Merck & Co., Inc. (NYSE:MRK) 6th Annual Evercore ISI HealthCONx Conference Transcript November 30, 2023 1:20 PM ET
Executives
Dr. Eliav Barr – Senior Vice President, Head, Global Clinical Development and CMO
Peter Dannenbaum – Vice President, Investor Relations
Analysts
Umer Raffat – Evercore
Umer Raffat
Thank you. Listen, thank you guys for being here. Apologies. I’m a couple minutes behind. Pleasure to have Merck management join us. This is our last fireside of this conference, at least on my end.
Dr. Eliav Barr
Okay.
Question-and-Answer Session
Q – Umer Raffat
So really looking forward to it. Peter promised it’ll be action packed. And so let’s jump right into it. I think it’ll be a great idea. Maybe let me turn it over to you, Peter, and to kick things off, maybe frame for us what’s on top in terms of priority list on your mind and we’ll jump right in.
Peter Dannenbaum
Sure. This has been a tremendous year for Merck and we’re looking forward to 2024. The things that are top of mind for us is continued news on KEYTRUDA, especially in early-stage cancers. The — you’re going to see a large number of Phase III starts for all of our antibody drug conjugates that we have partnered with Kelun and with Daiichi Sankyo. A large number of efforts in precision medicine and oncology, as well as, of course, V116, the filing and then hopefully, if all goes well, the approval of that.
Sotatercept is should be commercial — entering the commercial space and we’re looking forward to seeing that. There may be additional data coming from the ongoing studies that are event driven, like the ZENITH study. And as we’ve talked about before, our PCS — oral PCSK9, MK-0616 has started Phase III programs, including our cardiovascular outcome trial.
We have Phase III start for MK-7240, formerly PRA023, our TL1A antagonist. And then, of course, continued work on MK-6024, which is our compound for NASH and it has some weight loss benefits as well. So a lot going on, a very diversified pipeline, a very busy year going forward.
Umer Raffat
Excellent. I know you mentioned KEYTRUDA and I want to go through each of those, but maybe just before we get into more product specific stuff.
Peter Dannenbaum
Sure.
Umer Raffat
Peter, can I just start by asking, I know there was a fair amount of confusion on it a few weeks ago around the margin profile, what Merck is saying, whether the commitment to the margin target stays fully intact. Could you just remind us on that?
Peter Dannenbaum
Yeah. No. Thank you, Umer. So from a margin standpoint, we continue to point to the achievement of additional margin expansion. We’ve been on quite a record of margin expansion over the last several years, including in 2023.
We expect further margin expansion in 2024 driven by product mix. So as KEYTRUDA and GARDASIL continue to grow strongly, as we expect, that’s a benefit. And we also have the roll off of some significant royalties, both for KEYTRUDA and GARDASIL. KEYTRUDA rolls down from 6.5% to 2.5% and — on global sales and GARDASIL, there’s a royalty that we paid a Glaxo that is now 7% that will roll down to zero. So we’ll benefit from that.
And we will continue to tightly manage SG&A, but making sure we invest in our growth drivers. R&D, we will continue to invest and we’ve expanded our pipeline pretty dramatically. So we’ll continue to ensure that we fund those programs. So you’ll see R&D continuing to increase. As we look out to 2025, we have had a target for 43% plus operating margins and we continue to believe we’ll achieve that.
What Caroline said, to the degree the pipeline continues to expand, we’re not going to forego necessary investments that would fully optimize those pipeline assets and lead to better long-term growth. But right now, as we stand, 43% plus is something that we would continue to point to.
Umer Raffat
Okay. Excellent. That’s very helpful. And maybe just one more as a quick follow-up on that. I know there’s KEYTRUDA growth, a fair amount of growth still modeled in. I think, Eliav, you mentioned about some of the additional indications coming online. There’s underlying momentum and next year launch is ongoing as well. If I look at consensus numbers, KEYTRUDA is being modeled in from — in going from about $25 billion to perhaps $35 billion over the next five years or so. I know you guys have clearly expressed enthusiasm on the momentum continuing. Could you just expand on expectations on KEYTRUDA, because that’s critical to some of the margin expansion as well, obviously?
