Alector, Inc. (ALEC) Earnings Call Transcript & Summary

Good afternoon, everyone. My name is Graig Suvannavejh. I cover European and U.S. biopharma for the firm. Let me welcome you to the 3:50 p.m. session of day 2 of the Goldman Sachs Global Healthcare Conference. I've got the pleasure of introducing Alector to you all today. And joining us from the company, we've got 3 members of the leadership team. Shehnaaz Suliman, who's the President, and Chief Operating Officer of the company; Robert Paul, who's the Chief Medical Officer; and Sabah Oney, who is the Chief Business Officer. So let me welcome the 3 of you to your first Goldman Sachs Healthcare Conference. In normal times, we'll be doing this South of Southern California, a much better venue. Hopefully, we can get back to a time where we can do this in person. But thank you for joining us. Maybe just to start off, as Alector is a relatively new company, maybe I'll turn it to you Shehnaaz just to give us kind of a high-level introduction as to who Alector is, and what are the unique attributes of the company in terms of the science, and what's your therapeutic areas of interests are, for our audience.

Terrific. Thank you, Graig, and it's really a pleasure to be here with everyone today. Our mission at Alector is really to find novel therapeutics that address neurodegenerative diseases. And our founder and CEO, Arnon, always says, we're in it to cure it, which is terrific because we really have an ambitious goal, and that is really to make neurodegenerative diseases obsolete. Arnon has spent the last 4 decades or the better part of 4 decades working on neurodegeneration. And since founding the company about 7 years ago, we have been singularly focused on the discovery and development of therapeutics that recruit the brand's immune system to address neurodegeneration. Our approach is unique because we have been able to leverage human genetics, immunology, and neuroscience, to discover and develop genetically validated targets, and then test these targets in genetically stratified patient population. And I think this is something that really makes Alector unique as well as a profound focus on biomarkers to enhance the probability of success.

Thank you very much for that introduction. You've got an approach that you described as immuno-neurology. I think people are more familiar with all of the events that are happening in immuno-oncology, and you do have interests there as well. But maybe if we can get into kind of some of the finer details about what makes this immuno-neurology approach unique and exactly how are you going about this?

Sure. Absolutely. So this approach is being fueled really by significant progress, which has happened from GWAS in the past few years and gene sequencing and a lot of techniques that have elucidated that a vast majority of risk genes are associated with microglia, which is the brain's primary innate immune cell. And so as a result of our ability to have identified these risk genes, we were then able to engineer our drug discovery and development approach to find therapeutic targets that target these risk genes. And then, as I said, test them in patient populations that are even deficient for the geno protein and try to correct the underlying deficiency. We now know and understand that microglia is a central actor in maintaining brain health, and neuronal well-being, and it controls a number of functions that are extremely important, both physiologically as well as pathophysiologically, functions like immune surveillance, the phagocytosis of pathologic proteins like TAU and A-beta other functions like modulating synapses, are all critical functions of microglia. So by focusing our immuno-neurology approach on really looking at how best to activate microglia, and cause microglia to proliferate and do the important work that is necessary to maintain brain homeostasis and health. We feel that this immuno-neurology approach is really key to unlocking some of the pathology and pathophysiology that underscores the natural history of a number of neurodegenerative diseases. Graig, you're on mute.

Thank you very much. As a company, you've got a fairly broad and deep pipeline right now. I think most of investor attention is on AL001, which is your lead assets in terms of where it is the clinical time lines and your primary focus from a proprietary perspective. So with that said, perhaps, if you could just introduce us to AL001, what the target is and it's going after FTD, which perhaps many in the audience don't know that much about FTD. And if you can just talk about what the disease is and what the unmet medical -- unmet medical need is in FTD.

