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Bristol Myers on Why Neuroscience Could Be the Next Oncology · Vanguards of Healthcare by Bloomberg Intelligence

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  Speaker 1: Welcome to another episode of Bloomberg Intelligences Vanguards of Healthcare podcast,
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  Speaker 1: where we speak with the leaders at the forefront of
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  Speaker 1: change in the healthcare industry. My name is Sam Fazzelli
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  Speaker 1: and I'm a healthcare pharmaceutical journalist at Bloomberg Intelligence, the
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  Speaker 1: in house research.
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  Speaker 2: Arm of Bloomberg.
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  Speaker 1: I'm thrilled to welcome Christian Massa ches Did I say
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  Speaker 1: that right?
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  Speaker 2: Christian?
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  Speaker 1: Ask one of my Italian colleagues to make sure that
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  Speaker 1: I got it right, although he said Massach okay fine,
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  Speaker 1: Chief Medical Officer and Head of Development at Bristol Myers.
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  Speaker 1: Christian joined Bristol about ten months go there or thereabouts
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  Speaker 1: from Astro Seneca, where he was CMO CDO of Oncology.
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  Speaker 1: So Christian, I'm really glad and it's a great pleasure
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  Speaker 1: to have you with us today. It's not often we
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  Speaker 1: get folks that have recently moved from one company to another,
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  Speaker 1: so it gives us a much better opportunity to look
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  Speaker 1: at somebody who's looked at a business strategy, pipeline, et
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  Speaker 1: cetera with the fresh pair of eyes.
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  Speaker 2: So I'm really really glad to be able to do that.
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  Speaker 1: And before we move into the key topics we want
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  Speaker 1: to talk about, which is across everything pretty much. I
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  Speaker 1: would love to hear a little bit of a background
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  Speaker 1: to yourself and you know what took you to Bristol
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  Speaker 1: Myers and you know, and then we can get into
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  Speaker 1: the pipeline discussion.
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  Speaker 3: Thank you, Thank you, Sam, thank you for having me.
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  Speaker 3: First of all, a pleasure to be here and talking
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  Speaker 3: to you. Let me give you a little bit of
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  Speaker 3: background on myself. I'm a medical oncologist. I spent the
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  Speaker 3: last thirty plus years as a physician scientist. I was
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  Speaker 3: in academia, actually joined pharma about twenty years ago, but
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  Speaker 3: the core of myself is coming from clinical research. You know,
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  Speaker 3: I was in practice and I like practicing oncology. I
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  Speaker 3: like the relationship with the patients, but the frustration, especially
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  Speaker 3: those times, was very high because we didn't have enough
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  Speaker 3: treatment options. This was the reality. And I still remember
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  Speaker 3: the feel of importancy in front of young patients that
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  Speaker 3: I didn't have any options and ultimately see them dying
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  Speaker 3: in front of me. So this is why this was
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  Speaker 3: really the engine the motivation that brought me to continue
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  Speaker 3: to research, continue to dedicate my time to Yeah, my
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  Speaker 3: passion that is clinical research to try to find new
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  Speaker 3: your medicines and new treatments for cancer patients. First today
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  Speaker 3: is broader because I have the privilege also to treat
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  Speaker 3: patients that are affected by life treating diseases or very
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  Speaker 3: very difficult disease to treat outside outside oncology. This is
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  Speaker 3: ultimately going also to the second part of your question,
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  Speaker 3: what brought me to be a mess having a broader
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  Speaker 3: impact for what I can to through my teams of course,
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  Speaker 3: in try to bring medicines not only people that are
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  Speaker 3: affected by cancer, but also people that are affected by
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  Speaker 3: very very serious out immune diseases, cardiovascular diseases. And I
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  Speaker 3: really really was motivated on the commitment that Bristol my
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  Speaker 3: scripts as in neuroscience, especially in or degenerative diseases. We're
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  Speaker 3: going to talk about this, I'm sure, but for me
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  Speaker 3: this is personal and I think it's becoming an urgency,
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  Speaker 3: a huge medical need in front of us because you know,
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  Speaker 3: some people is aging more and more. We are, except
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  Speaker 3: for writing better, except for us too, But I think
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  Speaker 3: I think people is Yeah, the life expectancy. Let's take
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  Speaker 3: my country. When I was in practice, life expectancy in
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  Speaker 3: Italy for a woman who was seventy five for a
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  Speaker 3: man who was seventy three. Now is eighty for a man,
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  Speaker 3: in eighty three for a woman. And you know, because
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  Speaker 3: a week we treat better cancer, we treat beta carrivascar disease,
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  Speaker 3: we treat a better kidney and respiratory diseases. The brain
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  Speaker 3: is aging, and with the brain aging, we have now
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  Speaker 3: a huge increase in a dementia, in a disease, never
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  Speaker 3: the generative disease like parkinson like. So this became I
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  Speaker 3: really need and I think we are just at the
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  Speaker 3: beginning to have options for these diseases. So this moved
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  Speaker 3: me also to join BMS, that of course is a
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  Speaker 3: very very good company. I'm very happy about this moment.
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  Speaker 1: Yeah. I mean when we look at these Bristol Meyers
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  Speaker 1: assets and pipelines and products today, absolutely, as you rightly said,
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  Speaker 1: it touches all of those areas.
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  Speaker 2: I do remember.
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  Speaker 1: Twenty five years ago when you used to go to
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  Speaker 1: oncology conferences it was quite depressing because we were hardly
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  Speaker 1: getting just beginning to see the first insights into the
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  Speaker 1: targeted therapies.
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  Speaker 2: And then now look where we are today.
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  Speaker 1: So science is moving at an amazing pace, hasn't and
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  Speaker 1: I think the topic we'll talk about how it's coming
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  Speaker 1: to neuroscience or has come to neuroscience.
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  Speaker 2: But let's get to that.
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  Speaker 1: Just to talk about the pipeline vision going into twenty
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  Speaker 1: three that you have for Bristol Myers looking at the
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  Speaker 1: various therapeutic areas that the company is active in, just
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  Speaker 1: if you wanted to give us a quick top down
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  Speaker 1: view on that.
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  Speaker 3: You know, for a developer like myself, the first thing
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  Speaker 3: that you need to work with the easier portfolio, pipeline
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  Speaker 3: and portfolio, and you think this is of course a
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  Speaker 3: very important driver for me to be in this company.
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  Speaker 3: The portfolio of BMS is really rich. This is the
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  Speaker 3: world because we have we have a pipeline that is
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  Speaker 3: very broad, is also deep because we have multiple assets
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  Speaker 3: that are spanning from all stage of development from candidate
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  Speaker 3: to pre clinical and pre clinical candidates to phase one
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  Speaker 3: into into phase three, but also a lot of depth
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  Speaker 3: into the targets modalities. You know, we have antibodies, small molecules,
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  Speaker 3: a disease, radio ligence in ecology, we have you know,
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  Speaker 3: every kind of delivery for cell therapist. So this is
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  Speaker 3: the modality is very is very broad and of course
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  Speaker 3: we have focused without being too unfocused on We have
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  Speaker 3: focused in four main therapetic areas, so that is ecology, mythology, immunology, cardiovascular,
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  Speaker 3: and of course neuroscience. So I really like the fact
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  Speaker 3: that we want to we are, we have, we continue
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  Speaker 3: to build a portfolio that will continue to deliver hopefully
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  Speaker 3: medicines to patients with serious life threatening diseases in these
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  Speaker 3: therapeutic areas, so where we have expertise, drugs and of
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  Speaker 3: course investment capital are located. Looking not only TODAYMM looking
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  Speaker 3: to the future. You know you need to deliver today,
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  Speaker 3: and twenty six and twenty seven for US is going
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  Speaker 3: to be incredibly busy. We have so many redoubts across
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  Speaker 3: the ta is where where we are running our clinical trials,
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  Speaker 3: where we have our medicines, that really really is going
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  Speaker 3: to be very busy. But we are building now the
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  Speaker 3: two thousand and thirty in post two thousand and thirty.
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  Speaker 3: Our ambition by twenty and thirty, by the end of
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  Speaker 3: these decades is to have ten new medicines approved. And
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  Speaker 3: I tell you, for me, every time I have a
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  Speaker 3: drug that reached the finish line, that is approved is
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  Speaker 3: really a personal a personal fulfillment.
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  Speaker 4: I did.
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  Speaker 3: I had a pleasure to do this twenty times in
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  Speaker 3: my career across across the A is a MAINI in ecology.
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  Speaker 3: But believe me, every time one drug reach the approval
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  Speaker 3: means that I can reach thousands of patients. And this
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  Speaker 3: is why we do what we do. So with this ambition,
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  Speaker 3: of course, if we are able to achieve and bring
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  Speaker 3: these new medicines to patients in ecology, in neuroscience, in cardiovascular,
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  Speaker 3: in immunology, I think we can touch the life or
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  Speaker 3: millions of patients. This is this is the line, the
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  Speaker 3: line of sights in two thousand till twenty thirty, and
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  Speaker 3: then of course we want to build the post twenty
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  Speaker 3: and thirty with the next wave of pipeline.
