Gilead Sciences, Inc. (NASDAQ:GILD) SVB Securities Global Biopharma Conference February 14, 2023 11:20 AM ET
Company Participants
Merdad Parsey – Chief Medical Officer
Conference Call Participants
David Risinger – SVB Securities LLC
David Risinger
Great. Good morning, everybody, and thank you for joining us for this next session with Gilead. On behalf of SVB Securities, I’m very pleased to host Merdad Parsey from the company to discuss the company’s pipeline prospects.
And so, Merdad, it would be great for you to maybe just comment at a very briefly at a high level about the position you see Gilead in today versus obviously where it was even just nine to 12-months ago.
Merdad Parsey
Sure. Thanks, David and thanks for the invitation. Happy to. Look, maybe I will go back a little bit farther than nine to 12-months ago. When I joined, it is been just over three years now, we set out on a course of really adapting our pipeline and really building Gilead into a company that was going to be – is going to be sustainable for the long run.
Really building on the strength of our HIV and virology pipeline and portfolio, but really growing into oncology in particular, as well as building out our inflammation pipeline and so over that time, I think we have moved very aggressively to build our pipeline out.
As you know, with acquisitions in addition to our internal work and that spans everything from remdesivir in virology to Trodelvy in oncology. We are really happy with where we are right now, with a lot of potential for additional growth over the near-term – over the near to midterm.
And I would say, we do continue to have a goal to try to build the pipeline out to be a truly sustainable pipeline for the long-term. And I would say, we are midway through that journey. And hope to keep building the portfolio out overtime. So we can dive into whatever part of that you want to talk through.
David Risinger
Great. Well, let’s just pivot to specific products, and it would be great to try to cover a lot of ground. So it would be helpful for you to talk about what you see as being underappreciated about Trodelvy, including the event path ahead that could bring Wall Street views closer to Gilead’s views of its prospects?
Merdad Parsey
Sure. Yes, look, I think So Trodelvy, we are really excited about where we are with Trodelvy over the past couple of years now. We have built on the initial approvals in triple negative and the accelerated approval in bladder, which I think is under appreciated, with now the HR-positive/HER2-negative approval that we have.
And it really speaks to where we believe we are going to go. First of all, I think the value or the – and by value, I mean, the benefit it brings to patients really is emphasized by the NCCN guideline update that we just got recently where we are now category one. I think that really speaks to the importance of Trodelvy in the treatment paradigm for people with breast cancer. I think that is a very important piece of it.
The other part I think that is underappreciated is our underlying strategy from the get go, which was very much two key things. One is to expand the number of indications we are in, and the second is to go into earlier lines of the indications we already have approvals. And both of those things are underway. As we move into studies to look at earlier lines and triple negative and HR positive for HER2-negative and bladder cancer. So those are all moving along.
We are also expanding into non-small cell lung cancer, probably the most important part of our expansion for Trodelvy. And I think someplace where we feel very confident around where we are headed, given the validation of TROP-2, I believe in lung cancer as well as what I hope will be a differentiated profile for Trodelvy in the space.
And then we are exploring additional indications, I think probably the biggest thing is, when you work with a molecule that has this sort of breadth of activity, it is a clearly an active molecule that works across a number of tumor types. Our obligation is to identify the broad potential for a molecule like this and really to look for additional indications.
And so we have a number of exploratory earlier kind of studies ongoing to identify additional areas where we can expand Trodelvy. So trajectory from a revenue standpoint in 2022 is we are really excited about. I mean clearly the uptake is going well and then we really think there is only upside at this point.
David Risinger
Excellent. So then, let’s talk about non-small cell lung cancer. So if you could compare and contrast Trodelvy with AstraZeneca’s TROP-2, that would be helpful. And then also compare and contrast of one versus AstraZeneca’s TROPION-Lung01 trials?
