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Intrinsic Value is all-important and is the only logical way to evaluate the relative attractiveness of investments and businesses.
Thank you. I'm Terence Flynn, one of the biotech analysts here at Goldman Sachs, and we're very pleased to have Gilead with us this morning. From the Company, we have Robin Washington, Executive Vice President & CFO; and John McHutchison, Chief Scientific Officer. Thank you both for being with us.
Thank you, Terence for allowing us to join this morning.
So maybe to get started Robin, you guys have characterized 2018 as a trop [ph] year, just help walk us through kind of the key levers for driving revenue growth into 2019 and beyond as you think about the business?
Yes, we do believe 2018 is our trop year [ph] and provides us with a baseline on which we can grow the business in 2019 and going forward. And if you think about some of the key drivers as you asked there, I think one is we have belief in that the fundamentals of our HIV business are very very strong and that will provide us long-term growth -- for a long time in the future; so we're excited there. Also I think the promise of cell therapy, in particular, the momentum we're seeing with Yescarta also gives us another baseline as we think about growth.
And lastly, in our HCV, the fundamentals in business dynamics are stabilizing; so while not necessarily a growth platform I think stabilization in our belief if there is a long payout that provide us opportunity as well. If you think about 2019 in particular, the strength of our U.S. HIV business along with Yescarta will continue to grow and allow us to navigate on the full year impact of generalization of HIV in Europe, as well as the second half of this year in 2019 we'll see some generalization in our cardiovascular franchise. 2020-2021, you think about the opportunities from our NASH and inflammation franchise is driving growth.
And also, just keep in mind that we've got a very very strong balance sheet; so we're very confident about our future and our ability to achieve growth in 2019 and beyond.
And so do you feel you have all the pieces right now to drive that growth? It sounds like while you're walking through that you feel pretty comfortable about that.
I think we feel good in the short-term when we clearly -- and you've heard us articulate this before that with our balance sheet and thinking about capital allocation, our top priority is to think about M&A and partnerships, etcetera to augment our pipeline. So we definitely are very active in that regard and continue to pursue several opportunities in several different areas.
The other question we get a lot is just thinking about your operating margins, longer term -- I mean, you're currently I think remodeling 52% this year, how do you think about the sustainability of that kind of an operating margin level given some of the puts and takes? Obviously, cell therapy -- lower margin product versus some of your HIV business but as that mix changes, how do you think about that 50% operating margin?
So I'd say 50% percent plus is industry leading. Gilead is always following that camp and we continue to believe that we can achieve greater than 50% operating margin. We're very financially disciplined and -- I mean, at the end of the day fundamentally we know that investing in our pipeline, investing in the commercialization of our product is really going to yield long-term shareholder value and what we achieve -- the operating margin level that we have at the peak of HepC revenues, probably not, but our escalation is to be above 50% and even higher longer term as we bring more products to market.
Maybe just in terms of the first quarter inventory dynamics; I know that was a subject you guys have talked about it now over the last few weeks or so. Maybe just to remind us as we think, heading into second quarter has all this pretty much been worked through now? I know you guys have been constant on underlying demand but maybe just remind us how to think about this going into second quarter now?
Sure. Yes, extensively we've worked through it. The Q4 to Q1 dynamic is a seasonality trend that we've seen, appearance for the past eight year. It was magnified in Q1 because of the anticipation of the launch of Biktarvy, as well as keep in mind, we had exploration of Viread in the U.S., now that impacts HPV revenues but the combination of that, as well as the inventory adjustments related to Biktarvy resulted in north of $200 million -- $300 million when you add in Viread impacts on our HIV/HPV business line. But we do expect that to have first-time work through that and going forward, we don't anticipate to see inventory have a significant impact on our HIV revenues but we'll see that trend again next year as well.
Maybe moving on to the Biktarvy launch, obviously big commercial -- our focus of the Company right now. You're at about 65% volume in the U.S., maybe talk about your aspirational goal now for Biktarvy given it's on the market? And then, help us think about how to compare progress you've made in some of the key EU territories on this front?
