expenses: R&D expenses were $95.7 million for the fourth quarter of 2020 compared to $106.2 million for the fourth quarter of 2019 and $367.5 million for the year ended December 31, 2020 compared to $410.9 million for the year ended December 31, 2019. The decrease in R&D expense was primarily attributable to a decrease in TIBSOVO clinical development costs, including winding down the ClarIDHy Phase 3 study.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $39.8 million for the fourth quarter of 2020 compared to $34.8 million for the fourth quarter of 2019, and $149.1 million for the year ended December 31, 2020 compared to $132.0 million for the year ended December 31, 2019. The increase in SG&A expense was primarily attributable to increased workforce expenses and professional fees related to the Servier transaction, partially offset by a decrease in external spending due to cost savings initiatives and reduced employee travel related expenses due to restrictions.

Net Loss: Net loss was $97.7 million for the fourth quarter of 2020 compared to $102.4 million for the fourth quarter of 2019, and $327.4 million for the year ended December 31, 2020 compared to a net loss of $411.5 million for the year ended December 31, 2019.

Cash Position and Guidance: Cash, cash equivalents and marketable securities as of December 31, 2020 were $670.5 million compared to $717.8 million as of December 31, 2019. The company expects that its cash, cash equivalents and marketable securities as of December 31, 2020, together with anticipated product and royalty revenue, interest income and expense reimbursements under our collaboration agreements, but excluding any additional program-specific milestone payments, will enable the company to fund its planned operating expenses and capital expenditure requirements to the end of 2022. Following the closing of the Servier transaction and net of the planned capital return, Agios expects to be able to fund its operation through major catalysts and to cash-flow positivity without the need to raise additional equity.

CONFERENCE CALL INFORMATION

Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss fourth quarter and full year 2020 financial results and recent business activities. To participate in the conference call, please dial 1-877-377-7098 (domestic) or 1-631-291-4547 (international) and referring to conference ID 8442238. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.