Core Insights - Agios Pharmaceuticals is scheduled to present at the BofA Securities 2025 Health Care Conference on May 14, 2025 [1] - The presentation will be accessible via a live webcast on the company's website, with a replay available for at least two weeks [2] Company Overview - Agios Pharmaceuticals is a leader in cellular metabolism and PK activation, focusing on therapies for rare diseases [3] - The company markets a first-in-class pyruvate kinase (PK) activator for adults with PK deficiency, which is the first disease-modifying therapy for this condition [3] - Agios is advancing a clinical pipeline that includes investigational medicines for alpha- and beta-thalassemia, sickle cell disease, pediatric PK deficiency, myelodysplastic syndromes (MDS)-associated anemia, and phenylketonuria (PKU) [3] - Additionally, Agios is developing a preclinical TMPRSS6 siRNA as a potential treatment for polycythemia vera [3]

Financial Performance - The net loss for the three months ended March 31, 2025, was $89.3 million, compared to a net loss of $81.5 million for the same period in 2024, resulting in an accumulated deficit of $238.2 million as of March 31, 2025[89]. - Total revenue for the three months ended March 31, 2025, was $8.726 million, an increase of $0.5 million compared to $8.189 million in the same period of 2024[120]. - Total operating expenses for the three months ended March 31, 2025, were $115.355 million, an increase of $15.1 million compared to $100.261 million in the same period of 2024[121]. - Research and development expenses for the three months ended March 31, 2025, totaled $72.743 million, an increase of $4.1 million compared to $68.620 million in the same period of 2024[123]. - Net cash used in operating activities for the three months ended March 31, 2025, was $111.5 million, compared to $99.9 million for the same period in 2024[132][133]. - Cash provided by investing activities was $112.6 million for the three months ended March 31, 2025, compared to $124.6 million in 2024[134]. - Interest income, net for the three months ended March 31, 2025, was $16.087 million, an increase from $8.889 million in the same period of 2024[124]. - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities totaling $1.4 billion[131]. Product Development and Approvals - PYRUKYND® is approved by the FDA for treating hemolytic anemia in adults with PK deficiency, and a supplemental new drug application was submitted for treating alpha- or beta-thalassemia, with a PDUFA goal date of September 7, 2025[81]. - The company is evaluating PYRUKYND® in a phase 3 clinical trial for sickle cell disease and developing other candidates like tebapivat for lower-risk myelodysplastic syndromes[82]. - PYRUKYND® received FDA approval for treating hemolytic anemia in adults with PK deficiency and marketing authorization in the EU and Great Britain[99]. - The company submitted an sNDA to the FDA for PYRUKYND® for treating non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia, with a PDUFA goal date of September 7, 2025[99]. - Tebapivat has been granted orphan drug designation for the treatment of MDS by the FDA, with a phase 2 clinical trial expected to begin in mid-2025[114]. Clinical Trials and Results - In the ENERGIZE trial, 42.3% of patients on PYRUKYND® achieved a hemoglobin response compared to 1.6% in the placebo group, demonstrating statistical significance (p<0.0001) with 194 patients enrolled[102]. - In the ENERGIZE-T trial, 30.4% of patients on PYRUKYND® achieved a transfusion reduction response compared to 12.6% in the placebo group (p=0.0003), with 258 patients enrolled[105]. - The RISE UP study showed that 46.2% and 50.0% of patients in the 50 mg and 100 mg arms, respectively, achieved a hemoglobin response compared to 3.7% in the placebo arm (p=0.0003 and 0.0001) with 79 patients enrolled[109]. - In the ACTIVATE-kidsT study, 28.1% of patients in the mitapivat arm achieved the primary endpoint of transfusion reduction response, compared to 11.8% in the placebo arm[111]. - In the ACTIVATE-kids study, 31.6% of patients in the mitapivat arm achieved a hemoglobin response, while 0% of patients in the placebo arm achieved this response[113]. - The company is evaluating PYRUKYND® in clinical trials for SCD and pediatric patients with PK deficiency[99]. - The company has updated clinical trial protocols to include monthly monitoring of liver tests for the first six months of treatment due to potential hepatocellular injury risks[107]. - The company expects to announce topline data for the phase 3 portion of the RISE UP trial in late 2025, with a potential U.S. commercial launch in 2026 if approved[109]. Business Transactions and Collaborations - The sale of the oncology business to Servier was completed for approximately $1.8 billion in cash, with additional contingent payments based on future approvals and sales[83]. - In September 2024, the company recognized income of $200.0 million from the Vorasidenib Milestone Payment following FDA approval for vorasidenib[86]. - The company recognized income of $889.1 million from the sale of Vorasidenib Royalty Rights to Royalty Pharma, net of fees[87]. - The company entered into a distribution agreement with NewBridge Pharmaceuticals for PYRUKYND® in the GCC region, expanding its market reach[91]. - The company entered a distribution agreement with NewBridge Pharmaceuticals for PYRUKYND® commercialization in the GCC region[100]. Future Outlook and Risks - The company expects to continue generating revenue from product sales and potential milestone payments from collaborations or licensing agreements in the future[92]. - Research and development expenses are expected to increase as product candidate development programs progress, with significant uncertainty regarding costs and timelines[95]. - The company has historically incurred significant operating losses and expects to continue incurring significant expenses until achieving profitable results[89]. - The company expects expenses to increase as it continues research, development, and commercialization of its product candidates, including PYRUKYND®[136]. - Future capital requirements will depend on various factors, including the success of product sales and potential royalty payments from Retained Earn-Out Rights[139]. - The company is exposed to market risks related to interest rates and foreign currency exchange rates, with minimal liabilities in foreign currencies as of March 31, 2025[142][145]. - The company anticipates financing cash needs primarily through cash on hand, potential royalty payments, and product sales until substantial revenue is generated[139]. - The company may need additional capital resources to fund operating plans and capital expenditures, which could involve dilution of stockholder ownership[139].