Peter Dannenbaum
Yeah. So I’ll start from a commercial standpoint. Eliav, you have anything to add from a clinical perspective, feel free to. But we continue to expect strong growth of KEYTRUDA and we don’t give product-level guidance typically. But as I just suggested in your prior question, we do think that 2024 will be another year of strong growth for KEYTRUDA.
Albeit, I mean, we’ve had exceptional growth for KEYTRUDA over the last year or two years and the third quarter annualized run rate was $24 billion plus. So the types of percentage increases that we’ve seen in the last year or two are would be difficult to achieve. But I think consensus has already reflected that as they’ve modeled out 2024 and we think that’s appropriate.
Umer Raffat
Right. I think the point that was made previously was don’t expect 20% plus type of growth going forward. But conversely, wouldn’t EV-302 just create a very significant tailwind into next year, especially given the first-line, especially given the duration that we saw? There is a — it seems to me that there’s a realistic chance KEYTRUDA just vastly outperforms numbers into next year. It could actually approach meaningfully north of the types of 10% type numbers.
Dr. Eliav Barr
Well, it’s a great, the results speak for themselves. I think it’s outstanding results. And so, I really look forward to having those data come through and I think everyone that we’ve talked to, including the regulators, are very excited about the results. So I think that’s really great.
And KEYNOTE-671, KEYNOTE-564, those are two other ones that I think are really important. For the first time, there’s overall survival benefit for interventions in the perioperative stage state and they’re both with KEYTRUDA and they’re both only KEYTRUDA, not — no other of the IO compounds have been there. So I think that there’s some really exciting momentum from that, okay. He’s a commercial — probably, about the commercial stuff.
Peter Dannenbaum
I mean, I think, we are excited by KEYTRUDA’s move into earlier stage cancers, as Eliav suggests. So there’s a lot of opportunity for continued growth. We’ve pointed to early-stage representing over half of KEYTRUDA’s growth as we look out to 2025 and to represent 25% of global KEYTRUDA sales in that year. So the early-stage is important, certainly bladder, lung will become increasingly important as well. Some of the women’s cancers that Eliav mentioned as well.
Umer Raffat
Got it.
Peter Dannenbaum
Continue to be very confident with the growth of KEYTRUDA.
Umer Raffat
Makes sense. As I start to transition to pipeline, I thought maybe since we were talking about KEYTRUDA, let’s start with the oncology pipeline.
Peter Dannenbaum
Great.
Umer Raffat
There’s broad buckets. I think of it as IO-IO, where we could have new IO modalities, including the PCV, including TIGIT, we could have ADCs and then some small molecule efforts, unless I missed any other major chunk.
Peter Dannenbaum
That’s pretty good.
Umer Raffat
So on the IO-IO side, Peter would always tell you, TIGIT’s always on top of my mind. Is the Moderna cancer vaccine on top of Merck’s mind?
Peter Dannenbaum
I mean, look, we have a broad portfolio, each one of these is exciting and we’ve spent — we’ve invested quite a bit in it. The INT or V940, I think is a really big opportunity, because it’s very unique and it’s got the ability for long — for durable long-term drug-free effects.
So like every immunotherapy of its sort, the expectation here is that there’ll be benefits even after the medicine — the medical therapy is done and we’ll see how that goes. There’s going be further cuts of the data going forward for the study, the Phase II study in melanoma.
You’ve seen the melanoma Phase III program start. We’re going to have a heavy jump into lung coming up and there’ll be several other studies that will initiate in 2024. We have done a really nice job, Moderna has done a really nice job in building the capacity ready for clinical trials, so that’s really great.
TIGIT, there will be a presentation of KEYVIBE-002 in about a week at the ESMO IO Conference, which data is still embargoed until about 6 tonight and then you’ll be able to see what all the hoopla was about. So that’ll be exciting. And then, of course, the first-line lung and the adjuvant melanoma program continue apace. It’s just they’re big studies and they require both enrollment and follow-up, so.
Dr. Eliav Barr
Adjuvant melanoma, you’re talking about the PCV, right? Both, KEYVIBE-10, KEYVIBE.
Peter Dannenbaum
Oh! So you’re talking about…
Dr. Eliav Barr
Yeah.
Peter Dannenbaum
Yeah. So TIGIT, so — there –so with the PCV, with the INT compound, with the Phase III starts, Phase II should be in 2024 for TIGIT, KEYVIBE-002 will be presented in a week. The abstract should be viewable later on today and the Phase III program continues and we will — it’s just a matter of now enrollment and time. Protocol completion dates are late — or not next year, but the year to follow, but there’s interim analyses and we’ll have to see how that goes.