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  Speaker 1: So talking specifically about that, a lot of companies we
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  Speaker 1: look at we try and assess the number of compounds
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  Speaker 1: that are in the clinic or reach the finish line
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  Speaker 1: that have been generated internally versus in licensed versus MNA.
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  Speaker 1: What if you want to do I mean, I'm assuming
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  Speaker 1: you don't have a set number in mind that this
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  Speaker 1: number of drugs has to come from external innovation versus
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  Speaker 1: internal innovation.
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  Speaker 2: Do you have how do you think about that? As
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  Speaker 2: you're looking out to this.
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  Speaker 3: Actually for this I am, and we are very rigorous
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  Speaker 3: because our business in development specifically some is affected by
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  Speaker 3: attrition inevitably. And actually the problem is that still today
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  Speaker 3: the failure rate is very high. If you think in
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  Speaker 3: the moment in which drugs are rich in clinical stage,
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  Speaker 3: so first into human, first into patients till the approval,
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  Speaker 3: the attrition rate is around ninety percent. So it means
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  Speaker 3: that sometimes it's even lower. It means that one drug
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  Speaker 3: out of ten that get to patients get an approval,
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  Speaker 3: nine will fail. If you think incredibly incredibly high. So
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  Speaker 3: what does it mean. It means that you need to work.
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  Speaker 3: First of all, try to improve that rate, decrease that attrition. Second,
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  Speaker 3: is not only the failure the failure rate, but is
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  Speaker 3: also the time from first into human to approval that
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  Speaker 3: the average is between eight nine years. And third, of
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  Speaker 3: course are the costs that is really really very very high.
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  Speaker 3: Averagely is between seven hundred million to one point five
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  Speaker 3: two billion dollars for a drug because you pay also
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  Speaker 3: for the drug that are failing. You know, this is
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  Speaker 3: why drug development is so expensive today. So what we do,
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  Speaker 3: what I want to do, and we are actively proactively
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  Speaker 3: acting on insay is. First of all, we want to
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  Speaker 3: shorten the timelines because instead of eight nine years, you
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  Speaker 3: bring this down to six years and a half seven years.
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  Speaker 3: I think you're ready. First of all, are able to
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  Speaker 3: bring more medicines to pasient faster, especially novative medicines. Secondly,
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  Speaker 3: you can decrease also some of your costs. Second we
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  Speaker 3: need to increase the success rate, and to do this
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  Speaker 3: you need a lot of scrutiny. In each stage of
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  Speaker 3: the development. There are three main stages. One is when
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  Speaker 3: you put the drag in clinic, second in when you
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  Speaker 3: declare the proval concept, and then when you go in
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  Speaker 3: phase three and the phase t read out. So we
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  Speaker 3: are working very actively in also using technology artificial intelligence
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  Speaker 3: to improve the success rate in each one of these stages.
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  Speaker 3: The last aspect, of course, is how can we do
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  Speaker 3: more with less in terms of how we can gain
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  Speaker 3: efficiency and probability of a technical success any er. All
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  Speaker 3: the eye, all the tools are kicking in because this
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  Speaker 3: is where we are we are moving. Going back to
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  Speaker 3: your question, it would be simply not realistic believing that
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  Speaker 3: you can do everything only with your internal research and
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  Speaker 3: development engine needed to tap into external innovation to help
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  Speaker 3: in this journey. Of course, a company like ours, most
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  Speaker 3: of our I and DS, most of our drugs are
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  Speaker 3: coming from our internal research. MONE needs to be constantly
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  Speaker 3: implemented with external innovation also because you know, you have
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  Speaker 3: some internal strengths in some areas. BMS is very strong
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  Speaker 3: in targeted protein degradation, is very strong in cell therapy,
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  Speaker 3: it's very strongly in some of the large antibodies. But
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  Speaker 3: we need to continue to bring in innovation in the
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  Speaker 3: areas where we probably have less focus and less skills
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  Speaker 3: because these compliment and give us the breadth of our
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  Speaker 3: portfolio that we need to be able to bring the
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  Speaker 3: best drugs to patients.
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  Speaker 1: Yeah, I mean, so this actually teaches us up quite
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  Speaker 1: nicely to start going into some of the therapeutic areas Christians.
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  Speaker 2: So if we look.
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  Speaker 1: At naturally, I think it's probably best to stop with
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  Speaker 1: us go and oncology because just come out of it.
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  Speaker 2: So let's pick on three three assets actually two of
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  Speaker 2: which were.
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  Speaker 1: Ulicnsed and originated originally from China in fact, So which
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  Speaker 1: is a topic that if we have time we can
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  Speaker 1: touch on. But let's talk about and let's talk about
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  Speaker 1: Rosetta long ago two, which is your which is permit
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  Speaker 1: to meg, the PDL one veggef. I'm not going to
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  Speaker 1: go into the detail of the data, but because you
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  Speaker 1: know there's the PD one veggefs, there was a PDL
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  Speaker 1: one vegef another one that was presented very early data
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  Speaker 1: at the conference. If we think about this, there's one
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  Speaker 1: fundamental difference between permitted MEG and the PD one vegefs,
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  Speaker 1: including ibaness and habit set, and that is you targeting
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  Speaker 1: PDL one, your molecule functions within the tumor more eno
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  Speaker 1: micro environment than on the t cell, which is where
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  Speaker 1: PD one is.
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  Speaker 2: How do you think that's going to pan out?
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  Speaker 1: Do you have a view as to whether that will
• 14:56
  Speaker 1: eventually lead to some kind of differentiation between these roaches
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  Speaker 1: or because a lot of us just pile them all
• 15:03
  Speaker 1: into one bucket at the minute. And you know, and
• 15:05
  Speaker 1: you've got some good translational work too there in terms
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  Speaker 1: of PDL one internalization, et cetera.
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  Speaker 3: Thank you Sam for bringing this up. Let me start
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  Speaker 3: with the big picture. The big picture is my first
• 15:17
  Speaker 3: ask or B A mess. Probably I couldn't. I couldn't
• 15:19
  Speaker 3: pick a betterrea because for me, A mess was very
• 15:24
  Speaker 3: successful ASCO. We had sixty eight presentations and you know,
• 15:29
  Speaker 3: I think what is important is in my view that
• 15:32
  Speaker 3: we are moving from having most of the work that
• 15:36
  Speaker 3: was displayed focused on nivolume may be Belimo or something
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  Speaker 3: related to that, to the next generation of drugs that
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  Speaker 3: we are developing. And as you mentioned Pumita meg the
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  Speaker 3: PDO one BGF was really not a not topic and
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  Speaker 3: not spot or the We had a lot of presentations
• 15:56
  Speaker 3: on the sale mods so we can discuss about it
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  Speaker 3: and we have these a new wage. It is that
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  Speaker 3: we have a two orals two phase three data that
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  Speaker 3: that that that are important to highlight. So very very
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  Speaker 3: good ASKO. With a lot of volume and also a
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  Speaker 3: lot of quality data. PT one VEGF big big hot
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  Speaker 3: topic at the meeting and before and after the meeting. Actually,
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  Speaker 3: I think you you you started with an important aspect
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  Speaker 3: that is the mechanism of action. I believe that by
• 16:29
  Speaker 3: specifics are a better way to deliver to mechanisms, especially
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  Speaker 3: in ematology and oncology. I think in ematology out by
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  Speaker 3: specifics are changing some of the treatment of the most
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  Speaker 3: common disease like malma, like lymphoma, because you are really
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  Speaker 3: able to deliver mechanism anti tumor mechanisms. In this case
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  Speaker 3: in for pd pt one, PDO one MVGF, but in
• 16:59
  Speaker 3: a more selective and targeted way. This can also give
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  Speaker 3: you an apple an upside on a more targeted safety
• 17:09
  Speaker 3: profile because you bind the two antigens and two targets
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  Speaker 3: at the same time. We presented some data on the
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  Speaker 3: mechanism of action of pumitam pedio one BGF. What we
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  Speaker 3: have seen is a bra clinical worker that of course
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  Speaker 3: we will continue to develop and to confirm also in
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  Speaker 3: vivo and the true patient samples. What we have seen
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  Speaker 3: is that DGFA is in tuman mark environment like pdio one.
