Vertex Pharmaceuticals Q2 2021 Earnings Call Transcript

Quartr
Provided by Quartr
July 28, 2021

There are 16 speakers on the call.

Operator

Good day and thank you for standing by. Welcome to the Vertex Pharmaceuticals Q2 2021 Conference Call. At this time, all participants are in a listen only mode. After the speaker presentation, there will be a question and answer Please be advised that today's conference call is being recorded. At this time, I'd like to turn the call over to your host, Mr.

Operator

Michael Patridge. Sir, you may begin.

Speaker 1

Good evening. This is Michael Partridge. Welcome to the Vertex 2nd quarter 2021 financial results conference call. Making prepared remarks on the call tonight, we have Doctor. Reshmaekhewal Ramani, Vertex's CEO and President Stuart Arbuckle, Chief Commercial and Operations Officer and Charlie Wagner, Chief Financial Officer.

Speaker 1

We recommend that you access the Webcast slides on our website as you listen to this call. This call is being recorded. A replay will be available on our website. We will make forward looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission. These statements, including without limitation, those regarding Vertex's marketed CF medicines, our pipeline and Vertex's future financial performance are based on management's current assumptions.

Speaker 1

Actual outcomes and events could differ materially. I would also note that select I will now turn the call over to Doctor. Reshma Kewalramani.

Speaker 2

Thank you, Michael. As we reach the halfway point in 2021, our business is performing exceptionally well and is very well positioned for the future. Our CF franchise is strong and growing. During the Q2, we reached a number of new reimbursement agreements for the triple combination as well as other CFTR modulators in our portfolio, including in major markets like France and Italy earlier than expected. These reimbursement agreements are occurring in a timeframe that is far quicker than is typical for OUS markets.

Speaker 2

And importantly, We are achieving reimbursements at levels which are robust and reflect the value of our CF medicines. We also secured regulatory approval for the triple combination in the to 11 age group for the U. S. Taken together, these additional reimbursement agreements and regulatory approvals provide thousands of new patients with access to our medicines. As such, we are raising our 2021 guidance range by $500,000,000 to a range of $7,200,000,000 to $7,400,000,000 reflecting 18% year on year growth at the midpoint of the range.

Speaker 2

But our work in CF is not done. There are still more than 30,000 people with CF who are yet to be treated. And by reaching these patients, We see continued significant growth for the CF business. With regard to the pipeline, progress is accelerating across the portfolio. We now expect to achieve target enrollment in both CTX-one studies in Q3.

Speaker 2

We have initiated the VX-five 548 Phase 2 program in acute pain. We are on track to begin the Phase 3 next in class triple combination program in CF Shortly. And in the next 6 to 9 months, we expect important data readouts from multiple clinical stage including VX-one hundred and forty seven in APOL1 mediated FSGS, VX-five forty eight in acute pain and VX-eight eighty in Type 1 Diabetes. I'll now review the key clinical stage programs in more detail. Starting with CF, we are relentless in our efforts to maximize the benefit we can deliver for patients.

Speaker 2

Trikafta sets a very high bar and we recognize That any new medicine that aims to treat the 90% of people with CF with at least 1 F508del allele, including our own medicines, has to show clear potential to improve on Trikafta. We announced earlier this week that the once a day next in class Triple combination VX-one hundred and twenty one tezacaftor VX-five sixty one is advancing to Phase 3. We believe it holds the potential for greater efficacy and convenience for patients. It also has the benefit of ENAM's economics for our business based on the fact that the royalty obligation would decrease from low double digits to low single digits. We are also committed to developing therapies for the approximately 10% of patients who cannot benefit from CFTR modulators.

Speaker 2

Our lead program in partnership with Moderna uses an mRNA based approach and continues to make progress in late preclinical development. Let me now turn to our non CF clinical pipeline, which includes 5 mid to late stage programs using 3 different therapeutic modalities, including small molecules, cell and genetic therapies. The most advanced program in the pipeline is CTX-one, our gene editing therapy, which represents a potential one time functional cure for patients with beta thalassemia and sickle cell disease. This program continues to have strong momentum and impressive results. We've shared new data at EHA last month involving 22 patients who were treated with CTX-one and had at least 3 months of follow-up.

Speaker 2

In this data set, all beta thalassemia patients, including beta-zero, beta-zero patients who have the most Severe form of the disease were transfusion independent and all sickle cell patients were free of pain crises following CTX-one therapy. We now have dosed more than 45 patients across the program and are on track to achieve target enrollment in both CTX-one studies in the Q3. We are working with regulators to finalize the filing package for VX-one and anticipate filing for approval in the next 18 to 24 months. Moving to VX-one hundred and forty seven. VX-one hundred and forty seven is our lead molecule for the treatment of APOL1 mediated kidney disease and we anticipate clinical data from our Phase 2 proof of concept study in APOLL1 mediated FSGS in the second half of twenty twenty one.

Speaker 2

The VX-one hundred and forty seven Phase 2 study evaluates the safety and the reduction of proteinuria over the course of 13 weeks. The achievement of double digit decreases In proteinuria with this molecule would be a significant risk lowering milestone for the program as this would establish APOLL1 inhibition as a promising new mechanism that can be applied to the approximately 100,000 patients in the U. S. And Europe who have APOL1 mediated non diabetic, perturonic kidney disease. Consistent with the portfolio approach we take with every pipeline program, We have multiple molecules in development behind VX-one hundred and forty seven targeting the APOL1 pathway.