Financial Data and Key Metrics Changes - In Q1 2025, net PyroKine revenue was $8.7 million, a 6% increase compared to $8.2 million in Q1 2024 [30] - Revenue decreased by 19% compared to Q4 2024, primarily due to year-end stocking benefits and adjustments to revenue reserves [33] - Cost of sales for the quarter was $1.1 million, R&D expenses were $72.7 million, an increase of $4.1 million compared to Q1 2024, and SG&A expenses were $41.5 million, an increase of $10.5 million compared to the prior year [36] Business Line Data and Key Metrics Changes - The company reported a 5% increase in new prescriptions and new patient starts in Q1 2025, translating to 136 net patients on therapy, also a 5% increase versus the prior quarter [31] - The company expects growth in net revenue to be in the 10% to 20% range on an annual basis, consistent with other rare disease launches [34] Market Data and Key Metrics Changes - The thalassemia market is characterized by a well-defined patient population, with approximately 6,000 adults diagnosed in the U.S., and the company estimates that PyroKine's initial launch focus will address about 65% of the adult thalassemia patient population [27][28] - The sickle cell disease community is estimated to include 120,000 to 135,000 individuals in the U.S. and EU5, with a global prevalence exceeding 3 million [13] Company Strategy and Development Direction - The company aims to maximize the potential of the PyroKine franchise, advance and diversify key pipeline programs, and strategically focus capital deployment to sustain growth [7] - The company is preparing for a potential U.S. approval and launch of PyroKine for thalassemia in September 2025, followed by sickle cell disease in 2026 [6][16] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming PDUFA date and the potential to serve patients with unmet needs in thalassemia and sickle cell disease [46][66] - The company is confident in its strong balance sheet, which provides financial independence to support potential launches and advance existing programs [37][39] Other Important Information - The company has a robust early and mid-stage pipeline, with plans to file an investigational new drug application for AG-236 targeting polycythemia vera in mid-2025 [9][20] - The company has engaged in disease state education campaigns to prepare for the launch of PyroKine, focusing on both patients and healthcare providers [24] Q&A Session Summary Question: Has the mid-cycle review happened, and what are the next steps? - Management confirmed that no advisory committee meeting is planned and that the regulatory review is ongoing, with strong engagement with the FDA [45][46] Question: How has the withdrawal of Oxbreda impacted trial recruitment? - Management noted that while the withdrawal was disappointing, it has not affected their clinical trial conduct, and they see a significant opportunity in the sickle cell market [48][49] Question: What are the plans for launching mitapivat ex-U.S.? - The company plans to prioritize the Gulf region and Europe for launches, leveraging partnerships for effective execution [54][57] Question: Any changes in communication frequency with the FDA? - Management stated that communication with the FDA remains consistent, with no changes due to recent agency reshuffling [65][66] Question: Rationale for starting the Phase II tebapivat study in sickle cell? - Management expressed confidence in the unmet need for therapies in sickle cell disease and the potential to grow the patient population with multiple products [72][73] Question: Plans for marketing to non-transfusion dependent patients? - The company plans to focus on both transfusion-dependent and non-transfusion-dependent patients, emphasizing the value proposition of PyroKine for both groups [78] Question: Anticipated evolution of PyroKine's pricing? - Pricing decisions will be based on the value proposition of the label received, with positive feedback from payers regarding the product profile [98]

