Managing Risk And Development In A Growing Neuroscience Portfolio With AbbVie's Sean Kelley

0:03Sean Kelley: Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm speaking with Sean Kelley, Vice President for Neuroscience and Toxins, Portfolio Strategy and Program Leadership at AbbVie. Sean joined AbbVie six years ago after spending over 20 years at Eli Lilly, where he was steadily promoted and was most recently associate vice president of global immunology strategy. At AbbVie, Sean oversees the neuroscience division, the company's second largest and fastest growing therapeutic area. and I'm thrilled to have him on the show to talk about what happens after discovery, how decision-making in clinical development, diagnostics and biomarkers, formulation, manufacturing, and drug delivery can determine whether a promising new discovery ultimately reaches patients.

0:54Sean Kelley: We'll also discuss how AbbVie thinks about development risk and portfolio from a short-term and longer-term perspective. We'll talk about AbbVie's move into psychedelic medicine with the acquisition of Gilgamesh Pharmaceuticals, Brett Asillison. And we'll get Sean's thoughts on partnering in China and what the future might hold. We got a lot to get to, Sean. Thank you so much for being on the show today. Very happy to be here, Ben. Thanks for inviting me. I want to start off with your background. You spent 22 years at Lilly, mostly in commercial and corporate strategy, including pipeline strategy and sales leadership.

1:32Sean Kelley: what lessons from Eli Lilly did you bring to your new role at AbbVie? Or not new anymore, I guess, but yeah, go ahead. I've been here a little while now, but it was a great experience at Lilly. Over the time, I think there's a few things, Ben, that stand out. First, I appreciate that we need to rigorously pursue and internalize external insights. We have a tendency, once you get into development or within the walls of pharma, going to talk to one another and we forget that there's a world out there that we're serving. And the more we can understand the patient journeys, the more that we can understand the way clinicians are thinking about treating patients, the societal impact, those types of things, the better we can shape the development plans for our programs so that we can ultimately serve those needs.

2:24We need to stay connected. And that's maybe the most important first lesson that I took over my time at Lilly. The second, Ben, is that we need to place thoughtful bets and invest to win in those particular areas. I was involved almost 20 years ago now with our first at Lilly, our first GLP-1 development programs. And there were decisions very early to commit to that platform, not only in discovery, but in all the pull-through functions that are necessary in order to build that That is a long-term platform for the organization and a long-term leadership position. As you can see, that's played out very well for Lilly.

3:06At Avi, we're doing the same thing. We're investing and focusing on areas that we think we can be long-term leaders. And yes, we'll look at opportunities outside of those particular areas, but we intend to win where we place those bets. I think the third is in order to build long-term, with a vision of the long-term, we need to create a balanced portfolio, balancing both short and long-term risks, as well as incremental gains for patients, as well as particularly big swings, big wins. If you look at Lily's portfolio, Lily's been in diabetes since the 1920s with the insulin business and has remained a leader over the time, since that time, and continues to innovate in that space.

3:54And that's because of long-term commitment to understanding patient needs, understanding the science in that particular area. At the same time, psychiatry came and was a big thing for Lilly for a period of time. Immunology has arisen as a big thing. Oncology over time has been a big area. But really, that long-term commitment to a particular stable business has fueled that other innovation that's necessary. And I think Abby's looking to do some of the same things. While a much younger company, we look to be long-term leaders in some of these core disease areas. Yeah.

4:31Sean Kelley: And it's interesting what you said about the early decisions with the GLP-1s. I mean, obviously, Novo Nordisk was first to market. Now, Eli Lilly is currently the category leader. So, I think maybe that foretells a little bit of the discussion we're going to get into about you know, the importance of those decisions in the development process, you know, after the initial discovery is made. You left Eli Lilly about six years ago, I think, to join AbbVie. What can you say about, I don't know, the new experiences or opportunities that you saw, you know, at AbbVie that helped you decide to join, you know, the neuroscience division?

5:14You know, one thing, Ben, that may surprise people, AbbVie is still a very young company. While Lilly was founded post-Civil War and has been a continuous company since then, AbbVie has been a company since about 13, 14 years. and as a result, the growth has been phenomenal since that initial founding. But being part of building that massive organization in a short amount of time has been an exciting thing. You come to AbbVie and there's people at AbbVie from many different pharma companies bringing those diverse voices into what we can do to make this the best organization we can make it. And that distinguishes a little bit from a company like Lilly, who has a core group of people who have been part of the organization for a long time.