Umer Raffat
Got it. Okay.
Peter Dannenbaum
Yeah.
Umer Raffat
Anything notable on the KEYVIBE-002 we should keep in mind. It was a trial of triplet versus triplet PD-1 chemo TIGIT…
Peter Dannenbaum
Right.
Umer Raffat
… versus just PD-1, sorry, versus PD-1 plus TIGIT versus chemo. We know the doublet was dropped.
Peter Dannenbaum
Right.
Umer Raffat
We know the triplet was moved forward. Data’s tonight, you said exciting data, but also this is not a first-line trial, which is…
Peter Dannenbaum
It’s not.
Umer Raffat
Anything else notable we should just know about the trial design?
Peter Dannenbaum
Well, I think that the key there is to ask the question about, to try to figure out, are there ways to gain early looks at whether TIGIT added to a strong PD-1 has benefits? And there’s been — this study doesn’t directly look at that, because there’s no pembro-only arm, but at the same time, these are people who have all been experienced with — who’ve had PD-1s and we know what their objective response rates, which are usually single-digit to very low-teens.
And so I think it provides a piece of data. We’ve seen with the TIGIT compounds, however, and we have to acknowledge that there have been Phase II studies that have looked good and then there’s been Phase IIIs that have been more complex and so my — the way I see the compound is you will wait to see for Phase III and go from there.
We have a very robust program across the lung space, which is where we think this might be useful and melanoma. So I think that’s — those two sets of tumors are really important and have the best opportunity for showing incremental value that’s of sufficient size to be meaningful for patients.
Umer Raffat
Makes sense. Eliav also I think the other aspect of this TIGIT trial, which is particularly relevant is, so, A, you mentioned these are PD-1 experienced patients. The other dynamic is, they’re not selected for PD-L1 highs or lows. These are all comers.
Dr. Eliav Barr
Yeah.
Umer Raffat
Should we — again, there’s prior data from Roche focusing on PD-L1 super highs only. There’s other data sets suggesting the benefit did continue. There’s no reason why a TIGIT should work only in PD-L1 highs or lows.
Dr. Eliav Barr
No. I think you have to be careful about post hoc analysis. I don’t know what to make of — and small data sets as well. If you look at what we’re doing in our clinical trials program, we’re essentially following the paradigm of where pembro has been approved.
So pembro is approved as monotherapy in people with TPS greater than 1%, PD-L1 as monotherapy and so we have a trial of TIGIT plus pembro against pembro. The study is large enough to look at the greater than 1% and greater than 50% separately.
We have a study of pembro-TIGIT with chemo versus pembro with chemo. So the standard regimen against the standard regimen plus pembro and first-line non-small cell lung cancer. We’ve got a Stage 3 study, KEYVIBE-006 and then we’ve got studies in small cells. So we’ll see how that goes.
And then again, KEYVIBE-10 is a study in adjuvant melanoma in patients with Stage 2 and 3. Each of those studies is — every one of these studies is characterized by the fact that melanoma — that pembro is foundational for that tumor and that’s the — and so we’re just adding TIGIT on top of that.
Umer Raffat
Got it. One last, KEYVIBE-002, primary endpoint was PFS, not ORR and we should expect at the ESMO IO presentation both the ORR…
Dr. Eliav Barr
Have everything.
Umer Raffat
Have everything.
Dr. Eliav Barr
Yeah.
Umer Raffat
Okay. Got it.
Dr. Eliav Barr
And some OS data.
Umer Raffat
Got it. Excellent. Maybe perhaps starting to move on the Merck, sorry, on the Moderna PCV program, V940. One of the questions and I remember having some discussion with Peter on this too, there’s a presentation at ESMO which dug into data breakdown by BRAF mutation, BRAF-mutants are not wild type. And then further by, I forget now, it was the ctDNA status.
Dr. Eliav Barr
Yeah.
Umer Raffat
And it looked like the benefit was coming from one of the two subgroups and even within that subgroup in ctDNA. And I guess, I was just thinking out loud about how should we think about that, because there’s been always questions around how robust is the signal? It looks very good overall, but then the fact that it’s driven by one subgroup and not totality makes you wonder, could it be a false positive for it?
