Krystal Biotech, Inc. Q3 FY2025 Earnings Call

Thank you for joining us for the Krystal Biotech Third Quarter 2025 Earnings Call. As a reminder, today's conference is being recorded. I will now turn it over to your host, Stephane Paquette, Vice President of Corporate Development. Please proceed.

Good morning, and thank you all for joining today's call. Earlier today, we released our financial results for the third quarter of 2025. The press release is available on our website at www.krystalbio.com. We also filed our earnings 8-K and 10-Q with the SEC earlier today. Joining me today will be Krish Krishnan, Chairman and Chief Executive Officer; Suma Krishnan, President of Research and Development; Laurent Goux, Senior Vice President and General Manager for Europe; and Kate Romano, Chief Accounting Officer. This conference call will and our responses to questions may contain forward-looking statements. You are cautioned not to rely on these forward-looking statements, which are based on current expectations using the information available as of the date of this call and are subject to certain risks and uncertainties that may cause the company's actual results to differ materially from those projected. A description of these risks, uncertainties and other factors can be found in our SEC filings. With that, I will turn the call over to Krish.

Thank you, Stephane. Good morning, and welcome to the call. It gives me immense pride to realize that we're now in a position to help so many DEB patients within and outside the U.S. I would like to thank the entire team at Krystal for their contributions. In Q3, the VYJUVEK launch continued to build momentum and the updated U.S. label clearly strengthens our long-term outlook in the U.S. We're now launched in Germany, France, and Japan. We successfully negotiated pricing in Japan, and we believe the outcome bodes well for our payer conversations in Europe. We are looking forward to our readout in CF this quarter, and we're accelerating enrollment across our pipeline, including KB801 for NK. We are initiating a new clinical program for Hailey-Hailey disease. It is a rare genetic disease of the skin that is a strong fit with our HSV-1 gene delivery platform and our commercial footprint. Suma will share more about this program later on the call. Financially, we're strong and well-positioned to execute on our strategic growth plans and deliver value to shareholders. Moving now to our 3Q results. We are pleased to report another quarter of revenue growth with net VYJUVEK revenue coming in at $97.8 million. The patient pausing impacts due to summer holidays that we observed earlier last quarter were mitigated by patient adds and early traction in Europe. Net VYJUVEK revenues reported here do include a contribution from Europe following our launch in Germany in late August. This brings total net VYJUVEK revenues since launch to over $623 million. Gross margins were 96% for the quarter. Gross to net dynamics were stable as with prior quarters. I'm happy to report continued acceleration in new reimbursement approvals in the U.S. Our team added over 40 new approvals since our last earnings call update, bringing the total number of reimbursement approvals in the U.S. to over 615. This is now our second sequential quarter of reimbursement approval acceleration and a reflection of our field team's efforts as well as the ongoing sales force expansion. Our expanded field force is now fully hired and being deployed as training is completed. Full impact is expected in early 2026. We're also happy to report continued expansion of our prescriber work, reflecting increased penetration into the community setting with the total number of prescribers in the U.S. now exceeding 450. I would like to highlight a recent milestone achieved in the U.S., which was the FDA approval of our updated VYJUVEK label. This label update expanded the VYJUVEK eligible patient population to include DEB patients from birth and also provided patients with full flexibility in how they choose to dose VYJUVEK. This change reinforces VYJUVEK's leadership position as the most flexible and convenient corrective therapy for DEB and should serve as a tailwind for adoption and compliance in the future. Compliance to weekly therapy continued the trend we reported in previous quarters coming in the low 80s as more patients achieve durable wound closure and more mild and moderate patients come on to therapy. While the revised label change should have a positive impact on compliance in the future, we, as always, continue to expect some quarter-to-quarter waviness in the U.S. revenues as we build on our long-term growth trajectory. With that, I'll now hand it off to Laurent to share his excitement in Europe.

