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# Vertex Pharmaceuticals Incorporated presents at 2024 Cantor Fitzgerald Global Healthcare Conference

Tuesday, September 17, 2024 9:10 AM

# Event Participants

Analysts 1 Olivia Brayer

Executives 2 Susie Lisa, Manisha Pai

# Olivia Brayer Analyst

Thank you for joining us this morning at our Cantor Global Healthcare Conference. Really excited to have another year of it. My name is Olivia Brayer, I'm a senior biotech analyst here at Cantor. And we're really excited to have the Vertex IR team with us. We have Susie Lisa, who is Senior Vice President; and Manisha Pai, who's Executive Director of IR.

Thank you guys so much for being here.

Susie Lisa Executive

Thanks, Olivia. Thanks for having us.

# Olivia Brayer Analyst

Yes. Of course. Well, just to kick it o!. I mean, I think everyone in this room is very familiar with the Vertex story. So maybe just give us a sense of the state of Vertex today and the direction that the company is heading.

# Susie Lisa Executive

Sure. And thank...

# Vertex Pharmaceuticals Incorporated presents at 2024 Cantor Fitzgerald Global Healthcare Conference

Tuesday, September 17, 2024 9:10 AM

# Event Participants

Analysts 1 Olivia Brayer

Executives 2 Susie Lisa, Manisha Pai

# Olivia Brayer Analyst

Thank you for joining us this morning at our Cantor Global Healthcare Conference. Really excited to have another year of it. My name is Olivia Brayer, I'm a senior biotech analyst here at Cantor. And we're really excited to have the Vertex IR team with us. We have Susie Lisa, who is Senior Vice President; and Manisha Pai, who's Executive Director of IR.

Thank you guys so much for being here.

Susie Lisa Executive

Thanks, Olivia. Thanks for having us.

# Olivia Brayer Analyst

Yes. Of course. Well, just to kick it o!. I mean, I think everyone in this room is very familiar with the Vertex story. So maybe just give us a sense of the state of Vertex today and the direction that the company is heading.

# Susie Lisa Executive

Sure. And thanks again for having us. I'll start there. I think it continues to be a really exciting time at Vertex with a lot of strong momentum. Maybe to start with our commercial execution in CF, where we reported just last quarter -- last month, excuse me, and our Q2 results were very strong across the board.

And we raised guidance by $$ 100$ million. So now we're calling for $$ 10.65$ billion to $$ 10.85$ billion in total product revenues. That's $9 %$ growth at the midpoint. So continued strong

performance in CF.

And then two, I think as we continue to execute commercially in CF and then adding in CASGEVY, where we're providing early metrics on ATCs that we've authorized as well as patient cell collections, good progress there. And we're really excited for continuing this new era of commercial diversi"cation with the announcement that we had submitted and had 2 NDA "lings accepted and both are under priority review. So one is our vanzacaftor triple with a PDUFA date of January 2, of 2025, that's in cystic "brosis.

And then the second is suzetrigine for moderate to severe acute pain. And that's a PDUFA date of January 30 of 2025. So really excited to potentially 2 new launches in early 2025, and then from continued development of the pipeline, I'd say, broad strength and making good progress and 3 things that we highlighted. One is that also in our pain franchise on the chronic pain or peripheral neuropathic pain side of things. We accelerated the time lines for results of our Phase II study in lumbosacral radiculopathy or LSR will now have results by the end of this year.

As previously said, we just completed enrollment. So we saw faster enrollment there, which is always a good thing.

Then we also announced in VX-880, which is our type 1 diabetes cell therapy that we have completed enrollment and dosing in the "rst cohort of our Phase I/II study at 17 patients. We added an additional 20 patients, with regulatory endorsement of that as we move towards pivotal development. And then "nally, really excited post our Alpine acquisition earlier this year, povetacicept. We began the Phase III in IgAN last month. So good progress across the board there and more to come.