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  Speaker 3: When our drug goes there, bind these two targets and
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  Speaker 3: form a cluster, and this cluster the drug and the
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  Speaker 3: two targets is internalized in the cancer cell. What is
• 17:50
  Speaker 3: intriguing is that the internalization is actually independent of the
• 17:55
  Speaker 3: pdio one expression. I mean is intuitive that if you
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  Speaker 3: have a cancer cell with IPO one expression, of course
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  Speaker 3: the pd one or the PO one antibody is internalized,
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  Speaker 3: but it is not obvious. So when the cell is
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  Speaker 3: a period one negative and so VGF inhibition and this
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  Speaker 3: cluster and this internalization to me is the first evidence
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  Speaker 3: that actually support the clinical data because where we see
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  Speaker 3: really a big impact of PD one PDL one BGF
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  Speaker 3: by specifics is actually in perio one negative tumor. So
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  Speaker 3: there is benef you of course in PO one positive,
• 18:32
  Speaker 3: especially in P one negative where the medical need is
• 18:36
  Speaker 3: because drugs like involvement penbrolisma plus chemotherapy and land cancer
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  Speaker 3: for instance, that don't work so well when the cancer
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  Speaker 3: cells the tumors are not expressed in perio one. Then
• 18:48
  Speaker 3: if you repeat the same experiment with a PD one
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  Speaker 3: antibody and VGF antibody like SISM, actually you don't see
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  Speaker 3: internalization or the PG one. So this is a first
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  Speaker 3: ep dview that the by specific and doing something different
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  Speaker 3: than the two antibodies. And you know, on top of
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  Speaker 3: that radically data, there are multiple drugs including our on
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  Speaker 3: drug that are showing an increase response rate and increase
• 19:18
  Speaker 3: durability these responses and higher medium progression for survival. And
• 19:23
  Speaker 3: now we start to have also some other survivor data
• 19:26
  Speaker 3: with all the limitation of some studies that can be
• 19:29
  Speaker 3: run in some geography, only by showing that this by
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  Speaker 3: specific can bring benefit to the patients. To me, this
• 19:36
  Speaker 3: is relevant because not only because we have committam megama,
• 19:39
  Speaker 3: is relevant because finally we have two very well validated
• 19:43
  Speaker 3: antitumor drugs and mechanisms like epedio one and inhibition and
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  Speaker 3: VGF inhibition in the same drug together then potentially are
• 19:54
  Speaker 3: not only additive, maybeicin logistic and can represent the next
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  Speaker 3: steps to improve over p D one PERO one inhibitors
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  Speaker 3: because so far it's been very difficult to improve upon it.
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  Speaker 3: We try the toward different mechanism mechanisms like I do
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  Speaker 3: one teach it, but was very difficult. Actually most of
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  Speaker 3: them did not did not read out as we would
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  Speaker 3: would have liked. So I'm very excited about this because
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  Speaker 3: for me, it is the first step to continue to
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  Speaker 3: bring benefit to patients. And then of course this can
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  Speaker 3: open up not only the indication where PD one PERO
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  Speaker 3: one inhibitors are used, but you can bring these drugs
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  Speaker 3: where these drugs are currently not approved. If you think
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  Speaker 3: about forty five percent of patients we cancer today's solid
• 20:44
  Speaker 3: tumors are receiving PD one per one inhibitors. The vast
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  Speaker 3: majority are they have the so called the so called
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  Speaker 3: coal diseases or INCENTI, I you insensitive diseases like colon cancer,
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  Speaker 3: proceted cancer where you do not have the drug. I
• 20:59
  Speaker 3: think the VGF component or this by specific can open
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  Speaker 3: up that space. You know, I think col on cancer.
• 21:05
  Speaker 3: Now there are multiple studies on going colon cancer with
• 21:09
  Speaker 3: these drugs, including our.
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  Speaker 1: Did you become more confident the same or after seeing
• 21:17
  Speaker 1: the Harmony six data.
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  Speaker 3: I Harmony six data is another piece of the puzzle.
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  Speaker 3: I think that I was already confident because we have
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  Speaker 3: a multiple data sets in the class that are trending
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  Speaker 3: in the same direction. And you know, there was always
• 21:35
  Speaker 3: the discussion, is this similar to what we observed with
• 21:39
  Speaker 3: vascism in the past, where we had a better response rate,
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  Speaker 3: a better PFS, and I did not translate in OS.
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  Speaker 3: I think this is a different concept because you are
• 21:49
  Speaker 3: delivering a VGF inhibition and perio one inhibition with the
• 21:53
  Speaker 3: same drug, and ultimately I believe that the uplift on
• 21:57
  Speaker 3: OS will be given because you deliver the io together
• 22:01
  Speaker 3: with the GF. Is the I O tail that probably
• 22:03
  Speaker 3: can be can never lift lift up. This is where
• 22:06
  Speaker 3: my confidence is coming from because I don't think anybody
• 22:09
  Speaker 3: is disputing that response rates and pfs are higher versus
• 22:14
  Speaker 3: p D one inhibitor. It's more the question on OS
• 22:17
  Speaker 3: so I believe that this will translate in an OUs benefit.
• 22:21
  Speaker 3: The real question open still open, is how much the
• 22:25
  Speaker 3: benefit will be an o S This is this is
• 22:27
  Speaker 3: some for me, the main open question. But then I
• 22:30
  Speaker 3: put this in the context of the safety you can
• 22:33
  Speaker 3: deliver in astologies well, for instance, you cannot use acism
• 22:37
  Speaker 3: or lies cumus Lune answer. You can deliver in combination
• 22:41
  Speaker 3: with kimotherapy. You can deliver in combination with a disease,
• 22:44
  Speaker 3: and when we don't see an excess in adverse events.
• 22:48
  Speaker 3: So if you have a better response relator, better PFS,
• 22:51
  Speaker 3: and this translating in a benefit in the US and
• 22:54
  Speaker 3: the safety is acceptable. I think is an improvement. Of course,
• 22:57
  Speaker 3: so we need to wait larger data set, more data sets.
• 23:01
  Speaker 3: Not every indication will work the same way. It is
• 23:04
  Speaker 3: why we run a very large program. This is fine.
• 23:07
  Speaker 3: For instance, we have seven people to studies ongoing with
• 23:10
  Speaker 3: the Pumita MiG today and more than twenty studies in
• 23:14
  Speaker 3: which we are testing Pumita Mega and other combinations. But
• 23:18
  Speaker 3: we believe this can be really a backabone. The new
• 23:21
  Speaker 3: io backbone for moving forward for cancer patients.
• 23:24
  Speaker 1: I may have said that was my last question, but
• 23:26
  Speaker 1: something else popped into my head on that agent.
• 23:29
  Speaker 2: If you put your.
• 23:31
  Speaker 1: Oncologist hut on, what os benefit would be enough for you?
• 23:37
  Speaker 3: I think some just showing statistically significant to us that
• 23:42
  Speaker 3: can be in the magnitude of months a few months
• 23:46
  Speaker 3: would be enough because the profile and the safety is
• 23:50
  Speaker 3: already is good is okay, So the benefit risk balance
• 23:55
  Speaker 3: to me will be good enough. Then I believe we
• 23:59
  Speaker 3: have seen a plenary RASCO that the benefit the aserration
• 24:03
  Speaker 3: was very important in the context of channel only data
• 24:07
  Speaker 3: set with all the limitation that is bringing. But I
• 24:09
  Speaker 3: believe that to me is the totality of the data.
• 24:12
  Speaker 3: You know, the benefit that you show in strengthening to
• 24:16
  Speaker 3: the tumor the benefit you bring it to the patient
• 24:19
  Speaker 3: in delaying this is progression. This is already big benefit
• 24:22
  Speaker 3: for the cancer patient. And then if you have an
• 24:25
  Speaker 3: improvement in overall survival visa VI A safety profile that
• 24:30
  Speaker 3: is acceptable, I think is good.
• 24:32
  Speaker 2: Great. Let's move to multiple myeloma and your cell mods.
• 24:35
  Speaker 1: We had the success of two data which was impressive
• 24:39
  Speaker 1: and clearly that was on mesigdamid.
• 24:42
  Speaker 2: So maybe you could tell us a little bit about that.
• 24:43
  Speaker 1: But in the long term your vision as to clearly
• 24:49
  Speaker 1: you owned the space before after the acquisition of cell
• 24:53
  Speaker 1: gine with linarly to mind or reve limit, which has
• 24:56
  Speaker 1: now gone to generate everybody seeing the impact on revenue,
• 25:00
  Speaker 1: use and et cetera of that drug. You're coming back
• 25:02
  Speaker 1: in again in the context of having a generic drug
• 25:05
  Speaker 1: out there with a slightly with a lower price, slightly
• 25:08
  Speaker 1: big whatever you want to qualify it, however you want
• 25:10
  Speaker 1: to qualify it.
• 25:12
  Speaker 2: How do you see these.
• 25:13
  Speaker 1: Two not just music demand, but also I heard the
• 25:15
  Speaker 1: mind being positioned in the long term to enable you
• 25:19
  Speaker 1: to convince physicians that and the success to two data
• 25:23
  Speaker 1: I think gave you a meaningful step up into that
• 25:26
  Speaker 1: direction really to use either iber or Mezzi instead of
• 25:31
  Speaker 1: GENERICALLYTA mind.