Certainly. And before we do that, again, I'd just; say we're very proud of the fact that we have rapidly advanced full programs into the clinic. We have multiple first-in-class clinical programs and we did this at breakneck speed really, and Robert can speak to this, in less than 18 months going from basically IND to what will be our first pivotal trial in Phase III, which we hope to initiate in frontotemporal dementia patients with the progranulin mutation later this year. So you asked about the lead program. And about frontotemporal dementia. I think most people are familiar with Alzheimer's disease and the risk factors associated with Alzheimer's such as aging and the deposition of plaque. Frontotemporal dementia is particularly in patients with the progranulin mutation is a different kind of pathophysiology. These patients are often younger so in their 50s and 60s rather than their 70s and 80s. It's a devastating disease because it has an impact not only in the patient with respect to rapid progression to dementia and death. This can occur as soon as 5 to 7 years after the patient has been diagnosed. But also because of the havoc that the disease wrecks on families because these patients are often in the primer of their adult lives and are stricken rather suddenly. The patients and caregivers have to deal with a number of both language and behavioral issues associated with the clinical phenotype, and this can be exceptionally devastating for families. Alzheimer's can have more of a heterogeneous phenotype, and there's a lot of variability in terms of how patients progress. However, with FTD, these patients rapidly progress, and it is very devastating for families. There is no treatment at all. And our drug, 001, which is being developed for FTD patients with progranulin mutation is unique because it really attempts to replace progranulin, which is a secreted growth factor that has been found to be deficient in these FTD patients. What happens is that patients that have 1 good copy or and 1 bad copy of the gene tend to have a greater than 50% decrease in their progranulin levels, which when this occurs because of the high penetrance, leads to then developing FTD. And so there 001, our lead program inhibits a degradation receptor called sortilin, which has the effect of extending the half-life of progranulin and, in turn, upregulating levels by two to threefold so that we're actually able to restore progranulin to physiologically normal levels.

That's helpful. Maybe we can drill down just a little further on to the data that you have shown. So you've reported some early data in humans. I'm wondering if you could kind of bridge, what you've seen preclinically to what you've seen in humans. And I think there's a hope that you will be sharing additional data later this year. So can we talk about the data in itself in more granular detail?

Absolutely. We'd be delighted to do that. I think we've been asked a lot of questions and one of the quotes that stood out from this morning was, wow, you guys have effectively derisked the biology. We are very proud of the fact that we've shown -- been able to show meaningful and long-lasting expression and distribution of progranulin in both plasma and CSF. And we've been able to show this in both healthy volunteers as well as in FTD patients, both asymptomatic and symptomatic patients. I'm going to let Robert speak to the details in just a moment. But I think at a high level, as I said, we have achieved normalization of progranulin levels in both the brain and the periphery. And we think this is extremely important in counteracting both the central and kind of peripheral pathologies associated with progranulin deficiencies. We reported data from our Phase Ib study last year, both CSF and plasma levels of progranulin upregulated. And then we reported data from an Phase II open-label study in which we showed some very exciting but yet preliminary data on a key biomarker of disease that is known to be associated with neuroaxonal degeneration in the form of neurofilament. So maybe I'll stop there, and I'll give Robert an opportunity to just talk a little bit more about the details of those data sets.

Yes. So we started in healthy volunteers, and we were able to show basically after a single dose in the first patient that we have ever dosed with a drug that we can efficiently increase progranulin levels. So basically, after the first dose, we were able to show that we hit the target and the mechanism mode of action basically is true. And then we also measured progranulin in the CSF, and we were able to demonstrate that we hit the target in the brain and also have an effect. We basically increased progranulin levels in the CSF, in the CNS by two to threefold. And then when the next step we went into the patient population. For us, it is important how well we can actually restore progranulin levels. And we were able to show in mutation carriers that start with a low level of progranulin to bring progranulin levels in the CSF back to normal. If you take the analogy of like enzyme replacement, it's not a little bit or a temporary increase in this protein in dismissing enzyme. It's actually bringing it back to normal levels over the whole period of the treatment. And because we have so strong biomarkers, we were able to really be very fast in the clinic because basically, we had -- we knew exactly the dose and dose regimen. We had proof of target engagement. We actually have seen markers downstream of progranulin and that's why, for us, the priority was always to go to the clinic as fast as possible. I mean in the Phase III because at the end of the day, you have to show a clinical effect, and you can only do this, in a well-controlled, placebo-controlled trial where the cognition is the endpoint, and that's what we're doing.

