Krystal Biotech Inc (KRYS) 2024 Q1 法說會逐字稿

Thank you for standing by, and welcome to Krystal Biotech's first quarter 2024 earnings conference call. (Operator Instructions) As a reminder, today's conference is being recorded.

I would now like to hand the conference over to your host, Stéphane Paquette, Vice President of Corporate Development. Please begin.

Good morning, and thank you all for joining today's call. Earlier today, we released our financial results for the first quarter of 2024. 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 will be Krish Krishnan, Chairman and Chief Executive Officer; Suma Krishnan, President of Research and Development; Jennifer McDonough, Senior Vice President of Patient Access, Analytics and Operations; Christine Wilson, Senior Vice President and Head of US Sales and Marketing; 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, Stéphane, and thank you all for joining Krystal's conference call. I'm pleased to share that the momentum in 2023 continues with a strong start to 2024, driven by excellent execution across all parts of our business, commercial clinical and manufacturing. VYJUVEK is reaching more and more patients by the day and is rapidly changing the treatment paradigm for patients suffering from this debilitating disease, dystrophic epidermolysis bullosa or DEB.

Increasingly DEB patients are able to benefit from the durable wound healing afforded by VYJUVEK to the fundamental genetic correction and also the convenience of being administered at home as a topical gel. As a real-world experiences with VYJUVEK grows, it has been immensely rewarding to hear and see the improvements that patients have made while on therapy.

As you will hear this morning, our US commercial launch continues to progress very well, driven by robust demand, rapid growth and reimbursement approvals and high patient compliance. We're also moving quickly towards launching VYJUVEK outside of the US.

We recently successfully completed the efficacy portion of our open label extension study in Japan, putting us on track to file with the Japanese regulators before year end. This will be our second ex-US filing after submitting to the EMA last year. Global infrastructure buildout is underway, in anticipation of commercial launches in both Japan and Europe next year.

At the same time, we are building momentum across our clinical pipeline with accelerating enrolment and new trial starts setting us up for a wave of data readouts starting later this year. But the recent initiation of KYANITE-1, our study evaluating inhaled KB707 for treatment of solid tumors of the lung.

We now have five active clinical trials, and that poist to add a sixth for Ophthalmic B-VEC in the second half of this year. We expect that these studies, which spanned multiple tissues and target both rare and common diseases will showcase the breadth and power of our proprietary HSV based gene delivery platform.

We also continue to build out our manufacturing infrastructure in support of global VYJUVEK commercialization and pipeline expansion, including scale-up of our current approved manufacturing process, ongoing process improvements and initiation of a tech transfer of our current production process to ASTRA later this year to increase VYJUVEK user margins.

Finally, I want to highlight that strong execution in our launch yielded another profitable quarter for Krystal, even while accruing for previously settled litigation payments. And excluding litigation payment accruals, EPS this quarter would have been $0.47 per share, up sequentially from $0.31 per share in the last quarter of 2023.

With a strong balance sheet, growing revenues and two commercial scale GMP facilities, we have the resources we need to execute on our long-term growth plans and to continue building shareholder value for VYJUVEK and our clinical pipeline.

Before jumping into our VYJUVEK launch update, it's my pleasure to introduce Christine Wilson and Jennifer McDonough, two senior US commercial leaders at Krystal who are joining me today on the call. Christine recently joined Krystal as Senior Vice President and Head of US Sales and Marketing. She brings over 20 years of experience in specialty and rare disease launches and is an expert in patient finding, having previously launched multiple rare disease products with a community focus, including Gattex and ultra rare condition of short bowel syndrome and more recently [Filspari] for IGA and nephropathy.

Jennifer McDonough is Senior Vice President of Patient Access, Patient Services, Analytics and Ops at Krystal and has been instrumental in achieving the broad access and compliance we have today for VYJUVEK. Jennifer has over 25 years of experience in biotech and specialty pharmacy with a focus on rare diseases. We are fortunate to have them both on the team.

Now turning to our results. Net VYJUVEK revenues for the quarter came in at $45.3 million. Looking back over our first three quarters since launch, total net VYJUVEK revenues now exceed $95 million, keeping us on pace for the top tier of recent rare disease launches.

We're especially pleased to be reporting revenue growth Q-over-Q in spite of the onetime headwinds that we face to start 2024 due to the permanent J-Code switch. While the permanent J-code is a huge tailwind for reimbursement, the switch negatively impacted revenues [one time] in the first quarter.