So, we achieved that conversion and task in two and a half years, and that's something I think we're very proud off. I mean, it moved very rapidly which is an attribute to our task-based regiments. And we want to see that to continue to go higher, I would say we believe that by 2021 in the U.S. we'll see very few patients on TDF based regiments. Turning to Europe, we do have generalization as of last year in Europe, that means that we've continued to see adoption of the Skovy [ph] based regiment. As a matter of fact, I think about 50% of HIV subscriptions are for Genvoya and that's across the Top Five EU markets. Germany is a great example where you've seen significant uptake, upto 70% to task based regiments, both our pre-generatizations, and so we'll have the Biktarvy approval latter in Q3 of this year. And as you know, in Europe, it takes about a year to go through reimbursement across the various countries but similar to the U.S., we expect Biktarvy to allow us to continue to get that same uptake of task based regiments that you see in the U.S. overtime.
And then remind us, in Europe is there similar guidelines -- I know you've got on the DHHO's guidelines in the U.S. here but in Europe is there a similar kind of guideline?
Yes, there are various guidelines. I think the timing is over -- some started in the fall but I think very quickly what's Genvoya, I think about 6 to 8 weeks with them, Biktarvy and we hope to have similar type of guidelines, references for Biktarvy in Europe as well.
And maybe -- just the last question on Biktarvy is just a composition of patients here in the switch pool, so I think in the first quarter it's about one-third from Genvoya, 20% from dolutegravir. How does that mix evolve on the forward? Is that kind of the steady state that we should think about or is that mix shift like we'd changed one way or another?
That's a good question. I mean, it's very early in the launch but we continue to expect to see dolutegravir based switching, as well as PI and candidly, TVS in our older products switching overtime. As we think about the Biktarvy launch, it's doing extremely well, better than we expected and if that trajectory continues we expect to see Biktarvy surpass Genvoya as the number one single tablet regiment for treatment experiences, as well as naïve patients.
Terence, it's the ideal drug for patients with HIV. It has the fewest compromises. If you're thinking about test advantages, renal and bone advantages of a test for describing those regiment on those that integrate. You've got no compromises at some results with HIV, that's an advanced, which are some of these young and going to be treated for decades to fulfill advantage. So there is very few drug interactions, no resistance in the Phase 3 trial, so far. And you know, the pill size is a huge advantage as the smallest STR available. So it has all of these additional advantages that will help with the trajectory.
Very few compromises that our patients have to make.
And that's a good Segway for my next question, just as we think about the upcoming Gemini data from GSK for their doublet regiment here. Under what scenario would that be a viable competitor because of competitive drugs because again, you outlined the profile Biktarvy, again, seems like the ideal regiment but is there a situation where a doublet is competitive in some patient population?
Look, I don't want to particularly comment about that. I think what I think about the Gemini's -- like, I am hoping to see the Gemini's face it soon. And based upon what we saw in the AGTC in Phase 2 trail, 120 odd patients, it wasn't complete suppression in all patients and there was a patient with field collapse at distance [ph]. I think -- so let's say what the data shows but you know, I think in this process, creating resistance is really unacceptable for clinicians and for Tyson.
For the first line register…
Yes, absolutely.
Okay, so that's -- I mean, pretty much the resistance profile as the thing that we're on?
I think we'll look at all efficacy sites. Efficacy said you said, something I think that's the case, say what's the [indiscernible] from size latter.
Maybe just moving on John, in terms of your strategy in cancer; I mean Robin, you mentioned this as a growth driver now in terms of cell therapy. Maybe just outline for us Gilead strategy in cancer here -- obviously, in your new role as Chief Scientific Officer, you have Alessandro who is Head of Oncology but how are you thinking about the forward in terms of framing that for Gilead, given -- it seems like every week there is a change in the landscape in terms of what therapies and lead, and how to think about combination; so do you think about the forward for Gilead -- maybe talk to us about our strategy now?