I think the market and investors are anticipating that you're going to have additional data later this year. I was wondering if, a, we can talk a little bit about, first, what are you hoping from -- in terms of the biomarkers themselves, what you think you're going to be able to share with us? So that's the first question. I think the second question could be, is there an updated view on timing of when you'll be able to share this data? And I guess that the third question related to this really has to do, and it's a much bigger picture question is, and the question I get most from investors is what is really the confidence that the biomarker data will translate into clinical efficacy. So I realize it's a 3 questions in 1, but I appreciate if you could tackle this.

Okay. That's -- no, that's great. And those are great questions. And Robert and I will definitely be tag teaming the answers. So the -- just to level set, the Phase II open-label study that we are currently conducting with AL001 is really a PK/PD study. Our goals for the study were intended to show that we had safety with multiple dosing and across multiple patient types. So we have a cohort of symptomatic FTD progranulin patients, asymptomatic FTD progranulin patients as well as a small cohort of C9orf72 patient carriers. So we -- the goal for the study was to really focus on safety and PD. With respect to PD, we are measuring a number of biomarkers, of which progranulin levels over time, neurofilament levels over time are 2 of the key biomarkers, but we're also looking at a battery of proteins through a unique technology that we have with thermoscan, where we can evaluate and look at how a protein signature that we believe to be disease-relevant changes over time, and we showed some of that data at R&D Day as well. In addition to that, we are looking at volumetric MRI. This, of course, can only be measured once every 6 months. So we will likely have that data at the end of the year, and the clinical endpoint. And the clinical endpoint of relevance here is the CDR-FTLD sum of boxes, which is a registrational endpoint, the same endpoint we will be looking at in Phase III. So that's sort of the base case. At R&D Day last year, we showed some very, as I said, exciting and preliminary data from the symptomatic FTD cohort in which we saw a roughly 14% reduction in neurofilament about 2 months after dosing these patients, so at [ Day 85 ]. What was really key about this data, Graig, was the fact that we know from longitudinal registries that what typically happens in these FTD patients is that their neurofilament levels go up over time around the order of 25-or-so percent. So we were extremely encouraged to see that we were actually having an effect on reducing neurofilament in these symptomatic patients as early as about 3 months after dosing. We know from other examples in multiple sclerosis with ofatumumab and in spinal muscular atrophy, that it actually can take longer to see a change in neurofilament as long as 6 months. And more recently, we know up to 9 months in a year. So we thought this is a very encouraging preliminary trend. So maybe I'll stop there and give Robert an opportunity to build on that and discuss what else we are likely to see in July of this year and then at CTAD in November.

Yes. So the main difference between what you have seen end of last year and what are we going to see in July is people will be exposed to the drug for longer. The Phase Ib basically were dosed for only 4 weeks. And then we waited another 2 weeks, and then we did the blood draw, and that's where you have the [ Day 85 ] plasma levels. You will see more data from -- for patients that have been exposed longer. And we also see how sustained the progranulin effect is in the brain. And I think what's really important is or more -- I think it's actually at the end of the year because there, we also have volumetric MRI. And the patients will be exposed way longer for quite a while. What I actually also want to add for the Phase Ib, not only we have seen this trend in neurofilament decrease, which, of course, is very exciting. Actually, I was almost more excited to see the initial effect on some of the other biomarkers, thinking neuroinflammation and lysosomal function because this is not random. I mean this is exactly these pathways are affected in the disease. And by restoring this, we know that progranulin gets where it's supposed to go and basically reversing the biomarkers, the changes that are associated with the disease. So for me that was, quite frankly, almost as exciting as the neurofilament, specifically because there we actually saw a statistical difference, it was more than a trend.

Okay. Great. I think...

Yes. Graig, if I could just add, the field is really clamoring for data that is able to show a correlation between biomarkers and clinical outcomes. And we are extremely committed toward developing a composite data set that allows us to look at not just neurofilament and progranulin, for example. But as Robert says, a large battery of disease-relevant biomarkers that can enable us to look at not only the association but hopefully at some point to correlate the trajectory of those biomarkers with clinical outcomes.