# Olivia Brayer Analyst

Yes, you guys have a lot going on. Obviously, busy. It's going to be a busy 2025, and I'm sure for all of us covering the story. I do want to start with pain just because I think there's a lot of interest in pain. Maybe just to start, describe the excitement around the broader pain portfolio at Vertex today.

How you guys think about it "tting into your growth strategy going forward?

# Susie Lisa Executive

Yes. So pain is de"nitely -- we think we have multibillion-dollar potential essentially across our pipeline but pain is really excited for exciting for many reasons, one of them being the public health crisis with the opioid epidemic, the opportunity to help solve that. Secondly is the under management of pain but then from a "nancial perspective, we think it's just massive patient numbers here. And with that unmet need, we see multibillion dollar market potential both in acute pain, where we have the PDUFA date, as I mentioned, next January as well as in peripheral neuropathic pain, which is a segment of chronic pain that we are initially targeting.

And I think that our initial product, suzetrigine, which we're studying in both acute and the peripheral neuropathic pain market is a selective NaV1.8 channel inhibitor. So we're stopping pain where it occurs in the peripheral neurons. And because of that, we don't have any central nervous system e!ect. So you avoid all the side e!ects of opioids, including brain fog, constipation, nausea, et cetera, and there is no evidence of any sort of addictive potential.

And so I think that combination of e!ective pain relief without the side e!ects of opioids and the fact there's been nothing new in pain for 2 decades is a really exciting time for us. There are 80 million Americans who get a prescription for acute pain every year. There are 10 million who get a prescription for chronic pain every year. So massive patient populations. And suzetrigine is just the "rst.

We continue to deploy our cereal innovation strategy. We're already in the clinic in VX-993, which is the next gen that in addition to, we think it could enhance some of the properties of suzetrigine, it can be formulated IV. So we kind of own the patient across the entire experience. and it can also be combined with a future NaV1.7 inhibitor, which suzetrigine cannot.

# Olivia Brayer Analyst

Yes. Well, a bit of a -- it's a little early to ask this question because you don't actually have a drug approved yet. But what inning do you think we're in, in terms of just transforming the overall pain treatment landscape. I mean, obviously, we'll have to see what happens and how it plays out with the commercial launch. But like you said, you do have this sort of "rstgeneration agent.

You are developing next-generation potentially combination agents. I mean, where do you think we are today in terms of actually in the development stage for being able to tackle this landscape.

# Susie Lisa Executive

I think you laid it out exactly right. We're in the early innings, and it's really exciting with the potential launch early next year with suzetrigine, which is our "rst gen. I know our CF team, in San Diego, which is the same team developing pain talks about the scaling like in pain where we were with KALYDECO 10 years ago. So we think it could be that sort of potential. So NaV1.7 activates in the NaV1.8 propagate.

So the thought of having both agents, either singly or in combination, I think, is really compelling to continue to enhance the level of pain reduction, all of which are acting in the peripheral neurons. And so again, you avoid that addictive potential.

I mentioned brie#y that there's been nothing new in this space for 20 years. Obviously, there's trust issues in the market. There's the opioid epidemic and then this chronic mismanagement or under management of pain, given all the restrictions and guidelines and reaction to the opioid epidemic. So we think there's signi"cant potential and the word to use exactly what we're trying to do. We're trying to transform fundamentally and forever the treatment of pain.

# Olivia Brayer Analyst

Yes. And you mentioned acute and chronic, both pain categories, but obviously very di!erent. And I know you laid out some numbers, those are helpful. I mean how do you think about those 2 in terms of areas of priority in terms of obviously, commercial potential is a big part of the conversation, but really just your level of conviction, right, whether it's acute, whether it's chronic, whether it's maybe both, but do you have a higher level of conviction in one of the areas over the other, whether it's commercial, whether it's clinically where you feel like your wheelhouse as Vertex will be in this broader pain market.

# Susie Lisa Executive

Yes. The true answer is that we have equal conviction in both markets, right? I think a lot of investors say, well, for every one -- and it's true for every one chronic pain patient that you get a PNP patient, right? You have to go "nd 26 acute patients, right? the average prescription length in acute is about 2 weeks.

