 It's really my great pleasure to introduce the R&D Strategies and Trans Panel, which is made up of incredibly esteemed and respected R&D. And I'm not sure exactly the words that we go choose for your role, Andy, but they were certainly impressive. I can only echo the sentiment and say, great job to you and Karun on the summit. It's an outstanding. Joining Andy on the panel are Dave Rees from Amgen, John Reed from Sanofi, and Matai Mamam from J&J. And moderating the panel is the infamous and insightful Martin McKay. Martin, it's all yours. Thank you, as ever, Deval. It's truly my honor once again to chair this panel and with four really great leaders. I'm not going to introduce these guys. They need no introduction. I'll mention their names briefly, as you did, Deval. We have the old hands on the panel, Andy and Matai, at Takeda and J&J, respectively. And they know the form here and what they may expect over the next 40 minutes. So tough questioning. And then I'm delighted that David Rees, this is his second outing. As I mentioned to David earlier this morning, once Karun gets you twice, that's you for life. So you can expect to see Dave on this panel for a few years to come. And then we have a rookie. Not a rookie in terms of R&D head in John Reed, but this is John's first outing. So no pressure, John. You're with some great people. John and I actually met almost 30 years ago. And I'm going to come back to that in a particular question that I have for the panel around neurodegeneration. But thrilled as ever, I'm not going to introduce these guys. I'm not going to ask for opening comments, but rather we're going to get straight down to the questions. We also have a couple of questioners on hand, Dr. Pooja Sharma and Dr. Karen Reaves, who will be joining us to ask their particular question. So with that, here we go. My first question was really raised by David Rees in a discussion that many of us had a few weeks ago. And it revolves around this notion of with capital flowing into life sciences like never before and seemingly endless opportunities for investment. How do heads of R&D make that trade-off between those opportunities and perhaps technological obsolescence as more and more technologies come into play? And as David summed it up, there's a really interesting juxtaposition between golden age for patients, but perhaps more difficulties within company and the investment community. So with that, I'm going to start with you, David. Could you have a first go at that before I go around the other panelists? What's your view? Sure, thanks Martin and greetings everyone. This was a question on one of the polls a little earlier and the majority respondents were moderately concerned. I would put myself in the more significantly concerned camp here for the reasons you outlined. We've seen what we like to call a hyperabundance of capital flow into the sector. That's been, it's fueled new company formation at a pace that we really haven't seen ever in the industry. And all of that of course is being propelled by technical advances, technology moving along as coupled with a fundamental understanding of biology that is deepening. Now the challenge there is that I think a couple fold. Number one, if an interesting target arises immediately there are many players attempting to prosecute that target. That's great for patients because they are likely to see then the optimal modality or optimal drug. But how does one think about generating a return on investment when there are so many players on an individual target? And then the second factor is one that you mentioned and it's one that I think a lot about which is the notion of technological obsolescence. It used to be that for a fair amount of the patent life of a molecule one would have a reasonable market. Now one may be there with a, what's a first in class and best in class drug but three years later it may be and also ran because something better has come along. How do we think about managing a portfolio in that setting and to me it just goes back to the basics which is where do you think you can really bring something innovative to the field that's going to make a difference for patients and for physicians and where you think you have potentially insights that others may not have. Is there a competitive advantage and then balancing across the portfolio, all of those mixtures of investments that allow you to generate a return that allows us to continue what we want to continue to do but you know, I view this as a fundamental challenge going forward, I'm certainly interested in my copainless points of view here. Thank you, Dave and John. Yeah, the pace of innovation is really exciting and as I pointed out Martin there's plenty of money to fuel it right now. You know, I don't know that any of us have the incredible, you know, the great answers to this other than I think we have to try to stay as best we can on the cutting edge of this. As David said, I think really try to use our insights on patients and clinical context to really define where the molecules and the modalities can best play and try to leverage that as a core competency of companies like Sanofi and other large farmers which, you know, maybe is a perspective that's less mature in many small biotechs, et cetera. You know, it's great for patients as pointed out because there's almost any idea that's even half decent and maybe some that aren't even half decent, maybe a quarter decent can get funding these days which is very different than when we first met Martin as you were calling our foreign and neuro