Merdad Parsey
Sure. I think it is a great point where – I think that, it is very important to talk about the similarity in the sense of look, ADCs in the treatment of oncology have been – have struggled outside of the initial first few ADCs. We have all worked on ADCs for a long time. And I think with the AZ molecule and ours, I think we are really seeing a new emphasis on the potential for ADCs.
And they are different. They are different in that. There are three pieces to each ADC. There is the antibody and overtime, we have all gotten used to talking about the differences between say PD-1 inhibitors or antibodies directed against TNFs and the subtle differences between them. But here now you have to add the complexity of the linker and the payload.
Now the linker is different between ours and the competition. We have a hydrolyzable linker, and there is this more of a protease dependent linker. And we believe that the effect of the hydrolyzable linker and having the payload available is part of what gives us that sort of a zonal effect of tumor killing and I think that might be important in the long run.
And then our payload is, what I would describe as a more moderately toxic payload. It is an earner [TCAN] (Ph) derivative as opposed to an [XTCAN] (Ph) derivative, which can be more potent. And so I would expect that, we will see, as you see in other therapeutics, a bit of difference in terms of our overall efficacy and safety profile overtime.
Where we are excited, as I mentioned earlier about the lung approach, we are excited in that in lung. Our data so far, we have not seen, for example, on the safety side, a lot of ILD, any ILD at this point. And I think that could become important, especially in patients with lung cancer, who may have radiation to the chest. They have had lobectomies and that could be one of those differences in the constructs of the antibody drug conjugates that could play out in the long run in terms of nuanced differences.
From a side effect profile, that is another place where you see a bit of a difference. Ours I mentioned the ILD, and then ours are really neutropenia diarrhea. And those are better, more typical adverse events that oncologists are pretty used to managing. They are fairly predictable and manageable with things like dose reductions or things like that.
Whereas ILD can be a bit more challenging, given the sporadic nature of the ILD, and it is something that folks aren’t really used to tracking. So I think those are potential differences that we will have to watch overtime as our data evolve in multiple tumor types and especially in lung cancer.
And then I think you asked just to follow-up on then, the differences in our trials. There are a lot of similarities in our trials. Both of our trials are – we are roughly the same size in terms of sample size. They are, excuse me, essentially very comparable patient populations. We do have some differences in terms of the patient population, in terms of how we think about it.
Similarities, we both are looking at comparisons with docetaxel in the second line plus population and we are looking at people who have had platinum and PD-1 inhibitors in the past. So those are some similarities.
But in terms of differences, we are looking at stage four only, and theirs are looking at 3B four patients. And then, the other, I would say difference is that they are excluding patients with a history of ILD and pneumonitis, and we don’t exclude those. Both trials are ongoing and so, we will just have to see how the data play out, but I think we are on the right track there.
David Risinger
Got it, okay that is very helpful context. Great. So then, pivoting to TIGIT. So, there is obviously a lot of debate in the market about TIGIT given questions about how much efficacy it can really add and how helpful it can be in combination. So could you just comment on that and just highlight your combo development plans and next cards to turn over?
Merdad Parsey
Yes, look, we are really excited the data we presented at the ASCO Plenary, and we are looking forward to updating at ASCO in May – ASCO 2023 in May. I think really answer the key question that we asked in the design of that trial, which is, does TIGIT add to a PD-1 inhibitor in patients with non-small cell lung cancer?
And what we see there is that the PFS improvement with a hazard ratio of about 0.5 to 0.6, depending on which cohort you are looking at. As well as the absolute PFS itself of 10 to 12-months PFS in an ongoing dataset where we expect those numbers to mature over time.
Really I think, to answer the question that TIGIT does really add to a PD-1 inhibitor that is consistent with the public data so far. It is also the biggest dataset that has been made public by anyone to-date. So, we have a lot of confidence based on our own data and watching these data mature over time and about the ability of TIGIT to really be an important next generation immuno-oncology agent.
Obviously, there are other data pieces that have to come together. There is going to be additional readouts. I do think that people have paid attention to the Roche announcements in a way that I think from my perspective, probably a bit of an overreaction to they are not stopping the study or not announcing their data.