Speaker 2

Turning to the NAV1.8 program. As announced last week, the Phase 2 trial in acute pain following bunionectomy surgery With our selective NaV1.8 inhibitor, VX-five forty eight is underway and data expected by early 2022. NaV1.8 is both genetically and pharmacologically validated with our previous molecule VX-one hundred and fifty demonstrating positive proof of concept in acute, neuropathic and musculoskeletal pain. VX-five VX-five forty eight is more potent than our prior molecules, which allows us to use lower doses and also more fully explore the dose response curve. We expect to move faster with VX-five forty eight by conducting multiple clinical studies in parallel.

Speaker 2

Indeed, We are starting a second Phase 2 acute pain study following abdominoplasty in the coming weeks. The potential to serve patients suffering from acute pain is Substantial. And Stuart will share additional perspective on the market opportunity in his remarks. Moving on to Type 1 diabetes. The Phase III study with VX-eight eighty, our islet cells alone approach is underway and the first patient has been dosed.

Speaker 2

Ours is the only approach to use stem cell derived fully differentiated insulin producing islet cells distinguishing it from all other therapies in clinical development today. Similar to CTX-one, we anticipate that proof of concept for VX-eight 2, our optimism for this program and for the ability of VX-eight eighty to demonstrate clinical benefit comes from the cadaveric islet cell transplantation experience, which has already provided a precedent for transformational outcomes. Beyond Our cells plus device program is continuing to progress in late preclinical development. Finally, in AATD, As we shared with you in June, the VX-eight sixty four Phase 2 clinical data showed clear evidence of biological activity, though the magnitude of clinical effect did not support its progression to pivotal studies. Based on these data, we remain confident in and committed to AATD and to our small molecule corrector approach.

Speaker 2

This is the only approach that targets the underlying cause of AATD and therefore holds the potential to treat both the lung and liver manifestations of disease. We expect that our next wave of molecules will advance into the clinic in 2022 and that we will be able to move more rapidly through clinical development with the insights we have gained from the VX-eight sixty four trial. I'll now hand it off to Stuart.

Speaker 3

Thank you, Reshma. I'll begin by reviewing the Q2 revenue performance of our CF medicines. Our Q2 global revenues reached nearly $1,800,000,000 driven by increasing revenues outside the U. S. As a result of the launch of CaFtrio and continued strong performance in the U.

Speaker 3

S. In the U. S, the launch of Trikafta in ages 12 plus has been highly successful and just under 2 years since regulatory approval, The vast majority of eligible patients have initiated treatment. We have continued to see very high persistence and compliance levels And we're now focused on the ongoing launch of Trikafta in children ages 6 to 11 in the U. S.

Speaker 3

Following the approval in June. Outside the U. S, we have made significant progress with reimbursement for our medicines. We now have reimbursed access for CAF Trio in more than 15

Speaker 4

countries outside the U. S, less than 1 year following

Speaker 3

EMA approval. Outside the U. S. Less than 1 year following EMA approval. This compares favorably to the industry standard both in terms of the timeline in individual countries and the total number of markets in which we have reimbursement agreements.

Speaker 3

Our rapid reimbursement progress can be attributed to multiple factors. The transformative clinical benefits of the triple combination, The support and collaboration of governments and the CF community and the expertise of our commercial team built over the course of a decade. Importantly, as Reshma mentioned earlier, we are achieving reimbursement for our medicines at levels that recognize their considerable clinical value. The pivotal clinical trial data for Trikafta were unprecedented. And as with all of our prior medicines, we are continuing to to be able to fully understand and communicate the long term benefits of CFTR modulator therapy to all key stakeholders.

Speaker 3

We have previously shown powerful evidence that treatment with KALYDECO, ORKAMBI and SYMDEKO slows lung function decline, results in multisystem benefits and transforms the course of the disease in CF patients. Earlier this month, we obtained our 1st long term follow-up data with the triple combination. In the FF and FMF patient populations Treated for at least 96 weeks with Trikafta in the open label extension of the pivotal clinical trials, we do not see This is a first for any of our CFTR modulators. We look forward to sharing these data in a forthcoming medical forum. Although we are pleased with what we've achieved so far, We still have a long way to go to reach all CF patients.

Speaker 3

As we have previously communicated, we estimate there are 83,000 people Living with CF in the U. S, Canada, Europe and Australia and approximately 90% of these are likely to benefit from a CFTR modulator. We estimate that there are more than 30,000 patients who could benefit from our current CF medicines who are not yet being treated. Reaching these patients, which will drive significant additional revenue growth will be achieved by successfully launching our medicines where we have reimbursement, Securing additional new reimbursement agreements and label expansions to younger age groups. And we remain confident we will be able to reach Vertex now has taken global leadership for all aspects of the CTX-one program.

Speaker 3

As a result, We are in a position to leverage Vertex's demonstrated ability to develop and secure access and reimbursement for transformative medicines. We see tremendous potential for CTX-one. We estimate that there are more than 150,000 patients in the U. S. And Europe who have beta thalassemia or sickle cell disease, approximately 32,000 of whom have severe disease.