generation chasing eight but those as targets. But you know, and I think it creates challenges for us in large pharma because the flight of talent, you know, so many of our best and brightest are finding it quite attractive to move to where the grass looks greener in some of these well-funded startups. So it's both the best of times and the worst of times, I guess, in terms of some of those elements. Now, great points, John. Matai, you know, Jane, Jay, you've always pushed this innovation agenda. What are your thoughts, you're on? Sorry about that. There are obviously challenges and a couple of them have been highlighted here but I see definitely more opportunity even for larger pharmaceutical companies. It just requires a few things of us. You know, as John said, we've just got to do better. We've got to stay agile. You know, there was a time, you referred to technological obsolescence, there was a time where how a piece of innovation, a molecule kind of slotted into an organization was understandable, you know, it was very straight, it was a straight path and you would work on process development. There were stages you went through and there was a comfort of what the future would look like, whether it was manufacturing or commercialization. Now there's not that comfort but I tell you, that's the real world and that's the world in which most of the smaller company ecosystem exists anyway. There's a tremendous amount of uncertainty and ambiguity. So it's up to all of us to just get accustomed to that. And it's a good thing only in that, you know, right now there's gonna be more choice that we have to become expert at using. So it's like trying to think of the right analogy, it's like if you cook and you only have potatoes, it's fairly non-stressful to imagine like maybe how you go forward eating and now you have to like be able to use chicken and cauliflower and so it is more challenging but once the system gets revved up, I'm convinced, even with that large tool set as we become accustomed to manufacturing RNA or cells or small molecules with the equal ease, we will find it a really good thing at the end. We'll eat better. Very good Matai. So Andy, and just for the audience, Andy asked me recently if biotech existed when I was a boy and very humorous as ever. And of course I pointed out that biotech is the oldest science probably ever in relation to the Egyptians and the Greeks and although I don't go back quite that far Andy, but as I think about Takeda and your role, I don't know anybody that's done more deals in the innovation space and with partners and creative ways of partnering with this influx of capital how do you view that world? Well, firstly I have to reflect on Matai's metaphor to food and actually Matai gave me an idea because I was unsure what I was going to have for dinner tonight but now I'm going to have chicken, potato and cauliflower so thank you very much. But in all seriousness Martin, we have done many deals and some have not been so great and some have been fantastic. I think our focus has been to create a culture of partnership which includes having an outstanding internal laboratory as good as any laboratory I've been in or seen across the industry but one that understands the value of partnership and part of that requires building win-win relationships. And it certainly is a large biopharmaceutical company the more that we can do to enable our partners and not try to suck as much out of them the better off we're going to be. And then the other pieces we've been quite effective at aligning at all levels in the organization to our CEO, to our CFO, to our board to ensure that we're committing spend in research-based partnerships because that's where the greatest value comes as soon as you start to work into weight development or into the market you're paying top value especially in today's market. So I actually love the fact that there's capital infusion into the biotech space because it means more innovation and more choice and if there's an over flux then we've seen these pendulum swing, they'll swing back. So I think having more capital in a business that's driven by stoichiometry at some level there is a little bit of luck to what we do even though the science is progressing I think having more going on is better for all of us. Yeah, it makes great sense, Andy. I remember working out once that even in a very large pharmaceutical company with a massive budget we actually had less than 0.01% of the life sciences budget of the world and how could you possibly develop everything internally and not get access to that innovation? So I think all your answers were terrific. I'm gonna kind of come a little lower in the stratosphere now and ask about precision medicine and rare disease. And this is something I know Matai you've thought a lot about and particularly how data science impacts working in these spaces and maybe you could just expound on that for the audience before I call on the other panelists. Sure, Martin. And you have an entire panel on this I think coming up next which I think everyone should watch and pay attention to. I do think that there are a whole bunch of innovations from an advance in understanding a new biology and advance in a modality but my belief is that it's various aspects of data science and different manifestations that are together it constitutes the biggest change and part of it is challenging because it does involve a culture change within our organizations and we've been at it a number of my colleagues on the panel have been at it for a while and