As with most Phase 3 trials, we all build in interim analysis in our studies for two reasons for safety, but also to see if you have a much larger effect on your – treatment effect than you had initially planned for. But you really only power the study for the endpoint at the final analysis, the overall survival at the end of the analysis.
That is how our study is going to be designed, that is how we design all of our studies, and that is how Roche designs their studies. So it would have taken an outsized impact for them to be able to stop the study and announce positive data. They are not going to spend a lot of alpha on an interim analysis, nor should they, nor will we, or nor should we.
We power to make the study as large enough to get to a statistically significant outcome at the end of the trial and no bigger, because we want to go as fast as we can. And so those interim lyses can be helpful, but I don’t read too much into them when the studies continue.
David Risinger
Excellent. That is very helpful. So then turning to the pipeline for cell therapy. Could you talk about the steps you are taking to retain your leadership position, particularly as new technologies will be entering such as Galapagos’ program?
Merdad Parsey
Sure. I think I like where you started. We really feel that, Kite has really demonstrated that it is the leader in cell therapy, the ability to provide treatment to patients 96% of the time, the ability to manufacture reliably and the durable responses that have been shown time and again now over five-years after treatment. I think really establish that primary position, if you will, in terms of where we are as an organization with cell therapy.
And I remember a year or two-ago, I think the question was always, what are you going to do about [ALLO] (Ph)? And unfortunately, for patients, I think we have not seen that area develop the way people initially thought. I think it is going to make harder than people have thought.
And so I think providing the treatment approach that we have now with the CAR-T technology that Kite has and really working to optimize the delivery time, both in terms of reliability and in terms of being able to get the cells back to patients as quickly as possible.
Reduce the need, if you will, of the shelf. If you can turn around and, A for a reason and then treat a patient quickly, with what I will call standard CAR-T therapies right now. The value of being able to get to allogeneic is reduced, not eliminated, but reduced.
Now of course, we are really focused on what is going to come in cell therapy and we believe that, given our position, a lot of people seek out and work with us and we have a lot of partnerships and we keep a very close eye on where things are headed in cell therapy. And so we are constantly looking at that next generation of work.
As you know, you mentioned, a good example is Galapagos. Galapagos remains a partner of ours. We continue to have options on the programs that come out of Galapagos. So we will stay close to the Galapagos team. And as that evolves, if that becomes something that we believe will bring value to patients, it will definitely be something that we will bring into our armamentarium to help with cell therapy.
And in the meantime, with the deals you have seen, Kite met more recently with the BCMA agent, as well as the armored – I think all of those things are evidence. I think that we continue to work to innovate in the space, and look for new opportunities to bring our expertise, our manufacturing prowess and expertise to the evolving landscape in cell therapy. We are really excited about where we are headed there.
David Risinger
Excellent. Thank you for all of that color. So let me just glance at the time here. I want to make sure we cover as much ground as possible. But why don’t I just ask you to touch on Magrolimab quickly? So, I mean, obviously, the data at ASCO last year was encouraging in terms of efficacy but obviously, the toxicity needs to continue to be managed carefully. Could you just discuss how you see Magrolimab with respect to its opportunity news flow ahead and then how you see it potentially being positioned longer term versus next generation CD-47 bispecifics?
Merdad Parsey
Sure. Yes, look, I think Magro remains one of those areas where it is one of those pipeline products that we acquired in the past few years and are looking for its maturation and hopefully contribution.
I always think of CD-47 and two buckets, solid tumors and heme. Heme is obviously we are far out ahead and those Phase 3 trials are ongoing. We will look forward to the readouts of those studies as they mature over time.
And as you know, we have another interim coming up this year that as we were talking about earlier, we would have to see a big signal in to unblind and we are on pace to get to our event-driven outcome next year.
So, I think the potential in MDS and in AML remain sort of the cornerstone and we are far out in front there. I think, we are leading the pack there. In this business, I think competition is the name of the game. The days of being the only player are far behind us, but we think we are really happy with where we are from a timing standpoint in terms of the maturation of those studies and our ability to get to that answer before anyone else.