• 25:33
  Speaker 3: Some let me again start with a big picture, because
• 25:36
  Speaker 3: I think it's important to put these two drugs in
• 25:39
  Speaker 3: the context of the platform. The platform of targeted protein
• 25:43
  Speaker 3: degradation is a platform that allows us to deliver ural
• 25:50
  Speaker 3: drugs because these are auroral drugs in a different way.
• 25:54
  Speaker 3: It delivers more molecule like inhibitors. Because you can today
• 25:59
  Speaker 3: target key proteins in my roma, A caroos and iolos
• 26:05
  Speaker 3: in in b CL six that so far we're not
• 26:10
  Speaker 3: necessarily well dragonable because these are more ecual glues or
• 26:15
  Speaker 3: ligand the graders. So you bring these glues or these
• 26:20
  Speaker 3: these ligands, you bring to the targets the mechanism that
• 26:25
  Speaker 3: usually we use physiologically, the ensmatic mechanism to degrade proteins.
• 26:31
  Speaker 3: And this is done through the platform that, as you mentioned,
• 26:35
  Speaker 3: came from seale Gene mbms and mbms suspended. Today we
• 26:39
  Speaker 3: have eleven drugs and clinic coming from this platform. For
• 26:43
  Speaker 3: them are appy water stage to you mentioned, I bet
• 26:45
  Speaker 3: my music domain. We have many more that are between
• 26:49
  Speaker 3: phase one and two, between solitude ors andematology. So I'm
• 26:52
  Speaker 3: very excited about this. Take a BCal six way BCL
• 26:55
  Speaker 3: six the gradest BISIL six is a key driver for
• 26:58
  Speaker 3: informas and and so far was undragonable. B SEL six
• 27:02
  Speaker 3: the grater now is a good drug show very clear
• 27:07
  Speaker 3: monotapy activity and will represent an important drug in the
• 27:10
  Speaker 3: future in informa. So with this in mind, I think
• 27:15
  Speaker 3: you need to put the mesic DOMAIND and a verdomide
• 27:18
  Speaker 3: versus what was linalidomidepomelidomide in the past. These new drugs
• 27:25
  Speaker 3: are engineered and developed with a very different selectivity impotency
• 27:31
  Speaker 3: compare what was the predecessor. So is the innovation is
• 27:37
  Speaker 3: continue to build on better drugs because they are degrading
• 27:41
  Speaker 3: across and iolos in a much more selecting importent way.
• 27:46
  Speaker 3: Mesic domain is actually a more portent of a verdomide.
• 27:49
  Speaker 3: And this has been designed in this way because the convenability.
• 27:54
  Speaker 3: The view of how we want a position these new
• 27:58
  Speaker 3: cell modes in the landscape of myloma treatment is we
• 28:04
  Speaker 3: would like them to become one of the backbones in
• 28:07
  Speaker 3: the maloma across lines. You know. Multiple myloma fortunately is
• 28:12
  Speaker 3: becoming more and more a disease where the patients are
• 28:16
  Speaker 3: receiving one treatment after the other. I like to use
• 28:20
  Speaker 3: an analog that is CML. Remember CML was a very
• 28:24
  Speaker 3: difficult disease to glive. Kicking kicked in and then all
• 28:28
  Speaker 3: the terrorsen knes inhibitors and the next generation of drugs
• 28:32
  Speaker 3: made this disease like a chronic disease. Today, a patient
• 28:35
  Speaker 3: diagnosed with CMELA is dying for something else because as
• 28:39
  Speaker 3: multiple multiple options and the disease is controlled for a
• 28:42
  Speaker 3: long time, is not yet the case in myloma. I
• 28:45
  Speaker 3: want to be very clear, but in my loma today
• 28:47
  Speaker 3: there are so many treatment options and so active that
• 28:50
  Speaker 3: it is becoming more and more a chronic disease. We
• 28:53
  Speaker 3: believe that the cell motes, first of all, will replacemid
• 28:59
  Speaker 3: and pamelidum because they are better drugs. We have data
• 29:02
  Speaker 3: showing in the same setting with the same combination that
• 29:05
  Speaker 3: you gain in activity in a very clear way. Let
• 29:09
  Speaker 3: me use the example of mesic domain mesic domaid in
• 29:12
  Speaker 3: successful too. The study we presented a rasco is mesic
• 29:15
  Speaker 3: domind in combination with calfisomib and the themethoson versus KD alone,
• 29:21
  Speaker 3: and the medium PFS goes from eight months to eighteen
• 29:25
  Speaker 3: months in patients that are truly resistant to anti thirty
• 29:30
  Speaker 3: eight and lidamite. So this level of benefit was not
• 29:35
  Speaker 3: seen before. And we have data we pumelidomide plus KD
• 29:39
  Speaker 3: and the media pfess with pido akd in a cross
• 29:43
  Speaker 3: trial comparison and TRAMA is eleven months, so you see that.
• 29:47
  Speaker 3: And we have the same with the verdomide use the
• 29:50
  Speaker 3: postum transplant versus revelimid. The use a post transplant in
• 29:55
  Speaker 3: a phase to data setting their response rated the m
• 30:00
  Speaker 3: the negativity rate is much higher with a urdomide than litomite.
• 30:05
  Speaker 3: So we have clear evidence that this drug can be
• 30:08
  Speaker 3: better beyond of course the chemistry and the clinical work.
• 30:13
  Speaker 3: Of course they face they to wed. The studies are
• 30:16
  Speaker 3: ongoing and we will have more and more data. But
• 30:18
  Speaker 3: this is give us the uplift. Then think where maloma
• 30:23
  Speaker 3: patients also are treated. Seventy five percent of malama patients
• 30:27
  Speaker 3: treating community, and you know in community is sometimes there
• 30:32
  Speaker 3: are some difficulties to embrace more complex treatments like cartes
• 30:39
  Speaker 3: or more treatments like bispecifics that have a level of
• 30:45
  Speaker 3: infections that can be sometimes demanding for the prescribed the patient.
• 30:51
  Speaker 3: So adding oral drugs that you can combine across lines
• 30:55
  Speaker 3: with standard back bones, I think is very appealing. It
• 30:59
  Speaker 3: can be very for patients. So and of course we
• 31:03
  Speaker 3: continue to believe we're going to develop this drug to
• 31:06
  Speaker 3: engineer the new the best regiment, because the next combinations
• 31:11
  Speaker 3: will be with the bispecific and our cell mots or
• 31:14
  Speaker 3: integrating our cell modes with carties. Because you know, if
• 31:19
  Speaker 3: you use the by specific and then the patient progress
• 31:22
  Speaker 3: and then use the cartid, the activity is less integrating.
• 31:26
  Speaker 3: Bridging these maybe with the cell mode containing regiment can
• 31:29
  Speaker 3: help in having a more effective transport. There are CARTIS treatments.
• 31:36
  Speaker 3: We have some patients that receives in maloma cartism but
• 31:39
  Speaker 3: do not get emerdine negativity rates. So these are patients
• 31:43
  Speaker 3: maybe can benefit post the cell infusion of the cell
• 31:48
  Speaker 3: made treatment. So there are multiple optionality to integrate these
• 31:53
  Speaker 3: drugs across the maloma lines. I think is a great
• 31:58
  Speaker 3: thing for patients whoever the opportunity and this is to
• 32:01
  Speaker 3: me for BMS is important because together with our cell
• 32:05
  Speaker 3: therapy portfolio, because we have an important product like our
• 32:10
  Speaker 3: last celle that is a five D CARTI that we
• 32:14
  Speaker 3: read out soon Desia. We have a phase three conflamatory
• 32:18
  Speaker 3: studies ongoing. So our commitment to my loma is really I.
• 32:23
  Speaker 1: Before we go to the cartis just a very quick
• 32:25
  Speaker 1: question here. Do you feel that the tolerability profile in
• 32:30
  Speaker 1: combination specifically thinking about infections, is you need to be
• 32:36
  Speaker 1: able to manage that when it comes to combining with
• 32:39
  Speaker 1: a bispecific which they do have that specific issue.
• 32:42
  Speaker 3: It is the right question. The current profile of the
• 32:45
  Speaker 3: cell mods is very predictable because it's a meatological toxicity
• 32:50
  Speaker 3: and ematologists are very used to manage this, and we
• 32:54
  Speaker 3: don't see a discontinuation rate of the regiments where we
• 32:58
  Speaker 3: have tested the drug in combination with anti city thirty
• 33:01
  Speaker 3: eight and EXA or in combination with carfeesombe and EXA
• 33:06
  Speaker 3: measure problem in combination be by specific and we need
• 33:08
  Speaker 3: to test that this combination can be very powerful, but
• 33:11
  Speaker 3: the safety needs to be assessed. You're fully right. This
• 33:15
  Speaker 3: is why we are running out of phase one phase
• 33:18
  Speaker 3: one two studies to see that.