it's challenging. It's challenging at many levels within the teams at the various interfaces with regulators but for me like it impacts how we're currently picking targets. It certainly impacts or will impact I believe and we're early day for how to prosecute and invent molecules and some of the newer approaches there of using images or generative algorithms I'm convinced that they're going to work out and then I think it is currently impacting all sorts of aspects of how you define a patient and this is interesting and important because we're heading towards more precise connection between our biological mechanism and however we're defining a disease but however we're defining a disease if it's not traditional like if it's not kind of an everyday thing it's very challenging to define a patient in a mechanistic way. So we've been working on various ways of taking ordinary measurements and applying an algorithm on top of them to pull back what might be a precise measurement. Like as a quick example of that just to illustrate what I mean is everyone that has cancer gets if they can get a biopsy gets a biopsy and that is typically made into a slide in histopathology and various stains are done but it's still unusual at least in most of the world to get whole genome sequencing of that tumor. That's a less usual thing today in major academic medical centers, yes. So one of the things that our team has done is work on an algorithm through enough training sets where you can pull back from those images what a mutation is that is in that tumor and so it's just making practical and it's a massive impact for patients by connecting a drug to a patient. It makes very practical and efficient and good for everybody if you can apply data science that way. And then there's no shortage I can go on and on about system trials and real world evidence just kind of a component within data science but big picture is we have to just get accustomed to picking problems in the right way where there is suitable data and the problem is important and we have to get accustomed to kind of the culture changes within our organization to make it all happen. Yeah, it makes complete sense. Matai, how do you think about that and Gen D? Yeah, there's terrific examples by Matai. You know, perhaps I'll broaden the perspective a little. You know, one of my core beliefs is that this industry will, the underpinning of it for the next probably three, four or five decades will be what we're now calling human data. And by human data, we mean everything from genomics, other omic technologies to clinical trials data to real world evidence and the aggregation and integration and then ultimately and most importantly, the analysis of that data I think is what's going to drive not only drug discovery but the entire development spectrum. And so we've created a unit called Human Data that's really tasked with putting this all together. Of course, we have decode genetics which forms a core of what I'm talking about with a tremendous analytic engine. I can't overemphasize how important that last piece is because in 10 or 15 years, a huge amount of data is going to be available in the public domain. Making sense of it will be the challenge. So I think this sort of holistic view and thinking about the use of human data across the entire drug discovery and development spectrum will be one of the primary drivers. And so we're bending a lot of our efforts to build that capacity. Yeah, it makes good sense, David. Any disagreement, Andy? Well, no, I love the way David's framing this and I've kind of taken a mindset where, today the great value in what we bring to patients is the molecule and the data are an adjacency to the model but a necessity. At some point, whether it's five, 10, 20 or 50 years from now, it's going to flip. And the value proposition in medicine will be data, not molecules. Of course, there will always be a need for new molecules but I think what we'll have is we'll have a panoply of effective molecules and we'll need more data. And at some point, our business model changes. You know, why is it that the companies that have trillions of, there aren't no pharmaceutical company across the world has an evaluation, I think greater than 400 billion. I know in Matai, you guys have a massive number that I can't even begin to compute it's not anywhere near what tech companies have. It's probably 10%, you know, 10 to 20% of what some of the tech companies have and those are data companies. Why aren't they jumping in head first? Because today we're still a molecule risk-based business. At some point we transition and I agree fully with David it's going to be a data-driven company and only the top 10 organizations today won't be the top 10 organizations in our industry in 10 or 20 years because you'll have to be a data-driven company. Yeah, no, it makes good sense. I'm going to change tech here before bringing in a couple of our questionnaires. I'm going to start with you, John. I alluded to the fact that we met almost 30 years ago and this was when John was actually at the Burnham Institute in San Diego and had founded a company called Ido Pharmaceuticals. I was working in Switzerland at the time with Siba Geige in the neurodegeneration group or neuroscience as it was called in those days and we formed this partnership to see if we could apply some of the knowledge around programmed cell death to neurodegeneration. Interestingly, there was another part of that collaboration that was with the oncology group that you won't remember, John and that was the opposite