Thank you, Krish. It is my pleasure to share an update on our progress in Europe. Our first European launch in Germany is off to a good start. Since launching in late August, we have seen widespread interest and demand across the country. Based on available aggregate-level data, we estimate the number of patients prescribed VYJUVEK in Germany to be approximately 20. Just as importantly, we are seeing broad prescribing patterns across the country with prescriptions from over 10 centers to date. This breadth of prescribing is particularly helpful given the requirement for patients to start therapy in a healthcare setting. By growing the number of centers prescribing VYJUVEK, we can help patients to start therapy closer to home and avoid potential single center patient visit bottlenecks. Based on current trends, we expect continued steady growth in patient inclusion in the months ahead. We are also making rapid progress outside of Germany. In September, the Autorité de Santé, also known as HAS, the French HTA body, approved early VYJUVEK access under the post-marketing authorization Accès Précoce 2. And last month, we formally launched VYJUVEK in France. Importantly, the relevant authorities in France are also allowing VYJUVEK to be dispensed outside the hospital setting. This is the first time a gene therapy has been approved in such a setting in France, a tremendous milestone for our local team and patients across the country. Last month, HAS also appraised VYJUVEK under the Amélioration du Service Médical Rendu or ASMR classification system, a key initial step for pricing and reimbursement discussions in France. VYJUVEK received an ASMR III designation. This designation, which was only granted to 11% of the new drugs reviewed in 2024, acknowledged the added clinical benefit of VYJUVEK and may open up the possibility for EU priority list pricing in France. Finally, I'm also proud to report that VYJUVEK was granted the Prix Galien in Italy under the Advanced Therapy Medicinal Product category, a prestigious award recognizing excellence in scientific innovation to improve the state of human health. This award is an important acknowledgment of the innovative and transformational nature of VYJUVEK and a helpful touchpoint as we start to engage with the relevant stakeholders in Italy. With these recent achievements, we are excited about the long-term growth trajectory in Europe and maximizing VYJUVEK access to the thousands of DEB patients in the region. I'll now hand the call back over to Krish.

Thanks, Laurent. As I mentioned before, we have now also launched VYJUVEK in Japan. This summer, we were approved by the MHLW for the treatment of patients. And late last month, we successfully completed pricing negotiations with the Japanese authorities and launched VYJUVEK. We're very pleased with our pricing in Japan, and that is a testament to the clinical benefits achieved by DEB patients treated with VYJUVEK. Our core Japanese team has been in place for over a year and is now fully staffed to support the VYJUVEK launch. Our Japanese medical team has also been active for over a year, mapping key centers and patients, which will be the early focus of our launch. Although we expect contribution from Japan in 2025 to be modest, it will be another important revenue growth driver in 2026. Finally, I wanted to highlight one more contributor to the long-term growth of VYJUVEK. In addition to our direct VYJUVEK launches in the U.S., major European markets and Japan, we've started contracting with regional specialty distributors to support the commercialization of VYJUVEK in rest of the world markets. We have executed agreements in place with multiple leading distributors covering key markets in Central and Eastern Europe, Turkey, and the Middle East and expect to add more in the year ahead. Healthcare infrastructure and access vary significantly across rest of the world markets. But even after accounting for this variability, we estimate that a global distributor partner network could help bring VYJUVEK to thousands more DEB patients around the world and supplement our exciting growth strategy in the United States, Europe, and Japan. With that, I'll now hand it off to Suma to touch on recent pipeline progress.