6:09There's strengths and weaknesses either way. But that diverse view about how to make a successful company has been really fun to be a part of. I think also personally for me, shifting into earlier phase development was a major growth area for me. I have learned a tremendous amount about the value drivers in the organization from discovery transition into development and all that's necessary for us to create inflection points and value for our portfolio and to reduce or mitigate risks in the development. It's been an awesome learning experience. Yeah.

6:47Sean Kelley: And for listeners who who who don't know this, I suspect there are probably not many, but AbbVie was originally part of Abbott. And what what Sean is describing was the creation of AbbVie when it split off from Abbott. But I want to ask you, Sean, you know, about early stage assets and, you know, your desire to learn more about maybe some of the kind of, you know, value drivers in early stage assets. Is there anything that surprised you initially about how you think about potential value or assessing value in an early stage asset? And is there anything unique to CNS or neuroscience in that kind of calculus?

7:30You know, it's a good question, Ben. And I think maybe the thing that has been most surprising to me about neuroscience development and for context, 30 years ago, I worked on Prozac and Zyprexa. So I've been kind of around neuroscience for a long time. But the challenge in innovating in particular in psychiatry has been more than I anticipated. The thing that I've learned maybe the most about neuroscience or psychiatry development is that the way we execute the studies is just as important as what the drug contributes. And the expertise and discipline necessary to do that well has a meaningful impact on the outcome of the studies.

8:17And you can see in the psychiatry space, the landscape is littered with programs that have failed or early failed programs that ultimately led to important therapies that eventually got to market. So our ability to adapt, remain agile, but also execute with disciplined focus around psychiatry is really important to the outcome of our programs. And I had less appreciation of that coming into APPE than I probably needed. And so I've learned a ton about that.

8:50Sean Kelley: It's a notoriously difficult area for development. I think part of that comes from the fact that a lot of the kind of outcomes measures are more subjective. They're patient reported. Often, you don't have the same kind of hard biomarkers often that you do in other areas like cancer. So, yeah, it is really difficult, but I think also enables a certain amount of creativity and, you know, outside the box kind of thinking in this space. So I'm sure it's an exciting, exciting area to work in. And you may have answered this question in part already, but I wanted to get a sense of your current role and responsibilities right now at AbbVie and kind of what the day to day looks like, you know, in your in your current role.

9:37Sean Kelley: Sure. So the current role, I lead a team of program managers and what we call asset leaders. And we are, I guess, the stewards of our neuroscience asset and portfolio, meaning that we guide a cross-functional team in maximizing the value of these assets for patients and for AppV. And I work to integrate that work across those assets into an integrated portfolio strategy, along with my peers and other functions. So we work. It's inherently cross-functional work, pulling together regulatory and development, discovery, medical affairs and commercial to deliver comprehensive programs for these for APPE for patients.

10:23That's the essence of what we do in my team.

10:26Sean Kelley: And then are so are you making those kind of go no go decisions that maybe whether it's externally or internally, there's a new discovery, it's promising and a certain indication within the neuroscience field. Are you, you know, coming in at that level and saying, yeah, there you know, this is one that I think makes sense to move into development or no. I mean, is that part of your role? So, yeah, Ben, it's a good question. I inform those decisions and my team forms those decisions. But as you can imagine, those are massive investments many times. And so ultimately, the GoNodo rests with our more senior governance, typically, about investing in external innovation or advancing a program.

11:10But we are expected to influence and inform those choices and make sure that those are well thought out and well informed.

11:20Sean Kelley: Got it. Got it. You're providing the information needed to make the decision. Yeah. And in many times we're providing a primary recommendation as well as alternate development scenarios. Got it. What are the specific areas within neuroscience that AbbVie is most interested in? Yeah, man, we have five or six strategic pillars, depending on how you think about it. Our intent is to intentionally have a broad and diversified risk balance portfolio in neuroscience. Those areas are psychiatry and migraine and pain, movement disorders, primarily focused on Parkinson's disease and now with our novel toxin, essential tremor.

