Alector Inc Q4 2024 Earnings Call Transcript

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

Question: Pete Stavropoulos - Cantor Fitzgerald LP - Analyst : Hi, good afternoon and congratulations on all the progress. One question for me is, when you are thinking about the INFRONT study, treating earlier in the course of a neurodegenerative disease should result in greater clinical benefit and you see a larger separation between active arm and placebo. With that in mind, for the baseline characteristics of INFRONT, I believe 22% of the patients have a CDR-FTLD, global score of 0.5, 48% have a score of 1, 31 have a score of 2. What gives you confidence that you enroll the correct proportion of patients for each score that will allow you to see a clear separation between lotuzineumab and placebo and was there a cap for any of these patient populations? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. FEBRUARY 26, 2025 / 9:30PM, ALEC.OQ - Q4 2024 Alector Inc Earnings Call

Question: Pete Stavropoulos - Cantor Fitzgerald LP - Analyst : So a follow-up question. So when you do look at the NfL levels of those 16 patients that you enrolled that are presymptomatic and then you look at the GENFI data, are they -- is there an expectation that there's actually going to be progression within those 96 weeks?

Question: Pete Stavropoulos - Cantor Fitzgerald LP - Analyst : Okay. All right. Thank you very much for taking our questions. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. FEBRUARY 26, 2025 / 9:30PM, ALEC.OQ - Q4 2024 Alector Inc Earnings Call

Question: Alec Stranahan - Bank of America Securities - Analyst : Hey guys, thanks for taking our questions. Just two from us. First, on AL101, do you think given the shared progranulin targeting, there's anything to read through from INFRONT-3 or is this may be hard given the different indications? And then second question, I appreciate the new color on the ABC candidate nominations. Maybe just walk us through the preclinical optimization that's going on for these assets from here and sort of your thought process around bringing additional assets forward would be great. Thank you.

Question: Alec Stranahan - Bank of America Securities - Analyst : Yes, but that -- I mean, both is helpful.

Question: Alec Stranahan - Bank of America Securities - Analyst : That's very helpful. Thank you for the call.

Question: Emily Chudy - Stifel Financial Corp - Analyst : Hi. This is Emily on for Paul. Just to kind of like ask a little bit more about your ABC platform. Could you maybe highlight some of the key differences with your blood-brain barrier platform with others such as like Denali or Roche efforts? And then also just a bit more specifically on ADP037 and ADP050, could you maybe talk a little bit more about the rationale of like selecting those as your first two targets? Saraswati Kenkare-mitra - Alector Inc - President, Head - Research and Development Yeah, I can take that. Maybe, Arnon, you can add. So I think, firstly, to get to your question about our Alector ABC technology, I think it stands out in several ways. I would firstly say that our toolbox approach is versatile and tunable. And as you know, with ABCs, you're trying to maximize efficacy while minimizing the potential of safety of tolerability. And I think our technology provides because it provides for that very well because of that sort of versatility. It's not as rigid. We can fine-tune both in terms of the affinities, but also in terms of being able to match the right type of fragment with the right type of cargo. So overall, that gives us a very versatile, very tunable, and very adaptable platform that we can apply depending on whether it's an antibody, a protein, whether you need an Fc or you don't need an Fc, et cetera. Now coming to our two different programs, ADP037-ABC, which is our amyloid beta technology, we believe that firstly, it targets a validated epitope, which is the PyrGlu3 A beta epitope, which is with our brain penetrant ABC. We also have a fully active Fc, which is essential for the phagocytosis of amyloid beta plaque. And we're also sort of configuring the affinity to TFR. We've been able to fine-tune it to allow us to get sort of the most optimal half-life, minimal safety as well as maximal brain penetration. Now certainly, this is all preclinical, but we believe that the combination of all of this allows ADP037-ABC to have the potential to be a best-in-class molecule in the future. Now ADP050-ABC, which is our GCase ABC program in targeting Parkinson's disease, again, we are developing that. This is our natural GCase is a very unstable and short-lived molecule. We've engineered a much more stable and active GCase enzyme through mutagenesis, which also has a REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. FEBRUARY 26, 2025 / 9:30PM, ALEC.OQ - Q4 2024 Alector Inc Earnings Call minimal potential to be immunogenic. And ADP050, again, paired with our ABC technology really could enable brain penetration and the potential for treatment of Parkinson's disease.

Question: Thomas Shrader - BTIG LLC - Analyst : Good afternoon. Thanks for taking the question. More on the shuttle, I'm afraid. Can you talk a little bit about your decision to use fRNA versus ASOs? I think almost everyone else is on the ASO side. And specifically, are there good preclinical models for some of the problems that ASOs can run into like inflammation and protein buildup? When will you know if that's a differentiated approach? And maybe any thoughts you have about why you took this approach?

Question: Thomas Shrader - BTIG LLC - Analyst : A quick follow-up. Do you see this as a good place for M&A and some sort of another big deal? Or do most companies have the technology they want? Is that something we should be looking for as you outlicensing some piece of your technology for some non-dilutive funding?

Question: Thomas Shrader - BTIG LLC - Analyst : Yeah, great, thank you for the call.

Question: Yaron Werber - Cowen Inc - Analyst : Great, thanks for taking my question. I had a question maybe on INFRONT-3 as you're looking at the primary endpoint in symptomatic patients, can you give us a sense, just remind us how it's powered? And just remind us also the data that we're going to see by year-end, do you think that's going to be the fully mature data? Or are you going to continue to follow up at that point onwards?

Question: Yaron Werber - Cowen Inc - Analyst : Whether it's going to be all the data together.

Question: Yaron Werber - Cowen Inc - Analyst : And also supporting biomarkers as well? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. FEBRUARY 26, 2025 / 9:30PM, ALEC.OQ - Q4 2024 Alector Inc Earnings Call

Question: Sarah Schram - William Blair & Co LLC - Analyst : Thanks guys, thanks for taking the questions. So going back a little bit to the preclinical program. Can you just remind us specifically how that pyroglutamate A beta epitope that you're targeting with 037 differs from both the approved A beta antibodies as well as some of the other ones in development like Latozinemab, which does also use a brain shuttle technology and kind of how those different epitopes might lead to differentiation? And could you also just remind us if that 037 uses a TFR, or a CD98-mediated brain shuttle system? Thanks.

Question: Sarah Schram - William Blair & Co LLC - Analyst : Sorry, sir. Yeah, sure. So like how might the different epitopes lead to differentiation in terms of targeting potentially different plaque species?

Question: Sarah Schram - William Blair & Co LLC - Analyst : Got it, very helpful thank you. Saraswati Kenkare-mitra - Alector Inc - President, Head - Research and Development Thanks, Sarah.

Question: Graig Suvannavejh - Mizuho Financial Group - Analyst : Hi, this is Graig Suvannavejh, thanks for taking our questions. A couple on our end. For INFRONT-3, can you please remind us how you've enriched for patients and more generally optimize the trial design in order to give yourself the best chance of success to show efficacy? And also in FTD, knowing that there are several programs in clinical development, can you compare and contrast your approach versus the competitor programs and why you think natalizumab may offer an optimal therapeutic option when compared to the other programs? Thank you so much. Saraswati Kenkare-mitra - Alector Inc - President, Head - Research and Development Yeah, thanks. I'm going to have to ask you to repeat the first part of the question because there's a lot of background noise coming over with you. So I'm sorry about that.

Question: Graig Suvannavejh - Mizuho Financial Group - Analyst : That's really helpful color. Thank you so much.