But there are 80 million acute patients, right, and there are 10 million peripheral neuropathic pain patients. So -- and again, I think there are a real need, I think, particularly in the acute side, where patients who have nothing they have -- their lives are perfect. They go, they have a trauma or an injury or a surgery and they develop opioid use disorder and they die, right? It is a real issue. And so to be able to avoid that, I think, is really exciting.

And we intend to fully develop both of these markets at Vertex. We see them both the specialty markets. And longer term, given the mechanism of action, we know from our predecessor molecule VX-150, that it was -- they did have positive proof-of-concept in musculoskeletal, but that is something we look to partner with given that, that is a primary care market, and we're more focused on the specialty aspects of this market.

# Olivia Brayer Analyst

Okay. Understood. So for the specialty aspects of the market, there's no plan to potentially partner them out at this point. They are wholly owned program?

# Susie Lisa Executive

That's right. And our "eld -- you didn't ask this, but maybe just to jump to the next topic. Our "eld force has been hired, right? And sort of our leadership and strategy team has been on board a while. But in June, we completed the hiring and training of our "eld force.

So they are in the "eld now. And we've talked about that 80 million patients split into about half is an area where we won't focus and that's prescribed in the physician's o$ce market.

The other half is the prescription originates in an institution, it may be inpatient, outpatient or ambulatory surgery center, that's about $1 5 %$ of that $5 0 %$ . And the other $3 5 %$ is in the discharge segment. So the script is written in an institution of some form, but you "ll it at your retail pharmacy going home. So we will focus this "eld force on high-volume procedures where there is a heavier component of pain relief needed at home in the discharge segment because we think that will be a potentially faster uptake from working through the system of payer coverage, discharge orders, et cetera. We could see faster uptake there, but we're convinced in the opportunity across the board over time.

# Olivia Brayer Analyst

Yes. And you mentioned the payer coverage, obviously, PBMs and reimbursement is going to be a really important part of that commercial launch. So where are you in terms of those conversations? I mean I know some of them happen -- a lot of them happen once you're actually approved along the market. But is there a legwork that you can be doing now or are doing now as a company to set yourself up for success when it comes to the coverage side of the equation.

# Susie Lisa Executive

Absolutely, yes. And yes. So those conversations are underway, have been underway, recognizing the time lines that are required in this market for whether it's a hospital formulary P&T committee or it's a payer who puts a 6-month moratorium on any new branded medicine, right, but we are having these preliminary conversations through pre-approval information exchange, very formalized compliant method of having these conversations. And as our Chief Operating O$cer, Stuart Arbuckle say, there is no one that we've had a conversation with that isn't excited about the potential for something new in pain that's nonaddictive and provides e!ective pain really back to where your question started. So we're pleased with those.

We said that it will take time to work through this market, but I think we continue to be increasingly excited about the potential.

# Olivia Brayer Analyst

Yes. And then you mentioned earlier, you do have a PDUFA date coming up. The last I heard was FDA was not requiring an AdCom. Any update there? Or is that still, still the latest that you all have heard?

# Susie Lisa Executive

That is still the communication that they do not intend to host an AdCom. They can change their mind any time up to the PDUFA date, but the communication continues to be that they don't expect to happen.

# Olivia Brayer Analyst

Okay. Great. And then in acute, the goal, and you guys have spoken about this many times, but the goal is to get a broad label. But there are a lot of di!erent sort of subcategories, right, within the acute setting. So when you think about the biggest concentration of patients, the areas that you want to tackle "rst, I mean, what are some of those maybe subcategory is the wrong word.

But what are some of those sub-indications within acute pain that are the highest priority areas.

# Susie Lisa Executive

Sure. So maybe just to step back for a sec. We do think this broad moderate-to-severe acute pain label is critically important. There have been other launches recently in pain, but they've been very indication or procedure speci"c. This broad label not only enables us as we studied right, abdominoplasty, bunionectomy, and then an all-comers trial, but it also enables us to tackle that discharge segment, which is the majority of the kind of institutional script

writing.