Business Overview - Agios views PYRUKYND® as having a multi-billion dollar market opportunity [9] - Agios aims to maximize the potential of the PYRUKYND® franchise and progress key pipeline programs in 2025 [11] - Agios anticipates several clinical and regulatory catalysts in 2025, including a potential FDA approval for PYRUKYND® in thalassemia with a PDUFA goal date of September 7, 2025 [13] Clinical Development - Approximately 67% of thalassemia patients are non-transfusion dependent, representing about 4,000 adults in the U S [19] - Approximately 33% of thalassemia patients are transfusion dependent, representing about 2,000 adults in the U S [19] - Agios's PYRUKYND® has the potential to be the first and only approved therapy for all subtypes of thalassemia [23] - The Phase 3 RISE UP study of PYRUKYND® in sickle cell disease completed enrollment in October 2024, with topline data expected in late 2025 [31] - Tebapivat's Phase 2b study in lower-risk MDS expects patient enrollment completion in late 2025 [34, 41] Commercial Performance & Financials - PYRUKYND® net revenue was $8 7 million for Q1 2025, compared to $8 2 million in Q1 2024 [68] - Agios had $1 4 billion in cash, cash equivalents, and marketable securities as of March 31, 2025 [68, 74]

Financial Data and Key Metrics Changes - In the first quarter of 2025, net PyroKine revenue was $8,700,000, a 6% increase compared to $8,200,000 in the first quarter of 2024 [32] - Revenue decreased by 19% compared to the fourth quarter of 2024, primarily due to year-end stocking benefits and adjustments to revenue reserves [32] - Cost of sales for the quarter was $1,100,000, R&D expenses were $72,700,000, an increase of $4,100,000 compared to the first quarter of 2024, and SG&A expenses were $41,500,000, an increase of $10,500,000 compared to the prior year quarter [34] Business Line Data and Key Metrics Changes - The company reported a 5% increase in new prescriptions and new patient starts in the first quarter since the January label update, translating into 136 net patients on therapy, also a 5% increase versus the prior quarter [30] - The company expects growth in net revenue to be in the 10% to 20% range on an annual basis, consistent with other rare disease launches [33] Market Data and Key Metrics Changes - The thalassemia market is characterized by a well-defined patient population, with 67% of diagnosed patients in the U.S. having no approved therapies [12] - The company estimates that its initial launch focus will address approximately 65% of the adult thalassemia patient population [26] Company Strategy and Development Direction - The company aims to maximize the potential of the PyroKine franchise, advance and diversify key pipeline programs, and strategically focus capital deployment to sustain growth [6] - The company is preparing for a potential approval and launch in thalassemia in the U.S. by September 7, 2025, followed by sickle cell disease in 2026 [5][6] - The company is focused on disease state education campaigns to prepare for the launch, emphasizing the importance of monitoring and management of thalassemia [23] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential approval and launch of PyroKine for thalassemia and the Phase III readout for sickle cell disease, viewing 2025 as a breakout year [38] - The company maintains a strong