And then in terms of solid tumors, we have four ongoing Phase 2 trials that are fairly far along. And there I think, as you mentioned, there are a number of folks who are dabbling in the solid tumor space as well with CD-47. I think we are all looking to see proof of concept there, us included.
We are really happy with how far ahead we are in the breadth of our programs there to really — out things like which combinations could potentially be the best, and which tumor types we expect to see that efficacy most likely.
So, I think we are far ahead. It is too soon, honestly, with other agents to, especially the bispecifics, to really see how they’re going to play out. But we certainly think we have – we are very far ahead.
And then in terms of safety I think it is a great point to hit on and remember that we actually – the company 47 actually patented the dosing approach that we take. We believe that the anemia that you get with the CD-47 really has to do with those senescent red blood cells and it is on-target effect.
And so we have our dosing paradigm built in a way to minimize that adverse event with an initial low dose. And then we are able to escalate our doses over time to get to we better tolerability. And I think that is going to be key to finding the right therapeutic index, if you will, the right window of treatment to mitigate the effect – the on target effect for the red blood cells while getting to maximum efficacy. So we are really excited about where we are.
David Risinger
Excellent. Okay great. So let’s do a little bit more of a sort of rapid fire on some of your other key programs. So with respect to your oral COVID treatment, Pfizer has claimed that no other company will be able to compete with PAXLOVID label, because they were able to show high efficacy during the peak pandemic period. Could you discuss your strategy to demonstrate compelling efficacy and comment on Pfizer’s statement?
Merdad Parsey
Yes. Look, I think it is true that the pandemic has changed dramatically and certainly, it is difficult for me, from the outset with remdesivir, we tried not to predict where the pandemic was going to go and I certainly wouldn’t try to do that today. It is certainly more difficult. I completely agree that, it is much more difficult to conduct trials today, than it was during the high of the pandemic when there were no other alternatives.
And so what we have done is, we have initiated the two trials that we are moving on with. We have a lot of confidence in the ability 5245 to demonstrate activity and that it is based on similar MOAs remdesivir highly validated. We know it is effective and so we expect it to be highly efficacious.
The challenge will be finding in the two trials high risk patients and what we call standard risk patients. And I would be the first to acknowledge it is going to be challenged there, both in terms of recruiting those patients and then the severity of illness that we have seen with the newer variants.
And I think a couple of things are also true. One, that the pandemic will continue to evolve. PAXLOVID does have limitations in terms of the patient population that we know. It has a booster. There are patients with drug interactions who can’t take PAXLOVID. And of course, as with any viral infection and they are treatment for viral infection, resistance overtime is a possibility.
And so we believe that having another mechanism of action available for patients should the pandemic shift overtime is going to be important from a public health standpoint if nothing else. And so we will do our best to move that program forward for both standard risk and high risk patients as quickly as possible. And vagaries of the pandemic will be something we will have to manage overtime.
David Risinger
And then, so in terms of the design of those studies, how large are they?
Merdad Parsey
So they are both fairly big and I’m just going to look up real quick the sample size for our high risk study. For high risk study, it is about 2,300. And for our standard risk study, it is about 1,900 subjects that are going to be enrolled.
Those are all both based on assumptions that we have made around the event rates that are going to occur. So in the high risk patient population, we are looking for hospitalization, mortality, the usual, very similar in a sense to that high risk population that is been studied in the past.
In the standard risk we are looking to alleviation of symptoms, the time to alleviation of symptoms. And so because we have had to make a number of assumptions about the event rates there, based on, again, where the pandemic is going, we will overtime have interim analyses that we will check to see if the event rates are where we thought they would be, higher than what we thought they would be, or lower than we thought they would be. And then we can adapt the trials the sample size based on what we see in terms of event rates.
So we have tried to both move very aggressively forward because we think it is critical to be there. You can’t predict when you are going to need it. We have established sites globally to be able to capture if there are new outbreaks so we can capture patients should they appear and to adapt the studies based on what is actually happening on the ground.