Thank you, Krish. I would like to start today by acknowledging the hard work of our development team here at Krystal. In recent months, we have dramatically transformed the scope and ambition of our clinical stage pipeline, expanding our clinical programs in respiratory and oncology and starting up new studies in ophthalmology and dermatology. These are all important achievements, none of which would be possible without the outsized contribution of each Krystal team member. Our team also achieved another important milestone in recent weeks, a platform therapy designation from the FDA. This designation granted for our HSV-1 gene delivery platform and currently applicable to our KB801 program could significantly accelerate the path to approval, providing us the opportunity for more frequent interactions with the FDA and as well as the chance to leverage manufacturing and nonclinical safety data from VYJUVEK in our filings. The FDA may also consider previous inspectional findings related to drug manufacture. The platform technology designation is applied for on a program-by-program basis and is currently only granted to KB801, although we intend to apply for this designation for additional programs to ultimately secure the designation and associated efficiencies of our entire pipeline. I'm also excited to report that we remain on track to deliver multiple exciting readouts in the months ahead. We expect our next readout to come from our cystic fibrosis program, KB407. With the backing of the CFFTDN, we have expanded our clinical trial network and are now very close to study completion. We look forward to announcing interim data before year-end, including molecular data from null CF patients to assess the ability of the HSV-1 to deliver full-length wild-type CFTR to the lung. On success, we would expect to immediately move to a repeat dosing study, which should enable assessment of functionality, including longitudinal FEV1. With our now expanded trial network and without the requirement for bronchoscopies, we expect a repeat dosing study would enroll quickly, enabling a potential FEV1 data readout next year. Our KB408 program for AATD lung disease is also moving ahead well. Having already confirmed successful delivery of functional AAT in our single-dose study, this program is in repeat dosing, and we expect to be able to provide an interim data update in the first half of next year. Together with KB407, this will serve as a robust data set, demonstrating our platform capabilities in the lung. In ophthalmology, strong enrollment is providing us with greater clarity on the timing of our first readout. Based on current rates, we expect to complete enrollment of our Phase III trial evaluating KB803 for corneal abrasions in DEB patients by end of the year. Enrollment in our randomized placebo-controlled study for KB801 in NK is also progressing well as we continue to onboard new sites globally, setting us for a potential data-rich in 2026. I would also like to share a quick update on our work in oncology, which is increasingly focused on the development of inhaled KB707 for the treatment of non-small cell lung cancer, or NSCLC. As we shared at ASCO over the summer, NSCLC is an indication where we have seen early evidence of monotherapy efficacy even in heavily pretreated and checkpoint inhibitor-failed patients. Building on that readout, we were recently granted an end of Phase II meeting with the FDA to discuss potential development pathways for inhaled KB707. Based on FDA's feedback, we now expect that a single Phase III study evaluating inhaled KB707 in combination with chemotherapy versus chemotherapy alone in patients with advanced NSCLC could be sufficient to support a potential registration in combination for second-line NSCLC. In support of this potential registration pathway, we have opened a new cohort in our ongoing Phase I/II KYANITE-1 study to evaluate a fixed dose of inhaled KB707 in combination with chemotherapy. Enrollment in KYANITE-1 is ongoing. Our current expectation is to report interim data from KYANITE-1 in the second half of 2026, at which point, we would also be able to provide an update on registrational study plans and potential for Phase III initiation. Finally, I'm also happy to introduce today a new addition to our clinical pipeline, KB111 for the treatment of Hailey-Hailey Disease. Hailey-Hailey Disease is a genetic blistering disease of the skin linked to the mutation in the ATP2C1 gene and low expression of its encoded calcium-transporting ATPase. HHD is a rare disease with a prevalence that's not well understood. The most common estimate of prevalence is one case for 50,000 patients, although underreporting is possible. HHD is characterized by painful rash and blistering in skin folds with a relapsing-remitting course that is exacerbated by heat and sweat. Patients often report debilitating symptoms of pain, itch, burning, body odor, as well as infections, resulting in severe negative impacts on quality of life, psychological distress, and intimacy issues. There are no specific therapies available for treatment of this disease. Building on our experience and clinically validated HSV platform for skin delivery, we designed KB111 to deliver ATP2C1 directly to skin cells, increase ATPase levels, and hopefully change the course of this terrible disease. As with VYJUVEK, KB111 is formulated for topical administration directly to the lesions of HHD patients. We have already confirmed in preclinical studies that KB111 can efficiently transduce skin cells, resulting in functional ATPase expression and last month, cleared our IND. We expect to start an intra-patient randomized, double-blind, placebo-controlled multicenter study evaluating KB111 in HHD patients in the first half of next year. With strong execution across our pipeline and now the added benefits of the platform designation for KB801, we are well-positioned to make rapid progress with multiple readouts in the months ahead. With that, I'll hand the call over to Kate.