Okay. A question may be on the upcoming data around expectations on what would be a good results in the data. And maybe it's -- I'll let you answer it any way you want. But I think in this area where perhaps there's not a lot of understanding of the nuances and the complexity, maybe for our audience. If you could provide some high-level view on what you think would look good in whatever you end up sharing, whether it's in the July time frame and/or later this year?

Well, conceptually, I think it's useful to remind ourselves that nothing has been approved for Alzheimer's disease in over 20 years. And for FTD, there are no treatments. And this is the first time that a therapeutic will go into the clinic. And I would say, if we were to pull out physicians and clinicians they would say anything that can arrest the progression of this disease would be considered to be clinically meaningful, particularly in FTD. So when it comes to the question of what's the threshold that is likely to be predictive. I mean of course, this is the million-dollar question. And I would say that -- and I'm going to let Robert definitely chime in here. But what we know from the REGISTRY data is that neurofilament levels go up over time. And around 25% is what we've seen based on our own modeling of how this is going to occur. So in our minds, if we showed any change in neurofilament at steady state or currently continuing to decline along the levels of what we've seen, we would be exceptionally encouraged by that at the 14% level. I mean there is noise around this data even in our initial data, 1 patient declined by as much as 40%. So what exactly is the number? It's going to be hard to pinpoint. Also bear in mind that this is an open-label study. So we are really looking at the trend longitudinally, which I think will be the single most helpful thing to look for here on a patient-by-patient basis rather than being able to point to means and medians for this type of study. So maybe I'll stop there and Sabah or Robert, if you have anything else to add on this point, feel free to jump in.

No. Again, it's -- neurofilament indicates neuronal death. And every -- any decline in neurofilament that will indicate -- indicates that less neurons are dying. And if you think that the brain has neurons, it has something to do with cognition, you would think that this venture will translate into a clinical effect. How -- when this will actually be to what extent -- it's -- you can make a one-to-one correlation between neurofilament level and clinical effect. That's not the -- we don't have enough data to make any correlation between the levels of reduction in neurofilament and the client will benefit.

Okay. I just wanted to ask about COVID-19 and the impact on your clinical trials. I know you provided an update recently when you reported 1Q results. And so perhaps, could you remind us what commentary you made about the impact of COVID-19 back then? And how you assess what COVID-19 might mean in terms of ongoing and/or new clinical trial work for particularly this program. You can touch upon how the other programs that you have might be affected as well, but let's just focus on AL001 here?

Certainly, Graig. So we are in a very fortunate position to say that there has been minimal impact on our trajectory. For 001, we are fully on track to execute our Phase III. If anything, we are fortunate because we've been able to now look at some additional ways to conduct those trials creatively, whether it be through digital monitoring and the incorporation of at-home administration, for example. We're evaluating what might make sense for that trial. But in a nutshell, we are fully on track with the Phase II. I'd say the most significant impact, if I can call it that, has been on 002 where we had a Phase Ib study that was ongoing. But frankly, we've been able to pivot so rapidly and actually transition that into a Phase II study, which we will also initiate in the second half of this year. So for the most part, I'd say that we have been fortunate that COVID has had relatively little impact on our overall development pipeline. The only other thing worth noting is that our research team at Alector actually continue to come in even during the most severe phase of the lockdown. And in part, we were able to facilitate that because we have a very large facility. We also took all the appropriate precautionary measures. And many of our people really felt that the mission that we're trying to accomplish here and the need to continue to do that and the ability to do that safely was something we could continue to do. So we're actually almost at a full ramp-up on -- in terms of research. And as I mentioned, the rest of our clinical pipeline is continuing to be on track.

Okay. That's fantastic. Maybe just 2 last questions on this program before maybe switching into other programs. Obviously, this is a proprietary asset that you plan on, I believe, commercializing on your own. So I believe if you could provide just some commentary on how you're seeing the commercial opportunity. And then maybe wrapped into that there are lots of questions I get around pivotal trial design and when we might be able to see more details around that. So I realize it's a big -- a lot to answer in 1 question. But if you could provide some commentary, that would be fantastic.