12:09neurodegeneration primarily focused on Alzheimer's disease and neuroimmunology with a focus on MS and MG. We also think of therapeutic toxins as a pillar, but it spans across several of those disease areas or franchises.

12:26Sean Kelley: Okay. And I also wanted to ask about some of the kind of foundational deals that AbbVie has done to help build out the neuroscience division. I think you joined right around the time that the Allergan acquisition happened. Is that right? That's right. So I joined in 2020. And as you know, the Allergan acquisition was a major step forward at Abby's neuroscience business. Prior to that, we were mainly focused on Parkinson's and neurodegeneration. Brini and Allergan brought in a psych business with Ralar, brought in the migraine business with Eubrelvy and Q-Lipta and Botox. And then And not long ago, we also did the Cerevel acquisition, and that bolstered our neuroscience or our psychiatry portfolio.

13:13And we have several other external partnerships, both collaborations as well as acquisitions, where we are leveraging the best internal as well as external innovation to try and build out that portfolio.

13:26Sean Kelley: Yeah, I'm going to ask you a little bit more about Gilgamesh in a few minutes. It's you're also partnered with Gideon Richter, I believe, in this in this space. You mentioned some others. I want to circle back to something you said earlier, Sean, which is about kind of a balancing the near term product drivers versus longer term growth. Is there a kind of risk stratification process that you use to get to that balance of longer term, riskier development programs versus sooner products that are going to reach commercialization sooner that are in later stages of development? Or is that not how you think about it?

14:10I think maybe to step back, our objective in those strategic pillars that I mentioned is to establish a continuous flow of innovation in those respective pillars. And that means that we would need high probability investments in each of those pillars to ensure that we're developing that continuous flow of innovation. But at the same time, we want the big swings. We want those opportunities that are really going to have a meaningful impact. So I'll give you psychiatry as an example.

14:48Sean Kelley: We partnered with Gideon Richter to develop Raylar. And it's an on-market asset. It's the number one most prescribed branded product in psychiatry today. Gideon Richter and our partnership with Gideon Richter, we're also developing 932, which has an increased focus on a D3 receptor, reducing some of the D2 burden. It's similar in effect we expect to Vralar, but it's going to improve the patient experience, we hope, for patients who are dealing with depression. Um, that's an important improvement, but it's, uh, it's more of an incremental improvement for patients. And, um, we, we expect it to be meaningful, but it's going to be in the realm of what we already understand in psychiatry.

15:34Sean Kelley: But then with bretta sileson, that's a bigger swing. You know, we expect bretta sileson to, um, to maybe fundamentally change the way depression is treated and what patients can experience in the treatment of depression. So both of those are important innovations because they advance the patient care, they advance therapy, but they're very different in terms of our level of confidence and the potential delivery and value that it delivers in the future. Right. Does that make sense? Yeah, that does. That makes perfect sense. And I want to dig a little bit deeper on this concept of innovation beyond the molecule.

16:11Sean Kelley: And let's, you know, a promising discovery has been made. You and your team have provided the data to the decision makers. They say, let's go forward with this. Maybe there's some excitement. What comes next? What are the biggest opportunities for innovation in the drug development process, would you say? Yeah, I think you said this earlier. I think around precision medicine and biomarkers are important parts of innovation that are about the process of data generation and drug development more than they are about new, as you said, new molecules or new drugs. But one of the challenges that I mentioned earlier in depression is ensuring you get the right patients into clinical trials.

17:01At these times, you can get patients in who you get variability in raters. And as a result, you might have patients who are not clinically depressed in a depression study. So there are AI tools that are looking at voice and facial recognition, facial markers that give you a sense and that can supplement raters to help you understand if these patients are really clinically depressed that you're enrolling. the better we get at enrolling people who are clinically depressed, the less likely we are going to have elevated placebo responses. And we're more likely to be able to see what a drug contributes.

17:44So that innovation in precision medicine and these novel biomarkers is an important part of developing drugs. That's an example.

