Alector at Leerink Global Healthcare Conference: Strategic Advances in Neurodegeneration

On Tuesday, 11 March 2025, Alector Inc. (NASDAQ: ALEC) presented at the Leerink Global Healthcare Conference 2025, highlighting its strategic advances in neurodegenerative disease treatments. The company, led by CFO Mark Grasso, outlined both promising developments and challenges in its pipeline, including significant partnerships and financial positioning.

Key Takeaways

• Alector is advancing latuzinumab for frontotemporal dementia (FTD) in a fully enrolled Phase 3 trial, with data expected in Q4 2025.
• The company reported a strong cash position of over $400 million, supporting operations through 2026.
• Alector’s partnership with GSK includes a $700 million upfront payment and potential milestones totaling $1.5 billion.
• The Electra Brain Carrier technology is central to Alector’s strategy, enhancing drug delivery to the brain.
• Alector is pursuing multiple programs targeting Alzheimer’s, Parkinson’s, and Lewy body dementia.

Financial Results

• Cash Position:

- Alector holds over $400 million in cash, ensuring operational stability through 2026.

- This financial strength excludes potential milestone payments from GSK.

• GSK Partnership:

- The collaboration involves a $700 million upfront payment with $1.5 billion in potential milestones.

- Profit sharing in the U.S. is equal, while ex-U.S. revenues include tiered double-digit royalties.

- Milestones include $160 million for the first U.S. commercial sale and $90 million for the EU.

Operational Updates

• Latuzinumab for FTD:

- The Phase 3 trial is fully enrolled, targeting 103 symptomatic patients and 16 asymptomatic carriers.

- Data is anticipated in Q4 2025, aiming to confirm Phase 2 results of a 50% slowing in disease progression.

• AL101 for Alzheimer’s Disease:

- Phase 2 enrollment is nearing completion, with data expected in 2026.

- The study compares two doses against a placebo, focusing on changes in cognitive function.

• Electra Brain Carrier Programs:

- New brain-penetrant therapies for Alzheimer’s and Parkinson’s are scheduled for clinical trials next year.

Future Outlook

• Near-Term Goals:

- Alector aims to release pivotal Phase 3 data for latuzinumab and Phase 2 data for AL101.

- The company plans to advance its brain shuttle technology and proprietary programs.

• Longer-Term Goals:

- Regulatory approval and commercialization of latuzinumab for FTD-GRN are priorities.

- Alector seeks to expand its proprietary pipeline with novel treatments for neurodegenerative diseases.

Readers are invited to refer to the full transcript for a detailed account of Alector’s presentation and strategic initiatives.

Full transcript - Leerink Global Healthcare Conference 2025:

Mark Grasso, Chief Financial Officer, Elektor: Good morning, everyone. And thanks to Mark and the Leerink team for having us today. I’m Mark Grasso. I’m the chief financial officer at Elektor, and then we look forward to providing an overview, for, the group today.

Just to comment, I will be making some forward looking statements and encourage you to review our SEC filings for more information. So at Elektra, we have a bold vision, one in which we seek to make degenerative brain disorders history. And there’s been progress in the field recently, which is encouraging, including around the a beta therapeutics, but we see that there’s much more opportunity to go. And as shown on this slide, you’ll see on the left our core, scientific approach, which is a three r strategy where we’re removing unwanted proteins, replacing proteins that may be missing or enzymes that may be missing, and restoring activity, in the brain healthy activity in the brain. And we have novel, programs that are late stage in development, including a fully enrolled pivotal phase three in frontotemporal dementia, which has received breakthrough designation by the FDA, which we’ll be reading out in the fourth quarter of this year.

And we’re also approaching complete enrollment in our phase two study for our second pro granuline elevated program in Alzheimer’s disease. And both of these programs are partnered with GSK, and I’ll touch on those in more detail. In addition, we’ll also touch on our proprietary technology, which is a versatile brain shuttle technology, which enhances the delivery of novel therapeutics to the brain. We’re a well resourced company with over $400,000,000 in cash. We have strong leadership and significant resources, and we’re in a strong place relative to our partnering strategy as well.

So this slide is just a snapshot of our current portfolio. And at the top, you see the two pro granulan programs, latuzinumab, which is in, as I mentioned, a phase three study, and this is in the setting of frontotemporal dementia for patients with a GRN mutation, and I’ll touch on that in the data supporting that program today. And our second pro granule and elevating program, AL one zero one, which is an also which also is an antibody, and this is in the setting of Alzheimer’s disease. At the bottom, we’ll also spend some time today on our proprietary wholly owned portfolio of Electra Brain Carrier programs and novel programs, which are advancing towards the clinic and are addressing significant unmet need in the fields of neurodegenerative disease. We have over 400,000,000 in cash as mentioned at the end of the year, and this is runway through 2026.

