AGIOS PHARMACEUTICALS, INC. Q4 FY2024 earnings call

Mission and Focus

• Agios' mission is to develop transformative medicines for rare diseases affecting red blood cells, including pyruvate kinase deficiency, thalassemia, sickle cell disease, and lower-risk MDS.

Key Programs and Milestones

• Announced top-line results from the ACTIVATE KIDS Phase III trial with mitapivat in pediatric PK deficiency patients.
• Anticipate approval and launch of PYRUKYND in thalassemia in September 2025, and sickle cell disease in 2026.
• Phase IIb study for TevaPIVac in lower-risk MDS to complete enrollment by year-end 2024, with a Phase II study in sickle cell disease starting mid-2025.
• Plan to file an INDA for AG-236 in mid-2025 for polycythemia vera treatment.

Commercial Preparation

• Preparing for thalassemia launch with disease education campaigns, sales team rightsizing, and payer engagement to facilitate patient access.

In the fourth quarter of 2024, Agios reported net revenue of $10.7 million, a 51% increase from $7.1 million in the same period of 2023. This growth was primarily driven by year-end stocking and reserve adjustments. Cost of sales for the quarter was $1.3 million. R&D expenses were $82.8 million, an increase of $5.3 million compared to Q4 2023, driven by workforce-related expenses. G&A expenses were $51.7 million, up $16.4 million y-o-y, mainly due to increased commercial-related activities. Cash, cash equivalents, and marketable securities ended the quarter at approximately $1.5 billion.

Revenue Outlook

• 2025 revenues for PK deficiency expected to be flat compared to 2024.

Pipeline and Launch Timelines

• Anticipate approval and launch of PYRUKYND in thalassemia in 2025, and sickle cell disease in 2026.
• Phase IIb study for TevaPIVac in MDS to complete enrollment by year-end 2024, Phase II in sickle cell by mid-2025.
• Plan to file INDA for AG-236 in mid-2025.

Risks

• Regulatory uncertainties: Uncertainties in approval timelines and processes for new indications.
• Commercial challenges: Delays in payer access and launch ramp-up in new markets.
• Safety concerns: Potential safety issues with mitapivat observed in trials, requiring careful monitoring.

Q: Congrats on all the progress. Looking forward to another remarkable year in 2025. Maybe first for Sarah, what's the company's plan or strategy for updating the investment community on the safety profile of a few batch of NPA? Should there be any further cases of hepatocellular injury or any signals, what's lever there? And then for Brian, now for probably the past year or so, I think you've been talking about the multibillion dollar potential of mitapivat in these additional indications. How do you think about peak sales potential in either thalassemia or sickle cell disease as you construct that multibillion dollar estimate?

A: Sarah Gheuens: If anything would change to the safety profile of the drug as we currently understand it, and we make that call, then we would update you guys as well. Brian Goff: We're very excited for the position that we have right now with all the momentum, the backdrop of the clinical data as well as now the PDUFA date for thalassemia that we talked about. And just to characterize why we have such conviction in the long-term potential in thalassemia as we said on multiple calls, 2/3 of the patient population in the U.S. have no approved therapy option, which presents a profound opportunity in terms of unmet need for those patients.

Q: This is Divya on for Mark. Congrats on all the progress. Just one on sickle cell. So after the liver tox disclosure in Dow last year, can you provide any details on changes to the sickle cell trial protocol? Is it mostly in the OLE portion? Or were there any changes to the core portion of the trial? And then I have a follow-up.

A: Sarah Gheuens: We took a look at the monitoring across all of the trials. In the core period, we were already monitoring in our core period for liver test enzymes along the way in each of our trials in the blinded period. In the open label, we have to make a tweak to align the monitoring frequency to once a month to what we were doing into the core period of the sickle cell disease trial.

Q: Great. Brian and team, congrats on the progress in the year. Brian, maybe just dipping into the pipeline and as you get your hand on the PK activation portfolio, I just wanted to ask about just your enthusiasm on how you're characterizing your level of enthusiasm with respect to AG-1 that the PAH stabilizer. Maybe just remind us of that specific mechanism, how it stabilizes PAH and perhaps why it should work well with patients who don't respond to that co-factor treatment?

A: Brian Goff: The first thing I'll just say, Greg, is I'm not -- I do not pick favorites among children within our pipeline. We're really proud of all of the across the pipeline is my first comment. The second is we're in a really good position of strength from a diversification within the pipeline in both type of asset, disease as well as stage of development. With respect to AG-181, which is a phenylalanine hydroxylase stabilizer, in a way, it's similar to pyruvate kinase activation where stabilizes the enzyme that's needed for the conversion of phenylalanine, we're in Phase I now. And of course, we look forward to giving continued updates as we make progress on the development opportunity.