Krystal Biotech at Goldman Sachs Conference: Strategic Insights on VYJEVEC

On Tuesday, 10 June 2025, Krystal Biotech (NASDAQ:KRYS) presented at the Goldman Sachs 46th Annual Global Healthcare Conference 2025, offering insights into its strategic initiatives. The company highlighted both promising developments and challenges, focusing on the VYJEVEC launch, pipeline progress, and future plans. While the company showed optimism in its commercial performance and pipeline potential, it also acknowledged the need for strategic adjustments to enhance its market presence.

Key Takeaways

• VYJEVEC compliance rates have surpassed expectations, currently at 83%.
• Krystal plans to expand its sales force to improve prescription pull-through.
• The company is preparing for a European launch of VYJEVEC in Q3.
• Progress in pipeline programs, including inhaled delivery for CF and AAT deficiencies.
• The FDA’s supportive stance on ultra-rare diseases could accelerate approval pathways.

Operational Updates

VYJEVEC Launch and Commercial Performance

• Compliance rates have exceeded initial projections, reaching 83% compared to the expected 50%.
• The company is expanding its sales force, potentially increasing reps by 50% to 75% by year’s end.
• Pauses in treatment, driven by wound healing, are seen as a positive indicator for long-term use.
• The company is confident in the 1,200 addressable patient population in the US, with potential to expand by 1,800 patients.

European Market Strategy

• Krystal is set to launch VYJEVEC in Europe in Q3, with a focus on France and Germany.
• Administrative preparations, including pricing negotiations and team placement, are underway.
• The company anticipates a slower compliance rate in Europe due to a broader label.

Pipeline Updates

Inhaled Delivery Platform

• Programs include CF, AAT deficiency, and oncology, with demonstrated safety across 50-60 patients.
• The AAT program showed promising data in bronchial biopsies and lavage.
• The CF program aims to demonstrate protein expression in null patients, with plans for a redosing paradigm.

NK Program for the Eye

• Animal studies have shown successful delivery to the cornea, with sustained expression for a week.
• The company plans to dose patients in the coming weeks, aiming for a new label and NDC number.

Future Outlook

VIGAVAC Expansion

• Krystal is targeting the eye indication for VIGAVAC, potentially expanding the franchise value to over $1 billion.
• Pricing for the eye indication aims to match the skin indication if supported by data.

FDA Interactions

• The FDA’s commitment to ultra-rare diseases is seen as an opportunity for accelerated approval pathways.
• Krystal emphasizes the importance of demonstrating mechanistic functionality for drug approval.

Conclusion

For a comprehensive understanding of Krystal Biotech’s strategic direction, readers are encouraged to refer to the full conference call transcript below.

Full transcript - Goldman Sachs 46th Annual Global Healthcare Conference 2025:

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Everyone for joining us. I’m Andrea Newkirk, one of the biotech analysts here at Goldman Sachs, I’m super excited to be joined by the team from Crystal Krish Krishnan, Chairman and CEO, and Suma Krishnan, President of R and D. Thank you guys both for joining us.

Krish Krishnan, Chairman and CEO, Crystal: Thanks for having us, Sandra.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: So maybe before we dig into the pipeline, which has been having some really exciting advancements, most recently on the back of ASCO, and your upcoming data reads in CF and AAT. Krish, maybe we can start just on the VYJEVEC launch. What are you seeing right now in terms of where you stand in the transition from an induction to a maintenance phase? Where are we in the launch?

Krish Krishnan, Chairman and CEO, Crystal: Yeah. At the time of launch, eighteen months ago, we had assumed we would be at a 50% compliance by now. We’re ahead of that number. And no matter how you calculate compliance, we’re in the 83% plus or minus 5% range. So we’re ahead of that.

And that has to do a lot with the percentage of RDEB versus DDEP patients on the study. Right now it’s seventythirty. And at some point, when that ratio heads towards equally distribution, we expect compliance to come down to 50%. But I will say our conviction in the total market opportunity is just as strong, in fact stronger than it’s ever been. We realize that some of the low hanging fruit has been captured by Bejewet.