So let me turn now to our pro granulant programs. First, I’ll start with frontotemporal dementia. This is a rapidly progressive form of dementia. It’s the most common form of dementia for patients under the age 60, and it’s often misdiagnosed. It can be misdiagnosed with depression, Alzheimer’s disease, Parkinson’s disease, other psychiatric conditions.

And it’s a very devastating disease has compulsive behavior. You can have apathy, anxiety, aphasia. This is the form of dementia, for example, that Bruce Willis, recently, came public with. There’s no approved treatments to cure or slow the progression of frontotemporal dementia, and this is an area that, you know, we’ve helped pioneer in the field. So what is our approach?

So on the right hand side, you can see how latosinumab works, and what it’s doing is binding a degradation pathway for progranulin, which is called sirtillin. So our antibody is shown on the cartoon on on the right is binding the, sartellin receptor, and that’s elevating pro granular. And why is elevating pro granular important? Well, in the setting of frontotemporal dementia, there’s a genetic underpinning for this disease as shown on the left. If you have, two bad copies of the progranulone gene, you die at a very young age of a severe disease, a severe form of dementia and neuronal steroid lipofuscinosis.

If you have one good copy and one bad copy of progranulin or a heterozygous mutation, you have half the normal levels of progranulin and you general, you will have frontotemporal dementia with onset by about 60 years of age with a ninety percent penetrance. And this is the setting that we’re pursuing initially in our late stage development. And if you have other mutations, non coding mutations, approximately ten to twenty percent loss of function, you increase your risk significantly for a number of degenerative brain disorders, including ALS, Alzheimer’s disease, Parkinson’s disease, as well as frontotemporal dementia. So we see this as a key area for development and note, that progranial is a critical factor in healthy brain function as we get to later life, and it’s known to be a highly conserved protein throughout evolution. It’s a critical immune regulator, a neuronal survival factor in a lysosomal chaperone.

So by replacing this in the context of frontotemporal dementia with a GRN mutation or elevating this in the setting of Alzheimer’s disease, we see this as a breakthrough potential approach for, for frontotemporal dementia and other degenerative brain disorders. So shown here is just a schematic of the phase two that we have completed in, frontotemporal dementia. And you can see that we enrolled asymptomatic patients with frontotemporal dementia with a GRN mutation, symptomatic patients for patients with a GRN mutation, and then also some patients that had a C9orf seventy two mutation also with frontotemporal dementia. I’m gonna spend time today mainly in the middle section, which is the, population, which is also the setting for our pivotal phase three. And we looked at safety, tolerability, PKPD, and also a number of additional endpoints, including different biomarkers, brain imaging, and clinical assessments, and I’ll share that data with you today.

So turning to the key biomarker, which is the elevation or restoration of progranulin to normal levels, what’s shown here is a comparison prior to treatment and then post treatment as compared to levels seen in age matched controls for for healthies. And you can see that pretty consistently both in the plasma and in the CSF with administration of latuzinumab, you’re restoring the progranulin levels basically back to normal, which is, you know, a key finding for our approach. And then if you look at other markers of disease activity, this is a measure of glial glial fibrillary acidic protein, which is a which is an important marker of astrogliosis or inflammation in the brain, and you compare this to asymptomatic carriers of the GRN mutation population, you can see that, again, you’re restoring this disease marker back to the normal range, another key finding. And then, we also looked at the progression of disease from a clinical and functional standpoint. And this is basically an adapted CDR sum of the boxes for frontotemporal dementia.

Patients with frontotemporal dementia have speech and behavioral facets. So similar to the Alzheimer’s disease, CDR sum of the boxes, we have an adapted CDR, plus NAC FDLD sum of the boxes for front and temporal dementia. And this is a well studied approach in this setting, and we compare our disease progression in the phase two to age matched historical controls in the longitudinal databases available, which, you know, the the investigators studied closely. So this is a comparison that shows approximately a slowing of disease progression by nearly fifty percent over a twelve month period, and this is what we’re seeking to confirm in our Phase three prospective placebo controlled study, which I’ll turn to next. So here is the design of our phase three, and this is a ninety six week study.

It’s placebo controlled. It’s in a hundred and three symptomatic patients and sixteen at risk or asymptomatic FTDGRN carriers. And what we’re looking for as the primary endpoint is the slowing of disease progression as measured by the CDR plus NACFTLD sum of the boxes. Again, the sum of the boxes approach adapted to FTD. We’re also looking at key secondary clinical outcomes, and there’s a number of different measures here for cognitive and functional benefit, and there’s a significant range of biomarkers we’re looking at as well, including volumetric MRI and other biomarkers.