17:53Sean Kelley: Yeah, absolutely. I just want to ask about that. So these AI tools that you just mentioned, is that something that you're providing to your clinical recruiters out there, you know, who are pulling people into a study? That's something we're partnering with organizations that can do that kind of work. That's not a specialty, but we bring those into clinical studies as supplements to what the sites are doing. Interesting. Yeah. Are there any other examples that you might point to where, you know, ABV is innovating in these areas, whether it's kind of near-term biomarkers or novel formulations. What other examples could you give?

18:34Well, I don't know if this is a particularly innovative marker, but we've been using EEGs to ensure we're getting the right doses as we develop early phase programs. So, for example, it was fairly public, the MRAC-Ladine program and the EMPOWER studies that were negative in schizophrenia. And one of the things that we suspected was that we had too low a dose in those studies. So the max dose study in those EMPOWER studies is 30 milligrams. we've since gone back and done a multiple ascending dose study and included EEGs in that study to supplement the receptor occupancy data to look at brain activity.

19:20Is this making a difference in patients? And what we now see is that we probably need to be closer to 150 milligrams based on those EEGs to have the kind of impact that we expect to have in schizophrenia and psychosis. So that has given us, that use of an EEG has given us an increased confidence in the fact that we think we now have a dose that would work in spite of the 30 milligram failures that we had with the power studies. So that data, supplementing our traditional data packages with that has been very important for decision-making. You know, other areas of innovation that are important for us is our formulation development.

20:06You mentioned that earlier, device development. We have Violet as one of our Parkinson's programs. Violet is fundamentally a reformulation of levodopa carbidopa to enable continuous infusion over 24 hours. And that was rooted in this insight that people who go to bed at night without treatment are still struggling with rigidity and movement issues that can contribute to poor sleep and poor quality of life. But if you can have a continuous infusion over that time, you get treatment even in those sleep periods. And you don't have to make the trade-offs that people have had to make historically. The challenge in that case, though, is can you make that a more patient-friendly product?

20:58And that comes in some of the device and pump innovation, as well as ongoing formulation development to get to even smaller volumes, to hopefully get to things like patch pumps where insulin has gone, for example, in the past. If you can get to that and a patient with Parkinson's disease can put a pump on their arm and they don't have to carry one around with them, that gives a continuous infusion of levodopa carbidopa, but they can get back to perhaps as close to a normal movement and life as they had before the progression of Parkinson's. So those are the kind of, I think, beyond the drug innovations that I think will ultimately have a real meaningful patient impact.

21:41Sean Kelley: Yeah. And in that example with Parkinson's, does that insight come, you know, are you hearing from from physicians, from patients, you know, to to understand, you know, this like lack of sleep and how how, you know, a steady stream of drug through the night would would be a big improvement, quality of life issue for patients. Where does that insight come from? Yeah, that was what I was mentioning earlier, Ben, about this need for continuously going after external insights and bringing those into our development. We have ongoing market research that our commercial team engages in. We have ongoing registry studies that our med affairs teams conduct where they're assessing quality of life implications for patients.

22:29We have regular KOL interactions where we meet with people who are treating these patients on a regular basis so we can understand what the issues are. And all of that collectively gets fed back into the developer teams. So as they are developing evidence to support these for products, as well as developing the next generation of products. You know, an example, another example on Parkinson's that is related to these external insights, we have what we call market value drivers. And these are those important things that affect how people perceive products and ultimately how they use them with patients.

23:07And one of the market value drivers in Parkinson's is a delay of onset of troublesome dyskinesia. So what clinicians want to see is that if I treat a patient with one of these drugs, that there's a slowing in progression to this troublesome dyskinesia for patients. The problem is we don't have a lot of information that informs the clinical trial that would help us generate the evidence to support that. So we have to partner externally to bring in that data so that we can develop good clinical trials to show that our drugs have an impact on that market value driver. So that's an example of that external engagement that helps to drive how we shape our programs.

23:55Sean Kelley: Yeah, I appreciate that. That's an excellent example. On manufacturing and delivery, are those areas that you're working in as well, Sean? Is there anything to be said about things happening in manufacturing or delivery that are innovative, that are helping to move these products to market faster or just successfully? Or is that kind of outside of what you're looking at? I'm not sure. Oh, yeah. It's a good question. Honestly, that's an area I spend less time on. We have a very robust organization, CMC organization, that does supply planning, both in commercial supply and clinical supply. We partner with our development sciences group, the development of not only assets that are optimal from a formulation or device perspective, but some that we can ensure there's an assurance of supply.

