Summary of Agios Pharmaceuticals Conference Call Company Overview - **Company**: Agios Pharmaceuticals (AGIO) - **Focus**: Development of transformative medicines for patients with rare diseases, particularly those affecting red blood cells such as pyruvate kinase deficiency (PKD), thalassemia, sickle cell disease, and low-risk myelodysplastic syndromes (MDS) [6][7] Key Pipeline Developments - **Product Highlight**: PyraKine (Mitapivat) - **Mechanism**: Novel approach to enhance red blood cell metabolism, leading to improved energy and healthier cells [7] - **Current Status**: Commercialized for PKD; pursuing indications in thalassemia and sickle cell disease [7] Thalassemia - **Pivotal Studies**: Two phase three studies (ENERGIZE and ENERGIZE T) showed statistical significance on all primary and key secondary endpoints [8] - **Regulatory Filings**: Filed for approval in the US, Europe, Saudi Arabia, and UAE; FDA PDUFA goal date set for September 7, 2025 [8][14] - **Commercial Readiness**: Sales team fully prepared for the launch of PyraKine in thalassemia [9][35] Sickle Cell Disease - **Study Enrollment**: Fully enrolled the Rise Up phase three study, a 52-week trial [9] - **Data Readout**: Expected by year-end 2025 [9] - **Trial Design**: Focuses on hemolytic anemia and vaso-occlusion, with two primary endpoints [42][43] Financial Position - **Balance Sheet**: Approximately $1.4 billion in cash, positioning the company strongly in the current macroeconomic environment [10][12][61] - **Capital Allocation Strategy**: Focus on maximizing value from launches, advancing the pipeline, and exploring external opportunities for growth [64] Market Opportunities - **Thalassemia Patient Population**: Estimated 6,000 adult patients in the US and 70,000 in Saudi Arabia, with a prevalence rate significantly higher in the Middle East [32] - **Regulatory Engagement**: Positive interactions with regulatory bodies across multiple markets, indicating a smooth approval process [24][30] Competitive Landscape - **Treatment Paradigm**: Oral therapies like Mitapivat are positioned as accessible options compared to gene therapies, which may have more complex onboarding processes [54] - **Future Trials**: Plans to initiate a phase two trial for another PK activator, tebipivat, to provide additional treatment options for sickle cell disease [48][50] Upcoming Events - **EHA Presentations**: Agios will present data on pediatric PKD and sickle cell disease at the upcoming EHA conference, showcasing their commitment to advancing research and treatment options [58][59] Conclusion - **Strategic Vision**: Agios aims to build a multibillion-dollar franchise with PyraKine while maintaining a disciplined approach to capital allocation and exploring new opportunities for growth [64]

Core Insights - Agios Pharmaceuticals is presenting new data on its pyruvate kinase (PK) activators, mitapivat and tebapivat, at the upcoming European Hematology Association (EHA) Congress in Milan, Italy, from June 12-15, 2025 [1][2] Company Overview - Agios Pharmaceuticals is a leader in cellular metabolism and PK activation, focusing on therapies for rare diseases [1][17] - The company has developed PYRUKYND (mitapivat), a first-in-class pyruvate kinase activator for treating hemolytic anemia in adults with PK deficiency [9][17] Clinical Data Presentation - A total of 14 presentations and publications will be shared at EHA 2025, highlighting the efficacy and safety of PK activation in treating rare blood disorders [3][2] - Key presentations include: - Results from the ACTIVATE-KidsT Phase 3 study of mitapivat in children with PK deficiency, showing a clinically meaningful reduction in transfusion burden [6] - Long-term data from the ESTIMATE Phase 2 trial of mitapivat in sickle cell disease, demonstrating sustained efficacy and tolerability over three years [6] - Preclinical data on tebapivat's potential in reducing red blood cell sickling in sickle cell disease patients [6] Research Focus Areas - The presentations will cover serious conditions with limited treatment options, including sickle cell disease, thalassemia, PK deficiency, and myelodysplastic syndromes [2][6] - Ongoing investigations include the expression patterns of PKM2 in patients with myelodysplastic syndromes, supporting the potential of tebapivat in lower-risk MDS [6] Collaboration and Community Engagement - Agios aims to strengthen its collaboration with the global hematology community through these presentations at EHA [2]

Core Insights - Agios Pharmaceuticals is scheduled to present at the 2025 RBC Capital Markets Global Healthcare Conference on May 21, 2025, at 8:00 am ET [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]

Core Viewpoint - Agios Pharmaceuticals reported a narrower loss per share in Q1 2025 compared to estimates, but revenues fell short of expectations despite a year-over-year increase Financial Performance - Agios incurred a loss of $1.55 per share in Q1 2025, better than the Zacks Consensus Estimate of a loss of $1.80, but wider than the loss of $1.45 reported in the same quarter last year [1] - Revenues for Q1 2025 were $8.7 million, missing the Zacks Consensus Estimate of $10 million, but representing a 6.1% increase from $8.2 million in the year-ago quarter [1] - The company's stock has declined 5.8% year-to-date, while the industry has seen a decrease of 1.7% [2] Product Performance - All revenues in Q1 2025 were generated from Pyrukynd, Agios' only marketed drug, which is approved for treating hemolytic anemia in adults with PK deficiency [3] - Pyrukynd revenues declined 19% sequentially due to the absence of year-end stocking benefits seen in Q4 2024 [3] - As of Q1 2025, 136 patients are on Pyrukynd therapy, reflecting a 4.6% increase from Q4 2024 [4] Expenses - Research and development expenses rose approximately 6% year-over-year to $72.7 million, attributed to higher workforce-related costs [4] - Selling, general, and administrative expenses surged 33.9% year-over-year to $41.5 million, driven by preparations for potential approval and launch of Pyrukynd for thalassemia [4] 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 as of December 31, 2024 [5] Pipeline Developments - The FDA accepted Agios' supplemental new drug application for Pyrukynd to treat adult patients with thalassemia, with a decision expected by September 7, 2025 [9] - Agios completed enrollment in the phase III RISE UP study for SCD, with top-line data expected in late 2025 and potential regulatory filing in 2026 [10] - The company is also conducting two phase III studies for Pyrukynd in pediatric patients with PK deficiency [10] - Agios is developing tebapivat for myelodysplastic syndromes and has initiated a phase IIb study, with enrollment expected to complete in late 2025 [12]

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].

Agios Pharmaceuticals (AGIO) Q1 2025 Earnings Call May 01, 2025 08:00 AM ET Company Participants Christopher Taylor - VP - IR & Corporate CommunicationsBrian Goff - CEOSarah Gheuens - Chief Medical Officer and Head of Research & DevelopmentTsveta Milanova - CCOCecilia Jones - CFOHiromichi Nagayumi - Associate - Biotech Equity ResearchAmanda Acosta-Ruiz - Equity Research Associate - Biotechnology Conference Call Participants Gregory Renza - Director & Senior Analyst of Biotechnology Equity ResearchAlec Stran ...

Q1 2025 Financial Results and Business Update May 1, 2025 1 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 ...

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]