And now as we go further into the community, we’re proactively trying to figure out how to strengthen the commercial team in The U. S. To get those opportunities brought in a lot faster.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: You could speak to what those efforts are. You’ve talked about expanding the sales force. But how does that logistically improve the operations?

Krish Krishnan, Chairman and CEO, Crystal: Yeah. We started with 17 reps across 52 states, which is about three reps per state. And as you’re done with the low hanging fruit, just time wise, it takes a rep longer to drive to a physician. As awareness is low as you go into physicians further in the community, it may take a couple of cycles of visits before you help them understand a gene therapy that’s herpes based that’s dosed at home. And so one of the things which a lot of rare disease companies do is to maybe have a rep focused on two states or one state per rep, which is another proxy for saying we’re just increasing the effort required to pull a prescription through.

So logistically, we’re just trying to make it a little bit easier to get these prescriptions done faster for the patient.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: On the idea that some of these physicians use multiple cycles, on average, what is the number of cycles or number of visits that they need to really start to understand the value proposition of VIGIVAC?

Krish Krishnan, Chairman and CEO, Crystal: Well, it all depends on the physician, the type of patients they have. Some of the community physicians have had exposure to KOLs for one indication or the other. And they come up to speed. There are some dermatologists in the community on whom we have to help understand that it’s a neposomal virus and doesn’t integrate into your DNA. Realize that although it’s herpes based, it’s not replicating.

And some of the toxicities associated with herpes does not exist in the vector. So in terms of cycles, Andrea, it’s tough to say whether it’s one or two or three. But definitely longer than talking to a KOL in one of these centers of excellence or close to a center of excellence and being able to pull a smartphone through.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: That makes sense. And how quickly do you think you could start to see the benefit of this expanded sales force?

Krish Krishnan, Chairman and CEO, Crystal: My expectation is we’re starting to see some benefit in Q2, a much higher benefit in Q3. And by Q4, it should stabilize. But definitely we’re looking for an impact in the Q3, Q4 time frame starting now.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Okay. So you would look to reevaluate whether or not you needed to potentially even expand even further when you get into the back half of this year?

Krish Krishnan, Chairman and CEO, Crystal: Yeah. The max we can get to is just to have one state per rep. But obviously, in a rare disease, that doesn’t make too much sense, especially dealing with Alaska, Puerto Rico, Hawaii, or some of those states. So the answer is somewhere between fifty percent more versus seventy five percent more. And we’ll definitely get to that point.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Got it. Let’s talk about the nature of the pauses that you’re seeing right now, because that is probably driving some of the dynamics we’re seeing in terms of the maintenance and the utilization that you referenced. Speak to us about what you’re hearing from the KOLs or from the patients as to how they’re experiencing the benefits of VIGIVAC.

Krish Krishnan, Chairman and CEO, Crystal: Yeah. want to start with saying pauses are a really good thing for VYJOVAC. We try not to influence pauses in any way. Pauses is what leads to the drug having a long tail. And what I mean by tail is this is a chronic application.

We want patients to get their wounds healed, take a break, get back on drug when they see disruption or when new wounds appear. And we want that cycle to continue for a very, very long time. And that happens when patients pause. That’s a big positive for us. A lot of patients get engaged in more physical activity, a lot of patients doing things they’ve never dreamt or having done before.

So the number one driver for pauses is complete wound healing. There are always a small percentage. And I would say like ninety percent or a very high percentage there’s always mortality involved. Or some of these patients go through some other serious condition that’s above and beyond the skin, whether it’s blood related or blood transfusion related. We can go on and on.

In some cases, they have to leave the country for whatever reason. And there are some adults with mild indications who probably don’t like a nurse visiting them week after week and would rather apply Visovac themselves, which Suma is working on trying to get the label modified for caregiver or self administration, which is what we got in Europe. So what we try and do is to make sure the patient experience on the drug is fantastic. And so pauses, which are tough to predict because Q1 was the time we saw a somewhat meaningful pause after patients have been on drug for eighteen months and some of them in the OLE. And we thought that was great.

And we’re already starting to see some of those patients get back on drug in Q2. So we love this. And this is going to continue, right? So last night, in one of my described the launches and kind of technically an upward sloping sinusoidal curve. It’s the easiest for me to comprehend what our launch looks like, which means if I’m convinced of the market opportunity and I believe the patient experience, physician experience is good, I see no reason why we wouldn’t realize the opportunity to the 1,200 and beyond in The US.