Dr. Eliav Barr
I don’t think so, because I think we have, like, everything with the small Phase II studies, confidence intervals are very large and then there’s things that are — that favor the…
Umer Raffat
You mean baseline?
Dr. Eliav Barr
Yeah. The baseline things that are favor the — in the subgroups. Among all the different parameters that might impact presence of ctDNA, different PD-L1 status, whatever, all these different things, there is imbalance between the groups as you would expect in a Phase II study that’s so small. But things that a priority you’d think would favor control versus favoring the combo, pretty much evenly distributed. It’s really hard to tell.
But like, it’s fair to say, Phase III is where we prove efficacy and we’re very excited about this. Obviously, we’ve invested quite a bit not just in clinical trials, but also in the setup for manufacturing and we think that notwithstanding some baseline imbalances that go, that favor one arm or the other, that the overall picture is one that’s very promising indeed.
Umer Raffat
Got it. Maybe, okay, anything else on IO-IO before we transition on?
Dr. Eliav Barr
I think it’s same.
Umer Raffat
Okay.
Dr. Eliav Barr
Yeah.
Umer Raffat
On…
Dr. Eliav Barr
ADCs?
Umer Raffat
On perhaps ADCs because there’s several things to go through there. Obviously, there’s the collaboration that was announced with Daiichi recently. One of the questions that came up was, what was the primary basis of that deal, because there were three programs that came in. My understanding is it was perhaps the B7-H3, which was really the impetus behind it. I don’t know to what extent that’s true, realizing that HER3 was more further along?
Dr. Eliav Barr
Well, I think, each one of these assets is really exciting and I think Caroline had said that, that she hopes that, we pay all the milestones so that we, so that because that would mean the best benefit for patients, everything will work out great.
So B7-H3 is exciting because of the small cell and some potential in prostate and there are other things, obviously, we’re just at the beginning of the investigation for that. We really — I really like the HER3 ADC, because I think that it has opportunities to both to be active in various forms of driver lung cancer sort of settings and here, I mean, things, we know that EGFR mutant, but we’re also looking at other driver mutations like KRAS and also interested in other cancers.
So I think that there’s a really nice opportunity with Patritumab that we were really looking at and during the due diligence we were really excited about that as well. CDH6, I think is topical because of today’s news about the ImmunoGen acquisition by AbbVie because it’s about ovarian cancer at present. The early data as presented look very, very promising indeed. It’s Phase I. So we’re just beginning the investigation there. But I do think that we have a strong history in ovarian cancer and a really great basis for and a set of trials that I think will serve us well to help position CDH6 as an essential medicine in that treatment.
Umer Raffat
So maybe working off of that CDH6 ADC, I realize the efficacy was clearly very intriguing. It also is clear that a couple of higher doses were dropped because of therapeutic index reasons. Do you think at doses that are realistically possible for an extended interval dosing, we have the right therapeutic index and we have encouraging efficacy at those doses, which are realistic?
Dr. Eliav Barr
Yes. Because the dosing starts — the activity starts at 4.8mpk and we’re going, I think 5.6mpk and 6.3mpk, I think, is those three arms. And one of the things that has been very useful in our collaboration is that, our colleagues in Daiichi have learned a lot about the therapeutic index and dose selection based on their first two ADCs and I think that they’re much more sophisticated in the modeling and the approach to choosing the sweet spot for the next three and I think we’re not going to have the kind of ILD issues that we see.
Of course, at higher doses with all of these drugs, you will reach a point where there’s toxicity. But what’s interesting about CDH6, as an example, is that the activity well below the ILD doses is pretty exceptional. So we’re thrilled about this. It’s — and by the way, the activity was in an unselected population. Don’t need to know about folate receptor alpha status. So I think it’s going to be a very key part of future therapies for ovarian cancer.
Umer Raffat
Got it. HER3 ADC, this was being filed in EGFR mutant lung cancer.
Dr. Eliav Barr
Correct.
Umer Raffat
If you and I spoke a few months ago, I would have said, oh, your TROP-2 ADC is going into that indication. I guess, how are you guys thinking about that or do you intend to have two different programs for EGFR mutants?