• 33:20
  Speaker 1: So of course we're in the throes of completing our
• 33:23
  Speaker 1: rerun of my LOMO model. So you should feel sorry
• 33:27
  Speaker 1: for me because it's so complicated.
• 33:30
  Speaker 2: In weaving all these things together.
• 33:33
  Speaker 1: Now, just as I said before talking to about CARTI,
• 33:35
  Speaker 1: because that then is a bridge for us to talk
• 33:37
  Speaker 1: about immunology, let's talk about adecs.
• 33:40
  Speaker 2: So far, we've talked about.
• 33:41
  Speaker 1: How you've improved your cell mod platform and technologies. We've
• 33:45
  Speaker 1: talked about how by specifics, whether they are not CD
• 33:49
  Speaker 1: three or immune engagers, can be one plus one eCos three.
• 33:53
  Speaker 1: So that's great, and we look forward to seeing more data
• 33:56
  Speaker 1: from all these other types of BY specifics.
• 33:58
  Speaker 2: Coming on the A d C world. Obviously that's been
• 34:01
  Speaker 2: a revival. I remember the days.
• 34:04
  Speaker 1: Of Milo targ It shows you how old I am
• 34:07
  Speaker 1: and which was the first day. But now here we
• 34:10
  Speaker 1: see some interesting areas where you have, for instance, the
• 34:12
  Speaker 1: eg FR HER three by specific.
• 34:16
  Speaker 2: A d C, which is not only an A d C,
• 34:19
  Speaker 2: but also the eg FR and.
• 34:21
  Speaker 1: HER three are effector molecus. This is not just the
• 34:24
  Speaker 1: targeting thing. Talk to us about that. And you know,
• 34:27
  Speaker 1: we've seen some data which everyone's going to compare to.
• 34:30
  Speaker 2: DROP two A d C S, which of course is
• 34:32
  Speaker 2: in t NBC for instance. Talk to us about that.
• 34:35
  Speaker 3: This is thank you for bringing up. This is an
• 34:39
  Speaker 3: actually framing in the perfect way. EGFR and R three
• 34:44
  Speaker 3: are very important targets and are expressed in the vast
• 34:49
  Speaker 3: majority of tumors. This is the reality. And what I
• 34:53
  Speaker 3: like of this drug first of all, is that is
• 34:57
  Speaker 3: a bispecific DC, is a very table linker, and is
• 35:02
  Speaker 3: a potent DC because the DART is eight, it's delivering
• 35:05
  Speaker 3: a top one payload. What we have seen, as you said,
• 35:09
  Speaker 3: that this is an A DC that we are co developing. Yeah,
• 35:14
  Speaker 3: we acquire it to a collaboration with system Bioking, that
• 35:19
  Speaker 3: is a company that develop engineered this drug in China.
• 35:26
  Speaker 3: In China, there I'm all the six thousand patients treated
• 35:28
  Speaker 3: with this drug, so very very large that I said
• 35:31
  Speaker 3: multiple phase three studies, three of them already read out
• 35:35
  Speaker 3: and some of them multiple of them are are ongoing.
• 35:38
  Speaker 3: We already have a three peopletal studies globally ongoing with
• 35:42
  Speaker 3: the drug. I like the drug, as you said, because
• 35:46
  Speaker 3: first of all, can help in many tumor types. Secondly
• 35:51
  Speaker 3: because it is not only using each FI and A
• 35:55
  Speaker 3: three to anchor and deliver the pilode, but because as
• 35:59
  Speaker 3: the the potential to inhibit the signalings, and these are
• 36:03
  Speaker 3: important signals in cancer. Third is related to the fact
• 36:08
  Speaker 3: that the alph lie for the drug is short and
• 36:12
  Speaker 3: the link is so stable that the drug bind is
• 36:16
  Speaker 3: internalized kill direct true by standard effect and then is metabolized.
• 36:22
  Speaker 3: And this avoid one thing that I was a little
• 36:25
  Speaker 3: bit concerned there was some skin toxicity. This is we
• 36:29
  Speaker 3: don't have that. We have a metological toxicity with is
• 36:32
  Speaker 3: drug because of the potency of the payload and the
• 36:34
  Speaker 3: potency of the drug. But we have a very low rates,
• 36:38
  Speaker 3: almost irrelevant rates of pneumonatis ild. We don't have rush,
• 36:44
  Speaker 3: we don't have GI toxicity. So is a drug with
• 36:48
  Speaker 3: the profile that make it very appealing in as monotherapy
• 36:53
  Speaker 3: and in combination. The monotherapy level of activity in my
• 36:57
  Speaker 3: view is remarkable. I have seen multiple data sets across
• 37:01
  Speaker 3: two more types. And then there are the phase three
• 37:03
  Speaker 3: redos China only data. So far need to need to
• 37:07
  Speaker 3: really be cautious on that my phase three data sets
• 37:10
  Speaker 3: there are we presented the Asthmolastia nazova angel positive phase
• 37:15
  Speaker 3: three data and I did ask for the were two
• 37:17
  Speaker 3: data sets, one in zoa GA cancer and the other
• 37:20
  Speaker 3: one in triple negative risk cancer. You know, in both
• 37:24
  Speaker 3: studies PFS n us statistically significant and clinically meaningful with
• 37:30
  Speaker 3: other ratios quite dramatic in both traia in triple negatives cancer.
• 37:35
  Speaker 3: Just to mention one example, the PFS as a ratio
• 37:38
  Speaker 3: is zero point two nine and the mediam PFS is
• 37:42
  Speaker 3: a second third line patients versus and is isobran versus versus.
• 37:47
  Speaker 3: The name of the drug is isobrand versus standard chemotherapy.
• 37:52
  Speaker 3: And you know you go from three months around three
• 37:56
  Speaker 3: months media PFS with the standard Okay chemo to a
• 38:00
  Speaker 3: eight point five months and us the ratio is zero
• 38:04
  Speaker 3: point six and you go from around twelve months to
• 38:06
  Speaker 3: sixty months. So it's it's it's very good. It's very
• 38:10
  Speaker 3: good to see this level of activity. And this is
• 38:14
  Speaker 3: why we are now running global studies. You know, is
• 38:17
  Speaker 3: in EGFI three a d C. Of course, we have
• 38:20
  Speaker 3: registrational studies in e GFR mutant and nosmal cell and cancer.
• 38:24
  Speaker 3: We have a phase three studies in triple negative breast cancer,
• 38:27
  Speaker 3: and we have a phase three studies in the second
• 38:30
  Speaker 3: line in bladder cancer euterira cancer. But the real potential
• 38:35
  Speaker 3: in my view of the drug is in combination because
• 38:39
  Speaker 3: you know, I truly believe ADCs are better chemotherapy. Chemotherapy
• 38:44
  Speaker 3: is working simply it's not selective enough. ADC allows you
• 38:48
  Speaker 3: more selectivity, more targeted delivery of chemotherapy, cytotoxics, and I
• 38:54
  Speaker 3: think is a branding combination with for instance, a drug
• 38:59
  Speaker 3: like pumtamic can be a very powerful regimen across two
• 39:04
  Speaker 3: more types. This is why we are testing that combination,
• 39:06
  Speaker 3: for instance, other combination of course beyond this one.
• 39:10
  Speaker 2: Yeah.
• 39:10
  Speaker 1: Now, so we've got twenty minutes or so left, and
• 39:13
  Speaker 1: I'm very sad about that because it's such a fantastic
• 39:16
  Speaker 1: conversation if you want to just use this opportunity to
• 39:20
  Speaker 1: very quickly refer to your bispecific CARTI GPRC five, DBCMA
• 39:26
  Speaker 1: and also mono if you want to call it that
• 39:29
  Speaker 1: in my loma, just to touch on where you think
• 39:31
  Speaker 1: you are with that and lead us into immunology. Of course,
• 39:34
  Speaker 1: what you can do here is moving on to C
• 39:36
  Speaker 1: the nineteen carties is to downregulate or remove or reduce
• 39:41
  Speaker 1: B cells and.
• 39:42
  Speaker 2: All the diseases that be sell diseases.
• 39:45
  Speaker 1: Or too immune diseases, and then lead us into in vivo,
• 39:48
  Speaker 1: which seems to me there's going to be the more
• 39:51
  Speaker 1: patient friendly approach in terms of time and preparations. And
• 39:56
  Speaker 1: of course you're doing an RNA based CARTI, which to
• 39:59
  Speaker 1: me allows the ship for retreating if you need to retreat.
• 40:02
  Speaker 2: Could you just talk through us and get us to
• 40:04
  Speaker 2: the end of the minology.