24:58We can deal with issues where our objective is when we launch a product or patients have access to it. We don't want to have a risk of a supply shortage for patients. And so we partner along the way in development to ensure we've got a profile on a product that we can be confident we'll have an assured supply for patients. But beyond that, then I'm less involved in the innovation and our manufacturing side.

25:28Sean Kelley: I'm going to channel the audience here for this question, Sean. If a small company has, you know, a new CNS asset, a newly discovered product, are there any formulation or delivery questions that you would recommend, you know, they ask early on?

25:49I think that there are three areas where we have maybe four where we've worked through formulation questions as we've partnered externally. one of those is it may be appropriate for an IV deliterate for example of a like a migraine therapy but that my IV formulation has to potentially compete with a sub-q or something formulations and therefore it's got to offer something that the sub-q can't So I say, let's say once every six month IV instead of a monthly or a bi-weekly. So those early decisions that we make in formulation, they've got to tie back to that comment I made earlier about market value drivers.

26:46There's got to be something compelling about the profile in that formulation that would have caused us to want to advance it. So while it's important to identify those new therapies, how their delivery is sometimes as important as the therapy itself. And unless that new delivery offers something that can't be offered that's important to our marketplace, then we would typically move to either sub-Q injection or an oral therapy as a preferred. in migraine for example we also think about things like oral dissolving tablets versus just an oral tablet because that has an implication how people perceive how quickly the product works sometimes it has a direct impact on the actual function but it certainly affects if someone's dealing with a migraine right now and they take a medication it dissolves in the mouth feels like it's going to have a more immediate effect for patients right and sometimes it translates to PK and ultimately to clinical outcome.

27:48So all of those things, the decisions made in formulation early that we do at Avi with our DevSci team has implications on patient partners.

27:59Sean Kelley: Excellent. Regular listeners to this show know I have something of a personal interest in psychedelic drug development. And I want to ask you about Avi's acquisition of Gilgamesh Pharmaceuticals, Brita Silicin. I know we've touched on it a couple of times already, but I wonder, Sean, if you could tell me what you like about this candidate and how you would describe the opportunity. Yeah, thanks, Ben. First, I'll say we have a broad relationship with Gilgamesh. So we acquired their lead asset, Breda Sillison, but we also had ongoing partnerships around neuroplastogens with them. Oh, OK. Phylogenic or non-hallucinogenic as well.

28:40But Breda Sillison is very exciting. Just for context, our lead indication development for predestinism is in major depressive disorder. We also have a PTSD program underway. And in MDD, the current experience for patients with standard of care is if they go into a clinician's office and they start treatment, they could expect a response in six to eight weeks. and about more than 30 % have no response at all and very few actually get to remission. So the standard of care today leaves a lot to be desired on an efficacy front. And then from a tolerability front, they've got to trade off things like sexual dysfunction or weight gain or those types of things that come with those therapies that are there today.

29:31So like I said, I started my career working on Prozac. These SSRIs and SNRIs are very good therapies, but there's a lot of room for improvement. And I think when you look at something like bretacillicin and the data we've already seen on it, a very high portion of people after just two doses of bretacillicin get to remission. And that's as early as two weeks. So you can imagine the difference in someone walking into a clinician's office with, and who has struggled with, say, a deep depression for months or years.

30:03Sean Kelley: Or is in crisis, you know, is having some kind of acute episode. Yeah. And they started SSRI and it's six or eight weeks later that they might have a response or they started bretosilicin and it's perhaps at first dose, certainly at second, they could be in remission and within a couple of weeks. So that's rewriting the textbook for the treatment of psychiatry. That's a very different approach for the treatment of depression than what has been the standard of care, where it's kind of a wait and watch. It will try something new in two months if it doesn't work. So it gives a very different kind of hope for patients.

30:38And I think it has energized our KOLs and others. One of them said for a psychedelic clinical trial, they brought a patient in, initiated the therapy, and the patient walked out of the office and said it was the first time they've seen the sun in years. And that kind of dramatic difference is part of the reason why we do what we do is because we're excited about offering that kind of transformative solution for patients. And it's exciting to see what Brett O'Sillison can offer. So our hope is the majority of patients who walk into a clinician's office with depression or trauma or maybe anxiety, they can walk out of that office after having started Brett O'Sillison in remission or certainly within two weeks in remission.