Speaker 3

25,000 are severe sickle cell disease patients and the vast majority of these are in the U. S. We believe that a gene editing approach, which holds the potential for a one time curative treatment will be highly valued by patients, physicians and payers. Consistent with our own internal market research, published physician surveys in the U. S.

Speaker 3

Consistently indicate that they expect a quarter to a third of their sickle cell disease patients would be good candidates for a one time curative approach using the current conditioning regimen, which is in line with the estimates of the numbers of severe patients. And with gentler conditioning regimens in the future, We expect CTX-one to be an attractive option for a much larger proportion of the 150,000 beta thalassemia and sickle cell disease patients. Our pre commercial efforts are well underway. There are a number of notable features that are guiding our approach to this market, including: 1, patients with severe beta thalassemia and sickle cell disease are symptomatic and have a lifelong history We are developing health economic models to demonstrate the cost effectiveness of a functional cure for these patients. 2, new and flexible payment models will be needed for a functional cure for these diseases.

Speaker 3

We are engaged with payers to understand what models work best for them and for patients. And 3, patients are geographically concentrated. For instance, 75% of eligible sickle cell patients in the U. S. Live in 15 states.

Speaker 3

We will use these and other insights to establish a commercial operation that is both lean and highly effective as we have in CF today. Let me now turn to pain and share our perspective on the market opportunity for a novel medicine in this area. Acute pain therapies represent 1,800,000,000 treatment days a year in the U. S. Despite more than 90% of prescriptions being generic, Acute pain still represents a $4,000,000,000 market, underscoring the opportunity for a novel transformative agent.

Speaker 3

A new medicine that even takes a portion of the current treatment days has multi $1,000,000,000 potential. In acute pain, a significant component of the market is opioids. A medicine with high efficacy and without the limitations of opioids, Particularly their addictive potential would be transformative for patients and the healthcare system. With regards to commercialization, treatment is highly concentrated within hospital and post operative settings. 25% of U.

Speaker 3

S. Hospitals account for 80% of all opioid prescriptions. Given this concentration, Successful commercialization will be possible with a small specialist focused commercial model, again consistent with our lean SG and A approach. Finally, Type 1 diabetes. VX-eighty has advanced to patient studies and relatively soon we will begin to have a view of its clinical profile.

Speaker 3

We estimate that 60,000 patients in the U. S. And Europe with severe type 1 diabetes or type 1 diabetes with prior kidney transplant would be potential candidates for VX-eight eighty. In and of itself the islet cells alone program is a significant market opportunity and existing transplant approaches establish a basis for the high value of a transformative therapy. Beyond VX-eight eighty, the cells and device program could address the broader type 1 diabetes population, 2,600,000 patients in the U.

Speaker 3

S. And Europe. In conclusion, it's an exciting time to be at Vertex as we continue to bring our CF medicines to more patients And we still have significant growth ahead in CF with new reimbursement agreements and label expansions to younger age groups. And beyond CF, our mid and late stage pipeline is rapidly advancing with each program having both the potential to transform lives and presenting a significant commercial opportunity. And with that, I'll hand it over to Charlie.

Speaker 5

Thanks, Stuart. In the Q2 of 2021, Vertex again continued its record of outstanding financial performance. In fact, we're in the midst of our 8th consecutive year of at least double digit revenue growth. 2nd quarter total product revenues were 1,790,000,000 an 18% increase compared to the Q2 of 2020. This growth was primarily driven by strong international uptake of Captrio and continued performance of Trikafta in the U.

Speaker 5

S. Our 2nd quarter revenues included $1,260,000,000 in the U. S. And $536,000,000 outside the U. S.

Speaker 5

Ex U. S. Revenues for the quarter grew 71% over the prior year, reflecting the full quarter effect of prior initiations in Europe as well as any new patient initiations in countries where patients have access to Captrio. Our 2nd quarter combined R and D and SG and A expenses were $537,000,000 compared to $467,000,000 for the Q2 of 2020, driven largely by investment in our clinical stage programs and our research pipeline. As our pipeline continues to expand and mature, We expect our R and D investments will continue to be substantial while we drive to our proof of concept data and further clinical and regulatory progress across the pipeline.

Speaker 5

Our continued growth in revenues combined with carefully managed growth in spending translates to a 2nd quarter operating margin of 57%. With our strong revenue and profitability, we ended the quarter with $6,700,000,000 in cash following the one time $900,000,000 payment to CRISPR Therapeutics for the amended collaboration. Our strong financial performance to date, The future growth profile in CF and the tremendous potential of our broad and deep pipeline made this the right time for the $1,500,000,000 stock repurchase authorization that we announced in June. This authorization gives us the opportunity to repurchase stock at very attractive prices as we seek to offset Now to guidance. We are making a significant upward revision to our previously 20 21 guidance for total product revenues to a range of $7,200,000,000 to $7,400,000,000 This $500,000,000 increase in our revenue guidance Range reflects year to date business outperformance as well as the rapid progress we have made in reaching new reimbursement agreements.