end of it but the question really is here we are almost 30 years on and we haven't really served our patients well in neurodegeneration and I'm not alluding to the recent controversy over the recent approval but where do you stand on it now, John and that's to know what are you doing to try and redress that balance? Well, maybe I'll first just digress a second to say at least with the oncology effort that was the foundation that led to the drug Benedoclax the BCL-puligiviter and it took quite a few different tries and finally partnering with what was then called Abbott where Steve Fezick had that SAR by NMR technology the chemical fragment structure-based approach that finally laid the groundwork and then ultimately to the medicine but with that digression aside I think neurodegeneration remains a very challenging area it seems to be an area where we our fundamental understanding of the science is still quite rudimentary we continue to see disappointment after disappointment they had a kind of story notwithstanding and so I think it's one that really would benefit for more of this human specific interrogation of the underlying biology for one thing and a continued commitment and one that now does have the ability to bring in some new modalities gene therapy and other things are being explored in the context of CNS diseases and maybe with antisense oligos are now approved for some CNS diseases so with a broader toolbox perhaps some of these challenging targets and challenging biology will finally yield clearly the unmet need is so astronomical that it's not a space that we can ignore at Sinofia I would say if we have kind of an emerging theme it's kind of what I would call neuro-inflammation and the idea that it's an inflammatory component to many of these diseases and maybe we can first stall the inevitable if we can dial down the neuro-inflammation as one of the new strategy but it's certainly a field that's not for the faint of heart and it does require a long-term perspective of what the community will take Yeah, good points John Thoughts Andy, are you hopeful? Well you know me, I'm always hopeful I'm a glass whatever percent full it is but I'm hearing kind of the hesitancy in John's voice and you know I think it's the hardest not to crack you know and I think that we you know again as you kind of have a side we can talk about that ad infinitum I think it's just an area where the heterogeneity of the disease or lack of understanding or inability to easily correlate readily correlate biomarkers with clinical endpoints and the likelihood that the disease the course of disease is ignited at a point that's very early in its natural history perhaps before any symptoms emerge and so that creates immense challenges and understanding and studying potential medicines you know with all that said we're all in you know we're really keen our focus has been you know going back to something that Matai had brought up which I think is a trend that follows the science is to try to go after the most targeted focus patient population that you can you know where possible defined by you know human genetic etiology because you have the greatest likelihood of understanding the pathophysiology being able to intervene in a way that makes most sense and because you have the most homogeneous patient population you're likely to see the greatest effect sizes with your drugs so smaller trials that can more rapidly get you to endpoints yes it just makes complete sense to me Andy that that's the way that you know we will develop great medicines but Matai thoughts yes so you know I was just reflecting on the vaccine and the amount of time that companies been talking to one another with one another and sharing information and insights on endpoints and so forth and you know there aren't that many diseases like Alzheimer's disease that look like that vaccine effort it is it is it is a called arms kind of moment there are many companies and you know take HEDA for sure Johnson Johnson where we're in you know we are committed and there's a kind of an acceptance that it'll take a level of persistence that's high but if you crack this not to use Andy's phrase it's really big it's really important it's consistent with every one of our missions right in a major way it's a sidely incredibly impactful compared to most diseases it's a profoundly impactful fact if you could do it so there's plenty in it in a sense from a business sense for multiple companies to to work together so it might be one of those one of those rare situations where we really do want to work together I don't mean like starting a fund and funding lots of different things but I mean take take a few serious players that have long term commitment and work together like as if you're one one company and and that'll be what allows us to make sort of the investments needed to you know probe the the longitudinal histories of different genetic you know processes you know different environmental factors potentially it's too I think I feel like it's too hard for one company to go it alone I think you make a great point on the time I must say from my perspective I see you guys collaborating way more than happened in the past I'm not saying it didn't happen in the past but the concerted efforts that you folks have made over this last period are really quite profound to you Dave is that is that the way to go Matai yeah I'd like to pick up on that theme there's no question that you know the public health importance can't be overstated you know there is a tsunami of cases of neurodegenerative