31:26So it's an exciting thing.

31:28Sean Kelley: Yeah, I think that's one of the most exciting attributes about the development of new psychedelic therapies is that almost instant same day kind of treatment result that you can get with some of these, particularly given the context that you just provided about the kind of standard of care and the long wait and the chance that it may not work for you. So on the other thing, I'm sorry to interrupt. The other thing is, at least in the evidence we already have in hand, that that kind of response is a resilient response as well. So it's a durable response in the data we have up to 74 days. That's also very different than what you see with standard of care.

32:14Uh, so if, if in the end, let's say, you know, two to four times a year, a patient just needs to go in for their treatment and then they can keep their depression at bay. Uh, that's, that's an exciting outcome as well.

32:27Sean Kelley: Yeah. Yeah, absolutely. Um, from the clinician perspective, what does, what does easy for clinicians to use kind of look like in practice? I mean, is the goal with psychedelics to minimize the, the time of like the episode, the time on therapy and the amount of physician monitoring required, or is there some other consideration? You've got it. We don't want to add burden to a clinician's office. And if it requires a guided trip or it requires monitoring, it requires for six to eight hours, that's a very difficult thing for many clinicians to implement. We think with a bretacillicet, it could be as short as two hours in the office without required monitoring or any kind of facilitation.

33:18So I think that's the kind of thing we're aiming for, to your point, to make not only the patient's life better, but the clinicians can implement it. It also would increase the access that patients would have to that kind of a therapy. Because you could imagine if it required dedicated staff and extended periods of time in the office, not many clinicians' offices would have the capability of implementing that. if it's a much less burdensome approach, there are more clinicians who could use it. And now more patients have access to those kinds of therapies. So, yeah, that's a very important consideration as well.

33:54Sean Kelley: I think that's a great point. And particularly, I think, true for community, you know, kind of psychiatric practices that probably have, you know, a pretty large patient count and, you know, or, you know, maybe not as many clinicians as they would like to have in the office, that those hours start to really matter and really count and determine how many people can actually get seen. Yeah. And then on that circle, in the U.S., we're more familiar with these kind of therapies, you know, esketamine is on market in the U.S. Right, esprovado, yep. There are many markets where it's not on market yet.

34:31And so interventional psychiatry is not practiced broadly. So these are areas where if we can bring solutions that are easier to use, then you can extend into major markets outside the U.S. as well.

34:44Sean Kelley: Do you expect psychedelics to become a substantial part or a larger part of AbbVie's psychiatry portfolio in the future, say like five years from now? I absolutely do. We have already communicated that we expect to expand Breda-Sillis' indications beyond what was communicated in the deal model with Gildermash. And our goal is, once we establish that efficacy we need to demonstrate in MVD, is to look for other appropriate indications. and you could see this being a very large program for AVV, but also, as I mentioned, that follow-on partnership with GILGAMASH is to identify additional follow-on therapies that we could extend into indications that we'd be outside of the Baretta-Sillicin flip crown.

35:40Sean Kelley: Aside from clinic, like capacity at the clinic, which we've just been discussing, you mentioned durability. I think that that's something that these therapies so far have shown to be really good at. What are there any other, I guess, what are the other biggest risks in your mind? I mean, is it safety? Is it payer coverage? Something else? What risks do exist in terms of, you know, this new class of psychedelics coming into the market? Yeah. I think there's a number of organizations that we depend on that are also trying to figure out what this future looks like. So FDA and EMA are already writing guidance around the development of these therapies, as you can imagine.

36:26For example, it's difficult to run a placebo-controlled study with a psychedelic, and so they're providing guidance of what evidence generation needs to look like. They've been very good partners. FDA has already given breakthrough designation to Breda-Sillicin, EMA prime designation for Breda-Sillicin. But we've got the Japan health authorities, a PMBA that has yet to approve a treatment in this space and is working on what guidance for development looks like. So there's a little bit of uncertainty. We have increased certainty in the U.S. and in Europe, but there's some uncertainty about what development will need to look like for Japan and China.