Feels like Hepatitis C, there is cancer every week. That's exciting, it's super exciting. And you know, we -- you mentioned Alessandro, we've spent a year hiring our Head of Oncology, Alessandro Riva, and then we spent the best part of the next three quarters of the year deciding what we could lead? What could Gilead lead in oncology? And we've settled on the cell therapy, and we've settled on Kite [ph]. So that is our predominant strategy right now in oncology. And we believe with the durable responses with the platform -- with our ability to expand into earlier launch and other parts of the cell malignancies. Then to have subsequent generations of products that are safer and hopefully be able to get into solid tumors and then hopefully, have an off-the-shelf product, a generic [ph] product that could be clearly advantageous for patients and increase at the flow etcetera.
So it's a 10-year -- we're embarking on the 10-year plus R&D program here. We're excited that we can leave the field, just like we have in HIV, just like we have in Hepatitis C and our goal is to build our research group and to be able to do that and lead in all of these tough components of the cell therapy revolution if you like to call it. So that's our goal.
And do you feel like you have the necessary personnel and pieces now in place post-Kite because I know it seems like -- when I think back there were a lots of fits and starts in oncology for Gilead but now with Kite and the personnel that you guys brought over, building out in LA, Alessandro -- is everything in place for that 10-year journey or is there more that you likely need to kind of augment that?
I think we've made a very good start, we've made two major investments, one is in the Sanger Imogene -- it's a finger gene editing program that will help us in terms about gene editing that's necessary for off-the-shelf products and presumably also to some second generation or tolerated [ph] products. We also brought in cell engineering company, Cell Design Labs, that allows us to have a switch that we can target both a tumor antigen in solid tumors and also make it tissue-specific, so you remove the off-target effect. But I think we need to do more and we've spent an awful lot of time now thinking about what else do we need in this journey in these four different components of cell therapy that I've outlined going forward. So we'll do more things like I talked about today, but we will do more things that we think are going to be essential to allow us to lead.
Look in terms of the people, you asked us about how we're doing, do we have the people -- the staff? Cell Design has 50 fantastic scientists in Chiron, in Berkley, we've got over 100 people in the research part of this organization now. We've developed insider people to pick up out of it as well. So it's a huge growing organization, so we're on our way, and we're very confident about that right now.
We're growing in Monaco, as well as in Europe. We're continuing to explore other sites as well.
So we'll have a manufacturing facility in Amsterdam, we have another facility that we're working with Steve Rosenberg at NCI for solid tumors and neo-antigen. So we have lots of -- not all advances in this field will be made in one organization, I think we all realized that scientifically; so having a strong collaboration in our tangical [ph] road -- understanding what the field is doing, and the inherent knowledge internally to make the right decision that is critical in fee.
I'd say oncology is an area of focus for us from a BD standpoint, as well as under along with inflammation and other various liver disease also.
So it's not just focused on that I agree, and what other field -- what other part of oncology can we lead, we don't like to follow, we like to lead. So can we make a meaningful impact in some other way in immuno-oncology and so forth. So these are the sort of things we're thinking off about more broadly as well.
Maybe just going into some specifics on these cardio launch; obviously early launches have been pretty strong here. On the forward though, there are -- Novartis recently got approval for DLBCO, Cellgene has talked about potentially having JCAR17 in the market next year. So as you think about kind of the competitive dynamics changing here; maybe just talk to us about what's going to differentiate your approach here as first-to-market kind of the key advantage or are there going to be some differences -- and when we think about kind of the profile of Yescarta versus the competition?
Yes, maybe we can do double-duty [ph] on that question. I mean, I -- I'd say it's no surprise in -- we anticipated that we were going to have competition for -- with other CAR-T therapies for B-cell lymphoma. I mean, if you think about personal advantage, we do think both very well for Gilead and for Yescarta in general, I mean some in terms of service, speed and just reliability. We feel very comfortable with where we are. I was -- actually got a chance to go out and visit one of the oncology centers last week, so good momentum. I think people are feeling very good about our launch, our interaction with the center personnel; so we're very excited about our momentum there and believe we can be competitive.
I completely agree. Just to add on to little bit off -- it's about the product, it's about the service, first mover advantage and so forth -- that you've highlighted all of those critical and important, it's also going to make decisions based upon what they know; their experience, what the label says and how they -- and their experience with multiple products. We have the highest durable fee, a natural response rate, the shortest turnaround time vein-to-vein, and our patients with 600 clinical trials is hard to compare across trial. So we have these advantages right now but it will be a competitive field.
