Ladies and gentlemen, thank you for standing by. Welcome to the conference call being hosted today by Alector's management. At this time, all participant lines are in a listen-only mode. After the speaker's presentation, there'll be a question- and- answer session. To ask a question during the session, you will need to press star then one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star then zero. I would now like to hand the conference over to your speaker today, Michelle Corral. Please go ahead, ma'am.
Thank you, Sarah. Good morning, and thank you all for joining us on today's call. I'm Michelle Corral, Alector's vice president, communications and investor relations. Today, we are excited to be sharing the details of a collaboration with GlaxoSmithKline to jointly develop and commercialize our progranulin franchise programs, AL001 and AL101. A press release detailing the terms of this collaboration was issued earlier today and is available on our website. Leading today's call is Alector's CEO and Co-founder, Dr. Arnon Rosenthal. Arnon is joined today by Dr. Shehnaaz Suliman, Alector's President and Chief Operating Officer. Following their prepared remarks, we will open lines for Q&A, and Naveen Bazaj, our Head of Corporate Development, and Dr. Robert Paul, our Chief Medical Officer, will join us to aid in answering your questions.
As a reminder, the information discussed during this call will include forward-looking statements, which represent the company's view as of today, July 2nd, 2021. We undertake no obligation to update or revise any forward-looking statements to reflect new information or future events, except as required by law. Please refer to today's press release as well as our filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by these statements. With that said, I'd like to now hand the call over to our CEO. Arnon?
Good morning, everyone, and thank you for joining us to celebrate and discuss our global partnership with GSK. To the best of our knowledge, this partnership is among the largest that was ever executed in neurodegeneration. Alector was founded on the vision of eliminating neurodegenerative brain disorders by recruiting the brain immune system to counteract multiple neurodegenerative pathologies. By next year, we will have seven clinical drugs targeting Alzheimer's disease, multiple types of frontotemporal dementia, ALS, and Parkinson's disease. We concluded profit-sharing partnerships that cover the cost of four of our programs and retain commercial rights. In addition, we transacted regional partnerships that cover the proof of concept cost of a fifth program and retain exclusive rights in the U.S. and EU. The collaboration with GSK, as you know, covers our two progranulin elevating therapies, AL001 and AL101.
As many of you know by now, progranulin is a key regulator of immune response, lysosomal function, and survival in the brain. People with only one copy of the progranulin gene invariably develop frontotemporal dementia. Likewise, genetic mutations that lead to 10%-20% decrease in the level of progranulin are associated with the risk of developing ALS, Alzheimer's disease, Parkinson's disease, and limbic-predominant age-related TDP-43 encephalopathy. Our progranulin franchise, therefore, addresses the broad range of neurodegenerative indications. AL001 is already in pivotal Phase III clinical studies in symptomatic and pre-symptomatic FTD with progranulin mutations, as well as in phase II in symptomatic FTD patients with mutations in the C9orf72 gene. We are also on track to begin our phase II study in ALS later this year. Our AL101 program is being developed for Parkinson's disease and Alzheimer's disease.
This program is currently in phase I safety studies in healthy volunteers evaluating both intravenous and subcutaneous formulations. With a broad pipeline of pre-clinical and clinical drugs and multiple profit-sharing partnerships, we continue our quest to cure neurodegeneration as a fully integrated biotechnology company. Shehnaaz Suliman, our President and Chief Operating Officer, and a key architect of the GSK agreement, will now walk you through the strategic rationale and terms of the deal. Shehnaaz?
Thank you, Arnon, for that introduction, and good morning to all of you who have joined us for today's call. We are very pleased to announce this collaboration with GSK. The substantial nature of the deal and collaboration provides great validation for our immuno-neurology scientific approach and the potential impact that the progranulin franchise programs can have in a broad population of patients living with neurodegenerative diseases. I'd like to walk you through the strategic rationale and the terms of this partnership, which we view as a win-win for both parties. Firstly, the collaboration allows us to expand, accelerate, and fund the development of our progranulin franchise.