Thank you, Suma, and good morning, everyone. I'd like to provide some highlights from our third quarter financial results reported in our press release and 10-Q filing earlier this morning. VYJUVEK net product revenue for the third quarter was $97.8 million. This marks sustained growth as compared to the prior quarter, including the early sales from our German launch. Gross to net revenues remained consistent with prior quarters. Cost of goods sold was $4.3 million and gross margin was 96% for the quarter as compared to 93% last quarter. Note that the increase in gross margin this quarter was the result of U.S. product manufacturing process optimizations and the benefit of lower cost batches after FDA approval of this optimized process. While we expect these manufacturing efficiencies to continue benefiting our U.S. operations, the optimized process has not yet been approved for products sold outside the United States. As ex U.S. sales grow over the coming quarters, we anticipate gross margins will normalize towards historical levels until the optimized process is approved for products sold outside the United States. Research and development expenses were $14.6 million and general and administrative expenses were $37.6 million. Operating expenses for the quarter included noncash stock-based compensation of $13.2 million. You'll note on Slide 13 that we are revising our full year non-GAAP R&D and SG&A guidance to $145 million to $155 million compared to our prior guidance of $150 million to $175 million. This represents both a reduction and narrowing of the range to better reflect our performance so far this year as well as our continued confidence in our ability to execute with discipline for the remainder of the year. During the quarter, we released a majority of the valuation allowance that was previously recorded against our deferred tax assets, reflecting our confidence in Krystal's future profitability. This release resulted in a one-time noncash tax benefit that increased our reported EPS. We also benefited from the reversal of the Section 174 R&D capitalization requirement under the One Big Beautiful Bill legislation. This reversal was also nonrecurring. Net income for the quarter was $79.4 million, which represented $2.74 per basic and $2.66 per diluted share, reflective of these one-time benefits. And finally, our balance sheet continues to be a key point of strength for Krystal. We ended the third quarter with over $864 million in combined cash and investments, and we remain well-positioned to support our commercial launches globally as well as our significant pipeline programs in the upcoming quarters. And now I will turn the call back over to Krish.

Thanks, Kate. As we close today's call, I'd like to emphasize our excitement for the path ahead at Krystal in 2026. With launches in Germany, France, and Japan, VYJUVEK has now truly gone global, providing us the opportunity to dramatically expand the number of patients benefiting from VYJUVEK therapy in the months ahead. The hard part of a global VYJUVEK launch is now behind us, and Krystal's focus in 2026 is on our clinical pipeline. We have our first readout in CF before year-end. We're working towards readouts in 801 for NK and KB803 for eye lesions in DEB patients by midyear, and we shall update once enrollment is complete in these programs. These programs, along with KB111 for Hailey-Hailey, fit neatly within our core global commercial capabilities. At the same time, we recognize the significant optionality that HSV-1 provides as a redoseable non-integrating large-capacity gene delivery platform and the potential upside opportunities that exist in large market indications. We will continue to invest in these programs with the same operational discipline as we have in the past to ensure that we maximize the value that we believe exists in our pipeline and platform before entering into partnerships for these programs. Thanks for listening, and I'd like to now open the call for Q&A.

Your first question for today is from Alec Stranahan with Bank of America.

This is Matthew on for Alec. Congrats on the quarter. Maybe just two from us. On the ex U.S. launch, I guess, whether your focus is on expanding the breadth of prescribers or depth of prescribers that have already made some prescriptions? And then maybe on the optimized process that led to better gross margins. Just curious what was sort of optimized in this process and whether you can speak to timelines for this optimized process to be expanded to ex U.S. markets?

Thank you, Matthew. Regarding your first question about the ex U.S. launch, our primary goal in Europe is to accelerate the process for patients to meet with physicians as quickly as possible, since the initial clinical visit needs to occur in the physician's office. Logistically, it is much easier to start by partnering with centers of excellence, as Laurent mentioned, and then gradually expand into the community. Concerning the optimized process, this involves moving to a larger bioreactor that has already been approved in the U.S., and we are working towards applying for approval in Europe. I will ask Suma to provide an update on the timing for the approval in Europe related to the optimized path.

I mean we have already started the process. We have filed the scale-up. I mean it's pretty straightforward because we have a lot of data from the U.S. So we expect, hopefully, sometime next year to have the optimized and scaled-up process approved.

Your next question is from Roger Song with Jefferies.

Great job on the quarter. Regarding the ex U.S. launch, I understand that the contribution in the third quarter likely wasn't significant from Germany. I'm curious about your expectations for the fourth quarter and the next year. How should we view the revenue contributions from ex U.S. versus U.S.? Will you provide a breakdown later? Additionally, in terms of ex U.S. launches, how should we consider the pricing? I understand that negotiations will occur on top of the list price, and how might this evolve over time, especially with the U.S. MFN policy in play?