37:11So that's an area that is still developing as we get clarity. I think it's moving in the right direction. And we should in the, in very soon, hopefully have increased insight on that.

37:24Sean Kelley: I want to ask you a, yeah, go ahead. Well, I just, and the other one is I just mentioned was the infrastructure risk in certain markets where there's just not a, an interventional psychiatric practice. So when you think about developing it, it's great that we bring it to market. You've got to launch it somewhere and you got to have a receptive audience that's ready for it. So some of the building up interventional psychiatry, preparing practices for the launch of something like reticillus will be important. I want to ask you about China in just a second, but one one final question on psychedelics.

37:58Sean Kelley: Lilly, you know, completed its acquisition of a tie Beckley for, I think, two point eight billion in September. Do you think that other big pharma, Otsuka is the other one that comes to mind going back a couple of years that did a kind of significant acquisition. There are probably others. But do you think that we'll see more of that, big pharmas acquiring some of these psychedelic developers? I think it's fair to say that as the case, as we prove that there's opportunity here and that the market will embrace these therapies, you're going to see more large companies jump into the space. Some are probably allowing for others to work through the risks and uncertainties associated.

38:48Uh, but, uh, you know, I think it's important to be an early mover here. And I think that's why Abby moved as quickly as we did. Uh, yes, it, it creates some uncertainty on the front end, but we partnered well with health authorities and others to resolve that. Um, but certainly I think this is, uh, this is a category I expect to stay for a while. Um, and it's a category that I think is ripe for further innovation. You know, we're we're we and others are starting in large core psych diseases and disorders. But you could imagine a number of areas that have yet to have any meaningful therapies. One of those that we've already talked about is PTSD, but other areas that are that are going to need further innovation.

39:38And it just remains there's lots of open land, I guess, for development. Yeah, right.

39:46Sean Kelley: And, you know, we mentioned Spravato briefly, but I think, you know, J &J has obviously done a lot to forge a path on some of these areas, you know, get kind of a REM system together for testing in the office. So, yeah, that makes a lot of sense as more of these kind of rules coalesce and there's a clear pathway. It makes sense, you know, given the efficacy that we've been talking about and the outcomes that we'll see more of this. I want to move to China. AbbVie did, I think, a$745 million licensing deal with Hiasco earlier this year for two non-opioid pain products. What can you say about partnering in China, Sean?

40:29Sean Kelley: What's your experience there? Yeah, it's an important and stated priority for AbbVie to expand our partnerships in China for a number of reasons. One is, as you mentioned, the Heisco deal, for example, and one that we've recently announced with Bryce Pharma, it's a meaningful source of innovation in China as well. So as you described, the collaboration with High School in Pain, but with Bryce Pharma in Migraine, these are areas that there hasn't been a tremendous amount of innovation and you find the best options where you can find them. In this case, it was in China. So sourcing innovation is a big part of it, but also we are looking for partners to help accelerate and make more efficient our development programs.

41:23So as an example, in Alzheimer's disease, the government in China has a stated intent to deal with dementia as a national issue and has programs associated with screening patients over the age of 55 very assertively with biomarkers to look at potential for Alzheimer's disease development. With that large of a population and a stated intent to address Alzheimer's disease, it creates opportunity for us to develop more rapidly, perhaps, in Alzheimer's in China. We are working with sites in China in the development of 1758, our blood-brain barrier-shuttled amyloid therapy, and they've been very rapid in enrollment in those studies.

42:19and it's exciting. I was in Beijing this past week at a phase one unit and it's just exciting how aggressive they are about capturing data and monitoring their populations in the communities there. And as a result of that engagement, they're able to enroll these studies very quickly, more so than we could do in US or Europe. So it's important, not only, like I said, for the identification of new innovations, but also in accelerating and making more efficient the development of programs as large as Alzheimer's programs are, you know, and to get these done more quickly.

43:02Sean Kelley: Are you and I wonder if there were any conversations in in Beijing about this U.S. federal policy, the Coins Act potentially restricting deals in China. Is that something that that you're concerned about where your colleagues in Beijing asking you about that at all? You know, I I have not spent a lot of time been talking through those policy issues with our colleagues in China. the way we will structure our deals with Rebecca, we'll, we do these global development programs and we'll structure the way we do them so that we're aligned with federal policies, you know, and ensuring we're following those.

