Fulcrum Therapeutics Inc Pociredir Pioneer Study 12 mg Cohort Data Release Transcript

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

Question: Matthew Biegler - Oppenheimer & Co Inc - Analyst : Great, thank you guys so much for this event and congrats on the data. It's great to hear those comments from Wally. I remember back in the day with Global Blood Therapeutics, so. I agree, really exciting. So Alan, Alex, how do you kind of view these data in the context of the 6 mg cohort? What are expectations for the 20 mgcohort? And do you think you're starting to see a plateauing effect? And then I had questions for the doctors. Is really just kind of like how much weight we should put on the VOC trend here. Is this a real signal? I'm just kind of curious from your experience how subject to bias the VOC is given, that this was an open label trial. Thanks again.

Question: Joe Schwartz - Leerink Partners - Analyst : Great. Congrats on the really promising data and thanks for all the helpful context. It looks like you're seeing some very robust increases in HbF, as well as everything else pointing in the right direction, even though it seems like the strict enrollment criteria might be selecting for some. Very challenging patients. So now that you're seeing such a promising picture emerge, what is the path to be able to extend the duration of therapy that patients can receive look like as well as the potential to broaden the enrollment criteria? Is this one or two conversations, and when's the right time to have it?

Question: Kevin Johnson - Goldman Sachs - Analyst : Yeah, good morning and thanks guys, maybe for the physician following up on that last point, if you look at the data and the clinical benefit risk here, how do you think about the appropriate eligibility, for this agent and what would you kind of advise if you were part of this conversations, and then I think, Doctor Smith, you mentioned patients are feeling better on the drug can you just expand on. What key metrics you're using to make that assessment and, maybe, Doctor Alan, you can also talk about your patient's experience with that respect. Thanks.

Question: Edward Tenthoff - Piper Sandler - Analyst : Great, thank you and my congrats on the data to very impressive, both on the safety and efficacy side. What really struck me was that it looked like patients were continuing the benefit at the end of the treatment duration. And I'm just curious how far we think obviously the opportunity for higher dose with 20 margin to benefit. But also what do you think maybe is the top end of this 12 mg dose just based on potentially longer term dosing. Thank you. And maybe as a quick follow up, is this something where maybe we have multiple doses that ultimately get approved and there's either some kind of titration or some kind of right size. For patient need. Thank you.

Question: Andreas Maldonado - HC Wainwright - Analyst : Hi everyone, thank you. Apologies for that. Congrats on the data. Two quick questions from us, I guess. Do you expect a 20 mg dose to not only increase the HbF magnitude, but also the speed of induction? And how important is this in a real world setting? And then as a follow up, how REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JULY 29, 2025 / 12:00PM, FULC.OQ - Fulcrum Therapeutics Inc Pociredir Pioneer Study 12 mg Cohort Data Release should we be thinking about long HbF induction and X cell expansion persistence after the potential discontinuation of treatment, and could this maybe influence compliance of the patients are having a long lasting effect even if they're not adhering to the protocol? Thank you very much.