diseases primarily Alzheimer's disease but others as well that are going to overwhelm societies around the world driven simply by demographics and so collectively we bear an enormous responsibility to address that now to me the core challenge right now is our limited understanding of the fundamental disease processes and that makes it hard to generate higher probability therapeutic hypotheses so I really wonder if it's time for a moonshot approach for example on something like Alzheimer's it puts together the players who are involved knowing that it's going to be a long road but that any individual organization as Matai is saying is unlikely to crack this problem on its own and so do we conceive of some broader public private type of partnership that really tries to tackle the problem that there's a conversation worth having right now Yes indeed. One other thing there is you know John mentioned neuroinflammation neuroimmunology I do think that we have to look beyond the aggregates the protein aggregates itself that we see as they are present in the disease and you know that is where we're most interested in our all understanding as best we can sometimes internally sometimes through collaboration the processes that lead to that and result and you know maybe it's the cleaning processes it's the clearance of the system or degradation of bad actors that might lead to end stage pathology and I would encourage all of us to also watch some of the newer measurements that are being made whether it's immune characterization methods whether it's single cell or other methodologies for just characterizing the immune system that's present longitudinally and establish correlates there and I would also watch for different non-invasive measurements as well that may be good things to correlate the immunology too it's just the more diverse our approaches the better and we can do that if we are part of a collective rather than individuals very quickly on this point there's a fallacy that collaboration and competitiveness are in conflict with one another and it's quite the opposite in complex areas where we don't fundamentally understand the biology like Alzheimer's disease collaboration drives competitiveness absolutely Andy and you've been very consistent with that for many years and I couldn't agree more as you also know this panel has spawned many great initiatives in former years and maybe we heard the day the semblance of something that could be built around neurodegeneration taking those points don't miss that point Karun we will come back to it maybe when we're all together next year I'm going to bring in Dr Sharma now we have two great guests with questions so Pooja could you present your question please thank you so much for this opportunity so I just want to ask a small question since the new drug and clinical trial rules in 2019 and the resulting regulatory ease of work in India creation of several GCP compliant clinical trial networks disease registries tissue banks a lot of data positive public opinion around clinical research India still is very poorly represented in global clinical trials or multi-regional clinical trials especially that in early phases what do you feel are the reasons for that and how can that actually be tackled or addressed thank you Dr Sharma great question I'm going to ask the panelist to be brief because I'm going to bring in Karun Reid's next so Andy well certainly huge progress in India over the past three to five years when three to five years ago we couldn't do anything in India because of prohibitive policies around IPA so certainly provisions have changed we heard two years ago here at USAIC some of the progressive regulatory frameworks that are being put in place but I'll say that from my perspective there's still steps that need to be taken just to compare the regulatory environment in China to that of India they're vastly separated and you can see what's happened in China opening up the gates and then secondly I'll just end here the clinical trial infrastructure is still not at a point where at least my comfort and I would guess it's the same for my colleagues here I feel comfortable going broadly in India running clinical trials as part of global studies data management, privacy issues and quality issues there's still something that we need to work together to build in India Very good Andy, thoughts Dave? I really agree with Andy I think the regulatory component in particular is quite important and to the extent that you're able to effect policy that is one area that I think does have to advance but it's clearly progressed since three to five years ago and Andy pointed out but I think there's still a little room to grow there It was one area that you would like to highlight What would that be? It's definitely multifactorial though so I don't know if that's a good way to answer the question I am super impressed with the slope you know the rate of progress is extraordinary there's now political will and there's protection of the core systems that are needed like whether it's intellectual property whether it's working on infrastructure all the different elements of what it is to do GCP at the end of the day it's definitely coming together and we'll be one of the first in like as soon as we see that threshold kind of reached there isn't one overwhelming thing from my perspective or my company's perspective Anything from you John before we move on I don't think you need to add that the other panelists haven't already mentioned Dr. Sharma thank you Great question Carrie We've just