Speaker 5

Year over year, this guidance represents nearly 18% growth at the midpoint. As is our practice, the guidance only includes revenue for countries that are Currently reimbursed, future new reimbursements are not included. We are maintaining our non GAAP OpEx guidance for the full year 2021 at $2,250,000,000 to $2,300,000,000 Driven by R and D investment, we anticipate that our OpEx in the second half of twenty twenty one will be sequentially greater than in the first half of the year. Specific drivers include the new economic split under the amended CTX001 collaboration, advancement of VX-five forty eight to multiple studies in pain and investment to support Type 1 diabetes clinical development. For a non GAAP tax rate, we continue to guide to a range of 21% to 22% this year.

Speaker 5

Looking to the future, The financial profile of our business is exceptional in many ways. First, we expect to see continued significant top and bottom line growth from our CF franchise into the middle of the decade as we continue to reach more and more patients. 2nd, our CF revenues are well protected by the triple combination's strong IP, which extends to the late 2030s and which could be further extended with the new next in class triple now entering pivotal trials. 3rd, our differentiated business model and lean SG and A lead high margins and strong cash flow, which allows for sustained levels of investment into internal and external R and D and continued strong earnings growth. And finally, we have a number of multibillion dollar opportunities advancing in the pipeline, many with near term milestones, including those in beta thal, Sickle cell disease, APOL1 mediated kidney disease, pain, type 1 diabetes and AAT, each of which have the potential to drive significant growth beyond CF into the 2030s.

Speaker 5

With that, I'll turn it back to Reshma to close.

Speaker 2

Why don't we go directly to questions and open the phone lines now.

Operator

Thank you. Please standby while we compile the Q and A roster. I show our first question comes from the line of Michael Yee from Jefferies. Please go ahead.

Speaker 6

Hi, guys. Good evening. Thanks for the question. Reshma, I know that there is an important Phase 2 readout for FSGS later this year and you've talked about that and I know you've talked about what you're looking for in terms of reduction proteinuria. I guess my question was twofold.

Speaker 6

1, Are there scenarios where reductions are more modest and you have to think about what that would mean for going forward? And second, if it was really good reductions, production of coronary is a surrogate. So when you still need to run a Much longer study, appreciate it's a genetic mutation patient population. So maybe you could talk to those scenarios and how you think about the robustness of data? Thank you.

Speaker 2

Yes. Hi, Mike. The question you asked is about the VX147 program for The others on the phone, this is the APO L1 mediated FSGS program that is currently in Phase 2 and we are on track To read out the Phase 2 results, in the second half of this year. The way I see this program, Mike, and what we're really looking for It's safety for short. It's a Phase 2 program.

Speaker 2

And on the efficacy side, you're right. It is about percent reduction in proteinuria. And we are looking for double digit reduction in proteinuria because at those levels, it's meaningful and it is correlated with Improvements in GFR and the hard endpoints of time to ESRD. As with all of our programs, Mike, we have a portfolio approach Here, I am excited to see these results. The community, physicians, as well as patient groups and The regulators, particularly in the U.

Speaker 2

S. Have had multiple workshops and conferences over the last several years. And the regulators have expressed openness for proteinuria to be the regulatory enabling endpoint. Now whether that's an accelerated approval, whether that's a full approval, all of that obviously will need to be discussed as we progress the program and Have those discussions with the regulators. But I've been really pleased with how the regulators have thought about it.

Speaker 2

And the fact This is indeed a genetically defined renal disease and what the regulators have often talked about is a homogeneous Proteus neurotic kidney disease and that is what this is. So I feel optimism for proteinuria to be the regulatory enabling endpoint and Obviously, that makes for a more efficient trial.

Operator

Thank you. I show our next question comes from the line of Phil Nadeau from Cowen and Company. Please go ahead.

Speaker 7

Good afternoon. Thanks for taking our question. Kind of a 2 part regulatory question from us. You recently announced The design of the CF Phase 3 trial and it's notable because as a non inferiority priority primary endpoint, We're curious to know whether simple non inferiority is sufficient to support FDA approval or if the FDA ask for superiority or something else from the secondary endpoints. And then second part of the question is, when will we get similar details on what's necessary to file CTX-one.

Speaker 7

I think you've been guiding for FDA an FDA update Sometime this year, we're kind of curious, is that going to come sooner rather than later? And if you have any preliminary idea of what will be necessary for filing that candidate? Thank you.

Speaker 2

Sure. Let me take the CTX-one question first. As I mentioned in my prepared remarks, We are now looking to achieve completion of target enrollment in Q3. So that's really a very near term completion Of the target enrollment. So what we're really looking at now and I've described before, as we've had these conversations with regulators and we do have the benefit Really virtually every regulatory designation one can imagine.

Speaker 2

So we've had the opportunity to have productive discussions with the agency. It's about the size of the filing package. It's about the duration of follow-up and the CMC manufacturing controls I'd like to see. Achievement enrollment is really short term. So it's about the duration of follow-up in CMC Manufacturing.

Speaker 2

I do expect that we're going to bring those discussions to a conclusion in the next coming months. And I do anticipate Filing to be possible in the next, let's call it 18 months to 24 months. So that's really what it looks like on CTX-one. On the Phase 3 next in Class CF program, we've gone through our discussions with the regulators. We've Had our end of Phase II meetings and this trial design that you see reflects those considerations and those discussions.