David Risinger
Okay. And if I might push back, I don’t understand why the company isn’t spending triple and enrolling five times the number of patients you just described, given the fact that it would be, if successful, at least a five billion product annually, meaning it seems like a no-brainer to me given Gilead’s expertise in virology, given Gilead’s presence globally, that the company should be spending dramatically more money given the revenue opportunity. I mean, we can see it in PAXLOVID. Now, granted, PAXLOVID is collapsing, but could you just help me understand that better, why you are going so small with those counts? I’m surprised that you mentioned 2,300 for high risk in 1,900 for standard risk.
Merdad Parsey
Yes. And the answer is we will, if we need to. I think those sample sizes are based, as I said, on an assumption of what the event rate is going to be and how much of a treatment effect we are going to have.
If the event rate is lower or we see – we believe we think we have a good idea what the treatment effect size will be. If we need to expand those studies, we will. So, and that has to be balanced with trying to get it done as quickly as possible. So, we are going to do the study that will get us to approval as quickly as possible in the appropriate sample size. But if we need to go bigger, we will go bigger.
David Risinger
Okay, thank you. And then, why don’t we pivot to the lenacapavir combo development. So it would be helpful and I know that you have many, many molecules in development, but it would be helpful for you to educate us on how close you are to a drug with – like efficacy and dosing frequency?
Merdad Parsey
Yeah. We have 10 different molecules both in the oral space as well as in the parenteral space, the injectable space. And we will be seeing data really starting to roll out. As early as this year, we will be presenting data at [Coray] (Ph) coming up, I think, it is next week on our bNAb combinations, the broadly neutralizing antibody combinations with lenacapavir.
So that is one of our efforts. And I would say that is the one we felt we could go most quickly with. But we then have all the small molecule approaches that we have. And what will happen, what you will see evolve overtime is we will be looking at the PK of those molecules and the tolerability of those molecules. And as we get that information, we can move very quickly then into the appropriate trials in combination with those.
And we should see those data rolling out really fairly soon. I think over the next year to two we will see a lot of data and our goal is to provide, I think a meaningfully an important durability of those treatments. We believe that getting to three-months if not six-months of parenteral treatment is really critical to bringing something to patients people living with HIV that will matter and make a difference, and that it is tolerable. And so that is our objective.
And so looking at the characteristics of those molecules, both in terms of durability and tolerability, it is going to be critical in choosing the right molecule. We hope to have a lot to choose from them. We will those the ones with the best characteristics to move forward with.
David Risinger
Got it. Excellent. Okay. And then one final question. So Gilead has a number of inflammation programs that are progressing. Could you just frame those for us and what the key candidates are to watch over the next year or two?
Merdad Parsey
Yes. I think, as we have said for a long time, with our inflammation group is young but mighty and we are really looking to build that portfolio out overtime. It is an early portfolio, but we really are excited about things like we have an oral alpha4beta7 program, we have an IRAK4 program, we have a Triple 2 program, all of those are in early days and we will be moving into Phase 2 studies here in the next year or two.
Those studies will, as we design them and share them with folks, you will see the timing of rolling those out. But we will be looking at a broad array of indications obviously from IBD to other inflammatory indications.
We are really excited about our portfolio. We are really looking to bring first and best-in-class differentiated molecules there in the long run. And then obviously they are also potentially looking at combinations as we get to trying to move the needle on improved efficacy and tolerability for those molecules. So early, but very exciting portfolio, so we will update you as those as those studies get underway and we expect to see data.
David Risinger
Wonderful. That is great. You saw me typing away. We covered a lot of ground, so it has been super helpful. Really appreciate you taking the time out of your scheduled to be with us.
Merdad Parsey
Absolutely my pleasure. Thanks a lot, David.
David Risinger
Alright. Have a great rest of the week.
Merdad Parsey
You too. Bye.
Question-and-Answer Session
End of Q&A
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