Dr. Eliav Barr
Yeah. I think we will. I think that there is, while for the most part, the six ADCs are unique in their own areas, there are a couple of areas of overlap. I think it’s okay because there’s enormous opportunity for — in this space, because we already see that once patients fail, successive rounds of EGFR inhibitors, the cancers are really, they’re very, very short time to demise. And so I think that there’s a lot of opportunities there, both in terms of looking at TROP levels or HER3 levels or looking at sequencing the ADCs. So I actually don’t think that that’s going to be an issue, both agents are very active and I think we’ll be able to provide options for people with somewhat different AE profiles. So we’ll see.
Umer Raffat
Got it.
Dr. Eliav Barr
Both of them are going to go forward.
Umer Raffat
Got it. So I realized the TROP-2 ADC, which you guys got from the Chinese partner, Kelun…
Dr. Eliav Barr
Kelun.
Umer Raffat
… as well as your some of the newer stuff that you got from Daiichi including the HER3. They’re both topoisomers based payloads. But within that, you could have differences in potency on the exact type of payload. So my understanding is Daiichi’s exatecan, which is less potent…
Dr. Eliav Barr
Right.
Umer Raffat
… much less potent than irinotecan. Can you remind me, is the Kelun TROP-2 irinotecan?
Dr. Eliav Barr
No. It’s a derivative of belotecan. So…
Umer Raffat
Belotecan.
Dr. Eliav Barr
So, again — and you have different DARs and so it’s all — it’s very hard to do cross comparisons, but I can tell you 2870 again has been exceptionally active for us. We were really excited about it as well. We’ve seen two clinical studies already entering clinicaltrials.gov in Phase III. They’ve already started. We’ve started enrollment. And then next year there should be a pretty substantive number of trials for 2870 moving forward.
Umer Raffat
Got it. Excellent. Anything we missed on ADCs just before we move on?
Dr. Eliav Barr
No. I think MK-1200, there Claudin 18.2 ADCs moving along very quickly, and again, that’s a unique profile that’ll be…
Umer Raffat
Got it.
Dr. Eliav Barr
…exciting as well.
Umer Raffat
Got it. One minor question I forgot and I just got an email about it. On TIGIT, a couple of your competitors have talked about how Merck has lured the dose. What’s the back…?
Dr. Eliav Barr
Yeah.
Umer Raffat
…backstory there? I meant to ask that.
Dr. Eliav Barr
There isn’t — there’s no backstory. I mean, we never reached MTD. So, we went all the way up to 700 milligrams. There’s no reason to have it. There’s complete saturation of the receptor based on our modeling at 200 milligrams. There wasn’t a safety issue.
Umer Raffat
Okay.
Dr. Eliav Barr
We just reached kind of the plateau. There’s no reason to go higher than full saturation.
Umer Raffat
Okay. So all the trials are using 200 milligrams now going forward?
Dr. Eliav Barr
Yes. Yeah.
Umer Raffat
And the one that’s being reported in lung right now…
Dr. Eliav Barr
Got it.
Umer Raffat
The KEYVIBE both, that’s also 200 milligrams. They’re all 200 milligrams. Okay. Got it. Final point on oncology, just before we graduate on small molecules, a couple of programs high on my mind, HIF 2 and the BTK. We can discuss any other programs you’d like. On HIF 2, where do things stand? I feel like there was a lot of interest in this. I realized the initial approval was in a more tumor — a mutation selected, so it was a much more smaller subgroup. Do you see a path now to a much broader approval and when would that be?
Dr. Eliav Barr
Yeah. So, LITESPARK-005, which is our first study in all-comer renal cell cancer read out positive for PFS and achieved priority review and will have a PDUFA date in first quarter next year and I think it’s a great example of how HIF 2 alpha can be an excellent anti-cancer drug outside of this, the germline VHL setting.
Renal cell is going to be where the main focus of activities are, because there is a lot of somatic mutations of VHL as well that is associated with carcinogenesis. So we have studies in the frontline. We have in IO failures. We have in the adjuvant setting. And this kind of builds on the enormous body of data with KEYTRUDA in the renal cell space. There’s just — we’ll have offerings across the different levels of disease for clear cell and non-clear cell and I think that’s going to be very important.
We do have trials going on now with the HIF 2 alpha in patients with other kinds of mutations. Those data are cooking and may very well provide an additional area for use of this drug above and beyond renal cell. So there’s a lot still going on with WEL belzutifan, where we really are first and only.