Speaker 2

I will point out that as I look at the VX-one hundred and twenty one data, there are 3 really important elements that stand out to me. The first is that in our HBE assays and you know that our HBE assays translate very well into the clinic not only qualitatively but quantitatively, Singularly or in combination, so 121 alone or in combination with tezacaftor 561, the results are In our HPEs that 121 is more efficacious, more efficacious than even Trikafta. That's really saying something. And in the Phase 2 results, you can look at the sweat chloride, which is the real direct translation of chloride transport in vitro. And you can see that we're looking at numbers that are more like 45 millimolar to 45 millimolar with the 121 regimen versus 33 to 39, that's what we saw in Phase 2 with the Trikafta regimen.

Speaker 2

And then of course, PPFEV1, Which is more variable, but even that has indications for being better than Trikafta. So while the Primary endpoint is non inferiority. I see a lot of optimism in these data to even have the potential to be better Than Trikafta.

Operator

Thank you. I show our next question comes from the line of Geoff Meacham from Bank of America.

Speaker 8

Just a couple from you guys. So on the pipeline, I know there's been a lot of emphasis on BD, but for what you have today in the pipeline, are there investments that can accelerate to get into registration trials faster, for example, like in pain. And then When you look in CF, beyond rolling out across the EU and maybe adding younger patients across the board, What do you think I know you're not going to give long term guidance, but what does the normalization of the market look like in terms of the Maybe the incidence rate, what are you guys assuming? I'm just trying to get a sense for when CF is more moderate growth, Is that the timeframe where you think that you're going to have more of a P and L impact from sickle cell and beta thal from 1 or other elements of the pipeline? Just trying to get a sense to put all the pieces together for kind of the long term growth picture.

Speaker 8

Thank you.

Speaker 2

Yes. It's a great question, Jeff. And let me set it up for you and then I'm going to ask Stuart, to comment on market dynamics and then I'll come back and address your question about the pipeline and how we see that going. What I'd say to start with is, I really see continued significant growth for many years to come In our CF franchise. And I'm going to ask Stuart to outline those dynamics for why I say that.

Speaker 3

Yes, Jeff. So as you know, we updated our estimates of the epidemiology for people living with CF in the U. S, Canada, Europe and Australia earlier this year to approximately 83,000 patients. And we're probably treating about Half of those patients today and as you know, we updated our guidance today to a range of $7,200,000,000 to $7,400,000,000 What that means is, and I don't want to gloss over this, is that there is more than 30,000 patients remaining You are eligible for our CFTR modulators. They are likely to benefit from our existing CFTR modulators.

Speaker 3

And those 30,000 patients really fall into 3 categories. The first one is people who live in countries where we have regulatory approval and we've secured reimbursement And we are beginning the launches in those markets. And as you know, the launches of our CF medicines tend to be very rapid. 2nd group of patients are those who live in countries where we have regulatory approval, but don't yet have reimbursement. Obviously, we've had A great year securing reimbursement for Captrio, just a year just under a year from the EMA approval and I have full confidence that we're going to continue that run and additional reimbursement agreements in countries where we don't have it today.

Speaker 3

And then we have to get down into younger patients. And as you know, we've done that with KALYDECO and ORKAMBI and given the benefit risk profile of Trikafta, we fully We'll be able to get down to younger age groups. So over the next several years, we see multi $1,000,000,000 revenue growth potential through getting to those more than 30,000 patients. Additionally, we are also working on the 7% to 10% of patients Who aren't going to be eligible for our CFTR modulators using genetic approaches through our collaborations with amongst others Moderna. So we do see continued growth of our CF franchise for several years to come Based on continuing to execute in the way that we have done over the last few years.

Speaker 3

And then to tell you how the pipeline is going to layer on top of that, I'll hand it back to Reshma.

Speaker 2

The pipeline is progressing nicely and I actually would say it's accelerating and let me tell you why I say that. The pain program is now in Phase 2 for the bunionectomy study and in parallel and very shortly we're going to start up the abdominal The CTX-one program as I said in my prepared remarks, That one is going to achieve target enrollment in Q3 now. And when I think about 147 that is absolutely on track to have results in the second half of this year. And when I put all of that together, it looks like a really important next 6 to 9 months in terms of not only data readouts, but the opportunity to advance to milestones In each of these programs and that's not even talking about the programs that are in late preclinical development or in Phase 1. So we are investing heavily in our pipeline.

Speaker 2

It is because the pipeline is accelerating and there are many opportunities for us to get to the next important milestones in clinical development. I would be remiss if I didn't say a word about VX-eight eighty. This is the naked cells only approach. This one is a Phase onetwo trial and I would think about this one as similar to CTX-one In that reasonably small number of patients in a reasonably efficient timeframe will really tell us what we have. And so That was another one that I think is going to be important to keep our eyes on and to invest behind.

Operator

Thank you. I show our next question comes from the line of Salveen Richter from Goldman Sachs. Please go ahead.

Speaker 9

Thanks for taking my questions. For CTX-one on manufacturing, do you have an understanding of the assays required or How differences could play out regulatory wise versus gene therapy given this is a new technology? And then with Your work with Moderna on mRNA and gene editing, maybe you could just help us understand how that's progressing and when those might enter the clinic?