• 40:05
  Speaker 3: Here, please, Actually, again, you've fram very very well. It's
• 40:08
  Speaker 3: let me start with ematology, because I think inematology is
• 40:12
  Speaker 3: very clear. How powerful is a cart is the real
• 40:16
  Speaker 3: problem some inematology that this supply cannot fulfill the demand,
• 40:22
  Speaker 3: and then the scalability of autologus cart is still remain limited.
• 40:28
  Speaker 3: You know there are yeah, just only twenty percent or
• 40:33
  Speaker 3: so a patient that could receive a cartie that actually
• 40:36
  Speaker 3: receiving it out of all the eligible patients. So autologus
• 40:42
  Speaker 3: is working very well madrast some limitation. Despite that, we
• 40:47
  Speaker 3: are full invested in an autologus carti is because we
• 40:50
  Speaker 3: believe in ematologies. This is one other treatment option that
• 40:55
  Speaker 3: the patient should have. I'm excited about our gprc id
• 41:00
  Speaker 3: car tis called Arlo cell I mentioned before, because you
• 41:03
  Speaker 3: know a lot of patients are receiving b CM directed
• 41:08
  Speaker 3: therapist by specifics or carti is, and I think there
• 41:12
  Speaker 3: is a need for the patients that are progressing or
• 41:15
  Speaker 3: something else. I think this drug that can fulfill that need.
• 41:19
  Speaker 3: And then we need to see because gp GPRC five
• 41:22
  Speaker 3: d is a target that is expressed in a multiple
• 41:25
  Speaker 3: my looma upfront, so maybe this can be beneficial also
• 41:30
  Speaker 3: in patients are naive from BCM therapists. This is the
• 41:34
  Speaker 3: reason why beyond ourlow cells inematology, we have a dual
• 41:39
  Speaker 3: card that is a gp GPRC five d and BCMA
• 41:43
  Speaker 3: in the same product. Is an early product, is a
• 41:46
  Speaker 3: product that is the beginning of the development, but I
• 41:49
  Speaker 3: believe can be very interesting to see the level of
• 41:52
  Speaker 3: activity and safety of course versus b CM or five
• 41:56
  Speaker 3: D drugs. So this is the plan in amatoology and
• 42:00
  Speaker 3: you see you put together this in maloma with our
• 42:03
  Speaker 3: sell modes is give you the view our committed we
• 42:07
  Speaker 3: are to this disease. As you said, where I think
• 42:11
  Speaker 3: cardies that can make a huge difference is not only
• 42:13
  Speaker 3: in ematology and maybe in solitumor is still at the beginning.
• 42:17
  Speaker 3: We are at the beginning of the journey. But where
• 42:19
  Speaker 3: they can be very powerful is in out immune diseases.
• 42:24
  Speaker 3: In our commune diseases, you have clearly setting where if
• 42:29
  Speaker 3: you're able to reset the B cells you can really
• 42:33
  Speaker 3: bring benefit to patients because especially patients with more advanced disease,
• 42:40
  Speaker 3: this can be incredibly powerful. Our front running, front running
• 42:45
  Speaker 3: approach is with as you mentioned a CD nineteen CARTI.
• 42:49
  Speaker 3: It's called zola cell is an Autologus product and we
• 42:54
  Speaker 3: presented multiple data sets. This drug is very powerful. You
• 42:58
  Speaker 3: know these a young patients with the severe loopus or
• 43:04
  Speaker 3: other out immune diseases. After receiving one injection one infusion
• 43:10
  Speaker 3: of these product is discard. They have a completer emissions.
• 43:14
  Speaker 3: They stay out of steroids for many, many months, some
• 43:18
  Speaker 3: of them still do not relapse. So I think I
• 43:21
  Speaker 3: think it's very exciting to see the potential of this
• 43:24
  Speaker 3: approach because we believe this is our focus in immunology.
• 43:27
  Speaker 3: We want to focus in an immune reset because imagine
• 43:31
  Speaker 3: if now we have not only a tologus, now we
• 43:34
  Speaker 3: can provide to patients and off the shelf carty anaalogenic
• 43:39
  Speaker 3: oh as you mentioned, an in vivo where you just
• 43:42
  Speaker 3: deliver the drug and then these cells are manufactured by
• 43:47
  Speaker 3: the patient himself self. This becoming much more scalable, becoming
• 43:52
  Speaker 3: much more democratic, quote unquote, and you can touch many
• 43:57
  Speaker 3: more patients orfully with a level of safety that is
• 44:02
  Speaker 3: needed in this space. This is why as a company,
• 44:05
  Speaker 3: we have that focus. So we don't want to miss
• 44:08
  Speaker 3: any opportunity in the MUROS space because we believe that
• 44:13
  Speaker 3: cell therapy will be able to change the outcome of
• 44:17
  Speaker 3: some patients without immune diseases. Now we are testing in
• 44:20
  Speaker 3: later stages. I imagine if we can deliver these treatments
• 44:24
  Speaker 3: in patients before the organs are damaged kidney liver, so
• 44:29
  Speaker 3: this can really be transformative in a disease like yeah, Loopus,
• 44:34
  Speaker 3: scleroderma and many otherusietis and many others. So what we're
• 44:40
  Speaker 3: doing now we are in the water stage with dolar
• 44:43
  Speaker 3: cell in Loopus and scleroderma. We are in clinic with
• 44:47
  Speaker 3: an allogenic product, and we are entering clinic with our
• 44:51
  Speaker 3: indivo carti is called OxT to zero one is as
• 44:56
  Speaker 3: you mentioned, an RNA based platform that is appealing because
• 45:02
  Speaker 3: you don't deliver the in vivo or cells through viral.
• 45:09
  Speaker 3: That can give you a little bit less less concern
• 45:12
  Speaker 3: on a long term safety because in lengthy virus can
• 45:15
  Speaker 3: integrated with the gena the patients. So you know, we
• 45:18
  Speaker 3: don't know long term and safety an it should be
• 45:21
  Speaker 3: probably more predictable, but we need to see of course
• 45:25
  Speaker 3: the longer term follow ups. But this is exciting because
• 45:28
  Speaker 3: of course this is a platform will allow us to
• 45:31
  Speaker 3: enter out immune diseases. My inmaiview can be used also
• 45:35
  Speaker 3: side out immune because potentially can we can use this
• 45:38
  Speaker 3: platform two for products and then maybe we want to
• 45:41
  Speaker 3: bring in ematology.
• 45:42
  Speaker 1: Yep, since some data recently from me in vivo that's
• 45:45
  Speaker 1: beginning to show more of the progress.
• 45:47
  Speaker 2: Of course, those are most of the lent cell plenty viralty.
• 45:52
  Speaker 1: Now again, in the interest of time, I'm going to
• 45:54
  Speaker 1: skip for no other reason apart from the time that
• 45:57
  Speaker 1: we have on cardi basket or mill Vaccin obviously is
• 45:59
  Speaker 1: a key ass here, which and MAB Camptain and we
• 46:04
  Speaker 1: maybe next time we can start with cardiovascuer so we
• 46:07
  Speaker 1: don't lose opportunity neuroscience.
• 46:10
  Speaker 2: There's a reason I want to jump to neuroscience.
• 46:12
  Speaker 1: I'm a neuroscientist by background years ago, so it's been
• 46:15
  Speaker 1: a passion that I can't ever shake off. So you
• 46:19
  Speaker 1: have a lot of assets going on here, both treating
• 46:21
  Speaker 1: the aspects of Alzhemer's for example, agitation or you know,
• 46:27
  Speaker 1: and if Crystal Eyes has been in the space before
• 46:30
  Speaker 1: and now then you did the Krona acquisition, which of
• 46:32
  Speaker 1: course brought in an asset that's got multiple opportunities. Talk
• 46:37
  Speaker 1: to us about the broad division for neuroscience here and
• 46:40
  Speaker 1: why is neuroscience exciting today? Just explained to the audience
• 46:44
  Speaker 1: why it's exciting today and why I'm super excited to
• 46:48
  Speaker 1: be able to be still watching this space grow.
• 46:51
  Speaker 3: I started when we discussing at the beginning the American need,
• 46:57
  Speaker 3: you know, the American need is so important is becoming
• 47:01
  Speaker 3: a huge, huge, huge need that we are having in
• 47:07
  Speaker 3: front of us as people working in the healthcare and
• 47:13
  Speaker 3: in the life science space, independently if we are in academia,
• 47:19
  Speaker 3: in industry, wherever we are. Because my view neuroscience is
• 47:28
  Speaker 3: what it was oncology twenty years ago. You know, there
• 47:32
  Speaker 3: is one important aspect that I am very excited. This
• 47:37
  Speaker 3: is one of the reason be a Mess decided to
• 47:39
  Speaker 3: come back in euroscience. We know better at the biology.
• 47:43
  Speaker 3: We know beat at the biology of most multiple diseases.