balance sheet with approximately $1,400,000,000 in cash, providing financial independence to support product launches and pipeline advancement [5][36] Other Important Information - The company has a robust early and mid-stage pipeline poised for clinical advancement, with significant expected events for 2025 [8] - The company has welcomed Krishnan Viswanathan as Chief Corporate Development and Strategy Officer to enhance corporate strategy and capital allocation [10] Q&A Session Summary Question: Confirmation about no advisory committee for the September PDUFA - Management confirmed that there is no advisory committee planned and that the regulatory review is ongoing, with strong engagement with the FDA [42][43] Question: Impact of Oxbreda withdrawal on sickle cell trial recruitment - Management noted that they have not observed changes in clinical trial conduct and emphasized the need for multiple therapeutic options for sickle cell disease [46][47] Question: Plans for launching mitapivat ex-U.S. - The company plans to prioritize the Gulf region and Europe for launches, leveraging partnerships for effective execution [50][53] Question: Changes in communication frequency with the FDA - Management stated that communication with the FDA remains consistent and normal, with no changes due to recent agency reshuffling [63] Question: Rationale for starting Phase II tebapivat study in sickle cell - Management highlighted the large unmet medical need in sickle cell disease and the importance of having multiple therapy options for patients [66][69] Question: Anticipated evolution of PyroKine's pricing - Management indicated that pricing decisions will be based on the value proposition of the label received and expressed confidence in navigating pricing opportunities [94][95]

Financial Performance - PYRUKYND generated net revenue of $8.7 million in Q1 2025, up from $8.2 million in Q1 2024, representing a year-over-year increase of 6.1%[3] - The net loss for Q1 2025 was $89.3 million, compared to a net loss of $81.5 million in Q1 2024, reflecting an increase of 9.8%[7] - Cash, cash equivalents, and marketable securities totaled $1.4 billion as of March 31, 2025, down from $1.5 billion at the end of 2024[8] Expenses - Research and Development (R&D) expenses for Q1 2025 were $72.7 million, an increase of 5.2% compared to $68.6 million in Q1 2024[5] - Selling, General and Administrative (SG&A) expenses rose to $41.5 million in Q1 2025, compared to $31.0 million in Q1 2024, marking a 33.9% increase[7] Patient Enrollment - The total number of unique patients who completed prescription enrollment forms for PYRUKYND increased by 5% from Q4 2024, reaching 234 patients[3] Regulatory and Clinical Developments - The FDA accepted the supplemental New Drug Application (sNDA) for PYRUKYND for thalassemia treatment, with a PDUFA goal date of September 7, 2025[2] - The Phase 3 RISE UP study for mitapivat in sickle cell disease is on track, with topline results expected in late 2025 and a potential U.S. commercial launch in 2026[2] - Agios plans to file an Investigational New Drug Application for AG-236, targeting TMPRSS6 for polycythemia vera, in mid-2025[5] Strategic Focus - The company is advancing its pipeline with a focus on transformative therapies for rare diseases, aiming to create significant value for shareholders[2]