Speaker 2

Sure. Salveen, with regard to CTX-one, we really have had the opportunity to have Multiple discussions with the regulators, not just on what the potential filing package could look like in terms of the clinical data, Sample size, etcetera, but also on CMC and manufacturing. And we have a very good understanding of what the agency, both here and outside the U. S. Would like to see in terms of potency assays and release assays and that work is going very well.

Speaker 2

In terms of the mRNA program, you know that we have multiple programs for the last 10% of our CF patients, the most advanced of which is the mRNA program in partnership with Moderna. There's really 2 components here. It's the mRNA construct itself And it's also delivery. We have made solid progress on both of those. And I would say the important one is on delivery.

Speaker 2

A little too early for me to give you timing for when that would enter the clinic, but I will say that the progress has been very good. And I'm feeling very optimistic about our ability to get to that last 10% of patients, Maybe even compared to 6 months ago.

Operator

Thank you. I show our next question comes from the line of Robynne Knauszka from Chorus Securities. Please go ahead.

Speaker 10

Hi. Thanks for the question. Starting first a little bit on, I have

Speaker 2

to ask this question. I did not want to be

Speaker 10

the person who asked this question on the call, Rishna, but I have to. Your thoughts on the Galapagos Headwind as people are focusing on their data coming up. I know they're behind you, but can you just give any more additional color on the biology perhaps Steven, on how you view their drug? And second on pain, you mentioned like timelines, we could get some clarity on your pipeline over the next 6 to 8 6 to 9 months. When could we actually see data from pain?

Speaker 10

Those trials enroll really quickly.

Speaker 2

Maybe give us some sense

Speaker 10

of what your expectations are Or your next dataset and what the bar might be? Thank you.

Speaker 2

Yes, sure thing, Robin. Let me start with pain. I'm really excited about our pain program. You know that we have a program in NAV1.8 that's The one that's furthest ahead in our discovery and preclinical research, we also have programs in NaV1.7. The reason I'm particularly excited about NaV1.8 is it's a genetically validated target for sure, but it's also pharmacologically validated by our very own VX-one hundred and fifty.

Speaker 2

The molecule that's in the clinic now, VX-five forty eight, really is all the attributes we were looking for in terms of potency, As well as in drug like properties, DDIs, manufacturability, etcetera. So this one really looks Very exciting to us. It's already in the bunionectomy study that is up and running as a Phase 2 proof of concept study. The abdominoplasty is right behind it and that could start up very shortly. We are also interested in pursuing Peripheral neuropathic pain in the NAV1.8 area.

Speaker 2

And the reason for that is because, again, Our VX-one hundred and fifty molecule had proof of positive proof of concept data not only in acute pain, but also in neuropathic pain. So That one is another study that's coming. With regard to acute pain, the studies are very short in duration because it's Like a bunionectomy, you have treatment that is over a couple of days and so the results can be obtained in a reasonably efficient timeframe. I expect that the bunionectomy results will be ready by, let's say, the tail end of this year, beginning part of next year, abdominoplasty results thereafter. Sure.

Speaker 2

So that's really how I would have encapsulated the pain program. With regard to the Galapagos Data maybe Galapagos AbbVie data. Robin, I'd rather focus on our portfolio Tell you about how I see our portfolio. And maybe the best way to summarize it is VX-twelve-fifteen sixty one tesa. Captur holds the potential to bring greater patient benefit than even Trikafta, it's once daily dosing, which I think adds A level of convenience for our patients.

Speaker 2

And in all honesty, the greatest threat to Trikafta, The greatest competitor to Trikaftor in terms of the most advanced is our very own VX-one hundred and twenty one-five sixty one tesacaftor.

Operator

Thank you. Our next question comes from the line of Cory Kasimov from JPMorgan. Please go ahead.

Speaker 1

Great. Thanks. Good afternoon.

Speaker 11

I appreciate taking the question. I actually want to follow-up, Rustom, on what you were just talking about, kind of, Phil's earlier question on the QDCS study, But from a slightly different point of view, so recognize it's designed to demonstrate statistical non inferiority from a regulatory standpoint. But what do you think you need to show for this to actually displace a product as good as Trikafta in the market? I'm assuming dosing once versus twice a day isn't enough on its own. And did you say in the prepared remarks, just want to make sure we have this right, that the royalty on the QD goes to low single digit from low double digit.

Speaker 11

Did we get that right?

Speaker 2

Yes. Corey, with regard to the study, you're right. For the regulatory enabling endpoint, it Is a non inferiority study and that non inferiority is on PPFEV1. You're also correct that the royalties go from low double digits with Trikafta, Captrio to low single digits. Let me just take a step back though and Help maybe everyone on the phone line understand our perspective on The 121 program and why we're really doing this.

Speaker 2

So our long standing goals in CF have been threefold. First, bring forward a medicine that can treat up to 90% of patients with cystic fibrosis. Give that a check, that's Trikafta, Captrio. 2nd, get patients who can benefit from CFTR modulators to the highest levels of efficacy. And the way we've discussed that is to bring patients to carrier levels of sweat chloride.

Speaker 2

And that's really important because At those levels, when you look at carriers of cystic fibrosis, they really have no manifestation of disease. And when you look at our own data, other published data, it is absolutely true that the better the sweat chloride results, which is a Flexion of CFTR function, the better the outcomes for our patients. And the 3rd big goal has been to, get to the last 10% of patients. The 121-five sixty one tezacaftor program is all about that big goal number 2, get patients to carrier levels of sweat chloride. And certainly, it is the case that some patients on Trikafta can get there.