Umer Raffat
Got it. Peter, I see very modest growth in consensus numbers on the HIF 2, 200 million going to 300 million. Has there been much discussion on this on sort of momentum into a potential broader approval next year?
Peter Dannenbaum
So among analysts and investors, not a lot. No. So it has not received a ton of attention. We’ve strong expectations for WELIREG longer term and believe it can be a blockbuster.
Umer Raffat
Got it.
Dr. Eliav Barr
Yeah. I think it’s kind of like…
Umer Raffat
And next year, this PDUFA opens that up…
Dr. Eliav Barr
Yeah.
Umer Raffat
… is how I would think about it.
Dr. Eliav Barr
Yeah. I think so. And look, the VHL data were objective response rate data based on a single-armed study. So, obviously, people thought to themselves, these are for people with a specific genetic defect. I think that this is a breakthrough. What we see right now in the sense that it opens up a much broader patient population. I look at this kind of like Previmus [ph], it’s a drug that dissolves under the radar screen and yet it makes quite a bit of impact and therefore money.
Umer Raffat
Got it. Excellent. Finally, BTK, I feel like we’ve seen a lot of this. Loxo continue to be very active at ASH meetings with data updates, path to approval, et cetera. There was sort of a big — RQL datasets at Merck went into a big quiet zone for a while. I know you guys started to come out last year. But if we do some of the data comparisons versus data being reported by Loxo, I kind of get a sense, broadly speaking, mid-50s for you guys versus anywhere from 60s to 80s for Loxo, depending on how you look at NCLL, et cetera. How are you thinking about that? Is there baseline differences that explain some of those discrepancies?
Dr. Eliav Barr
There are actually. I think there are different patient populations. We can talk about the cross-study comparison issue and all that good stuff. But the specific elements are they looked at and had a very large number of patients who were intolerant to BTK inhibitor, to iBTK, to the irreversible ones. We were — we focused all of our attention on those with CE481S and related mutations. So we had more mutant patients.
The first sets of data from Loxo, they had a median, direct median, prior rounds of therapy of three. We had four. So it’s — I don’t think that it’s clear that these cross-study comparisons are like-to-like. I think it’s apples to oranges. As a measure of our commitment, you will have seen that we have a fairly robust Phase III study, including a study that Loxo has not done, which is our first-line study that just popped up on ct.gov, which is called BELLWAVE-10.
So I think you’ll see here that we have a lot of confidence and put money behind this. After, you’re right, there was a quiet zone. It was mostly we’re just ensuring that we got the dose absolutely right, got to that sweet spot and took our time to do so. But I think we’re in the right position now and it’s going to be an interesting next few years for the field.
Umer Raffat
Excellent. Maybe that might be a good point now to transition then towards some of the stuff beyond oncology. Unless there’s any questions on oncology in the audience…
Dr. Eliav Barr
Yes.
Umer Raffat
… and I’m happy to make it interactive. Okay. Sotatercept.
Dr. Eliav Barr
Yes.
Umer Raffat
Obviously, there was a big hit in the trial that came out. STELLAR was STELLAR, is what I call it.
Dr. Eliav Barr
Yes.
Umer Raffat
But I feel like amidst all the discussion on PAH, there’s almost a non-PAH or a different type of PAH where nothing is approved, the group two trial, which I think is a whole new indication.
Dr. Eliav Barr
That’s right.
Umer Raffat
It’s — where are we with that? Could you also remind people how’s that different from the standard PAH…
Dr. Eliav Barr
Yes.
Umer Raffat
Because it’s more like a HFpEF than not.
Dr. Eliav Barr
Yeah. Yeah. So there are different groups that WHO classifies PAH, pulmonary hypertension into different groups. PAH is the idiopathic genetic associated specific pulmonary vascular issue. Group two is where we are — what we’re talking about with this trial called cadence. It’s in patients who have both pre- and post-capillary pulmonary hypertension.
So they have heart failure, usually from HFpEF and their response in the pulmonary vascular chair is over exuberant. It’s really quite dramatic and you have substantial increase in pulmonary arterial pressure above and beyond what you might expect due to pulmonary venous congestion.