Great, Roger. Thanks for those questions. Look, the only requirement, as I mentioned in the prior response, is to start in a healthcare setting. But in spite of that, we think Germany is off to a really good start with like 10-plus centers starting to prescribe. But the only point I'll make with respect to the EU launch, I would expect it to be a steady launch upwards as opposed to expecting any kind of bolus early on in either country, whether it be Germany or France. But the demand and the physicians and the patients are pretty excited, I would say, both in Germany, France, and Italy is starting to go that way, too. With respect to pricing, look, we know Germany affords free pricing for the first six months. And then internally, we'll make a determination to start accruing for the next 12 months, depending on how pricing is proceeding. Negotiations are proceeding in France. Obviously, we start accruing from day one. So it's very country-specific. But I will say, based on the ASMR rating, based on the pricing we got in Japan, I think it bodes well. It remains to be seen, but I think the efficacy and the debilitating nature of the disease, I think that message, we're doing a really good job of conveying that, and it's being received well by these authorities in different countries.

Your next question for today is from Ritu Baral with TD.

I have been receiving many inquiries regarding the timing of the NK trial. Krish, could you explain the key factors involved in initiating that trial? How many sites are there and how challenging is it to begin operations at those sites? Has formal enrollment actually commenced? There seems to be significant interest in how quickly we can gather data and what that indicates about the overall prevalence of the NK population. Additionally, I have a brief follow-up question on CF.

Got you. On NK, I will just say, look, I think we have started to enroll patients in the study. Maybe Suma, you could add some color on how we're proceeding.

Absolutely. I mean we have quite a few sites up and running. We are actively adding additional sites. So really intend not just in the U.S. but globally because there's a lot of NK patients in Europe and the rest of the world, and we want to make this a global filing. So as you know, it takes a little while to get them up and running for the global studies, but we are right in the process. I think we will have most of our sites all completely signed up and ready to go hopefully by the end of the year. And as you know, we are enrolling patients. This is one of our top priority projects. So we are excited to see the progress on this particular trial.

And I will add, Ritu, our internal timing target is to announce some kind of interim data by the middle of next year.

Got it. Can you tell me what percentage of planned sites you currently have operational?

I mean we have quite a few sites. I mean, within the U.S., we got most of the academic sites up and running. We have a few more to go, but I think we should have most of the U.S. sites up and running by the end of the year.

Got it. And then for CF, can you tell us how many null patients that you plan to provide data on by the year-end update? And sort of what constitutes success on molecular response? What aspects of molecular response will you be reporting? And what's success in null patients?

Yes, Ritu, thank you for that question. We are planning to include a minimum of three null patients, with a primary focus on molecular correction since this is a single-dose study. Suma, do you have anything else to add?

Yes, we are bronchoscoping these three null patients after administering the drug. We will take biopsies from different areas of the lung and assess the expression of CFTR using immunofluorescence. We expect to see robust expression. Based on our non-human primate study, if we can replicate those results, we anticipate observing expression for up to 28 days and full-length molecular CFTR expression across all biopsies, which makes us feel quite confident. Currently, no one has demonstrated full-length expression of CFTR, so we aim to achieve that.

Could you report as like a percentage of normal and sort of what threshold could result in FEV changes at a later time point?

We know that minimal CFTR production is required, right? Even these patients do not produce any CFTR. If we can achieve anywhere from 5% to 10% of CFTR expression, that's quite significant. Our objective with the multiple lung biopsies is to show expression in most of them, which would boost our confidence in our ability to achieve sufficient molecular correction. This is particularly relevant for the null patients, who do not produce any CFTR.

Our next question is from Gavin Clark-Gartner with Evercore.

On NK, what makes you confident that you don't need to test any different doses and why the one that you picked is the right dose? And somewhat on this topic, do you think you need two efficacy studies for approval or may be sufficient?

Our confidence in the chosen dose is derived from our animal studies, where we observed clear expression and established a pharmacokinetic profile, allowing us to understand how long the expression lasts. This has informed our dosing regimen in the clinical setting. We are reasonably confident that a single efficacy trial will suffice, given that this pertains to a rare disease and aligns with regulatory guidance regarding requirements. Based on our study design and insights gained from animal studies and oxalate studies, we have structured our study to aim for a clinically significant improvement over placebo. If this trial is successful, we anticipate it will serve as the registrational trial. Additionally, we have robust platform technology and clear guidance on our CMC needs, which supports our positive outlook for this program.