Speaker 2

But We are looking to get many, many more patients to those levels, if not all patients. And that is, 1121561TEZA. And as I reviewed, From what we see in the HBE cells, in terms of chloride transport, sweat chloride from the Phase 2 studies and even PPFEV1, All these measures point us in the direction that this is possible with 121561. And of course, we're busy in the labs working on even more efficacious molecules.

Operator

Thank you. I show our next question comes from the line of Liisa Bayko from Evercore ISI. Please go ahead.

Speaker 12

Hi, thanks for taking the question. I want to ask a little bit more about the FSGS study design. Can you talk about sort of the background therapies that patients will be on? And will they be on steady background meds headed into the study? Or will there be any changes ahead of the study?

Speaker 12

And will you allow for these with steroids? Just Curious about some of the other factors. Thank you.

Speaker 2

Yes, sure thing. Lisa, in our Phase 2 study, we are looking at patients who have APOL1 mediated FSGS with 2 APOL1 allele. And we are looking for patients with heavy amounts of proteinuria. We are allowing patients to be on background therapy And we are looking for the double digit percent reduction of proteinuria that I was talking about earlier On top of whatever background therapy our patients may be coming into our trial with.

Speaker 12

Okay, great. Helpful. And then we'll

Operator

Sorry, thank you. Our next question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead.

Speaker 13

Hey, guys. Good evening. Thanks for taking my questions. So, two questions on 121. Can you talk about where you're planning to conduct the Phase 3 triple combo study?

Speaker 13

And is that going to be in the U. S. Or outside the U. S? Would you any medium term impact to Trikafta or Captrio revenues.

Speaker 13

And then it looks like the sweat chloride that you observed at least in was dose dependent. I'm wondering, do you feel you've fully explored the dosing curve here? Any safety or PD reason not

Speaker 2

Sure thing. Brian, we are going to be conducting the study in the usual countries, U. S, European countries, the standard. Remember, this study, both the studies in the 121 program Are compared to the to Trikaftrio, so this is not placebo controlled. So patients are going to be an active therapy In either arm, that obviously makes it a lot easier for patients to enroll into this study.

Speaker 2

With regard to impact on revenues for Trikafta, no, we don't see any impact on revenues through Trikafta. And with regard to how did we select the dose, how did we think about this program, we shared with you the results from the Phase To study, as is the case with all of our programs, we take all of that data. We do quite a bit of modeling and simulation To settle on the best dose that maximizes efficacy and has the greatest benefit risk profile. I think that's exactly what we've done with the regimen that we've selected. And as I mentioned, on my response to one of the other questions, What I see in these data with the regimen that we're selecting is in vitro chloride transport That is even better than Trikafta.

Speaker 2

Sweat chloride levels, which is the most Approximate translation of chloride transport, so the sweat chloride levels in our Phase 2 trial, that are higher than what we saw with Trikafta. And PPFEV1, which you know has greater variability, that is also showing us potential to be better than Trikafta. I have to Say what is obvious, Trikafta is a great medicine. What we saw in the clinical trials has been recapitulated in the real world. You heard Stuart talk about the longer term data with Trikafta that is just continues to look excellent.

Speaker 2

But we think we have something that might be even better than that with 121,561,561 tezacaftor And I'm really looking forward to the Phase 3 results.

Operator

Thank you. I show our next question comes from the line of Paul Matteis from Stifel. Please go ahead.

Speaker 14

Great. Thanks so much and congrats on the quarter. I just had a couple Other APOL1 questions, if you don't mind. One was just on finding these patients. I know the study or at least per clinical trial that's been going on for a little over a year and the implied sample size is estimated to end up at around 10.

Speaker 14

Has it been difficult Fine patients, is genetic testing a headwind? And then second, Reshma, I know you talked about this is obviously a first study, Double digit proteinuria is a goal. Can you just kind of contextualize that in terms of what thresholds have changed in proteinuria have predicted clinical benefit in the past? Is there some sort of minimum change that has been relevant to get FDA comfortable with accelerated approval? Thanks so much.

Speaker 2

Yes, yes, all great questions about the APOLL1 mediated FSGS program. Let me start with the clinical trials and the enrollment and such. 1st and foremost, We are on track to have results in this calendar year and the second half of the year. It has been a study that has taken some time to enroll and I'm not surprised about that. The factors that we need to think about are remember this study started right in the midst Of the pandemic, actually right when the pandemic was hitting a real high point in terms of case numbers here in the U.

Speaker 2

S. The second is that, this is a disease that for which we don't routinely employ genetic testing in renal medicine. So it takes a little bit of time to find the patients, genetically test them and have them enroll in our studies. And the third thing is APOL1 mediated FSGS is the smaller of the spectrum of APOL1 mediated kidney disease And the APOL1 mediated FSGS patients because it's a smaller component, they are spread across the U. S.

Speaker 2

And they don't necessarily live close To a testing center and so that was particularly difficult in the pandemic. With regard to what we are looking for, we are looking for percent decreases in proteinuria and I think double digit decreases in proteinuria In this Phase 2 study, which is a 1st in class molecule for this genetically validated target It would be just excellent. And the question around what is the agency looking for and such, It really depends on the kidney disease of interest. We are looking at a homogeneous kidney disease. It is all genetically defined and I think that that falls into a category in and of itself.