With this collaboration, we're able to expand the development of AL001 and AL101 into a broader range of neurodegenerative diseases, including FTD, ALS, Parkinson's, and Alzheimer's disease. Also pursue these indications globally more expeditiously than we would otherwise be able to do on our own. The upfront payments and milestones fully fund the development costs associated with this expansion into these broader indications. Secondly, we're able to participate and retain financial upside. We have the potential to benefit from downstream value creation via profit share in the U.S. and high-tiered royalties outside the U.S. Thirdly, the partnership accelerates our transition to be a fully integrated company and commercial organization. We are able to lead commercialization in orphan indications in the U.S. and have the option to co-promote in bigger neurodegenerative diseases should we choose to do so, enabling us to establish a focused commercial footprint in the U.S.
Fourthly, it leverages GSK's global late-stage development, regulatory, and commercial capabilities. We have a science-driven partner committed to immunology and genetics with a proven track record of bringing novel treatments to market in an accelerated manner. Turning now to the specific deal terms also described in this morning's press release. GSK is granted an exclusive worldwide license to the program and franchise programs, AL001 and AL101. Alector will receive a total of $700 million in upfront payments. Alector will also be eligible to receive a further $1.5 billion in potential development, regulatory, and commercial launch-related milestone payments. We will lead and fund the phase II studies for all indications. Alector and GSK will co-develop and co-fund the phase III studies at a rate of 60% GSK, 40% Alector in terms of the cost share.
In the U.S., Alector will lead commercialization in orphan indications, and GSK can promote co-promote up to 30% on the orphan indications. Reciprocally, GSK will lead the commercialization of larger indications such as Alzheimer's and Parkinson's disease in the U.S., with Alector being able to co-promote up to 50% on these indications. GSK will lead commercialization outside the U.S. GSK and Alector will have a 50/50 profit share arrangement in the U.S., and ex-U.S., GSK will pay Alector tiered royalties ranging between 20%-24% on net sales. We are very pleased with the structure of this agreement. We believe it reflects the value of the franchise and provides us with optionality and flexibility to execute a comprehensive development program to explore the broad potential of AL001 and AL101. We maintain an important role and control in the execution of these programs.
We have a significant stake in future commercialization and share the upside, and we can do so alongside a partner that is fully aligned with our vision. We are able to continue our quest to build a fully integrated company. We believe this will allow us to translate the promise of this biology into therapeutics that can make a difference in the lives of as many patients as possible. We'd like to open the line to your questions. As a reminder, joining me for the Q&A are Arnon Rosenthal, our CEO and Co-founder, Robert Paul, our CMO, and Naveen Bazaj, our Head of Business Development, all of whom were intimately involved in the execution of this transaction. Operator, over to you.
As a reminder to ask a question, you will need to press star then one on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from the line of Matthew Harrison with Morgan Stanley.
Great. Good morning. Thanks for taking the question. I guess two from me. One, can you just comment on whether GSK has seen or to the extent that they have seen the data that you're going to be presenting at AAIC and how important that was in terms of their decision about this partnership? Secondly, could you just give us some practical examples of the potential acceleration in non-FTD indications in terms of how much quicker we might get data or how much larger some of your sort of interim studies in terms of signal finding might be? Thanks.
Thank you for the question, Matthew. First and foremost, a thorough due diligence process was conducted as part of the deal process, as you might expect. We continue to look forward to sharing the data from the ongoing phase II study at AAIC. With regard to your second question, clearly what this allows us is to expand into indications that we have been quite thoughtful about doing but in a more expeditious manner. Those indications include the ALS study is already about to start, but also starting proof of activity or proof of concept studies in Alzheimer's and Parkinson's disease. I think that the broader indications in particular are likely to benefit from acceleration, and we're very pleased to be able to do that in conjunction with GSK.
Thank you. Our next question comes from the line of Graig Suvannavejh with Goldman Sachs. Your line is now open
Yeah. Good morning. Thank you for taking the questions and congratulations on the new partnership. I've got several. Maybe the first, if I could just maybe follow up on Matt's question around expectations for the data at AAIC. Assuming that a thorough diligence process was done, it to me infers that indeed GSK has seen what that data looks like and certainly was comfortable enough with moving forward to do the transaction. I just wanted to just get a confirmation of that. Maybe my second question has to do with has it always been a view that you would partner AL 001 and AL 101 or was it part of just an evolving thought around the opportunities with those two assets?