Perfect.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: How meaningful is that, Suma? Chris just talked about caregiver self administration. You have that on the label in Europe. What activities are underway right now to bring that to The US? And how could that impact utilization?

Suma Krishnan, President of R and D, Crystal: I mean, we had to do some human factor studies, which we completed. Unfortunately, it was not within the time of the BLA. We didn’t want the BLA to get delayed to get that into the label. But all those studies were completed to support getting that in the label in Europe and soon in Japan. So we have provided that data to the FDA.

And they’re in the process of extending the label. So the FDA is completely aware of this. And it’s something we already submitted the protocol. So it’s just the timing.

Krish Krishnan, Chairman and CEO, Crystal: I would say on utilization, look, it obviously doesn’t affect the young, severe patients in the study. Parents are pretty good about utilization. What it will impact utilization is on 20, 30 year olds suffering from mild to moderate forms of the disease, which is predominantly dominant, EB, we really think that getting that on the label is a tailwind to compliance. While on one hand, I’m talking about compliance going from 83 to 50, Getting caregiver administration of the label could make that even longer if we get that in a timely fashion.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Got it. So the path to getting to 50 just makes sense instead of dropping

Krish Krishnan, Chairman and CEO, Crystal: Look, trying to get a patient, especially if you’re an adult, and you see what a nurse does on dominant wounds, which is drop the gel and put a bandage, scheduling week after week is a bit of a chore if you’re mild to moderate for them. But it’s a great way to start and know that they’re seeing benefits. I think trying to get this label change in a timely fashion we’re already halfway through the process right now. So we’re excited that we’re timely in terms of making that label change and getting them back on drug within higher utilization.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: So you mentioned that you’re already starting to see some patients come back. So if you could characterize for us what the extent of these pauses has been. Do you see a variation between RDEB versus DDB patients? And then just logistically and mechanically, how easy is it for patients to restart Vigevac?

Krish Krishnan, Chairman and CEO, Crystal: Correct. I do want to say that if you are a severe patient, you’re not at the point of complete wound closure yet, twelve, eighteen months, most of the pauses we see are predominantly on the mild moderate side. We expect the wound to be healed for about ninety days based on science, because the half life of collagen is about thirty days. That’s the median average expectation to come back. But not all wounds heal at the same time.

So while a patient achieves complete wound closure, there could have been a prior wound that has been closed already for sixty days. So in terms of coming back, anywhere between 30 to 120 is fair game, depending on the severity, depending on when the wound closed. So it’s tough to put a finer point on that number. Maybe over time we’ll get a better idea. But right now, it’s really in a month and four months is my best guess.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: In aggregate, how many of your patients who have started Vigevac have paused?

Krish Krishnan, Chairman and CEO, Crystal: You mean what percentage? Do you have

Andrea Newkirk, Biotech Analyst, Goldman Sachs: a sense as to what percentage are taking a pause that’s more than just a missed weekly dose that maybe they’re traveling, but have paused because their wounds are closed?

Krish Krishnan, Chairman and CEO, Crystal: Well, the reason they hesitate we haven’t shared that information. I wouldn’t characterize it as a significant impact to the revenue line today. But the problem with all these stats is they’re so dynamic in nature that any number I say has no indication of what’s going to happen in the future, including on pauses. For a long time in Q1, we thought about, hey, should we estimate? So investors can have a good idea of how much is the demand versus how much is the pause.

But it is really difficult for us to especially with patients coming back, pauses are not unidirectional, which is why I talked about this upward sloping sinusoidal. But I will say we haven’t had a single instance, or at least to my knowledge, of somebody pausing or not being on drug either because of the safety or the efficacy of the drug. Every reason I’ve heard is some kind of administrative annoyance on the nurses or some serious problem with their health. None of it is and some obviously would like the the one comment I’ve heard on Vaishevac from the severe patients is, is there an opportunity to increase the weekly dose? Outside of that, I have not heard any particular criticism on the safety or the efficacy of the drug, which tells me that this could be a franchise that extends for a long time.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: You mentioned earlier that you continue to have confidence in what the addressable population is, the 1,200 patients. Just help us understand what work have you done to continue to have that confidence? You’re almost two years into the launch. What’s helping that?