got time to squeeze in your question Carrie Ruiz So here's my question I think we can characterize the last year as the best of times and the worst of times and building on the best of times how do we actually accelerate the can-do results that we saw the enthusiasm the energy how can we continue that accelerate it expedite it in three areas research policy and regulatory because there are many other diseases that we all face Great question Karen 30 second answers please John You know I think let's just focus maybe on the R&D side you mentioned three different areas but you know and I know from previous discussions with my colleagues here all of us who sit in big company land have learned a lot about how to be more agile to push decision-making down to the team level to be willing to take smart risks you know to work remotely and distribute a decentralized clinical trial so capturing these learnings I think is actually maybe the biggest silver lining of this whole pandemic experience because I think we've really realized there are better ways to work and we're going to now institutionalize those as the go-forward process Let me give a specific example you know the opportunity to really make rapid progress on what you might call the virtualization of clinical trials so not bringing the patient to the site but bringing the site and the trial to the patient using a combination of digital technologies other technologies we've demonstrated that we can do that we shouldn't regress after the pandemic number one number two I think that gives us another big opportunity which would be the democratization of clinical trials to then reach patient populations who are not currently well served so to me those are two areas where we absolutely have the opportunity to capitalize going forward absolutely Matai yeah there's maybe to pick up where David left off I think it is in the conduct of the clinical trial whether it's site initiation we believed we had to do it a particular way or investigator meetings we believed we had to get a whole bunch of people to fly somewhere and do it together or it's the visiting of certain sites we've been doing for a long time but what does that actually mean and what's remote monitoring mean and how good can you have it if you can walk around with an iPad pretty effectively and so there's all sorts of stuff that we just had beliefs we're not going to be as robust or high quality that turned out to be just fine so there's no way we should let ourselves retreat from that you know our clinical development operations group is thinking that way and is trying to reinforce certain things that we were doing over the last year and a half last year or so well you've certainly been at the forefront with others Matai and I just can't give you guys enough credit for the speed and the accuracy and the efficiency and the ultimate wonderful things that you and others have produced has really been marvellous Andy thoughts I love the digitalization topics that Dave and Matai brought up I think that's going to stick but I'll go to a different area I'll mention the same way that John did which is unconstrained thinking you know necessity is the mother of invention we had a burning platform over the last year and we saw amazing heroic efforts by many companies Matai yours included to do things that we never thought was possible we have that same burning platform in every disease area that all of our companies are working in and there are patients who are dying who don't we're not cared for and don't have therapy to treat their diseases we have to remove the constraints that burden us we're so comfortable failing in the ways that we felt that we failed years and years and years even you know since you were a child in this business Martin we're very comfortable with that we accept those failure rates because people understand that when you fail doing something new it invokes a very different emotion that people are very afraid of and I think we need to release those burdens Great point Sandy well a wonderful place to end the panel and as always I just think you guys are terrific great questions from Karen and Pooja that was a really nice end to the session and here's the great news next year we're going to be together we'll all be in the same room because of the differences made by your companies and other companies that will allow us to be human beings again and no doubt in Boston and having a lot of fun with that I want to thank everybody and I'll bring the panel to the end and back to you Karun or maybe to you Andy Oh no I'll come on I need some time also on the screen thank you can you put that Paul slide can you show that Martin wonderful on time absolutely fantastic I think it's like an old you know your scratch it gets better and better every year like a single mall from the Highlands right so it's 14th year for you 14 times so you are there so thanks a lot so can you put the Paul slide please the question is beyond COVID where do you expect mRNA technologies to have the biggest impact let's now 60 seconds thank you hello everybody welcome back before we jump into the last panel of the day let's look at the answer to the most recent polling question if we could please flash that up onto the screen so we can look at everybody responded so the question was beyond COVID where do you expect mRNA technologies to have the biggest impact and we almost had a tie and all of you believe that the biggest impact was likely to be in the areas of cancer vaccines and infectious disease vaccines so thank you very much