But then as I mentioned, within that, we're focusing on high-volume procedures where there's a heavy discharge component to the pain therapy. So if you want to think orthopedics, some general surgeries, ER physicians, we're also targeting anesthesiologists, pain specialists, et cetera. So those are the areas of focus.

# Olivia Brayer Analyst

Okay. Understood. And then you said, again, you mentioned earlier, but you guys did pull up time lines for your Phase II LSR readout. That's not expected in the fourth quarter. I know everyone in this room is highly anticipating those data myself included.

Maybe just help us -- help frame what we're looking to see in that study what you all plan to present, maybe how you all plan to present that data? I know that's top of mind for a lot of people as well.

# Susie Lisa Executive

Sure. Yes, we're really excited about the opportunity in chronic pain and peripheral neuropathic pain. We will begin this month, our Phase III in diabetic peripheral neuropathy, which was the "rst indication we tackled within peripheral neuropathic pain, which, as I mentioned, is about 10 million patients, 2 million of those are DPN patients. LSR, lumbosacral radiculopathy or sciatica is the largest patient population. It's about 4 million patients.

So between these 2 indications, again, ultimately, our goal here would be a broad peripheral neuropathic pain label. We have studied positive studies in $6 0 %$ of the patient population.

# Olivia Brayer Analyst

Maybe I'll ask you before we get to the LSR readout for that Phase III trial, how are you guys thinking about enrollment time lines?

# Susie Lisa Executive

We haven't said because we're just beginning now, but we'll update as soon as we have a better sense of enrollment dynamics.

# Olivia Brayer Analyst

You could announce it here.

# Susie Lisa Executive

I think we need to start before we're ready to give a time line. But that is a 1,000-patient study, right? It is a larger study, and we're excited to get going, but we haven't given time lines. On LSR, one of your questions, we'd expect to release top line results in a press release as we did with DPN last December. And the study is looking at -- it is roughly 200 patients.

It is randomized, double-blind and there is a placebo arm for comparison.

There's nothing speci"cally approved in LSR and hence, the placebo control arm. And what we're looking for really is the magnitude of treatment e!ect so that we know how to size appropriately size our Phase III study. And we are looking, just to be clear, within group change from baseline through the end of the study, which is a 12-week study. So there'll be that change in NPRS score, it's a leg pain score on a numerical pain rating system that within group change for the LSR arm and then within group change for placebo. So we'll have 2 numbers, and then we'll look at how they're not powered to be compared directly, but we'll have those to help because placebo e!ect is a very real thing in these studies, as you know.

# Olivia Brayer Analyst

Yes. And I know it will be a press release, but for your initial Phase II chronic readout, when was that last year, maybe December?

# Susie Lisa Executive

December, yes.

# Olivia Brayer Analyst

You did have a call. You did have slides, you did actually show the change.

Susie Lisa Executive

Curves responder, yes.

# Olivia Brayer Analyst

So again, I'm giving you the opportunity to tell us all today. Is that the plan as well? I mean sort of give that level of detail.

# Susie Lisa Executive

Frankly, we always look to be as transparent as possible. So we'll look to make it as helpful and informative as we can. I will say a secondary end point is sleep interference, which has been another an end point that had been in other prior LSR studies. So typically, we cover the primary and then the key secondary endpoints and more to come.

# Olivia Brayer Analyst

Okay. Understood. And then you did mention that it is versus placebo, but no statistical comparison, right? It is a single dose study? That's correct.

So how are you guys thinking about -- I know we'll have to wait and see what the data look like. But in an ideal world, the data meet maybe the internal bar for success, whatever that may be. How do you think about what the Phase III will eventually look like?

# Susie Lisa Executive

I think -- I guess maybe the closest I can come to answering that is similar to what we did in acute pain in certain pursuit of a broad label. Here, you can think that we'd like to try and do the same thing. So potentially a similarly sized study to the DPN Phase III. And then with those 2 indications, perhaps in all comers in practical, but it's really early, and we are not at that

point to -- for us to opine and then, obviously, we need to meet with the agency. But in theory, that could be one avenue.