Krish Krishnan, Chairman and CEO, Crystal: Look, 81.2 is the ICP10 code for claims data. It can be analyzed through multiple data sets. And you can actually pinpoint a unique claim to a patient. I would also advise that any investor interested in doing so can obtain their own ICP10 data and do exactly the same analysis we’re doing. And we have been doing it every week, every month for the last twelve, fifteen months.

And we’re significantly convinced that the opportunity does exist. Yes, is true that some of the patients, it takes a bit longer. But that does not reflect on the market opportunity. And actually, we can go as far as saying we also get claims hits on non DEB specific but symptomatic related ICP claims, which is maybe 81.9. And if you analyze ICP 81.9, you will also align on that while there are 1,200 identified patients, there is a definite potential of another eighteen hundred that we can get over time.

Obviously, will take a bit longer. But we feel very confident about the opportunity in The US. And I will say, when we see when we speak with high confidence on the 1,000 identified patients between France and Germany, or the 200 to 400 patients in Japan, it’s inconceivable to believe that The US market could be that much smaller.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: That’s a good segue to Europe. And your prelaunch activities are underway ahead of launching later this year. Where do you stand with preparations? When could VIGEFEC be commercially available there?

Krish Krishnan, Chairman and CEO, Crystal: We’re looking to launch in Q3. Most of the work we’re doing right now is administrative in terms of getting the labels and the cartons and the right language and the right shipping mechanisms in place, both in France and in Germany. In France, it’s technically not called a commercial launch. It’s under this AP2, which is kind of like an access slash it’s kind of like the access protocol you’re in while you’re negotiating a price with France. Given the broader label we have in Europe in terms of caregiver administration or self administration, We believe compliance could be would take longer to get to 50% than in The US.

So overall, we’re very excited about the European launch. Based on the drugs profile, we actually believe we could get to a good price that we’re comfortable with, at least in Germany and in France to begin with. The team is in place. So we look forward to a Q3 launch and then build upon that rest of the year and next year.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: You’ve spoken in the past about some potential bottlenecks as it relates to just logistics of patients coming in, seeing their physicians, starting treatment. What is Crystal doing specifically to kind of work through those bottlenecks?

Krish Krishnan, Chairman and CEO, Crystal: Yeah. Just to clarify, the hurdle is the before the physician writes a prescription, they would like an in office visit with the patient. And we’ve been aware of this issue for a while. And we’ve been working very hard to figure out a way to allow a lot more patient visits. To give you an example, once we pinpoint the launch date in Germany, we would have the reps detailing the physicians and work with them to find a way to get patients into the office, given that launch date.

So that effort will start to happen once we figure out whether the launch is on a particular day or a particular week. We’re also working with the KOLs to one of the time consuming parts of an appointment is the bandaging and unbandaging of the wound in a patient. And so what we work in terms of additional nursing assistants to the extent we can under compliance make sure that we make the life easy on the physician to see a patient and write a prescription. So I know Laurent, who runs who’s the general manager in Europe that is, if there is a hurdle with respect to The US launch, it’s getting the patient to come into the physician for the time. And anything we can do to make that faster will significantly help with the launch dynamic.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: And as you think about potential other expansion opportunities for BVAC, most notably in the eye, Maybe give us an update here on where that stands ahead of your phase three trial.

Suma Krishnan, President of R and D, Crystal: I mean, we should be dosing patients pretty soon, as we said. So that’s moved along. We have a natural history study. We have collected substantial data on patients from the natural history studies. So we have patients ready to go and launch.

It’s a decentralized study. This is one of the I think we are the company to do a decentralized study, which is good and easy too because the drug can be taken by the option care nurse. And patients can administer at home. And they don’t need to come into the clinician’s office quite often. So it’s great that they’ll be compliant.

So we have the patients ready to go.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: It’s just getting it up and running. So we expect that to begin shortly. And you’ve spoken in the past about VIGAVAC in the skin being a 1,000,000,000 opportunity. When you think about the incremental opportunity afforded by expanding to patients with eye lesions, what does that represent?