So, again, this is a placebo controlled perspective, and it’s fully enrolled at this point, and data will be in q four of this year. In addition, we’re also advancing a second progranulin elevated antibody, which is AL one zero one, and this is in the setting of Alzheimer’s disease. As you can see here, this is the schematic for the study, and we’re looking at two different doses, a higher dose and a lower dose as compared to placebo in a phase two, and this is a randomized prospective study. We’re looking at the primary endpoint as change in baseline from the standpoint of CDR some of the boxes, and we’re looking at this at fifty two, sixty four, and, seventy six weeks. We’re also looking at key secondary endpoints, including a number of different cognitive and functional endpoints and a range of biomarkers, including amyloid PET, tau PET, CSM CSF and plasma.

So this study, has enrolled quite well. We’re ahead of our target. We’re guiding that we’ll complete enrollment by mid this year, and I think, we’re we’re nearly there. Just to touch on our our partnership with GSK, we have a significant partnership with GSK on both of our progranial and elevating antibodies. This was a $700,000,000 upfront deal with a billion and a half in development and commercial milestones.

It’s a $50.50 profit share in The US, and we share commercialization with GSK. We take the lead in the orphan indications, including FTD GRN. And then outside The US, it’s tier double digit royalties that are economically approximate to the fifty fifty in The US. So very significant, downstream economics, and there’s also significant milestones. There’s a hundred and $60,000,000 milestone payable to us for the first commercial sale in The United States, and there’s a $90,000,000 milestone for the first commercial sale in The EU.

So as noted earlier, this is an exciting program that’s advancing towards phase three data in q four this year for latuzinumab and phase two enrollment completion by mid this year with data we anticipate in the 2026 time frame. And I should note that latuzinumab also received breakthrough designation from the FDA in the setting of FTDGRN. So a lot to be excited for on the progranulone front. Shifting gears with the remaining time, I’d like to touch on our, Electra Brain Carrier technology in our earlier proprietary portfolio. So what is Electra Brain Carrier?

This is enhanced brain delivery for novel and best in class therapeutics, and what we’re seeking to do is widen in the therapeutic window for these, you know, critically important brain therapeutics. Why is this important? We want to lower the cost of goods. So when you’re giving systemic naked antibodies that have relatively poor penetrance into the brain, you have to do it often at very high doses, and that can be expensive. And it’s also potentially inconvenient.

So if you’re having to go in for, you know, as currently is the case for the A beta therapies either, you know, once monthly or twice monthly, you know, infusions in infusion centers, that’s much less convenient than if you can have an at home subcutaneous delivery. So this approach potentially allows much more appropriate cost for goods and better convenience. In addition, there’s really critical pieces in terms of how we’re optimizing the therapeutic window for these, novel therapeutics. So there’s a versatility, so we can apply this to antibodies, to proteins, to enzymes and nucleic acids, so that widens the opportunity from the standpoint of therapeutic approaches significantly. There’s also tunability.

What does this mean? This means affinity, for pairing to, the shuttle technology, and this is really critical when you’re trying to tailor and and minimize side effects and maximize the therapeutic potential, and we’ll we’ll touch on that in more detail. And then there’s also translatability, which is, you know, really speaking to how rapidly we can progress these programs to patients and and to the eventually, the market. So shown on the the right hand side is the most well known example, which is using the transferrin receptor on the surface of reticulocytes basically to allow internalization transcytosis and exocytosis across the blood brain barrier. And this is an approach that that we’re using along with our proprietary therapeutics in an optimized way.

That’s shown on the top here, so the iron transport approach, and this has potential for for neurons, for microglia across the brain. It has high expression level on the blood brain barrier, and we can get the drugs where we want them in high penetrance. Shown below is a second approach that we’re also evaluating, which is an amino acid transporter called CD98 heavy chain, and this also has significant potential for therapeutic cargos delivered locally in the brain. So this shows schematically the difference between using the brain shuttle and, just a naked antibody. And on the first panel, you see relatively significant penetration only on the periphery.

But if you look on the right hand side, you see very significant penetration across the entire brain section. And this is, again, an opportunity to use a much lower dose and have much higher penetrance and a better therapeutic window. So let me now take this technology and apply it more specifically to our programs. The first one I’d like to talk about is a brain penetrant anti A beta antibody, and this, we believe, has best in class potential. For those following the field, they’ll know that, you know, Roche has made some progress with what was a naked antibody called gantenerumab, which had mixed results in the clinic and high, incidence of side effects including ARIA, which is a pretty significant concern for the a beta therapeutics.

And then they applied a transferrin receptor brain shuttle to this, and they’ve been able to show that they’re able to reduce the ARIA quite significantly, enhance brain penetrance while they are still managing some concerns around the side effect and with with anemia. So what we’re doing is seeking to take the best of what’s been developed in the anti A beta space and optimize it with our own proprietary approach. So the first thing we’ve done is we’ve optimized the engineered binding to the plaque epitope, and we’re using, the anti pyroglu three, epitope, and this has been shown to have, you know, the best in class plaque removal. We’ve also optimized in the second piece the constant region for the antibody, and this is really critical, we believe, to optimizing the immune system’s removal of the plaque. So you’re basically using the antibody to bind the plaque, but then the constant region is recruiting in the brain’s immune system to clear the plaque.