Speaker 2

And as I said, there is no precedent for this. We are the first to bring a targeted therapy for APOL1 mediated kidney disease. But I do think a percent reduction in the double digits would be very meaningful.

Speaker 4

Thanks a lot.

Operator

Thank you. I show our next question comes from the line of Brian Skorney from Baird. Please go ahead.

Speaker 15

Hey, good afternoon, everyone. Thanks for taking my question. Mine is really on the diabetes program. Just strictly thinking about the opportunity in patients who are going to require lifetime immunosuppression. How do you kind of think about differentiation from your cell line from sort of the cell trans donor cells, which I think Should probably get approved in the next month.

Speaker 15

Is there a supply constraint there due to sourcing that you think over you overcome with the sort of the stem cell line? Are there other characteristics of differentiation that you think can make Your technology worked better. And then in terms of I know you're working on sort of encapsulation for protecting the differentiated islet cells reduce immunoreactivity. But are you exploring other ways, such as the induction of immune tolerance or cell editing to Get around the need for immunosuppression as well and any thoughts on sort of those pathways?

Speaker 2

Yes. Really, really great questions, Brian, thank you for those. I'm really happy to talk about the Type 1 diabetes programs. I'm sure you can hear from the enthusiasm in my voice. It's One of the ones that is, really holds enormous potential for patients.

Speaker 2

So let's just start at the very top of the funnel. There are more than 2,000,000 patients with Type 1 diabetes in the U. S. And Europe. So the potential to help patients is enormous, when you look at it from that perspective.

Speaker 2

I'll take your second question first about encapsulation. I do think that it will be important to have the cells being capsulated in a device or in some way Be immune evasive so that you don't require immunosuppressants to be able to get to all of those patients. I think that the device approach is elegant because it has the benefit of simplicity. That's not to say that it's a simple device, but it is to say that the cells encapsulated with this device Then don't require any further manipulation, which is elegant. That all being said, we are very The lead approach is with the cells encapsulated in the device.

Speaker 2

With regard to the Cadaveric cells and the cells that are available currently. The big differentiator and this is really important to understand because it's fundamental. Those cells are cadaveric cells And those cadaveric cells have all of the limitations that have made the procedure difficult for patients to undergo. That is to say quality and quantity of cells are limited. Our approach is a stem cell derived, Fully differentiated insulin producing islet cells and that makes quantity not an issue And quality not an issue.

Speaker 2

And so that's really the foundational difference between our approach, and the other.

Speaker 15

Great. Thank you, Ashma. That's very helpful.

Speaker 2

Yes, sure thing.

Speaker 1

Operator, we have time for one more question.

Operator

Thank you, sir. Our last question comes from the line of Alethia Young from Cantor Fitzgerald. Please go ahead.

Speaker 2

Hey guys, thanks for squeezing me in.

Speaker 4

Just a quick question on how you're kind of thinking about maybe kind of external deals, maybe or is there an interest in kind of Concept or are you still kind of focused on kind of earlier stage deals? Thanks.

Speaker 2

I'm sorry, Alicia. I didn't We couldn't hear your question in the room. Could you repeat your question?

Speaker 4

No, I think you can see external bills kind of in Early stage or in the late stage? Because I guess, just thinking about timelines with the alpha antitrypsin program being a little bit more delayed than we thought. Thanks.

Speaker 3

I think the question is about deals, external deals we're looking at, what phase might we be looking at?

Speaker 2

Hello? Sofia, we're interpreting your question

Speaker 6

and then talk about Can you

Speaker 4

hear me now?

Speaker 10

Can you hear me now?

Speaker 2

Can you hear me now?

Speaker 1

We can hear you.

Speaker 2

Yes. Basically, I'm just asking about kind of external time lines, external development, Kind of aspirations like whether you're looking at more proof of concept still or are you looking at kind of earlier stage development programs that you kind of

Speaker 4

have gone with in light of what's been going on with alpha

Speaker 2

Sure thing. I think you're asking about business development and how we're doing That's right. Yes, okay, and external innovation. Althea, we are we have been and we remain today very focused on innovation, both internal and external. And we've talked in the past about our And we've talked in the past about our areas of interest and how we view this, namely in CF, In tools to augment our toolbox and assets that fit our sandbox diseases, all of those Stay exactly the same.

Speaker 2

Our R and D strategy encompasses both internal and external innovation. You have never seen us invest more in our internal innovation. Our pipeline has both Sources of assets both from our own pipeline and what we brought in from acquisitions like Sema and Axonics and partnerships like CRISPR and Moderna, and you should expect us to continue in the same way.

Speaker 4

Great. Thank you.

Operator

Thank you. This concludes our Q and A session. At this time, I'd like to turn the call back over to Mr. Patrick for closing remarks.

Speaker 1

Thanks, operator. Thanks, everybody, for tuning into tonight's call. The Investor Relations team is in the office, and we look forward to any additional questions that you have. Have a good night.

Operator

This concludes today's conference call. Thank you for participating. You may now disconnect.

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Earnings Conference Call
Vertex Pharmaceuticals Q2 2021
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