At ASCO there was some discussion -- a number of the sessions about the different definitions of CRFs and neurotox, also tumor debulking and also the knowledge about the side-effects to look for now and maybe being more aggressive with IL-6 treatment earlier on. So as we think about -- kind of the dataset that you guys and Novartis generated versus maybe what's going to come with JCAR17, maybe just help to talk about those couple of things coming out of ASCO because I think that was on the minds of lot of investors, given that just came up in a couple of the sessions?
Yes, I was there. It's still hard to compare across trials. When the trial is a single arm and the population is heterogeneous and very sick. But given all those caveats, we didn't use debulking chemotherapy in any of the Yescarta programs, whereas the other two programs you highlighted from Juno [ph] and Novartis, did you -- people I think came out and said, 'that can influence the way you interpret the side-effects'. We had a fantastic post from the Yescarta experience in the trials that looked at the tumor burden and the relationship to the tumor burden to CRS and other side-effects. And in the lowest quartile of the patients in the trial with the lowest tumor burden, you get the lowest CRS, cytokine release syndrome, and incidental prevalence.
So there is an interplay between the two here that makes it difficult to understand but I think we haven't used debulking chemotherapy, that's not going to affect our tumor burden, it does with the other two drugs. So it's hard to compare the CRS right across the trials and the side-effect across the trials. Also, Terence as you know, everybody knows here there are different scales in these things as well in different trials which makes head-to-head comparison difficult.
So you feel pretty good about your profile relative to what you know about the competition right now?
Sure. You know, early use of IL-6 is at the papers recently out suggesting that neurotoxicity in the cytokine release syndrome in animal models generated by the individual macrophages, not the CAR-T cells. So blocking with IL-1 -- blocking might affect neurotoxicity, other strategies to improve other products that might -- or manufacturing process set by far the rate of CRS or side-effects as well as not affecting durable response rate in graph is important as well, we're looking at all of those things internally as well.
And that's a good segaway maybe in terms of thinking about earlier lines of treatment. You mentioned this is one of the growth opportunities here; so as we think about moving into second line DLBCL [ph], you know, would be assumed lower tumor burden. So does that data have implications where you think about the tumor 7 study and maybe just talk about timing of that dataset and that market opportunity versus where you are right now?
I hope so, if you are right. It has crossed my mind as well but then the 7 is a very exciting study, so just briefly it's head-to-head versus standard-of-care for the second line. So people who have relapsed the initial therapy then usually go to repeat chemo and in this aim to remission or response that go onto stem cell transplant. So we are comparing that standard-of-care pathway with early use of Yescarta CAR-T therapy. But the global trial, first actually randomized Phase 3 clinical trial in the field, 350 patients here year-over-year at U.S. were enrolling now, it's going well, huge amount of enthusiasm. And I think we have a huge opportunity with the trial and stem cell transplant with it's issues with rejection graph, apoptosis, recurrence and relapse and so forth is not an ideal option for these patients. So I'm hoping and we'll watch the data of course but I'm hoping it will be a great step forward for the patients in an earlier line of therapy.
Look, in terms of other diseases, just a few other updates. I think mantle cell lymphoma, and also indolent non-Hodgkin's lymphoma will have completed the Phase 2 studies or completed enrollments in those two this year. And as another update, we'll be starting the Phase 2 portion of the two ALL trials in children; pediatric ALL and in adults as well, if decides one day to support, of course witnessing some of that data so far [ph].
Could we see the mantle cell and indolent NHL data had asked this year? Would that be a target given or is it still likely next year given you just completed enrollment?
I don't know -- I rather not comment on what maybe and I don't know the timing of the meetings at the top of my head. But we would want to publish the data and have it presented as soon as we can.
Maybe moving on your BCMA CAR-T; I think we're expecting some data later this year, another exciting target. Here you guys are unlikely to first to market given where the competition is, so maybe just talk to us about that dynamic first. And the second question I had is just -- there was some discussion at ASCO about MRD negativity and it reminded me John about RVR4 and HEP-C [ph], unlike the predictability of driving a disease on detectability early on; so is there a difference in MRD negativity in kind of latter stage patients versus earlier myeloma patients?