So we’ve optimized that piece. And then the third piece is optimizing the brain shuttle, and that is a combination of the binding epitope and the affinity to the brain shuttle and optimizing the linker. And we’ve done this in a way that, we believe is going to have best in class potential in terms of minimizing the side effects and maximizing the therapeutic window. This is scheduled to be in the clinic next year. We’re excited about the progress in this program.

The next program I’d like to touch on is our Brain Penetrant GCase Replacement Therapy. So those following the field know that there have been g cases developed peripherally for the treatment of Gaucher disease, but there’s also central involvement, not only in Gaucher disease, but associated with, you know, significant aspects of Parkinson’s disease and Lewy body dementia. So having a brain penetrant GKS replacement could have significant potential. Naturally, the naturally occurring GKS enzyme is unstable, it’s short lived, it’s difficult to manufacture, and it’s unable to cross the blood brain barrier. So what we’ve done is engineer an active, stable, developable, developable, minimally immunogenetic GKS enzyme, which is proprietary to ELECTOR, which is compatible with a brain shuttle format.

And we’re able to demonstrate that we can increase GKase levels and have significant potential benefit in these neurodegenerative diseases of significant unmet need. So our approach is shown on the right. So we have an engineered enzyme and a linker to the rest of the antibody construct. We’ve optimized a transferrin, epitope, and we’ve optimized, again, the affinity. And we have a constant region, which is designed to be optimal.

This is a case where you’re not trying to have immune activation, or you’re not trying to have, you know, a, immune system that’s coming in enhancing any activity, what you’re what you’re really trying to do is just get this enzyme across the blood brain barrier and into the brain in the in the areas where it can have its enzymatic activity, which is gonna be helpful and beneficial. Again, this is wholly owned proprietary to Elektor and is advancing to the clinic next year. Just touching on a few other exciting programs that we’re advancing, We are also advancing a novel real in modulator. This is something that is replicating the protective effects of a gene mutation, which is very interesting in the field of Alzheimer’s disease. As folks may know, Alzheimer’s disease has pathology both from the standpoint of amyloid deposition in the brain, but also tau deposition in the brain.

And there’s a mutation, a presenilla mutation, which has been shown to basically decouple the amyloid pathology and the tau pathology, and there’s a population that is basically, you know, significantly protected from the development of the pathological consequences of Alzheimer’s disease. And we’re seeking to basically replicate this protective genetic finding in the context of a novel therapeutic approach. So more on this to come. At this point, we believe we’re the only company that we’re aware of that’s, you know, developing a real modulator. And lastly, I wanna touch on our two tau programs.

We are developing a tau antibody that has potential best in class and also a tau siRNA. These are both using our electro brain carrier technology. The most promising current anti tau antibodies target the tau microtubule binding region and show you know, early potential promising results in in human trials. But again, you know, these are naked antibody approaches, and we’re seeking to optimize the therapeutic window and and maximize the therapeutic benefit by attaching a brain shuttle and more to come on the antibody approach. And then with an siRNA approach has the potential to directly address tau and prevent the synthesis of tau mRNA and protein.

This has the potential for peripheral delivery with our brain shuttle and also potentially, you know, have significant change in disease progression. So excited very much about the progress with the proprietary pipeline and and more to come on all these programs in the near term. So with that, I’ll just summarize our accomplishments to date in the first panel. We’re pioneering first for patients. Our current Phase three for latuzinumab in FTD GRN, as noted, is fully enrolled and we anticipate data in Q4 of this year.

Our Phase two for AL101 is nearing completion of enrollment and will have data in 2026. And we’re excited about the progress we’re making on our proprietary pipeline of first and best in class approaches for a range of unmet needs in the brain. Our goals for the next three years are shown in the middle panel. We’re seeking to deliver our data from the pivotal phase three, the phase two for our second program, as well as providing critical data around our blood brain barrier technology and our wholly owned portfolio of novel and best in class therapeutics. Beyond that, we’re looking to obtain regulatory approval and commercialize latuzinumab and FTD GRN in the coming years.

And then, we’re also looking forward to sharing additional clinical data for our proprietary programs over this time frame and advance the science in these areas of significant unmet need. As noted, we’re doing this from a relatively strong cash position, $413,400,000 in cash at the end of the year is runway through 2026. That doesn’t assume any of the milestones from GSK, doesn’t assume any partnering of any of our proprietary programs, and we’ve had a strong record of partnering in the past. So thank you very much for your attention today and happy to take any follow-up.

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