Core Insights - Agios Pharmaceuticals is progressing with the regulatory approval of PYRUKYND (mitapivat) for thalassemia, with a PDUFA goal date set for September 7, 2025 [1][2] - The Phase 3 RISE UP study for mitapivat in sickle cell disease is on track, with topline results expected by late 2025 and a potential U.S. commercial launch in 2026 [1][2] - The company reported a net revenue of $8.7 million for PYRUKYND in Q1 2025, showing a slight increase from $8.2 million in Q1 2024 [1][3] Financial Performance - PYRUKYND generated net revenue of $8.7 million in Q1 2025, up from $8.2 million in Q1 2024, with 234 unique patients completing prescription enrollment forms, a 5% increase from Q4 2024 [3][5] - R&D expenses for Q1 2025 were $72.7 million, compared to $68.6 million in Q1 2024, primarily due to increased workforce-related expenses and clinical trial costs [6] - SG&A expenses rose to $41.5 million in Q1 2025 from $31.0 million in Q1 2024, attributed to increased commercial activities in preparation for potential PYRUKYND approval [7] Cash Position - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities totaling $1.4 billion, down from $1.5 billion at the end of 2024 [8] - The company anticipates that its financial resources will support the potential launches of PYRUKYND in thalassemia and sickle cell disease, as well as the advancement of existing programs [8] Clinical Development - The FDA accepted the supplemental New Drug Application for PYRUKYND for both non-transfusion-dependent and transfusion-dependent thalassemia patients [3][11] - The Phase 3 RISE UP study for sickle cell disease has completed enrollment with over 200 patients worldwide [3][11] - Positive topline results were reported from the ACTIVATE-Kids Phase 3 study of mitapivat in children with PK deficiency, marking a significant advancement in pediatric treatment [3] Corporate Developments - Krishnan Viswanadhan joined Agios as Chief Corporate Development and Strategy Officer, focusing on corporate strategy and long-term growth initiatives [4]

Group 1 - Agios Pharmaceuticals, Inc. (AGIO) has been added to the Zacks Rank 5 (Strong Sell) List due to a 19.7% downward revision in the Zacks Consensus Estimate for its current year earnings over the last 60 days [1] - Chegg, Inc. (CHGG) is also on the Zacks Rank 5 (Strong Sell) List, with a significant 96.8% downward revision in the Zacks Consensus Estimate for its current year earnings over the last 60 days [1] - Equifax Inc. (EFX) has been included in the Zacks Rank 5 (Strong Sell) List, with an 11.3% downward revision in the Zacks Consensus Estimate for its current year earnings over the last 60 days [2]

Core Insights - Agios Pharmaceuticals has granted inducement equity awards to its newly appointed Chief Corporate Development & Strategy Officer, Krishnan Viswanadhan, as part of his employment agreement [1][2] Group 1: Inducement Grants - The inducement grants include a nonstatutory option to purchase up to 55,374 shares of common stock, restricted stock units for 24,300 shares, and performance stock units for 16,200 shares [2] - The option has an exercise price of $33.95 per share, with a ten-year term and a vesting schedule over four years [2] - Restricted stock units will vest in equal annual installments until the third anniversary of Mr. Viswanadhan's start date, contingent on his continued service [2] Group 2: Company Overview - Agios Pharmaceuticals is a leader in pyruvate kinase (PK) activation, focusing on therapies for rare diseases [3] - The company markets a first-in-class PK activator for adults with PK deficiency, which is the first disease-modifying therapy for this condition [3] - Agios is advancing a clinical pipeline that includes investigational medicines for various hematologic diseases and a preclinical TMPRSS6 siRNA for polycythemia vera [3]

Core Insights - Agios Pharmaceuticals has granted inducement equity awards to its newly appointed Chief Corporate Development & Strategy Officer, Krishnan Viswanadhan, as part of his employment agreement [1][2] Group 1: Inducement Grants - The inducement grants include a nonstatutory option to purchase up to 55,374 shares of common stock, restricted stock units for 24,300 shares, and performance stock units for 16,200 shares [2] - The option has an exercise price of $33.95 per share, which is the closing price of the company's common stock on March 5, 2025, and has a ten-year term with a four-year vesting schedule [2] - Restricted stock units will vest in equal annual installments over three years, while performance stock units are contingent on achieving specified performance milestones [2] Group 2: Company Overview - Agios Pharmaceuticals is a leader in pyruvate kinase (PK) activation, focusing on developing therapies for rare diseases [3] - The company markets a first-in-class PK activator for adults with PK deficiency, which is the first disease-modifying therapy for this condition [3] - Agios is advancing a clinical pipeline that includes investigational medicines for alpha- and beta-thalassemia, sickle cell disease, pediatric PK deficiency, myelodysplastic syndromes-associated anemia, and phenylketonuria [3]