# Olivia Brayer Analyst

Sure. What about potential time line for initiating a Phase III? I mean you'll have data in hand, maybe even in the next few weeks, couple of months. And then obviously, by the end of the year, we'll see it publicly. But how do you think about mean similar time lines to -- between Phase II and Phase III and time for results in December and then starting in Q3, there's always a sense of urgency at Vertex.

So yes, and I think we're really excited about this opportunity, but stay tuned.

# Susie Lisa Executive

And obviously, we would have to meet with the regulators to talk about what that is the actual...

# Olivia Brayer Analyst

To slow things down, I'm sure. Okay. Great. Well, I know we're all looking forward to those data. And then maybe last question on pain is I know you guys have the NaV1.8, NaV1.7, you've obviously talked a lot about sodium channel blockers in general.

What about other mechanisms that you could potentially use to treat pain, right? I mean, is sodium channel blockers. Is that kind of the wheelhouse that you guys are hoping to continue with the next generation, and the next generation, and the next generation of pain products? Or are there other MOAs out there that you guys are interested in exploring?

# Susie Lisa Executive

I think our view is that it really is kind of the holy grail is a term we use of pain inhibition. And given that you're essentially inhibiting right at the source. And to avoid any sort of CNS impact or all of those side e!ects. But where we'd like to go beyond just suzetrigine inhibiting 1.8, right, as we talked about is continuing to serially innovate along 1.8, so IV and better potency, et cetera. And then with -- to inhibit as well the 1.7 channel, which actually activates the whole system, you could see that use singly, we think, or de"nitely in combination for more e!ective pain release.

So there's a whole pipeline.

As I mentioned, we're already in a Phase I study in the IV formulation for VX-993. And then we're getting underway for 2 studies, both in acute and PNP for 993 as well, and then there are follow-on molecules. And then we'd hope to have something to talk about in 1.7 over the coming quarters, if you will, and then move on to combo beyond that.

# Olivia Brayer Analyst

Well, looking forward to all the progress that you guys are making in paying and all the progress to come. Maybe we'll switch gears to CASGEVY. Obviously, another area that we get a lot of questions on, I'm sure you all get a lot of questions on I mean maybe I'll just come out

and ask it. Have any patients been infused with CASGEVY?

# Manisha Pai Executive

Yes. So we have begun infusing, but as is our practice, we'll provide updates on launch progress on our quarterly earnings calls, speci"cally on patient cell collections and ATCs activated.

# Olivia Brayer Analyst

Okay. Understood. Stay tuned. And then fertility preservation has been a big topic of conversation, and I think a lot of people maybe view it as a gating factor. I mean, how are you all thinking about fertility preservation in -- and maybe that's not just me coming up with that, right?

But I know you all have been blocking and tackling, so to speak, around that as well. So how does fertility preservation come into play? How has that sort of gotten better as the launch has gone on? And how do you think about fertility preservation as you try to have a successful commercial launch there?

# Manisha Pai Executive

Yes. So it's a hugely important question for any of the genetic therapies in the hemoglobinopathy space. The busulfan conditioning that is used to make room in the bone marrow for the edited or otherwise adjusted cells, is a chemotherapy and it can cause infertility. And so it's a hugely important issue. And for our patients with commercial insurance, eligible patients, we have a fertility preservation program in place.

We'd like to be able to do the same for patients with government insurance and we are working toward that goal. But as of right now, we are not able to do that.

# Olivia Brayer Analyst

Okay. Understood. And then Manisha remind me for the revenue recognition, right? Obviously, you sort of initiate that cell collection process. I know it's a lengthy process

Eventually, you infuse a patient. Where along the way does that revenue recognition happen for CASGEVY. And then as kind of a follow-on question to that, when you do plan to provide an update on your third quarter earnings call, maybe give us some insight into, right? I mean, I assume if there is a patient that's been infused, we'll get some sort of revenue breakdown? Will you give us the number of patients that have o$cially been infused.