Then a third question, if I could, is as we look at your pipeline now, most of your most advanced assets are either partnered with GSK or AbbVie. Looking at the proprietary pipeline, could you point us to the asset or assets that you feel that we should next from an Alector proprietary pipeline perspective be paying most attention to? Thanks.
Hey, Graig. Thank you for those questions. As we said, a thorough due diligence process was conducted on both programs and at AAIC we look forward to presenting the 12-month data. Robert, I don't know if you want to comment on that?
Yes. As we mentioned also at our progranulin day a couple of weeks ago, we're going to present 12 months data in up to 12 patients that include safety, PK/PD biomarker data, target engagement, downstream biomarker like lysosomal function complement and volumetric MRI. I think most importantly, also clinical outcomes. We cannot actually speak, of course now about these data because they're under embargo. We're looking forward to present the data at AAIC in July 29th.
Thanks, Robert. With respect to your second question about the partnership, we believe this is the right collaboration for us to undertake at the right time for Alector to accelerate the franchise. We are already well underway, as you're aware, with the FTD progranulin phase III study, and this is really an opportune time to continue to explore the biology of these programs across multiple indications. We're feeling confident that the ability to do so essentially fast-tracks our overall global development program as well as our growth as a company as we continue to move into late-stage development and also anticipate in the future the ability to build a commercial franchise. Arnon , would you like to comment on the pipeline?
Yes. For the pipeline question, first, our partnerships allowed us to retain 50/50 profit share and commercial rights. We did not really give up any of our programs. Means we have basically covered the cost for their development, but we still retain very significant upside potential, and this is the strategy that we are going to continue to pursue. Means we prefer to develop additional drugs and share the cost and the upside rather than develop a smaller number of drugs on our own.
By next year, we are going to have three additional programs in the clinic. We have another exciting Alzheimer's and neurodegeneration target that targets the MS4A4A, which is a unique hit gene for Alzheimer's disease. We fully own this program, and we will have a multi-siglec inhibitor for cancer, and we have a TALE program that's going to the clinic. We have a very broad pipeline of fully owned programs that we are pursuing.
Okay. Thank you. I'll jump back in the queue.
Thank you. Our next question comes from the line of Geoff Meacham with Bank of America. Your line is now open.
Hi, this is Alex Hammond on for Geoff Meacham. Can you guys hear me?
Yes.
Great. Thank you. Any plans for additional capital, whether that be in the large pipeline or maybe potential modalities outside of antibodies, let's say CNS monogenic situations?
Sorry, would you mind repeating the question? I'm not quite sure we got that.
Yeah, sorry about that. Any plans for the additional capital that you have freed up now that you have this big collaboration? Would you focus on your pipeline or maybe other modalities outside of antibodies?
I see. Thank you. It's a great question. I would say that we're very excited about the fact that the collaboration fully funds the global development of the progranulin franchise, which does indeed allow us to continue to exploit the rest of the pipeline. We intend to do so. We have a number of risk genes that are targets for potential therapeutic development, as you may be aware. Now we can use the rest of our resources to fully perhaps even accelerate our research pipeline, which is part of the goal now that the progranulin program continue to be fully funded.
We are excited about the overall company bold thesis that this deal allows us to do because now we have, again, just a plethora of resources to apply, not just across the progranulin program to expand into new indications, but also to really continue to accelerate the potential of our research pipeline. I don't know if you wanted to add anything.
With regard to drug modalities, we are fundamentally agnostic to the drug modality. We are really focusing on the human genetics and immunology and neurodegeneration. We are constantly exploring additional drug modalities, and at the right time, we will discuss them publicly.
Great. Thank you. Thank you. Our next question comes from the line of Neena Bitritto-Garg with Citi. Your line is now open.
Hey, guys. Thanks for taking my question, and congrats on the deal. My first question is just around, since it sounds like it was a pretty thorough diligence process, I'm just curious what attracted you guys to GSK specifically? That would be my first question. Just curious around what would be potentially the next milestone payment from this collaboration? Would that be starting a phase II study for AL101? If you could give us any sense of when we could expect to see the first milestone payment post the upfront, that would be great. Thanks.