Krish Krishnan, Chairman and CEO, Crystal: It’s too early to talk about pricing on VijoVac in the eye. But the eye look, you saw that New England Journal paper of a kid going from blindness to twentytwenty vision. I’m not saying that all patients with lesions in the eye are blind to begin with. But the value proposition in the eye, as you can imagine, is far bigger I wouldn’t say far bigger is bigger than the value proposition in the skin when it comes to site. Depending on the data and the phase three study, our objective is to make thing I want to say is we hope to get a new label and a new NDC number of feedback in the eye.

And I think if the data supports it, we could have a value proposition to price at parity to the extent we can. That would be the objective. Obviously, it affects about half the RDEB patients and ten percent to fifteen percent of DDEB patients. So definitely it would take the value proposition of the Vizurex franchise with the eye and the skin north of $1,000,000,000 But it remains to be seen what the impact is in other countries in Europe and Japan. Right now what we’re focused on is getting the clinical study going and getting a good result by the end close to the end of the year and filing for approval.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Maybe we can focus on the pipeline here, Suma. There’s been so much focus in 2025, even starting the end of 2024, on your inhaled delivery platform. Maybe just to level set for everyone here, what have you seen across these multiple data sets that gives you the conviction in your platform’s ability to go into the lung?

Suma Krishnan, President of R and D, Crystal: I mean, as you know, we have three programs in the lung. And data from all of those three programs consisting that the message is very safe to administer the drug. Because there’s a lot of safety concerns when you deliver bacteria into your lung. Does it cause pneumonitis or any kind of other lung complications? And clearly we’ve demonstrated we’ve dosed over fifty to fifty five patients or 60 across all our three programs.

And we know it’s safe across different concentrations or doses from all the way from E8 to E10. We know it’s safe. So we have a good dose ranging, different doses that we can play around with depending on the kind of disease or the indication. So it’s certainly safe. We’ve also seen preliminary data of basically mechanism because we know, as you we shared data on four zero eight end of last year where we did do bronchial biopsies in lavage.

We clearly see expression of A1AT. And we also show that not only does this produce the protein, but it also does functionality. I mean, the main reason for AAT is to neutralize the neutrophil elastase because that’s the one that destroys your lung tissues and is the issue. So we know that A1AT the A1AT we produce is functional. It’s a wild type protein.

It can bind to neutrophil elastase and it can reduce neutrophil elastase in the lungs. So mechanistically, we’re very confident with a single dose and at the mid dose level that we show I mean, expression and functionality. So that means it does transfuse and infect the lung cells even through mucus membrane. And it can produce the protein. Hopefully our next goal is in CF to demonstrate the same because we’re going to start dosing patients, null patients.

And hopefully we intend to do bronchoscopy and validate that expression of the vector can transduce the right cells. And I mean, we already know that it transduces the right cell based upon monkey cells. It transduces the globulin cells, the cells, for example, in CF. That’s the cell type that you need in faction to produce the protein, because in CF it’s a membrane bound protein. So we feel pretty confident based on NHP model.

We hope to validate that in our null patients. And of course, four zero seven zero seven in the lung with oncology, again, we have shown that obviously we’re delivering IL-twelve, IL-two directly to the lungs. So we do see immune response. And we have seen early signals of efficacy by we see some partial responses, some stable disease. So very promising data, which we presented into ASCO, which we feel very confident now to move that program into the

Andrea Newkirk, Biotech Analyst, Goldman Sachs: next step. As you think about those three data sets two we’ve seen, one is coming shortly. How do you think about prioritizing one, two, maybe all three of those programs across the respiratory portfolio?

Suma Krishnan, President of R and D, Crystal: That’s a good question. I think the beauty is I mean, the biggest obviously, the clinical is a challenge. I mean, enrolling patients, getting the studies going. But the biggest hurdle is CMC. So CMC is manufacturing, making the validation batches, the And as you can see, many of the companies in gene therapy stall with CMC because that causes them the delay.

That causes them consternations with all of the assays and CRLs because of the issue. I mean, obviously the vector is common across all our programs. So our CMC is going to be a platform technology, which we are obviously going to take advantage of and file. As you know, our CMC has been audited not just by manufacturing. It’s been audited just by FDA, twice by the FDA, by EMA, by Japan, globally.

