Alector Inc Q2 2025 Earnings Call Transcript

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

Question: Thomas Shrader - BTIG LLC - Analyst : Hi. Good afternoon. Thanks for taking the questions. I just wanted to clarify in the statistical analysis plan. Is the only change that you've added progranulin or is there something else there? And just give us a sense of why you added that? Did progranulin, I mean, on average, it, normalized, but did it normal, does it normalize in every patient in the prior trials? I'm just trying to understand why you're doing this. And then on the ABC portfolio, is it mostly transferring receptor-based or are you using other receptors? Thank you.

Question: Myles Minter - William Blair & Company - Analyst : Yeah, following on from Thomas's first question, why did that reviewer request plasma progranulin? Like this is an antibody, I assume it's largely peripherally restricted with some minimal getting into the brain. I know tapping these patients in terms of CSF and measuring for progranulin is probably problematic at this stage. But is that reviewer, like, are they basically agreeing that plasma for a granulin with a largely peripherally restricted antibody driving that up regulation is predictive of functional benefit in a CNS disorder like frontotemporal dementia. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 07, 2025 / 8:30PM, ALEC.OQ - Q2 2025 Alector Inc Earnings Call That's the first one. And then if Dr. Darby is still on the line, I think INFRONT-3, at its bare minimal, was powered to show a 25% improvement in the slowing of cognitive decline in this trial. Just on the background of what we've seen with the uptake of anti-amyloid therapies in Alzheimer's disease showing a 27% of decline, I know there's some safety concerns with that. But if it was 25%, is that still an attractive product to prescribe to this patient population? Thank you very much.

Question: Myles Minter - William Blair & Company - Analyst : Beautiful. Thanks for the questions.

Question: Alec Stranahan - Bank of America Securities - Analyst : Hey guys, thanks for taking our questions. One on AL101 from us as well. Curious how changing the SAP at this stage could affect powering on the modified CDRM boxes and plasma of PGRN is now a co-primary, and in your discussions with the FDA or and or GSK, I get curious if expanded enrollment INFRONT-3 was part of your discussions at all. And given the FDA's apparent focus on PGRN levels, have you gotten a sense whether plasma PGRN could make its way onto the label as well for selection?

Question: Alec Stranahan - Bank of America Securities - Analyst : Yeah. Just given the focus of the FDA on plasma PGRN and I'm curious if this could be a potential of the population on the label?

Question: Alec Stranahan - Bank of America Securities - Analyst : Understood. Thank you very much.

Question: Stephen Ayanov - - Analyst : Thank you very much for the question. This is Stephen Ayanov on for Yaron Werber. Did the FDA mention any particular threshold that they wanted to see for progranulin , or is that just statistical significance? And then to follow up, you mentioned the 90% power to see a 40% lowering. Was that, are you tying that in any way to the progranulin levels or is that just still the sum of boxes and point? Thank you. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 07, 2025 / 8:30PM, ALEC.OQ - Q2 2025 Alector Inc Earnings Call

Question: Stephen Ayanov - - Analyst : Understood. Thank you very much.

Question: Michael Patrick Riordan - Morgan Stanley - Analyst : Hi, this is Mike Riordan on for Sean. Thank you for taking our questions and congratulations on completing enrollment for progress. We have two questions. First one for Dr. Darby. We'd love to hear your thoughts. Assuming success, restoring progranulin to normal levels and FTG progranulin like slowing CDRSP, would that increase your confidence in elevating progranulin above endogenous levels, like being beneficial to patients with Alzheimer's?

Question: Michael Patrick Riordan - Morgan Stanley - Analyst : Oh thanks. That makes sense and then maybe just, sorry, just a quick follow up what would be like your view on like other FTD subtypes. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 07, 2025 / 8:30PM, ALEC.OQ - Q2 2025 Alector Inc Earnings Call

Question: Michael Patrick Riordan - Morgan Stanley - Analyst : Thank you so much. It's been really helpful. I appreciate the color.

Question: Douglas MacPherson - Mizuho - Analyst : Hi there, this is Doug MacPherson on for Greg. Thank you very much for having me on and taking my call or question rather. So thinking about the relative subjectivity of the end points of clinician severity score and the rating scales compared to biomarker data, is there anything that can be done or has been undertaken in order to try to minimize perhaps a placebo effect or to optimize for like the spread or separation between active drug and placebo?

Question: Douglas MacPherson - Mizuho - Analyst : Sure. Thank you for that. I appreciate it. And then a quick follow up, should we at all be concerned about Arya, for [TRAEs]? And if so, what would be sort of an acceptable Arya prevalence or severity in treated patients?

Question: Douglas MacPherson - Mizuho - Analyst : Oh. I'm still on the FTD Phase 3 study.

Question: Douglas MacPherson - Mizuho - Analyst : That's great to hear. Thank you very much. I appreciate you taking the question. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 07, 2025 / 8:30PM, ALEC.OQ - Q2 2025 Alector Inc Earnings Call

Question: Samantha Schaeffer - Cantor Fitzgerald - Analyst : Hi, this is Samantha Schaffer on the line for Pete. Thanks so much for taking our question. So a question for the team, Dr. Salvador and Dr. Darby, related to INFRONT-3. We know that 16 asymptomatic patients were enrolled who will not be included in the primary analysis, based on their REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 07, 2025 / 8:30PM, ALEC.OQ - Q2 2025 Alector Inc Earnings Call baseline NFL levels though, and what we know about natural history, do you expect signs of progression and potential differences between Latozinemab and placebo within the 96 weeks? And then I just have a follow up question. Thank you.

Question: Samantha Schaeffer - Cantor Fitzgerald - Analyst : That's very helpful. Thank you. And just to follow up, we know that there's a part two of the INFRONT study on it's an open label extension. Can you give us a sense maybe quantitatively or qualitatively how this part of the study is progressing? Is there a high rollover rate into the [OLE]?

Question: Samantha Schaeffer - Cantor Fitzgerald - Analyst : Great. Thank you, guys.