Agios Pharmaceuticals Inc Topline Results Phase 3 RISE UP in Sickle Cell Disease Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Eric Schmidt - Cantor - Analyst : Thank you for taking my question and for the very detailed review of the Phase III data. Maybe for the company and Sarah, first on safety. You mentioned no sign of liver injury, but were there any grade 2 or grade 3 increases in liver enzymes. And then for Dr. Andemariam, -- it sounds like you're quite convinced of the benefits here, though with a lack of statistical significance on some of the clinical outcomes, how would you communicate the benefits to your patient with this drug to be approved? Thank you.

Question: Salveen Richter - Goldman Sachs Group Inc - Analyst : Good morning. Thanks for taking my question. I was just wondering what the registrational path forward is here and what you would tend -- what you think the focus of the pre-sNDA meeting with the FDA will be in the first quarter.

Question: Ellen Horste - TD Cowen - Analyst : Hi guys, I'm on for Marc. I'm wondering if this drug is approved, how long might you treat a patient waiting for a response given that 40% of patients do seem to do really well? I guess, yes, how long would the duration of treatment have to be before you decide this is not benefiting a patient?

Question: Alec Stranahan - BofA Merrill Lynch Asset Holdings Inc - Analyst : Hey guys, thanks for taking our questions. Maybe one for the team and then one for Dr. Andemariam. I guess first one for Brian and Sarah. When you think about potential differentiation with TEVAPIVAT versus mitapivat, I guess do you think a functional benefit is still in the realm of possibility with Teva now that you've seen the data from RISE up? And if so, what's driving that confidence? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 19, 2025 / 1:00PM, AGIO.OQ - Agios Pharmaceuticals Inc Topline Results Phase 3 RISE UP in Sickle Cell Disease And then one for Dr. Andemariam appreciate the disease characteristics were fairly balanced between placebo and Mita arms, which I think speaks to the quality of the study overall. But I guess how does the 3.05 pain crisis on the placebo arm sort of compared to what you'd expect for this patient population broadly? And same thing on fatigue score, did this, I guess, maybe seem higher than you would expect for placebo.

Question: Emily Bodner - H.C. Wainwright & Co., LLC - Analyst : I guess first one, were there any trends in certain baseline characteristics that were more likely to be hemoglobin responders -- and then also curious on the blood transfusion comment, what percent of sickle cell disease patients get blood transfusions or have more severe anemia? And do you see that as a subset of patients to maybe focused commercialization on.

Question: Tessa Romero - JPMorgan Chase & Co - Analyst : Team, thanks so much for taking our questions this morning. So two from us. In your view, does this result qualify as hemoglobin and which I think you've been talking about for a while. Given the PROMIS Fatigue score did not get met here in the eyes of regulators -- and this endpoint seems to rise to the top for KOLs in terms of level of significance. And then my second question is should we expect the price ofPYRUKYND to change on the approval in thalassemia or not?

Question: Luca Issi - RBC Capital Markets Inc - Analyst : Thanks so much for taking my question. Maybe, Sarah, if we can kind of circle back on maybe prior question, maybe ask a little bit differently. Can you just talk about your confidence that this drug actually gets approved by the FDA at the end of the day is your understanding of hitting one of the two primary endpoints and two of the secondary endpoint that are at the top of the hierarchical analysis sufficient to get this over the finish line. Or do you think that the FDA was looking for this trial to hit more than two secondary endpoints? And any context there? I much appreciate it. And then maybe second, on fatigue, if I may, and I apologize if I missed it, but -- can you talk about fatigue when compared to placebo and not maybe baseline? Again, it looks like there was no effect in the ITT population. There was a benefit in the responder population. So does that apply to fatigue endpoint all the way around in a nonresponder population? Or is that not the right way to think about it? Sarah Gheuens - Agios Pharmaceuticals Inc - Chief Medical Officer & Head - Research and DevelopmentC Cecilia Jones;Agios Pharmaceuticals Inc;Chief Financial Officer Okay. So for the first question around the likelihood of approval and all that, your is going to hear this for me. I'm not going to comment on what the we'll do or not do or as always, it will be a matter of review. And that is something that happens when you feel you have a data package and you go talk to the regulators, ultimately, they do their own independent reviews and engage and make their own independent assessment. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 19, 2025 / 1:00PM, AGIO.OQ - Agios Pharmaceuticals Inc Topline Results Phase 3 RISE UP in Sickle Cell Disease As we mentioned, we really feel we have a very compelling data package to go and have that engagement with the agency. Because again, like we see very consistent data on how mitapivat act that hemolytic anemia improvement, the clinical context just around the hemolytic anemia improvement was highlighted by Dr. Andemariam very well a couple of times. I think it's really by itself already meaningful in this patient population that if you remember the slide from our presentation, if you look at the treatment options for this disease, a very bare landscape -- but then to see actually that there is robust data that speaks to clinical benefit in the hemoglobin responders on so-called hard core endpoints as it relates to sickle