43:50But I think it's hard. You can't ignore the fact that there are really good global partners that are in those locations. And our business is inherently a global one. You know, we're trying to serve patient populations around the world. To do so, in many cases, we have to generate local evidence in these markets to support registration and approval in those markets. So we're always going to have a partnership with sites there. And if that can help us develop global data early and faster, I think that's good for U.S. patients and it's good for Chinese patients.

44:27Sean Kelley: Absolutely. And I think it's probably premature to like really get hung up on specifics, you know, in the Coin Act as an example, because it's still very much unsettled policy. I mean, there's still a comments period out. So, you know, we'll see how all of that lands. But I appreciate your commentary on that. I wanted to ask, as we're starting to run out of time here. If a biotech founder working in CNS wants to get on AbbVie's radar, what advice would you give to him or her? Yeah. Well, we are actively looking all the time externally for good solutions in those core areas that I mentioned earlier.

45:10Sean Kelley: So in psychiatry, migraine pain, movement, neurodegenerative, and neuroimmunology. So if it's in one of those areas, is we're interested in talking. And our business development search and evaluation teams are actively engaged at JPMorgan and other meetings where we meet regularly with the kind of organizations you're describing. I would say that it's important to clearly articulate the value proposition for patients in the therapies that are being developed and more clearly that that can be articulated when the evidence to support it is demonstrated, the more likely we are to want to jump in and do diligence and move quickly.

45:54If it's on us to understand that and to build a case for it, we certainly have done that, but we're slower to move, you know, in that case.

46:06Sean Kelley: So does that mean like a preclinical asset is sort of off the table? You want to see like some clinical data or not necessarily? Well, not necessarily. I mean, if there are good preclinical models that support development in those areas, we have done both preclinical deals as well as, you know, deals like Cerevel where we had phase two data on hand. But when there, if you can remove areas of uncertainty, that's a good thing. And I think preclinical models help us do that. We have a number of experts who have been working in these spaces a long time that evaluate preclinical assets as well and diligence.

46:49Um, but, you know, reducing risk, uh, reducing elements of risk is important for us to be able to move quickly. And if, uh, if one of the abuse, uh, organizations you're describing have eliminated, um, you know, off target activity, or if they, if they've demonstrated, uh, some, some safety evidence, if they've got good preclinical models, those things will help us, um, in making rapid decisions. Right.

47:16Sean Kelley: Right. Last question that I have for you, Sean, what are your top priorities for next year for 2027? What are you most excited about? Yeah. So we're our, I guess, top priorities. We've got a number of data readouts that are coming that are important to us. Brett O'Sullivan program startup and getting those phase two and three studies initiated and enrolling are important. I think, you know, you've you've seen publication of menstrual migraine data with our migraine program. So submitting and getting those approved to launch with a Tojapan menstrual migraine, the first drug to have demonstrated this benefit.

48:04And it's a massive opportunity for patients who right now don't have very many good solutions for their treatment. So there's a number of key inflection points for the neuroscience business in this coming year. We've got to make sure we close those programs out well and start up these big, like in particular, the right of citizen programs. Our venture into neuroimmunology is really getting started next year as well. And that's an important potential growth area for our business, depending on how these programs work out. So there's a big, 2027 is a big year for us in transition, both, like I said, in data coming as well as getting started some of these really big programs.

48:53Sean Kelley: Sean, thank you so much for coming on the show. It's a real pleasure to speak with you. I enjoyed it, Ben. Thanks for asking. I think that's been a great, great rest of your day. I want to just say, if I could, this is neuroscience is really a personal area for us of EPI. We are aiming for people with and struggle with depression who are losing their identity with Alzheimer's disease. With these therapies, we hope to restore for people what makes them who they are. And it's an important mission for us. Excellent. Excellent. We've been speaking with Sean Kelly, vice president for neuroscience and toxins, portfolio strategy and program leadership at AbbVie.

49:38Sean Kelley: I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts and be sure to check out our weekly video cast of these conversations every Monday under the Business of Biotech tab at lifescienceleader.com. We'll see you next week. And thanks, as always, for listening.

50:00We'll be right back.