I don't know, actually. I don't feel comfortable that I know the correct answer to that. But the myeloma field -- as you've articulated is very crowded or more crowded, and we aren't ahead but we are executing very well as we have done in all of these programs so far with CAR-T and with CS CAR-T and the other programs. So we always want to feel we had the strength to incredible execution and clinical development, we seem to be able to do that now and all the other therapeutic areas, so that's good.
Let's see how our pipeline data looks. Look, it's a single chain variable fragment humanized, so that should minimize antigenicity. In animal models, we do see an effect of the product in low BCMA expression. It's a CD28 called stem domain as well, and I think the other thing from ASCO is that the PFS advantage is less than 12 months now, so let's see what our Phase 1 data looks like later this year and we'll see how we stack up. We have other programs in backup as well, of course, like everybody else is…
Going after BCMA federations?
Yes.
The other area in terms of just your cancer strategies, there was a recent Nature paper until plus PD-1 in advanced breast cancers, one patient with Dr.Rosenberg, maybe just talk to us about the advantages and hurdles of the neo-antigen approach and how we think about kind of next steps for that program because that was something else that came out of Kite but I think it was more kind of -- in the background here.
It was a fantastic paper and just sort of helpful feeling for the potential of what this can do in solid tumors if we can get it right. So this woman with breast cancer who watched this tumor and it just disappeared over weeks to month, it was just incredibly. So Steve Rosenberg at NCI has been doing this since the 80s in melanoma and we have a very close relationship with him and many credits, and almost recent credit or relationship with him is since based upon the next-generation of this two approach which is the neo-antigen based process that Dr.Rosenberg and others at NCI have got a way of detecting neo-antigens in solid tumors that are immuno-reactive, it will then create TCRs for them and be able to infuse them.
So we actually have this broad relationship of the second-generation, above and beyond the TIL approach which is a more non-specific approach. And we actually even have a manufacturing facility that we're setting up for him in -- so we can do some of the early clinical trial work there. So we are very excited about what we're doing with Dr.Rosenberg and subsequent generation of neo-antigen.
And have you guys talked about the timelines and all in terms of when we could move that into the clinic? It sounds like there has been a lot of pieces in place but when could be the second-gen approach actually be in patients?
I'm not sure that we have disclosed what we're doing exactly but Dr.Rosenberg is doing this on some of the initial patients at the NCI now, as well with some interesting responses.
And would this be broadly applicable -- again, for those who are estimating the technology this was breast cancer, you mentioned melanoma -- would this be broadly applicable to most solid tumors or are there certain tumor types that would be more minimal to…
That's a very good question. There might be a small group of people with pancreatic cancer where it might be more broadly applicable and there is a huge need there. But each individual patient solid tumor is different, it's one of the driving immuno-dominant mutations or immuno-reactive mutations that's different today with every tumor; so we have to sort this out and we have to sort out how the scale is up and how to be able to do it in real-time, that's an issue.
And maybe in the last minutes I want to get to both, the NASH program and Filgotinib. Maybe on NASH, just -- John given your background here, I know you've spent significant lot of time working on the liver diseases, maybe just remind us of Gilead's approach here with your portfolio and the next kind of key data readout that we should think about on the forward?
We started our NASH programs about six years ago and we felt we should focus on the three components that underlie the disease and codes the disease. The first is accumulation of fat within cells and people who are overweight and have all the other features of the metabolic syndrome. That leads to damage to cells which we call lipotoxicity that leads to inflammation within the liver, that inflammation in the liver then leads to eventually scar tissue being laid down in fibrosis. So we have always thought we need to hit all of these targets ideally to create those therapies that are most likely to have the greatest effect in these patients. So we have programs in the clinic in all three targets.
Our first program is going alone in Phase 3 as an ASK inhibitors and apoptosis signaling -- enzyme that's in that inflammation cascade. It also affects hepatic starlight [ph] cells which are the cells that cause the laying down of fibrosis and the liver activates them; so it has a dual mechanism of action. In Phase 2 we said it's dose-dependent effect on liver histology. And now since Phase 3, the stellar program, most advanced liver disease patients only in those trials, pre-cirrhosis and cirrhosis, the reason for that cause -- is that's where the greatest need is, and that's where we can make the most difference. So those two trials enrolled way ahead of schedule and they will rebounce in the first half of next year, Terence. And if successful, we would then be able to file shortly near after. That's the first program.