Certainly. Let me take the question on commercial strategy. At this point, we are prioritizing the U.S. and EU markets first. And our base case would be to anticipate a launch certainly in the U.S., and we are currently evaluating what a launch in the EU5 territory -- well, EU4-plus the U.K. might look like. But that said, beyond that, we're exploring other regions such as the Pacific, Asia, Latin America. As part of our global clinical trial program, we feel like we're going to learn a lot about what FTD looks and feels like in those territories. And what it would take to launch in those regions. So I think for a company of our size, in all honestly, doing a launch for the syndication in the U.S. feels very manageable. And we're currently evaluating what it would take for the rest of the world. So maybe with that, I will hand over to Robert to talk about the Phase III design.

Yes. The Phase III design, it's a placebo-controlled study, roughly 180 patients. It's a combination of a prevention trial and a treatment trial because we're also going to include asymptomatic patients that are at risk of converting to symptomatic patients. And then we focus on the very mild and mild population for -- in the symptomatic patients. We are using a disease-progression model to basically measure the disease progression, and that's actually why we can't combine the asymptomatic with the symptomatic patients. The primary endpoint is the CDR-SOB FTLD. We've been with this study design with the FDA and agreed on the clinical endpoint patient population. And we're still in, of course, very strong communication with the FDA to make sure that the study meets then all the criteria for a pivotal study once we have the data. Also how the study is designed is that we can multiple different interim analysis. So we have always a chance depending on the effect size to have to declare early success. And we're going to start -- we expect to start the study within the next couple of months.

Thank you very much for that. Maybe what we'll do with -- perhaps we've got a little bit more than 10 minutes left, and I want to make sure we touch upon your Alzheimer's disease portfolio, AL002 and AL003. Clearly, Alzheimer's remains a significant unmet medical need, and you've got a partnership with AbbVie around these assets. So perhaps in the time that we have, and maybe we could use 5 to 6 minutes around this. If you could tell us about 002 and 003 and kind of what the mechanisms are? Why you think in a space like Alzheimer's disease, which has, as you mentioned earlier, nothing has been approved in 20 years or so. What gives you the confidence that this is the right approach?

Absolutely. And again, I think what's really interesting here is how deeply entrenched the choice of these targets were in human genetics and the recognition that for TREM2, for example, this is one of maybe the second highest risk factor that's been identified in Alzheimer's disease and can be thought of, frankly, as an immune checkpoint for microglia. We know that in heterozygous form the risk of Alzheimer's disease increases by something like threefold. And there is a [ snip ], which is associated with increased TREM2, which is actually protective. So our goal with 002 is really to develop an agonist here, which aims to actually mimic the protective variant and in so doing, optimize the function of microglia, which we think is incredibly critical in -- for the reasons I mentioned earlier on. Similarly, for SIGLEC 3, which is the other Alzheimer's disease program partnered with AbbVie. Here, we also think about this as an immune checkpoint. It's a very prevalent risk allele and CD33 is one of the main determinants of Alzheimer's disease risk as determined by GWAS. And it's actually widely prevalent. So it's actually present in about 80% of Alzheimer's disease. The loss of function mutation here is actually protective. So our AL003 antibody is really an antibody to SIGLEC 3 to block the inhibitory function and, again, mimic the protective allele to improve the survival and proliferation of microglia. So both of these targets, I would say, there's a lot of literature around this, they -- the -- a lot of strong biology and, of course, a lot of genetics. And so we feel like these are 2 of the kind of front runners. TREM2 is often called the darling of neurology by some targets. What's unique about us and what we're doing is the fact that we were perhaps one of the first to focus on these targets, our TREM2 program is the furthest along to the best of our knowledge. And as I mentioned, we're about to initiate that Phase II this year. I wonder Sabah if you want to take a few minutes and just talk about the collaboration with AbbVie and how that's going.