The reason why it’s taken a while to enroll that study because there’s nothing for these patients. So it’s not like they’re warehoused or pre-identified. A lot of work that we’re doing now is actually to do the right kinds of right heart caths and screening patients so that we can identify the patients.
This is true in a variety of diseases where there’s zero opportunity to help these patients. So you end up with having to start the screening process to bring out the patients. But once there’s something that will make a difference for them, then the docs will have a reason to do the screening.
So Phase II is always for these kind of new indications where there’s not much out there. It takes a while and we’ll get there. We have a PCD next year and hopefully the results will warrant further study.
Umer Raffat
Got it. Excellent. Recruiting, could you remind us how is that tracking in the group two trial?
Dr. Eliav Barr
It’s been slower than we expected. But again, this goes back to this whole business of, it’s not like there’s a whole warehouse of patients waiting for something, because there hasn’t been anything for them. So there’s no reason for docs to pre-identify them as a patient population. So we have to go and screen for them and that’s why it’s taken a little longer. But we have a lot of really great sites and I think we have slow and steady wins the race kind of thing.
Umer Raffat
Okay. Excellent. Any questions in the audience?
Unidentified Analyst
[Inaudible]
Umer Raffat
Oh, it’s up. Oh, I thought it was going to be up at six. Okay.
Unidentified Analyst
Yeah. [Inaudible]
Umer Raffat
This is not…
Dr. Eliav Barr
This is PFS?
Umer Raffat
Yes. PFS. Okay.
Dr. Eliav Barr
Yeah. The study was — so remember the study was a Phase II trial. We weren’t really planning on looking at it from statistical significance point of view. The poster you’ll see some interesting results on the shape of the curve and what we anticipate will be the overall view.
I think that these results again in second-line are encouraging to us, because we have — it’s not a filing study, right? And it was just designed as a signal finding evaluation. They’re encouraging for us because again, it just shows that when you add the TIGIT to the docetaxel, you get a pretty substantial improved outcome.
And again, this is small numbers of patients, has a ratio of 0.77. It translates to a trend in OS, good enough for us for what we were looking for to confirm the investment for the first-line. Yeah. Now, there is — we’re waiting first-line so might as well.
Umer Raffat
Got it. Okay. Anything else in the audience? Can we perhaps transition then to some of the other parts of your business? I know — so I want to talk about pneumococcal vaccines, obviously. I want to talk about the oral PCSK9, as well as the broader cardio strategy. Let me just hit up on a couple of questions that came in from…
Dr. Eliav Barr
Oh! Sure.
Umer Raffat
… the audience as well. One question was, can you ask about other oncology modalities like T-cell engagers, cell therapies, interest in those?
Dr. Eliav Barr
I know where we want to go is we want to go to places where we can do the best benefit for patients and leverage the huge infrastructure that we have here. We’ve chosen at present not to go into cell therapy, although we have some collaborations going on. We’re always looking for exciting opportunities and so there are interesting T-cell engagers or other modalities that we have going forward, we’ll definitely…
Umer Raffat
Internally.
Dr. Eliav Barr
I’m talking about externally.
Umer Raffat
Externally.
Dr. Eliav Barr
Yeah. So we have a collaboration with Dragonfly and TriNKET. It’s an NK cell engager work. And as I mentioned, and as Peter noted, we’re always looking for new agents and we’re modality agnostic. We just haven’t been in cell therapy, because the infrastructure for that is a lot. We already have seen that in something less complex like the INT. Cell therapy is an order of magnitude bigger than that.
Umer Raffat
Okay. Another one that came in is, broadly speaking, you have an oral PCSK9. You have a GLP-1, I think, which…
Dr. Eliav Barr
No. We have the NASH compound, the GLP-1/GCGR.
Umer Raffat
GLP-1/GCGR. It doesn’t have an A1c benefit. It has a weight loss benefit.
Dr. Eliav Barr
It has — the most important thing is it’s got a NASH benefit.
Umer Raffat
It’s got a NASH.
Dr. Eliav Barr
But that’s outstanding and much more robust than semaglutide or any other drug. But it has also about 10% to 12% weight loss benefit. So it’s a really good drug for NASH.
Umer Raffat
Great.
Dr. Eliav Barr
And we’re looking forward to evaluating it there. I think we have a whole cardiometabolic program and I think that our focus here is NASH as the anchor around which we build other things.