In order to ensure continuity of therapy, we bridged patients with free vials. In total, we estimate that approximately 400 free vials were dispensed in 1Q as a result of one-time disruption. That said, the J-code issue requiring bridging patients with free drug is resolved and the fundamentals of the launch look very good for the remainder of 2024. We are confident in our ability to meet if not exceed 2024 net revenue projections. Christine and Jennifer will elaborate more in their sections.

Gross margins were 95% for the quarter, up 2 percentage points over last quarter. We continue to expect margins to be above 90% in the coming quarters gradually improving to over 95% in a couple of years. Gross-to-net adjustments in the first quarter were 14% in line with the previous quarter.

Our long-term guidance on gross-to-net is unchanged and we expect it will settle into the high teens, reflecting a roughly even split of DEB patients between commercial and government plans.

Please note that the net VYJUVEK revenues reported today also include an accrual for patients on contracted commercial plans who are projected to potentially hit the cap of $900,000 gross per patient per calendar year in 2024.

Overall, I'm really pleased with the growth in the underlying drivers of our commercial launch and will now hand the call over to Jennifer to share additional details on the launch, including recent successes in securing patient access to VYJUVEK. Jennifer?

Thank you, Krish. Moving to slide 5, it has been exceptionally rewarding to lead patient access in Krystal connect team in support of this transformational product. But hundreds of US patients now benefiting from access to VYJUVEK, we really are changing the treatment paradigm for this terrible disease.

Commercial and Medicaid access continues to improve for VYJUVEK. We now have received positive policies or decisions for roughly 96% of all covered lives. This is up from over 93% in our last report and driven mostly by an additional seven state Medicaid programs, including taxes now providing coverage for VYJUVEK following the issuance of the permanent J-code earlier this year.

As we entered the first quarter, we were prepared for the challenges of January insurance verification season and the VYJUVEK permanent J-code reauthorization process. We are very proud of the team's success in supporting continuing coverage for existing patients.

At the same time, new patient conversions continue to progress well, and as of April, we have secured over 330 patient reimbursement approval. We did see a onetime impact to our overall reimbursement approvals in Q1 due to a cybersecurity incident affecting our specialty pharmacy provider, but this has now been resolved.

This incident is not unique to us and affected many of our other colleagues in the pharmaceutical industry. With strong payer access, the permanent J-code assigned and ongoing operational improvements, the team is laser focused on patient experience and optimizing time to first VYJUVEK application.

With that, conversion times continue to shorten, albeit at a slower pace than we previously expected. As patients are increasingly identified in the community setting where physicians are a bit less familiar with dystrophic EB and the reimbursement process for rare disease medicines, we are finding that additional support is needed to navigate these patients and their physicians to access.

This is, of course, exactly what Krystal Connect patient services team is built to do, and as we work through each patient case, we are seeing great results and ultimately authorizations for VYJUVEK therapy.

We continue to implement additional education and tools to support the process and are still on a trajectory for conversion times to compress down to under a month later this year. With notified you that reimbursement approvals covering an initial treatment period of six months or more, we have still not encountered a large number of reauthorizations, the same as last quarter, albeit reauthorizations to date have been either approved or in process.

As we move to slide 6, the split between RDEB and DDEB patients at the reimbursement level is roughly in line with the start forms what we've reported previously, and consistent with the steady progression through to conversion.

We are also very happy to report that we are seeing reimbursement approvals across all ages as we continue to communicate to patients, physicians and payers that all wounds matter and that is never too late to change the course of this disease.

At the same time, it is also encouraging to see strong uptake in the paediatric segment, where establishing corrective therapy early has the potential to change the trajectory of these patients' lives.

Moving to slide 7. Moving to the patient experience and compliance, we continue to report strong patient preference for at-home administration with 97% of the weekly treatments occurring in the patient's home.

And even with the increase in both the patient base and average length of therapy, we are pleased to report the compliance to weekly application remains above 90%, particularly when compared against many other chronic therapies with compliance rates often around 50%, which we believe is a reflection of the clinical benefit VYJUVEK is bringing to patients while on drug.

Although our work is just beginning, I am proud of the progress our team has made to date, rapidly growing the number of patients, accessing VYJUVEK and one start and ensuring they are able to treat their wounds conveniently at home.

I will now hand it off to Christine to talk about what comes next for our US VYJUVEK launch. Christine?