I mean what level of granularity will we get around revenue recognition, obviously, but obviously, patient numbers.

# Manisha Pai Executive

Sure. So revenue recognition happens at infusion. I don't think we've said one way or another yet whether we will report out on the number of patients infused. But of course, you would see it in revenues. We will probably still focus on the launch metrics that we set forth at the beginning of the year around ATCs and cell collections.

And the second part of your question was...

# Olivia Brayer Analyst

Yes, just revenue recognition which you answered. Okay. Understood. And then obviously, it is an expensive franchise to say the least. And I know you guys haven't necessarily come out with when you expect to hit pro"tability.

But how do you think about spend around the franchise? Are you comfortable with what you're currently spending around the franchise? And then maybe to that pro"tability question, is there sort of a target year when you hope to hit pro"tability? Or maybe it's a sales "gure or whatever you can tell us around pro"tability for that franchise?

# Manisha Pai Executive

Yes. So I think with bespoke therapies like CASGEVY, they're necessarily going to be a bit more resource intensive than, say, a small molecule therapy would be. We are very excited by the physician and patient interest that we've had, the payer engagement that we've had. And as Stuart, our Chief Operating O$cer, said on the last quarterly earnings call, it's becoming more and more clear to us that CASGEVY has the potential to provide transformative bene"t for many patients around the world and become a multibillion-dollar opportunity. Having said that, we are not going to give guidance at this point on long-term pro"tability and time lines.

# Olivia Brayer Analyst

Okay. But safe to say it's still an area of priority for the company.

# Susie Lisa Executive

Absolutely. And one thing if I could just add is as we look at the portfolio over time, right, there's a compelling mix of gene therapies and cell therapies, which certainly don't have the same margin pro"le of small molecules, but there is all the pain therapies, AMKD, pove has attractive margins in addition to CF. So we think the overall portfolio over time o!ers us obviously compelling opportunities for patients and the revenue opportunity, but then an attractive margin pro"le as well.

# Olivia Brayer Analyst

Sure. Well, let's talk about pove. I mean big acquisition for you all something we don't see often from the Vertex team, so maybe just talk through why you decided to make that acquisition, why you felt like it was the right time and really how you think about IgAN, right, and your potential opportunity commercially in the IgAN space?

# Susie Lisa Executive

Sure. So the Vertex approach, I think, can look from outside a little disparate in terms of our disease areas, but it's a really strict corporate and R&D strategy to focus on what we call sandbox disease areas, which have a strict set of criteria and the IgAN space had been in our sandbox. But the approach that we bring in terms of internal programs, that same set of criteria is what we apply to looking at M&A.

And I think given the con"dence in our pipeline, frankly, we haven't felt the need to chase later-stage assets or to get in competitive situations with companies that are facing LOEs, given the patent protection on CF. But we had been watching very closely the development in the IgAN space, and I would say, B cell-mediated diseases broadly. And what we do from an M&A perspective is look at things that can accelerate our existing programs or help us establish a presence in key sandbox disease areas where we don't have one. On the acceleration side, Entrada deal we did in myotonic dystrophy type 1 is the best example. And then on the establishing a presence Semma Therapeutics and T1D and now Alpine Immune Sciences and IgAN and other B-cell mediated diseases is a great example of that.

We -- it was Phase III ready. As you know, we're already in Phase III as per last month.

And I think there is a lot of work being done in this space, as everyone knows. But there were multiple factors that led us to make the decision about Alpine. First was we think the dual pathway inhibition of both BAFF and APRIL is very important in this disease area and others. Secondly, we were really excited by their preclinical data, where we think there is evidence of greater potency. Thirdly, the clinical data, admittedly small ends and early, but continue to see, I think, remarkable reductions in proteinuria and hematuria.

And then 2, I think in this market where it potentially could be competitive, delivery is an important part of it. So subcu every 4 weeks, 80 mg, smaller volume, I think that could be important from a patient's factor and convenience aspect. And then also, I think just the breadth of the development program and their clever design for their basket studies, all of that was what was compelling to us. And we're really excited that integration is essentially done. We're o! and running.