Umer Raffat
I guess the question that comes up is, to the extent you have an injectable increment, you have an oral PCSK9, I would have thought they might even be interested in expanding the oral PCSK9 to beyond, let’s say, oral GLPs, maybe oral hypertension molecules. There’s like orals in development that are novel programs. Is there anything going down the directions?
Dr. Eliav Barr
So the macrocyclic platform that we’ve built, I think, is really useful and we’re very interested in looking at a whole array of things where there’s injectables, because we really think that oral administration democratizes access. And so — but the key has to be something that’s differentiating and is valuable and we’ve seen that there are orals, obviously, RYBELSUS and then Orforglipron is out there. We’re looking at the developments, we’re thinking about second and third generation sort of things.
What are the things that are missing in the current therapies? They’re amazing in terms of weight loss. It’s been really beautiful to see the field grow. But we have to think about long-term durability and tolerability. We have to think about whether the kind of weight loss that is being affected is the right kind of weight loss in the sense of muscle wasting versus fat. And so I think that there’s still opportunities to improve on these and I know that all the companies, including the…
Umer Raffat
Are there pockets out there which could do this without hitting muscle?
Dr. Eliav Barr
There might be opportunities. I mean, I think, that there’s a lot of, there’s some groups are at myostatin. Some people are looking at other, a completely different mechanism of action. I think the problem with, as you know, with muscle wasting sort of issues with these drugs is that, if people go off drugs, first of all, you lose muscle and it’s not what you need when you’re, especially as you grow older.
The second piece is that when you get off therapy, then you have a real big jump up in weight because muscle is where there’s a lot of energy sink and just in the resting state. So people are in a much more, much lower basal calorie use and so you get this kind of over overshoots of weight gain. So it’s not such a good idea to have that if you can get around it. I think everyone’s looking for that secret sweet spot, but we’re, I think, the data aren’t quite there yet. There’s a lot of opportunities in the basic space to think about it.
Umer Raffat
Got it. Maybe I realize we’re short on time, so I want to be respectful. Pneumococcal vaccines. This is the last question from my front, unless there’s anything in the audience. Obviously, Merck’s been able to go beyond just the PCV20 based on V116, which doesn’t have a lot of the shared serotypes, et cetera. Is there a future program where Merck could deliver all the 13 shared and an additional 11, have something in the well into the 20s on one vaccine, which works in infants and in adults?
Dr. Eliav Barr
Well, I don’t — the reason to do that is because if the biology is the same or the epidemiology is the same and it’s not. So we’re perfectly comfortable as we have now with separate vaccines for babies and for adults and so we’ll continue to build the adult platform for babies. Of course, we’ve talked about V117 and the growth of the new more — the franchise and we have V117 which is, has more types that are going to be added on. So I don’t — we’re not shy about adding onto the pediatrics, but we’re — we would do that in the context of what makes sense for pediatric disease.
Umer Raffat
Yeah.
Dr. Eliav Barr
So I’m not worried about having a vaccine that has multiple more types than 15, which is what we have.
Umer Raffat
Got it.
Dr. Eliav Barr
But it just has to be the right ones. It may not be the same as V116.
Umer Raffat
And does V117 have to be beyond PCV20 to be competitive commercially?
Dr. Eliav Barr
I think it depends how the field goes, because remember there’s a lot of excitement, but then you need to get the pediatric data. You need GSK, Afinivax, the Sanofi has something…
Umer Raffat
Right.
Dr. Eliav Barr
I’m sure that Pfizer is going through. So we’ll just have to see what transpires, but we’re planning to go and to add more types and to do as many as we can that makes sense, not just to say, oh, X is greater than X minus one, but to really hit the important ones that cause both invasive pneumococcal disease, pneumococcal pneumonia and otitis media in babies. But the point is, is that the epidemiology, the types included have to be what’s relevant for the kids and adults, they get their own vaccine, because they have different disease. That’s just the way it is.
Umer Raffat
Excellent. Unless you have everything else, we’re going to go ahead and wrap up at least my HealthCONx for 2023. All right. Excellent.
Dr. Eliav Barr
All right.
Umer Raffat
Thank you for joining us.
Dr. Eliav Barr
Well, thanks for having us.
Umer Raffat
Great seeing you all.
Dr. Eliav Barr
All right.
Peter Dannenbaum
Thank you.