First, this was a very competitive process, and we selected to work with GSK because GSK is giving us a very strong control over our destiny. We are developing orphan indications all the way to approval with AL 001. We are developing the proof of concept for the large indications, Alzheimer's and Parkinson's disease, on our own. We have very significant control over the programs. We are not dependent on any third party to advance them. In addition, GSK is really sharing with us the vision of using immunology and genetics to develop drug. We have known Hal Barron for many years, and we really trust the motivation, the ability to take risk on a novel mechanism of action. We generally found GSK to be our ideal partner to develop these novel drugs.
Correct. I might add on that AL 001 and AL 101 are going to be flagship programs in GSK's neuroscience portfolio. They have an early research portfolio, and this will significantly advance their portfolio. In addition to, I think, what Arnon said, I would just underscore they are a global development partner with operations, regulatory, and commercial expertise and market access capabilities that we stand to benefit from as well. Neena, with respect to your second question, those $1.5 billion in milestones are largely actually clinical and regulatory milestones rather than approval milestones. We expect those milestones to start hitting just as soon as we get going on the overall clinical development program.
Perfect. Thank you.
Thank you. Our next question comes from the line of Yaron Werber with Cowen. Your line is now open.
Great. Thanks so much. I got a couple questions, maybe Robert for you one. The data that we're going to see at AAIC in up to 12 patients, is it going to be 12 patients at six months? If I recall, is it nine patients at 12 months? Is that sort of the way we should think about it? Then secondly, for AL101, you're testing both IV and subq. Any initial thinking whether you can formulate this as a subq, whether the formulation lends itself and dosing as well? Thank you.
Yes. We will show six and 12 months data. We have clinical outcome data, CDR Sum of Boxes of nine patients at 12 months. We have also CSF data from nine patients. If we actually have from more patients other assessments, because some patients were not able to come to the site, some of the assessments were not done in all patients. The overall analysis actually includes data from 12 patients, but nine patients and nine patients, we have core data at 12 months.
IV and subq.
IV and subq. As you know, we're going to complete the phase I study in AL 101. We're going to actually present the data of this trial end of this year. Actually, the poster at CTAD was just accepted yesterday. There you'll get a first impression about the TK and PD data of AL 101 and also the subq availability. We're still adding more cohorts to this study. Once we have the complete data sets, we will make the decision exactly how the dose and the dose regimen will work in the future.
Thank you. Our next question comes from the line of Tom Shrader with BTIG.
Good morning. Congratulations. I can't say I'm surprised at this deal. On the big market indications, can you flesh out the structure? Are you going to do a full phase II program, then there'll be some sort of joint steering committee for phase III? Are you pretty committed to phase III already, and you think it will be mostly lysosome function, sort of general biomarkers? A follow-up question on that, are you sure what you're going to do in Parkinson's and Alzheimer's? Is it going to be an all-comer program, or do you think you might be looking for subgroups based on some of your early data? Thanks.
Thank you, Tom. In terms of the collaboration, we have a joint governance structure, which is pretty customary for a deal of this type. Secondly, I would say that the way the actual control and works with respect to the studies is that we conduct the initial phase II studies for all of the indications and in particular, the larger indications. With respect to the overall global development strategy, we are very fortunate in that we are completely aligned with GSK on our overall approach in PD and AD. As is consistent with our approach, we prefer to start to generate proof of activity data in genetically stratified patient populations.
For example, in PD, we have in the past talked about PD GBA1 as the signal-seeking patient population to conduct the initial phase II study and then would follow that with a more traditional all-comer patient development strategy in PD. Robert, I don't know if you wanted to add anything to that.
Yes. The strategy is basically to figure out where the science will lead us, what is the best patient population. This is also the goal of the phase II studies to make sure that we actually collect the right patient population, and based on that, we will decide how to conduct the phase III studies.
Got it. If I could just follow up quickly. In Alzheimer's, do you expect it is likely to be an Aβ positive population, or might there be some subpopulation that only you could tackle?
Yeah. Actually, similar. In the phase II study as a proof of concept study, we'll probably go broader, but we will stratify patients appropriately, and then based on our analysis, we're going to decide how to go forward in the phase III study.
Okay. Thank you very much.
Yes. As you know, progranulin mutations, polymorphism in progranulin is a risk for Alzheimer's disease. About 30%, 35% of the population carry this risk mutation, both for Parkinson's disease and Alzheimer's disease. That's also something we are looking at.