The second program comes back to the combination approach. So we have the ASK inhibitor, we have a drug that's been ACC inhibitor that inhibits denovo life of genesis or fat accumulation in the cells as well, and then we have an FX [indiscernible] agonist that also works on this lipotoxicity. We've shown each agent has in small trial individual agent activity. We've shown in a recent trial that the combination and the various different permutations and combinations at that stage in small trial, and now we're embarking on a large Phase 2b trial where there will be 350 patients, 70 patients in each combination, there will be two biopsy's a year apart, and that will help us to determine which is the best combination to take forward in a Phase 3 trial.
So it's less successful in NASH, we have our first product which would be [indiscernible], the ASK inhibitor, standalone for advance fibrosis. I'll add Gilead followed by a follow-on combination program that would hopefully be more effective in phase as well.
And what you raised as endpoints for both the Phase 3 and the Phase 2b?
Phase 3 endpoint is one-stage or greater improvement in fibrosis with no worst thing as NASH. And in Phase 2, we'll look at the same endpoints that did well.
And there has also been some competitive data out there recently about the different mechanism. Any thoughts on how that mechanism compares to what you guys are working on?
Look, we have a number of other preclinical programs as well looking at other mechanisms that we haven't disclosed as yet but we would when the time is appropriate of course. And I think you're referring to the Med-Rule's [ph] data, the mechanism of action from the Meds 12-month beta-agonist. Look, it's interesting data, potentially a trial in mild disease -- and if that reduction in fast without a significant improvement in fibrosis as well. So look, I've seen what you've seen in press releases, I look forward to seeing the data presented at another scientific meeting but it's still evolving and there will be other mechanisms of action and it will be us at Gilead to make sure we have the most important mechanisms of action.
And as Robin alluded to, before we always look, the best signs can be internal or can be external as well.
It sounds like you have other internal programs that we'll be getting more data on over the next…
We have other programs of different mechanisms of action internally as well that are relevant to NASH and metabolic syndrome, that's correct.
Maybe just the last question is on Filgotinib. My first question here is, could this be your cornerstone drug for the company in autoimmune disease? And then, just confidence in the safety tolerability profiles, I know there has been a lot of noise on the jet-class [ph] recently, so how do you think about that versus some of the other drugs and mechanisms that are out there, particularly on safety tolerability?
Look, we think it could be the cornerstone. We would like to drive response rates higher for the same patients with these diseases as well. Just briefly, ACR-20, have been 20% of you join the bed, 80% of you joined [indiscernible], surely we can do better than that, and that's what we'd like to do. Could Filgotinib be the backbone and we can add on to that to drive that? That's our long-term goal. In terms of differentiation, Filgotinib is the most jack-1 selective drug, that's been shown independently by multiple academics, it doesn't get jack-2, so we don't have an increase in place. We so far are in place to have a lower incidence or prevalence of [indiscernible], let's see how it panes out in Phase 3. We don't have a hemoglobin big rate which is jack-2, we have a hemoglobin increase which is a good thing, particularly capable within inflammatory.
We're excited about the programs in RA which accelerated quickly but we're really excited about IVD, we could be the first jack approved for CRAM, second for [indiscernible]. And we need to accumulate the large dataset, and then jack-3 -- we don't hit jack-3, so we don't have a NK cell decline that could be related to infected protection. We want to get all the Phase 3 dataset, we want to say the safety profile continues to be differentiated with those large datasets that prove the community at large. And then we'll see where we go in terms of the filings, etcetera. But we're excited about the program and I can tell you from the day we started these collaborations now, the drug continues to appear more differentiating as we go on.
And we're expecting the first Phase 3 data I think in the second half of this year, right?
That's right, and then the other two trials to follow. That's right; there are three trials, early line, second line like one.
Well, with that I think we're out of time. Thank you so much for your time today. We really appreciate it.
Thanks, Terence.
Thank you.