• 47:47
  Speaker 3: Compare a few years ago. We understand why what is
• 47:51
  Speaker 3: driving Alzheimer's disease, We start to understand or other neuodogenerative diseases,
• 47:58
  Speaker 3: and we have none now a better understanding how to
• 48:03
  Speaker 3: monitor and diagnose patients with these diseases, because if you
• 48:07
  Speaker 3: think through a plasma test test in TAO or other biomarkers,
• 48:13
  Speaker 3: you can know if a patients as al Zheimer even
• 48:17
  Speaker 3: before the patients start to develop symptoms. Then the problem
• 48:21
  Speaker 3: some is becoming we don't have anything to offer to
• 48:24
  Speaker 3: these patients, you know, we don't have treatments. And neuroscience
• 48:27
  Speaker 3: is specifically and neur generation has been a very difficult
• 48:31
  Speaker 3: space in a drug development for multiple reasons. First of all,
• 48:36
  Speaker 3: because the biology was not clear, and when you don't
• 48:38
  Speaker 3: know well the biology you can engineer the right drugs
• 48:42
  Speaker 3: Now is better and we start to have also more biomarkers. Second,
• 48:47
  Speaker 3: because the end points are a little bit less established
• 48:51
  Speaker 3: than end points that we're using in other diseases, in
• 48:55
  Speaker 3: other thiases like oncology for instance. But again and we
• 49:00
  Speaker 3: are now consolidated that knowledge and try to work toward that.
• 49:05
  Speaker 3: So there are multiple reasons why we need to see
• 49:09
  Speaker 3: this with optimism. We are at a turning point in
• 49:13
  Speaker 3: my view, and I think the effort is to bring
• 49:18
  Speaker 3: more options to these patients. Our commitments start with alzeimer
• 49:22
  Speaker 3: We have you know, in Alzheimer's disease, you can treat
• 49:26
  Speaker 3: symptoms if the unfortunately the patient has already in an
• 49:30
  Speaker 3: advanced stage start and in a symptomatic stage. And currently
• 49:35
  Speaker 3: we have our carrect that is a multiple devotal studies
• 49:40
  Speaker 3: to try to treat symptoms specifically. The drug seems to
• 49:45
  Speaker 3: work very well, example in schizophrenia, in productive symptoms like hallucination, delusions,
• 49:52
  Speaker 3: symptoms that are linked more to psychotic behaviors and the
• 49:58
  Speaker 3: character can be beneficial to this pasion, and this is
• 50:01
  Speaker 3: what we are testing now in multiple phase three. There
• 50:04
  Speaker 3: is a taxty is a direct agonist of the muscarinic
• 50:08
  Speaker 3: receptor one and four and is a novel mechanism that
• 50:12
  Speaker 3: currently is not being tested in used in some of
• 50:15
  Speaker 3: these diseases and dementia, specifically in alzhymer in patient with
• 50:19
  Speaker 3: psychotic events. But beyond that, of course, the focus, the
• 50:24
  Speaker 3: short mid term focus is very much on this product.
• 50:27
  Speaker 3: But we have a substrate in Alzeymer because we have
• 50:32
  Speaker 3: another drug called ira funderstata that is a fanmaggle drug
• 50:38
  Speaker 3: that also can work in agitation in patient with alzeimer
• 50:42
  Speaker 3: and agitation is a drug that is exploiting a different
• 50:47
  Speaker 3: path more related to androphine path and neto transmission, and
• 50:53
  Speaker 3: this can be helpful or fully in patient with alzheimer
• 50:57
  Speaker 3: dimension and agitation. This drug is in FACE two hopefully
• 51:01
  Speaker 3: well will be another drug that we will be able
• 51:03
  Speaker 3: to bring to patients. But what I'm also very exciting
• 51:06
  Speaker 3: is that with the disease modifier, the drag I mentioned
• 51:09
  Speaker 3: so far and more on the symptoms, we want to
• 51:12
  Speaker 3: really change the outcome of the disease and what we
• 51:15
  Speaker 3: want to do is bringing drugs that can target the
• 51:21
  Speaker 3: reason why enzyme is happening. There are some good example
• 51:25
  Speaker 3: of a drug working on amyloid that are currently approved.
• 51:29
  Speaker 3: The patient can use them. Our approach is on antibody
• 51:34
  Speaker 3: anti tao. Tao is a clear driver in the exopathogenesis
• 51:40
  Speaker 3: of this disease and we believe that by clearing TAO
• 51:45
  Speaker 3: this can potentially bring benefit to patients. So we have
• 51:49
  Speaker 3: an anti micro turble binding region. Anti tao is an
• 51:54
  Speaker 3: antibody in phase two the study is completing. We are
• 51:58
  Speaker 3: within the results. Of course, is not only being able
• 52:01
  Speaker 3: and demonstrated that there is a clearance and must see
• 52:03
  Speaker 3: also the clinical outcome in the patients. We have a
• 52:06
  Speaker 3: fast trug designation for this drug by FDA, so I'm
• 52:10
  Speaker 3: excited and hopefully we will be able to continue the
• 52:13
  Speaker 3: development is drug beyond that. Of course, we have an
• 52:17
  Speaker 3: early pipeline because you know, some of the real problem
• 52:20
  Speaker 3: in this space is delivering drugs that can go into
• 52:24
  Speaker 3: the brain at a dose and with an exposure that
• 52:28
  Speaker 3: allow you to therapeutic WINDO or the therapeutic index that
• 52:32
  Speaker 3: you need maintaining of course safety profile systemically that is acceptable.
• 52:38
  Speaker 3: There is a new technology that called the brain shuttles
• 52:41
  Speaker 3: that allow to do that because you use fundamentally the
• 52:45
  Speaker 3: same molecules, but you have a way to let them
• 52:49
  Speaker 3: go into the brain in a more efficient way. We
• 52:51
  Speaker 3: add higher dose. These allow you to have higher concentration
• 52:55
  Speaker 3: in the brain less systemic exposure, your therapeutic window, your
• 52:58
  Speaker 3: therapeutic index is high. So this is in my view,
• 53:02
  Speaker 3: probably the next steps where the future development will mainly
• 53:07
  Speaker 3: rely in this.
• 53:08
  Speaker 1: In this space, great we obviously have TAO has always
• 53:13
  Speaker 1: been probably my more favorite target than favored target than
• 53:18
  Speaker 1: amyloid and and app and the etcetera. So, and we've
• 53:24
  Speaker 1: got some data coming up in a couple of weeks
• 53:26
  Speaker 1: at the conference in London from a tow targeting anti sence.
• 53:31
  Speaker 2: Now let's spend a bit of time.
• 53:33
  Speaker 3: I'm gonna be there. I'm gonna be there watching it.
• 53:35
  Speaker 2: You are okay, well, I mean London too. If you
• 53:39
  Speaker 2: wanted to meet up the AI. Now you've promised me
• 53:44
  Speaker 2: to give me.
• 53:44
  Speaker 1: You promised to give me a little bit more meat
• 53:46
  Speaker 1: on the bone on the value of AI to Bristol
• 53:51
  Speaker 1: in terms of how you're I know, we're like five
• 53:55
  Speaker 1: minutes left, but if you could squeeze it into the
• 53:58
  Speaker 1: five minutes.
• 53:59
  Speaker 2: I mean you can go to little bit over if
• 54:00
  Speaker 2: you if you if you.
• 54:01
  Speaker 3: Have I because as you said, the next time we
• 54:04
  Speaker 3: need to talk about our cardeology portfolio, our committement in cardiology,
• 54:09
  Speaker 3: our committement in pulmary fibrosis. We have a very important
• 54:13
  Speaker 3: novel mechanisms drug there with Ami Paranta that are reading
• 54:17
  Speaker 3: out as soon, so we are very excited. These are
• 54:19
  Speaker 3: two important areas in where BMS is a huge focus
• 54:24
  Speaker 3: in anti trombosis and primary fibrosis. With the next redoubts,
• 54:29
  Speaker 3: so next time we can discuss this AI. AI is
• 54:34
  Speaker 3: very very important for the reasons that I mentioned you
• 54:37
  Speaker 3: before in regards to the inefficiency of drug development, and
• 54:43
  Speaker 3: now we can we need that. We must change that narrative,
• 54:47
  Speaker 3: you know, and we cannot change the drug development narrative
• 54:50
  Speaker 3: unless we do things differently, you know. I am in
• 54:54
  Speaker 3: this in this business. We developer fundamentally. In the last
• 54:57
  Speaker 3: two decades, the development has been very similar, you know,
• 55:01
  Speaker 3: similar similar way phase one, sometimes from phase one to
• 55:06
  Speaker 3: phase three, phase two. In some thas you need a
• 55:10
  Speaker 3: phase two and then the phase three larger phase three failure. Okay,
• 55:14
  Speaker 3: we need different. AI is the opportunity AI like to
• 55:20
  Speaker 3: because I don't think there is one solution for everything, okay,
• 55:25
  Speaker 3: and I want to focus probably on the development because
• 55:27
  Speaker 3: we can speak about researcher. We don't have time about that.