Absolutely. We're very pleased with our partnership with AbbVie. We struck that partnership in 2017. It's been going on for almost 2 years now. And in terms of the partnership at the high level, these were preclinical molecules when we partnered, and it was a $225 million upfront to start the partnership and then about $900 million in development milestones. And on the back end, it's a 50-50 global profit and cost share arrangement. And it's a very collaborative approach. We are taking the lead on developing the molecules through Phase I and Phase II. And at the end of the Phase II, which we call the proof-of-concept study, AbbVie has a option to opt in into these programs. And if that option is exercised, there is a milestone, about $250 million per program. And after that, AbbVie takes the lead on the development of these programs into Phase III and also commercially. So that's the way that it's been structured. And so far, it's been a very collaborative approach on deciding what's best for the programs and moving them forward. And that's best evidenced by the latest decision that we have taken together of actually skipping Phase Ib with the data that we have had from healthy volunteers and also preclinically and accelerating the program into Phase II as quickly as possible.

Thank you, Sabah, on that. I do want to talk about your other pipeline assets as well. But before I do that, I think that if we look at 002 and 003, certainly very intriguing approaches. Is there anything that you've seen, whether it's the preclinical model that actually gives the investor who might be skeptical just on investing in any company that is interrogating Alzheimer's disease? Is there anything that you can speak to in terms of the data that might predispose you to feel that the probability of success might be higher than any other Alzheimer's disease, which, I think, generally speaking, the market thinks POS is quite low in Alzheimer's disease? So can you speak about that?

Yes. And that's a fair point. And again, it's part of the reason why we are so rigorous and focused on incorporating biomarkers as part of our clinical hypothesis. And with respect to TREM2, we have, in fact, shown that we have an effect on soluble TREM2 level, which we, I think, showed last year. And I'm going to let Robert just talk a little bit to both sort of the peripheral biomarkers that we see for TREM2 as well as 003.

Yes. For 002, we showed target engagement in the brain. So we saw a decrease in soluble TREM. But not only this, we also saw an increase in biomarkers that are specific for microglia function. So not only we hit the target in the brain, but also we know that we can actually impact the biology of the microglia cell. And this, quite frankly, is more than, I guess, any other molecule, let it be a better focused medication or a TAU has ever been able to demonstrate. So that's why this is exactly we approach. We have a step-wise approach. We also want to check, okay, do we actually have sufficient exposure. Do we have hit the target? And does we actually have an impact on the biology? And that's what we're going to do. We did this for 001 and 002, and we'll do this for 003 and for all the future molecules. And again, for 003, for example, we already have shown in the periphery that we can efficiently downregulate SIGLEC 3 and monocytes. Since we can actually access microglia cells directly from the brain. That's a little bit more challenging in the CSF. But we have seen a very profound and very long-lasting effect on SIGLEC 3 in the periphery.

Okay. Thank you for that. I also wanted to ask a question that just popped into my head. When we think about diseases of the central nervous system, and you think about interest in delivering antibodies into the CNS. The question that I often get from investors is, is this the best delivery approach? And while the biology makes sense, does a monoclonal antibody that needs to cross the blood-brain barrier. How is this going to work? So I'll throw it out to any of you who want to answer that question. How do we think about your antibody-based approaches in trying to get into the CNS?

Maybe I'll just start and say that the best surrogate marker that we have of our ability to demonstrate target engagement with 001 is showing that CSF levels of progranulin are, in fact, upregulated in the disease. And so while it's true that the PK/PD suggests that very little of what is administered peripherally actually gets into the brain. At the end of the day, it's very useful to be able to measure surrogate biomarkers of the protein that you are trying to replace and see that go up in a very compelling manner. And because in the case of FTD, we really think that this ability to upregulate progranulin to physiologically normal levels should be sufficient in order to affect the phenotype of the disease, the clinical phenotype, and we then see levels go up by two to threefold. We feel pretty comfortable that biologically, we're having -- our drug is having the intended effect. And I don't know, I'll let Robert or Sabah maybe add a little bit more color on the antibody blood-brain barrier question.

