The following is excerpted from the question-and-answer section of the transcript.
(Questions from industry analysts are provided in full, but answers are omitted - download the transcript to see the full question-and-answer session)
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: <_ALACRA_META_ABSTRACT>So maybe, Samit, just to start big picture rather than diving right into some competitive data. Let's start with six months ago, we
saw Bristol stock at $40 a share, sentiment uniquely cautious. And while the threat of generics is unchanged, shares are now trading
at $55. From your position in R&D, obviously, what's changed?
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
I think those shares might be a little bit different right now.
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Great. And Robert, maybe you can just chime in on the sort of the focusing of the portfolio and working with Samit to really kind of
streamline the portfolio.
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Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Great. And there's I guess, risk profile in drug development and kind of the consideration of competitive assets. We just got competitive
data this morning. What -- in terms of your sort of team development approach drew you to COBENFY and what sort of maintains
and sustains your excitement for that program and that product as we enter the sort of full launch in 2025 and advancing from there.
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Right. And when we just sort of think about the big opportunities incremental to schizophrenia, obviously, the things that come to
mind are always bipolar depression sort of first and foremost as a major driver of commercial uptake and commercial opportunity.
But Alzheimer's agitation is also seeing a resurgence. Maybe talk a little bit about the profile that you think COBENFY offers in
Alzheimer's agitation in particular? And then what's the hope for this mechanism in bipolar depression potentially? (multiple speakers)
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
It's Bipolar Mania -- . Because -- .
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Okay. And then for one of the critiques of COBENFY has been, one, tolerability is sort of one critique. But maybe the bigger one that
some physicians we've talked to have sort of critiqued as the twice-daily profile and the challenge of treating a schizophrenia patient
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Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Great. Robert, you mentioned Milvexian. We got some updates on the third quarter results conference call. Maybe you could just
walk us through some of those updates, but also a little bit of the battle that you've actually had to fight in the wake of another
competitive failure.
I mean I would also argue like thankfully, this other -- maybe the trial hadn't failed of your own Phase 3 clinical program. As it relates
to COBENFY. But the Asundexian situation from buyer really put -- was a headwind for the Milvexian program. Maybe tell us how
you feel about it today.
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: And your confidence and conviction that the result is just like clearly is not an asundexian result seems extremely high at this point.
Can you just remind us why it's so high?
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Question: Seamus Fernandez - Guggenheim Partners - Analyst
: And in previous conversations, you mentioned, it is important to keep in mind this is a non-inferiority trial design. Can you just help
everybody understand why it's okay in a non-inferiority trial design to increase the size of a study and not be concerned?
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
Yes. So non-inferiority really means that both your drugs will be similar in terms of the efficacy, but our hope over here is that from
a safety perspective, this will have a better profile. Now as we think about the event rate, as we said, we were hoping for 1.33. Right
now, we're running behind. There are only two ways to keep watching it now, either you just wait for events to happen, but then it
will read out much later or you can increase the sample size, so you can accumulate more events.
So we wanted to keep the '27 time line in hand. The reason for doing that is we wanted to have the three studies read out in close
proximity to each other. And the other two are running as planned, and they should read out in 2026.
So getting SSP, ACS in 2016 and AFN '27 gives us that ability to bring all of this together. And we've always talked about in the era
of IRA, it is going to be important to have the maximization of that commercial potential starting right at the beginning that you're
not losing at the back end from an ROI perspective.
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: It seems pretty high impact would be an ability to just sort of sustainably reduce or even eliminate prednisone, oral prednisone,
things like that.
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Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Great. In terms of sort of other assets, there's a lot going on at Bristol. Maybe we can sort of take a quick step back and go through
-- Samit, I went through this earlier, so we can go through -- the family tree of assets that are coming. But if you wouldn't mind,
maybe walk us through the assets that are most important, and then it'll will give us an opportunity to walk through LPA1.
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
Yes, absolutely. So maybe I'll change my family tree a little bit because the big brother I said was milvexian, but today morning, I
think it's Milvexian is now Twin Brothers with COBENFY, which is already there. And both of them are going to be very critical. And
I think the way to think about it is for COBENFY, there is pretty much a readout for an indication every year until the end of the
decade. So next year, we're looking at ARISE. The year after that would be ADAPT. The year after that could be agitation. The year
after that could be bipolar, the year after that could be cognition, the year after that autism.
And of course, in between whatever else might come because even in AD psychosis, there are two indications. There is the acute
and then there's a relapse prevention, for example. Both studies are ongoing right now. If you think about Milvexian, we've talked
about in '26, two studies read out, '27, third study reads out. This year itself for (inaudible), you have the readout of psoriatic arthritis,
2 studies before the end of the year. And then in '26 will be SLE and '27 will be Sj÷gren's.
If you think about Camzyos, next year, first half, non-obstructive hypertrophic cardiomyopathy. And then we have Reblozyl reading
out next year for myelofibrosis, the independent study, and then there will be a lot of the Phase 1 data that comes out. '26 is a big
year. '26, we'll have the radioligand therapy first Phase 3 study that should read out. GPRC5D, multiple myeloma study should read
out. Iberdomide, one study should read out. Mezigdomide, at least one of the studies should read out for multiple myeloma.
SLE, I've already talked about, what else am I missing out? (inaudible). (inaudible) is late though. [Vketamide] would be late because
that's first-line diffuse large B-cell lymphoma. And then once we start the other studies, then it will add on. So early pipeline will start
a lot of studies next year as well. PRMT5 will go into Phase 2 studies that could lead to regulatory discussions as to how to conduct
these studies. EGFR and HER3, ADC starts Phase 3 studies next year. So that will start to contribute towards the back end of the
decade.