And we have come out globally well in all of the CMC. So very confident in that CMC. And the CMC is, across all of these programs, very similar. So we feel that can that should not be an issue. We should be able to and our assays are common across multiple of these programs.

So we need to execute on the clinical side for both CF, especially for CF and null patients. I mean, I had the opportunity to meet with the leadership team at the FDA at the CEO meeting at the Silver Spring. And I was able to have discussions one on one and in a group forum. I feel like the new FDA leadership is very committed to specifically ultra rare diseases. So mean, so much to so I mean, I’ve heard them say that as long as you have a drug that shows mechanism, that if you have a gene that’s missing and able to deliver protein and you can show expression of the protein and functionality of the protein, they’re willing to approve the drug because they think these patients need them now.

They are Okay with no clinical studies proceeding based on that and then confirmatory trials, just like what they do in oncology. So I think we have a very favorable leadership right now. Mean, was concerns with Peter Marks leaving because we worked with him on getting approved. So I feel that we have a path forward. We just need to get the data.

And we’ll have those discussions with the agency and figure out an accelerated path for some of these programs that have a real unmet need for these patients.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Maybe frame expectations for the CF read. What is the extent of data? Or how much can we understand from this initial tranche?

Suma Krishnan, President of R and D, Crystal: I mean, obviously, we are going to our goal is to show mechanism. That means we will be bronching and biopsying these patients and looking for protein expression. That’s the key. I think that’s something that has not been demonstrated clearly because we express I know in the past with AAV and other companies, they have done expression of the protein. But in that case, the protein was mini protein.

In our case, it’s going to be the wild type protein that will show expression. So at least there’s no doubt that this is the real wild type protein expression. So our intent is to show expression by biopsy by using immunofluorescence. And also we look at transcript levels to transcript levels of the wild

Krish Krishnan, Chairman and CEO, Crystal: I just want to add, I know we’re dosing a combination of both null patients and patients already on modulators. Our primary focus is on showing a good level of expression in null patients. And if we and I don’t want to get into what exactly is a good number because any you have to remember that we’re a redosing type mechanism. And similar to what we’re doing with alpha-one, once we see expression, we’re going to move into a redosing paradigm. So we’re pretty excited about, like we’re eagerly awaiting results of the CF program.

It shouldn’t be too far.

Suma Krishnan, President of R and D, Crystal: I mean, re dosable is a real thing, right? Because if you look at skin, it’s the most immunogenic organ. The fact that we can show that we can deliver BVAC in this highly immune I mean a region that’s open wound, full of immune cells that we can repeat administer and demonstrate functionality, we feel very confident about our re dosability, as Chris said. And also with the of doses, we can we’ve learned so much from VBAC, which we can improve and use that further in programs to make sure we get dosing right, the frequency right. So there’s a lot of lessons learned that we can adapt to a

Andrea Newkirk, Biotech Analyst, Goldman Sachs: new program. What is the relative immunogenicity of the skin versus the lung?

Suma Krishnan, President of R and D, Crystal: I mean, skin is the most immunogenic organ because that’s the So if we can I mean, I feel like in an open wound, I mean, lung, even it’s not open? There’s no I mean, yes, since we have patients, they do have mucus and infections. And so is in skin. So we are able to treat skin that has infection, has stuff. So we feel like the mechanism is proven.

And we should be able to achieve the same in the lungs.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: And how much will we be able to understand on FEV1 improvement? Is too early? It’s too early. Because again, we have to

Suma Krishnan, President of R and D, Crystal: I mean, in a single dose you can’t I mean, FEV1 is there’s also logistical issues. It’s spirometry. There are challenges with the patients. Patients are pretty sick. You can take an FEV1 six times within half an hour and get different readings with 10% variability.

So there’s complexities around it in these sick patients. So we need to see overall improvement with time. We have to repeat administer. And hopefully, we will collect that data with time. But I think for these null patients where they have nothing at the moment and they have the challenges.