Thank you. Our last question comes on the line of Paul Matteis with Stifel. Your line is now open.
Hi, this is Katie on for Paul. Thanks so much for fitting in my question. I guess to follow up on a previous question, from a timing perspective, when should we expect updates on prioritization of earlier-stage assets or perhaps assets from the research pipeline? Thank you so much.
Hi, Katie. Our goal is to continue to provide updates periodically, much in the way that we have with the KOL event that we hosted recently. There'll be an event around the time of AAIC with the data, then later in the year, we'll be providing more of a progranulin franchise update, then sometime next year, we'll continue to provide more of a broad-based pipeline update. I would suggest you just stay tuned as we continue to flesh out our overall strategy with respect to the rest of the pipeline. We have talked about follow-on programs such as the MS4A4A program, a master regulator of microglia, which we're very excited about, and that program will enter the clinic sometime next year. That as well as other research pipelines that have programs that have been undisclosed will be coming, and we'll provide that update in the first half of next year.
Great. Thank you so much.
Thank you. We do have a follow-up question from the line of Graig Suvannavejh with Goldman Sachs. Your line is now open.
Yeah. Thanks for the follow-up. I just wanted to see if I could tackle a modeling question or two. Just in terms of the milestones, can you just guide us on the breakout between the two programs, if they're evenly split or if there's some split that we should keep in mind? Then in terms of the upfront payment, should we just assume that will get amortized over a certain period? If you could help us think about the length of that period. Thanks.
Hi, Graig, this is Naveen. Great question. Maybe I'll tackle your second part first, yes, the upfront payment, you can just assume it's going to get amortized over a certain period. As Shehnaaz has mentioned, this was really dedicated to the progranulin program and self-funding the deal. That's where a lot of those resources will go to. In the first part of your question on the milestone, it's a fairly even split between AL001 and AL101, given AL101's for the larger indications. You can see the milestones for that one will be a little bit larger compared to AL001, which is in orphan indications.
Okay. Thanks for that, Alector.
Thank you. We do have another follow-up from the line of Yaron Werber with Cowen. Your line is now open.
Thanks. I think you just answered some of the question, Naveen. Just so we understand correctly, it sounds like AL001, you will not take that into orphan indications at all, including no preliminary POC, right? All POC for broader indications is going to be done with AL101 only. Thank you.
Yeah. Yaron, sorry, let me just clarify. 001 is meant Orphan indications. Our AL101 program is the one we'll be taking to non-orphan indications, specifically Parkinson's disease and Alzheimer's disease.
Yeah. Our overall strategy with AL001 has not changed. We continue to reserve that molecule for orphan indications such as FTD, progranulin, C9orf72, and idiopathic FTD, as well as the ALS study, which will commence in Q3, is also with AL001. AL101, because of its potential to be used subcutaneously, is therefore reserved for larger indications such as Alzheimer's and Parkinson's. This is basically a two molecule strategy in the franchise based on differences in formulation. That part of the strategy hasn't changed. Again, the approval milestones and clinical milestones are equally split across those molecules. The value of these milestones are weighted more towards the Alzheimer's and Parkinson's indications. Overall, more than 80% of these milestones come before approval. They actually are intended to really incentivize and continue to fund the overall development program all the way through approval.
Thank you. There are no further questions. I will now turn the call back over to Shehnaaz Suliman for closing remarks.
Thank you, operator. Thank you to everyone for joining us today to discuss the collaboration with GSK, which really does allow us to accelerate and expand the development of our progranulin franchise. We are proud of what we have accomplished with the AL001 and AL101 programs thus far. We look forward to building on that momentum with this collaboration. As a reminder, we will be presenting data from our phase II study of AL001 in patients with symptomatic FTD at the upcoming Alzheimer's Association International Conference, it's rather large, that takes place in Denver at the end of this month, which will provide an opportunity for us to share 12-month safety, PK/PD, biomarker, and importantly, clinical outcome data on patients.
We look forward to sharing those data with you. We plan to host an investor call in conjunction with the data announcement. Thank you again, everyone, for joining us. We wish everyone a really good day and a happy holidays weekend.
Ladies and gentlemen, this concludes today's conference call. We thank you for your participation. You may now disconnect.