Agios Pharmaceuticals, Inc. Q3 FY2025 earnings call

• PYRUKYND has multiple high-value catalysts, with its PDUFA date for thalassemia supplemental NDA extended to December 7. Top line results from the RISE UP Phase III trial in sickle cell disease are expected by year-end.
• In the third quarter, $12.9 million in net revenue was reported, with approval for PYRUKYND in adults with thalassemia in Saudi Arabia and a positive CHMP opinion recommending PYRUKYND for marketing authorization in Europe for thalassemia.
• Tebapivat's Phase IIb trial in lower-risk MDS completed enrollment, with top line data anticipated early next year. The company has a strong balance sheet with approximately $1.3 billion in cash and investments.
• Capital allocation strategy includes a capital-efficient global commercial model, investment in ongoing clinical programs, and opportunistic pipeline expansion.

In the third quarter, Agios Pharmaceuticals reported $12.9 million in net revenue, which was derived from PYRUKYND. This underscores the strong value proposition of PYRUKYND.

• PDUFA date for PYRUKYND thalassemia supplemental NDA extended to December 7.
• Anticipate top line results from the RISE UP Phase III trial of PYRUKYND in sickle cell disease by year-end.
• Expect to report top line data early next year from the Phase IIb trial of Tebapivat in lower-risk MDS.

• Regulatory risks related to the specific REMS program required by the FDA for PYRUKYND thalassemia, which could impact the timing and execution of U.S. launches.
• Uncertainties around the pace of commercial adoption in regions like Europe and the Gulf due to processes like pricing and reimbursement negotiations.

Q: Maybe first, just on the thalassemia review process. It's been almost 2 months now since you've got the PDUFA extension. Do you have a better sense of what type of a REMS program the FDA is interested in here? I know there's a spectrum of maybe more or less onerous REMS programs. And then just a second follow-up question. I think both Cecilia and Brian mentioned actively looking for external assets. What type of BD makes sense for the company at this stage? And would you wait until the sickle cell readout to transact?

A: Sarah Gheuens responded that they don't comment on REMS details per process but anticipate it will include monitoring and education. Brian Goff stated that the pursuit of external assets isn't timed to specific events, focusing on rare diseases with transformative potential for patients, early derisking opportunities, and best-in-class therapies.

Q: Just on the thalassemia review process. It's been almost 2 months now since you've got the PDUFA extension. Do you have a better sense of what type of a REMS program the FDA is interested in here? I know there's a spectrum of maybe more or less onerous REMS programs. And then just a second follow-up question. I think both Cecilia and Brian mentioned actively looking for external assets. What type of BD makes sense for the company at this stage? And would you wait until the sickle cell readout to transact?

A: Sarah Gheuens responded that they don't comment on REMS details per process but anticipate it will include monitoring and education. Brian Goff stated that the pursuit of external assets isn't timed to specific events, focusing on rare diseases with transformative potential for patients, early derisking opportunities, and best-in-class therapies.

Q: Just on the liver events. Can you maybe just as you've continued to dose people and follow them for longer and longer, just kind of comment on if any additional events have been observed kind of across the PKR trials? And to the extent any have, have they continued to conform to the kind of description before of occurring within 6 months and importantly, the patient returning to baseline whenever they do stop mitapivat as a result? And then maybe on the commercial side, if you -- I recognize it will take quite a while to work through case-by-case access and actually get to revenue for any of those patients, let alone the reimbursement negotiations. But maybe can you comment on just any level of demand you're already seeing kind of in the Gulf to kind of start that process?

A: Sarah Gheuens stated that observations in the thalassemia program haven't changed the understanding of hepatocellular injury risk. Tsveta Milanova mentioned seeing interest in Saudi Arabia with physicians requesting individual patient access, but the process takes time for broader market access.

Q: So for the Phase III portion of RISE UP, has the last patient exited the trial yet? And what are any considerations in terms of the steps and timing to get to your top line? And then I have a follow-up.

A: Sarah Gheuens stated they are on track to deliver top line data by year-end, not commenting on individual patient status but emphasizing the team's readiness to move from database locks to top line results. Brian Goff added praise for the team's operational excellence in handling multiple ongoing initiatives.

Q: Just another one on the REMS program. Do you anticipate the requirements to apply kind of across the label to PKD and sickle cell as well? And have you received any physician feedback on how this might impact uptake, particularly with sickle cell where some of these treatment centers might not see PKD and thalassemia patients as well?

A: Brian Goff responded that the REMS request is specific to thalassemia, and the most important next step is the RISE UP Phase III data for sickle cell disease, after which they'll better assess impact.