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Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Maybe an unfair question. --
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
And by the way, CD19 CAR-T for SLE. (multiple speakers)
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: So let's maybe move back to immunology. There were some programs that you didn't mention in immunology that I think are worth
talking about. You have a positive cendakimab result. It was just presented at a recent meeting in [EoE]. Maybe just give us your
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Question: Seamus Fernandez - Guggenheim Partners - Analyst
: It's an unfair question because we're not talking about commercial, but the clinical commercial.
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
No, I think the way to think about it, we presented the data, as you said, the trial did meet its endpoint. And we now -- the discussions
that we are having is putting in the context of what is the incumbent right there. And it's a very strong incumbent that's out there.
So we'll have to put all of that in that framework as we think about conversations on regulatory path and moving forward. I don't
have an answer for you as to what the time lines are and how it looks. But those are the discussions that we truly have to have on
the table. And that's why we have to keep in mind the commercial opportunity, what it truly is and then make the decisions on the
time lines and what the next steps would be.
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Multiple Myeloma, the level of expertise there is obvious, unquestionable. The dynamics in the market in Multiple Myeloma, I think
are interesting. But when you look at the pipeline, Robert was talking about segmentation. How important is segmentation going
forward in Multiple Myeloma and how is Bristol approaching it?
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
Yes. I think it's a natural segmentation because of the modalities and because of the need. As things start to become used earlier
and earlier, unfortunately, because the disease is not being cured, you're accumulating the prevalence population as you go later
and later. So as we think about, we just saw the data of CD38 getting into a newly diagnosed patient population.
So what happens as we look to the future as cell therapies like [BCMA] or CAR T or move earlier, what happens after that, as T-cell
engagers move earlier what happens after that. And I think we're only talking about biologics right now, but small molecules will
have their own space. because combinations are just easier with the small molecules, hard to combine CAR T with something, hard
to combine T cell engages for their profile with something right now.
So we'll have to continue to find what is the best way to continue to provide combination therapies for better outcomes from an
efficacy and tolerability for these patients. And that's why we've taken a multi-modality approach to it.
First, we have this small molecules. We were developing a bispecific or rather the -- yes, the T-cell engager aloptimab, which we took
away because we were not going to be first. In fact, we were going to be fourth or fifth. So we took that away. But we have the
broadest cell therapy approach to it. So [Beckman] was the first one. GPRC5D is the second one. And the third one is a dual card,
which is the BCMA and GPRC5D on the same car. So that's the third one.
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Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Right. And coming up, we've got ASH. It's right around the corner, it feels like, but it will still probably feel like it's decades away. --
Can you maybe just walk us through what's coming at ASH. Are you excited about anything that could be presented there?
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
With the portfolio that we have in hematology, we have to be excited, right? There's so much happening. And there will actually be
an encore, by the way, although it's not a rheumatology meeting, but there will be more data presented for the cell therapy CD19
in autoimmunity at ASH. But beyond that, I would say watch out for gold caramide data, further updates on the large B-cell lymphoma
as well as I think follicular lymphoma is there as well.
If you think about Mezigdomide, more data being presented over there, especially novel combinations. As we think about the
Mezigdomide cell therapy, cell therapy data should be the additional cell therapy data, including GPRC5D updated data that will be
presented over there. What am I missing?
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Okay. Great. Maybe go to some other assets, HFpEF, the EMBARK study, you mentioned the opportunity there. And I guess, with the
second-gen 224 asset. Can you just talk a little bit about what sort of separates the two? What you think is going to really differentiates
224 from CAMZYOS?
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Great. This is sort of like a random walk down Wall Street conversation on the very robust portfolio of choices that we have to go to.
But LPA1, we haven't talked about yet. Let's kind of go through the opportunity in IPF and PPF. As well as, again, what differentiates
your LPA1 program from some others that have been challenged separately?
Question: Seamus Fernandez - Guggenheim Partners - Analyst
: Great. So I think we only have two-minutes left, slightly wrong up there. But -- maybe just we -- I think we went through a little bit
of the family and the grandchildren as well. But if you were to just sort of say, okay, these are data sets that I'm particularly excited
to see in the next 12 to 18 months in the sort of Phase 2 plus time frame. What are you most focused on?
Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of
the Leadership Team
So I mentioned a lot of them in terms of the Phase 3's. So all of those are going to be important from a company perspective and
our own drug development progress and research perspective. Beyond that, so beyond the general ones that I've already spoken
about at Milvexian, GPRC5D, COBENFY and SLE. So all life cycle management in the Phase 3 program.
The ones to watch out also are going to be the anti-TAL molecule. It's in randomized Phase 2 study right now. That is '26 and '27
time frame and it's because it's a long follow-up that you need for these patients. So that's going to be important. Another drug that
we are taking into Phase 2 is [fine MAGLipase] inhibitor. Again, dual inhibitor, very there are lots of others who are doing it as singular
inhibitors. The dual inhibition approach that we are taking in Alzheimer's disease is going to be important. So watch out for that
again, '26, '27 time frame.
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Question: Seamus Fernandez - Guggenheim Partners - Analyst
: And I'll apologize to all the people who are looking for a laundry list of BD development targets from Bristol-Myers Squibb. I didn't
even get to that question because there's plenty going on. So thank you so much for joining us. Really thrilled to have both of you
here with us today. Samit and Robert, thanks for taking the time.
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