• 55:30
  Speaker 3: I see more tangible advancement of what AI can bring
• 55:35
  Speaker 3: in research already.
• 55:36
  Speaker 2: Today.
• 55:37
  Speaker 3: Let's talk about development. The development. To me, you need
• 55:41
  Speaker 3: to break it down in three main pillar. Our I
• 55:45
  Speaker 3: allow you to lower costs and have smarter investments. I
• 55:50
  Speaker 3: think this is probably the today play. We have a
• 55:55
  Speaker 3: clear example on which we are using optimizer. Cost of optimizer,
• 56:01
  Speaker 3: we have a Ynova tool that allows us to optimize
• 56:04
  Speaker 3: the cost of our trial through an AI platform, and
• 56:08
  Speaker 3: this really allow you to already shave a lot of
• 56:13
  Speaker 3: cost upfront from EU clinical trials. We have designers AI
• 56:19
  Speaker 3: based that give you ready solution to set up an
• 56:23
  Speaker 3: accelerated the startup of the trial. We have a tool
• 56:27
  Speaker 3: called navacs that are processing safety cases. You know we
• 56:30
  Speaker 3: are processing four hundred thousand cases every year safety on
• 56:35
  Speaker 3: our drug commercially and in development. And this is a
• 56:39
  Speaker 3: tool increase twenty five percent of our productivity because if
• 56:44
  Speaker 3: we save twenty minutes for each case and is incredibly accurate.
• 56:49
  Speaker 3: So imagine how much time and money we save just
• 56:53
  Speaker 3: this tool. This is a concrete examples our AI can
• 56:56
  Speaker 3: lower cost and optimize your investment. There is another aspect
• 57:01
  Speaker 3: wherever AI is already starting to deliver some benefits and
• 57:05
  Speaker 3: is in timelines. Our ambition, my ambition is to shorten
• 57:10
  Speaker 3: the development timelines from fasting to human to approval by
• 57:14
  Speaker 3: thirty percent. And you need to do these through smarter
• 57:18
  Speaker 3: investments without okay, jeopardizing quality or what you do, because
• 57:23
  Speaker 3: this is not going fast without quality is not a
• 57:26
  Speaker 3: way you need to go faster. I need to preserve
• 57:28
  Speaker 3: the quality. We have the tools now that allow us
• 57:32
  Speaker 3: to optimize the trial request is a tool called Faroh
• 57:37
  Speaker 3: that is fundamentally already giving us twenty nine percent reduction
• 57:43
  Speaker 3: in protocol complexity. And when the protocol is as complex
• 57:47
  Speaker 3: also the way the burden to the patient, the burden
• 57:50
  Speaker 3: to the sites, and the cost savings are there. And
• 57:53
  Speaker 3: when you have this kind of approach you can start
• 57:57
  Speaker 3: the study, you can run the study faster. This is
• 58:00
  Speaker 3: one example. Another example is in submission. We have a
• 58:03
  Speaker 3: tool called called Velocity in which this tool allows us
• 58:07
  Speaker 3: to reduce submission cycle times multiple weeks. Imagine that if
• 58:12
  Speaker 3: instead of twelve weeks from a submission from data redout
• 58:16
  Speaker 3: to submission, you take six weeks or nine weeks. Imagine
• 58:20
  Speaker 3: how many multiply for all your trials, your pivuter trials,
• 58:23
  Speaker 3: you go much faster into submission. These are concrete examples
• 58:28
  Speaker 3: how we start to have tools that can speed up
• 58:31
  Speaker 3: our timelines. The real game changer anyway, is increasing the
• 58:36
  Speaker 3: probability of technical success, the predictability there. I think we
• 58:41
  Speaker 3: are still not completely there. I am happy the progress
• 58:45
  Speaker 3: that we have done there because, for instance, I have
• 58:48
  Speaker 3: a model informed drug development tool that give us more
• 58:53
  Speaker 3: confidence on the registration and studies that we're running. We
• 58:59
  Speaker 3: are using digital twins and this biasian generative model fundamentally
• 59:06
  Speaker 3: to predict the outcome of the trial before running the trial,
• 59:11
  Speaker 3: integrating data multiple data sets internal and external, and by
• 59:17
  Speaker 3: generating yeah, digital to patient digital twins and so you
• 59:21
  Speaker 3: can start to understand, okay, based on this population the
• 59:24
  Speaker 3: outcome should do that one. This is increasing your accuracy
• 59:28
  Speaker 3: or prediction on how the study can read out. Bring
• 59:32
  Speaker 3: us from a probability technical successor that is approximately around
• 59:38
  Speaker 3: sixty five percent maybe to seventy seventy five percent. The
• 59:41
  Speaker 3: question is when we will be able to reach ninety
• 59:44
  Speaker 3: ninety five percent. When every phase tree study we readout positive,
• 59:49
  Speaker 3: you know this is the should be the ambition sun
• 59:53
  Speaker 3: because I think technology will ultimately help us to reach
• 59:58
  Speaker 3: that ambition. Nobody is there. This requires a lot of
• 1:00:02
  Speaker 3: models that integrate multiple data sets, data sets that are
• 1:00:07
  Speaker 3: not only clinical, but also a mixer and geo mixer
• 1:00:12
  Speaker 3: that able to predict the outcome of a drug in
• 1:00:17
  Speaker 3: a certain patient population with an accuracy that today is
• 1:00:20
  Speaker 3: not simply possible. This is our AI will help us,
• 1:00:24
  Speaker 3: and I don't think without this we will be able
• 1:00:27
  Speaker 3: to continue to develop drugs because the costs are too
• 1:00:30
  Speaker 3: I and the time and the and the duration is
• 1:00:32
  Speaker 3: too long. So all our industry is under pressure with pricing,
• 1:00:37
  Speaker 3: with a lot of some headwinds. So we need to
• 1:00:41
  Speaker 3: be more efficient, faster and increase the productivity in R
• 1:00:46
  Speaker 3: and D and the true AI. I'm optimistic we will
• 1:00:50
  Speaker 3: do that. We need to be.
• 1:00:51
  Speaker 1: Fast absolutely, last question, it's going to be very quick.
• 1:00:54
  Speaker 1: A lot of this return is down the road.
• 1:00:57
  Speaker 2: Cost is today.
• 1:01:00
  Speaker 1: I'm assuming that's something that Bristol has accepted as the
• 1:01:04
  Speaker 1: cost of doing business. Is that right?
• 1:01:06
  Speaker 3: So, Sam, thank you for this question. You cannot imagine
• 1:01:10
  Speaker 3: how many times I received the question. This is the
• 1:01:14
  Speaker 3: key effort that we are putting in place, for instance,
• 1:01:17
  Speaker 3: a BM MESS because we are investing very heavily on
• 1:01:21
  Speaker 3: this space. But as I mentioned before, we already are
• 1:01:24
  Speaker 3: able to measure some of the return or these investments.
• 1:01:28
  Speaker 3: Some of the tools I mentioned before are ready generating
• 1:01:31
  Speaker 3: cost savings. We can already have millions of dollars in
• 1:01:37
  Speaker 3: savings in efficiency that we do. The real question is coming.
• 1:01:41
  Speaker 3: How do we measure how we were able to capture
• 1:01:44
  Speaker 3: when we will have when we will go into the
• 1:01:46
  Speaker 3: next the next generation of integration of a I into
• 1:01:52
  Speaker 3: the way of working, for instance, when we will have
• 1:01:54
  Speaker 3: a layer of agents integrating with our teams. How these
• 1:01:59
  Speaker 3: can be measured also financially. This is something that still
• 1:02:03
  Speaker 3: is under work. But I believe that deficiency that you
• 1:02:09
  Speaker 3: can generate and the accuracy that you can get through
• 1:02:13
  Speaker 3: this tool ultimate that it will be worthing the investment
• 1:02:16
  Speaker 3: we are doing today. But it's something that we need
• 1:02:20
  Speaker 3: to continue to monitor very carefully.
• 1:02:22
  Speaker 2: That's Christian message.
• 1:02:23
  Speaker 1: Zy Cmo of Bristol Myers, thank you so much for
• 1:02:26
  Speaker 1: joining us for our last latest episode. Please don't forget
• 1:02:30
  Speaker 1: to give us a review and make sure to click
• 1:02:33
  Speaker 1: the follow button on your favorite podcast app or site
• 1:02:36
  Speaker 1: so you never miss a discussion with the leaders in
• 1:02:39
  Speaker 1: healthcare innovation. And we certainly had a fantastic conversation here.
• 1:02:43
  Speaker 1: I'm san Fazeli and you've been listening to The Vantguards
• 1:02:45
  Speaker 1: of Healthcare podcast by Bloomberg Intelligence. Until next time, take.
• 1:02:49
  Speaker 4: Caress as bases uses bases