Morbidity is another one of the biggest concerns for these patients because they’re pretty sick. If we can show something that we are able to express with CFTR protein and they can tolerate the drug, I think we have a good path forward.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: What does the path look like if you wanted to start redosing? Is it a one month process? No, it’s pretty quick. Mean,

Suma Krishnan, President of R and D, Crystal: we finished this dose and we right away go into redosing. It should not be yeah. I mean, it’s just finishing up this and then amending the protocol.

Krish Krishnan, Chairman and CEO, Crystal: I mean, we’re doing that with alpha-one right Yes,

Suma Krishnan, President of R and D, Crystal: the same patients.

Krish Krishnan, Chairman and CEO, Crystal: So I wouldn’t say like overnight, but within a few weeks we can get into a redosing paradigm.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: And then very quickly on AAT, because you are going to have additional data this year, What should our expectations be for that disclosure? Some of

Suma Krishnan, President of R and D, Crystal: the repeat of what we completed in more patients, additional patients. I mean, obviously this was our study. And we learned some of the challenges because in AATs, it’s little more complicated. Unlike CF, you just bronch any biopsy. You have to lavage.

So there’s trickiness to lavaging. So we have learned some of that because of that. We had patient samples that we were not able to get. Now we’ve gotten better at writing the Lavage protocol. So hopefully we can get additional patients with some more robust data, which you can reproduce some of

Andrea Newkirk, Biotech Analyst, Goldman Sachs: the data that we announced last Have you started dosing in the higher dose cohort?

Krish Krishnan, Chairman and CEO, Crystal: We are working to redose

Suma Krishnan, President of R and D, Crystal: Okay. In the mid-.

Krish Krishnan, Chairman and CEO, Crystal: But we are working to enroll patients in the high dose with thinking about zero point seven micromolar that we saw in the alpha-one, we actually believe we have a good beachhead to redose. The safety profile was excellent, right? So while we could potentially get a much higher number, the internal conviction is, look, with a couple of redosing paradigm and a clear safety profile, we should not ignore the mid dose. So I think our just in terms of steps, both are happening, we’re trying to quickly get the protocol. Like we’ve already got the protocol modified and go into the redosing while we continue to look for one or two patients just to see if the high dose is meaningfully different.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Maybe in the last couple of minutes here I want to touch on NK since this is here. I think this is an exciting new program for you. Talk to us about what makes you so excited about the opportunity here.

Suma Krishnan, President of R and D, Crystal: We’re super excited about NK because we already shown that we can deliver to the cornea, front of the eye, with our VBAC program. Clearly, we see that in our animal studies. In our animal studies, which is a big proxy for what’s going to happen in the humans, we know with a single dose recombinant NGF protein, it’s gone in minutes. And if you give a single dose versus our vector just topically applying to the eye, we see sustained expression for a week. So we are super excited about that because I think it’s a known mechanism, well proven.

And we know exactly the number of patients you need to show statistical significance. So understanding based on what Oxovate has done, which is considering that they have to administer six times a day in these patients. And now speaking to a lot of the experts and physicians in this area, they are super excited about having a product that where these patients, especially elderly patients, that you have to just put one dose. They can remember it. It’s easy.

They’ll be compliant. They say OxoAg works, but the challenge is patients don’t like it because they’re not compliant. So it doesn’t work the way it’s supposed to. So I think knowing the mechanism, knowing a pathway, knowing I think it’s just execution.

Krish Krishnan, Chairman and CEO, Crystal: We’re hoping to dose our patient in the upcoming weeks. We’ll definitely provide a pretty comprehensive review of the market opportunity, number of patients across U. S. And the rest of the world, and the study design that we’re going into phase onetwo with. And Simone will probably talk about next steps to get the drug approved during that call.

Great.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Well, looking forward to it. I mean, sounds great. De risk mechanism, known regulatory pathway. That’s half the battle, pal. And CMC.

Yeah.

Krish Krishnan, Chairman and CEO, Crystal: So we don’t have to debate or depend on the FDA. If you know the endpoint and you know the design, it should be execution.

Andrea Newkirk, Biotech Analyst, Goldman Sachs: Great. Well, you guys both for joining us. You. You, everyone.

Krish Krishnan, Chairman and CEO, Crystal: Appreciate it.

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