Yes. I mean in terms of the blood-brain barrier, your target is as important as the limitation with the blood-brain barrier. And these targets that we're going after, the 001, sortilin receptor with 002 TREM2. Just to give you 2 examples of that, that we have right now. These are rare receptors in the brain. So although the antibodies cross inefficiently, we have shown data from both of them that we can completely such rate this receptor in the plan -- in the brain with once-monthly IV injection. We have done the presentation of AAIC last year in July to show that our antibody is at a five to tenfold excess to our target in the brain after just once monthly IV injection into these patients. So that's a very straightforward answer to us. And I think from our point if your target is A-beta, which there's gobs and gobs of it in the brain, that might be a challenge. But for our targets that we're picking, you don't see this as being a challenge. And you see it is actually a really good approach right now in the absence of any other technology that we see as efficient -- [ comfort ] and efficient ability for these antibodies to cross, that this is a really safe and good approach to move forward with.

Okay. Great. We've got maybe a few minutes left. Maybe if there is an additional pipeline assets that you'd like us to pay attention to, whereas 001, the Alzheimer's portfolio seems to garner most attention. We don't want to be sleeping at the wheel in case or something else that you feel is important.

Well, we showcased AL014 program in our R&D Day last year. We think this is an extremely exciting target, the MS4A4A inhibitory receptor for microglia because it's another incredibly important risk gene for Alzheimer's disease. And we know that it modulates TREM2 expression as well as having an effect on the kind of functional interaction with microglia. That's a program that we hope to have in the clinic pretty soon in the next 12 months. And then we have a burgeoning IO pipeline. And Sabah can speak to the deal we just did with Innovent around 008, which is a dual-function kind of SIRP-alpha inhibitor and Fc gamma receptor to activated. And much like we are doing in immuno-neurology, the goal here with our immuno-oncology pipeline is to repair innate immune dysfunction in cancer. Now we know that many others are doing that. But just the 2 programs that we've showcased, we believe have the potential to be best-in-class here, too. Sabah, I don't know if you want to say anything quickly about the Innovent partnership.

Yes. I think we have a very unique asset coming out from our expertise in being able to modulate innate immune system. And we can use that for the brain disorders, which we are doing already, but some of these molecules are very well suited for oncology as well. So we're moving them into the clinic as quickly as possible. We have 2 programs moving forward, actually. One of them, we have partnered with Innovent with -- for the China rights. We hold the global rights for that molecule. And we're really excited about working with Innovent. We think that their ability to quickly move these programs forward and also be able to combine with many other checkpoint inhibitors. I mean these patients, both adaptive immune system and innate immune system that we're working on could create really value for the patients. So we're going to move that program to clinic together. And then depending on the results that we get from our Phase Ib study, we'll make a decision on how we want to develop it further globally.

Great. My last 2 questions, cash and upcoming milestones. Who wants to take that?

Yes. We have over $500 million in cash as a result of the follow-on offering we did earlier this year, which gives us 2.5 years of runway. That is sufficient for us to execute the current plan and get through Phase III data readout, which we are relentlessly focused on doing. As I've mentioned, COVID has had a minimal impact, fortunately, on our clinical development pipeline. So we will continue to be very focused on that. At the same time, we -- the reason we want to be focused on execution is primarily to get drugs to patients, but we also recognize how that creates opportunities for us to finance opportunistically should we see something really interesting. So in terms of the biggest catalysts for the company over the next 6 to 12 months, the Phase III initiation for 001, the Phase II initiation for 002, additional Phase II open-label data for 001, biomarker data and potentially volumetric MRI data later this year. And then Phase Ib data from 003 and Phase Ia data for 101. So we continue to be, as I said, relentlessly focused on executing the plan on getting drug to patients on making a difference to neurodegenerative diseases, and we couldn't be more excited about this in the future.

Well, that's all very, very exciting. Clearly, a lot going on for the company. Thank you, Shehnaaz, Robert, and Sabah, for joining us. We look forward to your updates. And congrats on the success and best on your future success. So thank you very much, and thanks to the audience for dialing in. Have a great rest of your day.

Thank you.

Thank you, Graig. You too.

Thank you.