And excited to have started the IgAN study and more to come on the other indications as well.

# Olivia Brayer Analyst

Yes. Congratulations. Trying to "gure out a PC way to ask this, but were there other companies that were potentially in the running in IgAN because it is a very competitive space. There are a lot of companies that are developing assets. I mean I understand the rationale, but were you all looking at other companies?

Were there other companies that maybe you were considering in IgAN.

# Susie Lisa Executive

I think that at Vertex, we pride ourselves on leaving no stone unturned, right? And doing all the research we need to do. There's been a lot of data publicly available in this space over some time. And so really it's all the factors that I mentioned previously about Alpine that we felt it was the clear winner where we wanted to place our bets and acquire Alpine. So we're really excited about the opportunity.

# Olivia Brayer Analyst

Okay. Great. And like I said earlier, you all don't do M&A very often, at least bigger, maybe more public setting. Is that something that we should expect to see more from the Vertex

team going forward?

# Susie Lisa Executive

I think we actually have had a consistent drumbeat of it, but they've been smaller deals. And so I mentioned we apply the sandbox criteria to what we're looking at just as strictly as we do internally. And truly size within that is not one of the criteria. Just typically, though it has been earlier stage in the smaller dollars. But I wouldn't say that we're precluded from doing something like Disney given pove and its pipeline in a product potential, there's a lot to chew on there for a while, just from sort of management time and expertise and integrating and gaining full leverage from that asset.

But from a cash #ow perspective, right, $$ 5$ billion there still leaves us with about $$ 10$ million, and we'll probably replace the cash that we spent for Alpine within about a year's time frame. So we'll continue to look to be acquisitive, but really, size is not one of the key criteria. It could stay small, it could be large again.

# Olivia Brayer Analyst

Understood. And then the other program that you guys are focused on and I've had some interesting data is diabetes, obviously, right? And you do have 2 programs there. You have VX-880 and then you have your islet cell program. Maybe just give us an update.

I know you had some data at EASD. Where do both of those programs stand? And what should we expect next, right, in terms of next data disclosures, et cetera, et cetera?

# Manisha Pai Executive

Yes, sure. So to take a step back, we have 3 programs in type one diabetes that we got when we acquired Semma Therapeutics and they are all based around the same cells, which are the allogeneic, fully di!erentiated pancreatic islet cells. So the VX-880 program is what we call the naked cells program. And there, the cells are infused through the portal vein and patients take immunosuppression to prevent -- to protect the cells essentially and we see this as being suited for the patients with the most severe disease where they have severe hypoglycemic episodes, impaired awareness of their hypoglycemia, which can be very dangerous.

And we think there's about 125,000 of these patients across North America and Europe. So we did share updated data from the Phase I/II study at EASD on Friday. And what we saw was that 4 patients now have reached a year of follow-up and all 4 of those patients have met the primary endpoint of elimination of the severe hypoglycemic episodes and an HbA1c below $7 %$ . And then the one of the key secondary endpoints, all 4 patients are now insulin independent as well. So that's very exciting.

Next steps there. We've expanded the study with permission from regulators from the original 17 patients now to a target of 37 patients and we look forward to having those end of Phase II meetings with regulators to talk about the pivotal path.

Second program, VX-264, we take those same cells and we encapsulate them in a novel proprietary device to essentially protect them from the immune system and the devices implanted in the abdomen. That is in a Phase I/II study as well. It has completed Part A, which was the sort of low dose of it to look at safety and tolerability. And now we're enrolling and dosing in Part B of that study.

And then the third program is hypoimmune program, once again, those same cells, but we gene edit them to cloak them from the immune system, and that is still in the research stage. So not too much to say about it yet.

# Olivia Brayer Analyst

Okay. Great. Well, I know I went a little bit over time. Apologies for that. But Manisha, Susie, thank you so much for joining us today.

I really appreciate a great discussion. Ironically, I didn't talk about CF today, but that's okay.

Susie Lisa Executive Thanks.