And is there any commentary you can provide on the safety you're seeing in the ocular DEB study or even the NK study on a blinded basis?

I mean, so far, we have not seen any adverse events of concern.

Your next question is from Sami Corwin with William Blair.

Congrats on the progress. I also have one on NK. Could you remind us if you're excluding patients that have had a prior ocular HSV infection? And if you think a prior HSV infection could impact the efficacy or safety of treatment? And then in terms of the initial data set, what exactly will we see in that?

Regarding your first question, no, we do not exclude patients who have had a prior infection. The only requirement is that they should not have an active infection. That's the only exclusion criteria. What we will announce is that this is a randomized 1:1 placebo-controlled study lasting 8 weeks. We will evaluate complete healing, which will be assessed by an independent reader. If we observe complete healing at 8 weeks compared to placebo, then that would be a positive outcome, similar to Oxervate.

Got it. Great. And then just one question on VYJUVEK. Could we expect some guidance or full year revenue guidance for VYJUVEK early next year?

No, because we have so many launches and the distribution you see, it will take us some time to kind of get comfortable with how the different launches are going in different countries. So fortunately, Sami, we will not be guiding on revenue for 2026.

Your next question is from Josh Schimmer with Cantor Fitzgerald.

This is Alexa Deemer on for Josh Schimmer, and congrats on a great quarter. So can you please provide some more color on the contribution of U.S. and ex U.S. sales in the third quarter for VYJUVEK? More specifically, what was the percentage breakdown from the U.S. versus Germany?

Yes. Look, the decision not to break down in this particular quarter was somewhat accounting auditor driven and the goal is to establish a consistent long-term practice on segment reporting. And if you follow that thought, we will be starting to break down geographies at some point in 2026. It's just that now it is so modest contribution relative to the overall net revenues of the company.

Okay. Got it. And can you provide any more specifics on how U.S. sales were in the second quarter versus the third quarter?

Yes. Definitely, I would say that the U.S. was a bit lower than what we saw in Q2, but not to the extent like based on my comments from the last quarter, definitely, reimbursement approvals were on an uptick. And so overall, we ended up getting to a number that was higher than Q2.

Your next question for today is from Andrea Newkirk with Goldman Sachs.

This is Morgan on for Andrea. With 615 reimbursement approvals, what do you attribute this growth to? Are you seeing more patient adds from the community setting? And then how are you thinking about the path to 60% penetration from here?

No. That's a great question, Morgan. As I mentioned in previous quarters, it was taking us a bit longer to navigate the start since we were focusing on getting patients into the community and reaching physicians who are not located near a center of excellence. By expanding our sales force, I believe we have addressed that issue. We observed some acceleration last quarter and continue to see that this quarter. We anticipate this trend to persist as more representatives are trained and deployed in the field. Regarding the 60% market share, that's a figure around 720. We reported 615, so we might be one or two quarters away from achieving that number with simple calculations. Overall, we are very optimistic about the progress of the launch and how we've managed to reverse a quarter of deceleration in Rheumatoid Arthritis.

Your next question is from Yigal Nochomovitz with Citi.

This is Jon Kim on for Yigal. Maybe just two quick ones from us. On KB408, can you just talk a little bit about your expectations there, whether you're expecting a significant uptick in AAT with repeat dosing versus a single dose and what sort of boost you'd be expecting to see or would you want to see?

Yes. Obviously, we're expecting an uptick, but we're not particularly talking right now about how much of an uptick.

I mean, right now, we have a couple of sites that are open because remember, again, these sites have to be able to do bronchoscopy. In the case of 408, it's a little more complex because it's not just biopsies. They also need to take lung lavage fluids out to measure the A1AT and the protein levels. So there's only a few sites that are capable of doing this. So we have those sites. We have the patients. So hopefully, once we finish that cohort with the repeat dose administration in A1AT levels, then we hope to have a meeting with the agency to potentially talk about a path forward.

There are no further questions in queue. Thank you. We've reached the end of the question-and-answer session and today's conference call. You may disconnect your phone lines at this time, and have a wonderful day. Thank you for your participation.