Thank you, Jen. I'm incredibly excited to have joined Krystal and to build on the great early momentum we are seeing in the VYJUVEK launch. I know firsthand the challenges that come with launching a rare disease medicine in the community setting. Patients are often undiagnosed or lost to follow-up.

Genetic tests have never been run, familiarity with innovative therapies and navigating reimbursement is low. And sadly, disillusionment with a health care system is all too common. Even if you would expect a patient suffering from a severe disease to proactively seek care, many of these patients have been disappointed by their treatment options in the past and have disengaged.

However, none of these issues are unique, and we have at our disposal an extensive toolkit to help find and activate rare disease patients wherever they are in the US. We are also starting from a strong position with great early adoption of VYJUVEK, giving us plenty of success stories to amplify and disseminate.

Today, I would like to touch on some of the key strategic initiatives, which we are pursuing to drive sustained long-term growth of VYJUVEK in the US. Our commercial efforts can be grouped together into three main pillars.

The first is data analysis, our analytics hub includes real-time claims alerts to identify potential patients. Through this data, we can quickly deploy our seasoned rare disease sales team, while in parallel engaging HCPs through nonpersonal promotion.

The combination of these two activities drives awareness and education of VYJUVEK to our targeted HCP audience and is already helping to grow our identified patient pool. There are also future opportunities to expand the scope of our analytics work to include DEB adjacent claims codes on our path of finding all debt patients across the US.

Importantly, these clean base patient finding efforts are distinct from our sponsored genetic testing program, Decode DEB, which has had great uptake and is helping clinicians identify previously undiagnosed patient. Education of HCP is also a key strategic imperative and is being expanded through peer-to-peer programs by leading KOLs and EB as well as early VYJUVEK adopters.

Peer-to-peer educational programs are the most impactful approach of bringing information to new EB treaters. An early adopters who do not always practice in major centers, bring unique perspectives relevant for potential community prescribers.

With over 5,000 HCPs now having been reached by the sales team, the desire for ongoing education and dialogue amongst the HCP community for better patient outcomes continues to grow. The open-label extension study, demonstrating long-term safety, efficacy and durability results will be published in the second half of this year.

These top line results were well received during a late breaker session at the AAD meeting in March. The results solidify the VYJUVEK's impact on the DEB patient population and further establishes VYJUVEK safety profile. Patient engagement is our third top priority, in-person and digital programs are providing the patient community and opportunity here real world VYJUVEK experiences from other patients and their caregivers.

This is a powerful approach to establishing understanding and confidence in the benefits of VYJUVEK to the patient community. Social media has become a powerful tool in reaching patients, particularly those who may not be engaged with the health care team. Targeted ads have been deployed on the most established social platforms and we are expanding to other social media channels in the second half.

An example of one of our social media ads is shown here, this approach allows us to engage patients for their ad, raises awareness levels and allows them to engage digitally to learn more and seek treatment.

Altogether, by amplifying initial patient and physician experiences with VYJUVEK, we expect to drive adoption build on a prescriber base that is already in the hundreds and deliver on our mission of reaching as many DEB patients as possible.

Before handing the call off to Suma for pipeline updates, I will also take the opportunity today to highlight a few trends that we are already seeing in the field that we expect will reinforce by VYJUVEK leadership position in DEB and sustain our launch in the long term.

First, patients are seeing the compounding benefits of corrective therapy of VYJUVEK as they treat more wound. Unlike palliative approaches, we are able to deliver the collagen 7A1 gene directly and to patient wounds and enable durable wound closure.

As patients treat and close more and more wounds, they are increasingly able to get control over their disease. The positive patient experiences are building excitement amongst patients and HCPs. In addition, thanks to the work of Jennifer's team, home administration is becoming further entrenched as a standard of care for patients with DEB.

Wound care in the home is an established routine for DEB patients and families. Home administration with VYJUVEK integrates into this routine and we are seeing the overwhelming majority of patients choose that as part of their improved standard of care. Our specialty pharmacy provider and home dosing infrastructure is supporting compliance, ongoing patient progress monitoring and integrating into a patient's lifestyle treatment approach.

Momentum continues to grow, familiarity with VYJUVEK is rapidly increasing and positive patient experiences are expanding utilization, inclusive of the DDEB population. Altogether, we expect these trends to establish VYJUVEK act as a standard of care for DEB in the years to come.

Now I will hand it off to Suma to share pipeline highlights.

Thank you, Christine. Our development team has made great progress to start 2024. As we work towards our ultimate goal for treating DEB comprehensively and globally, while simultaneously advancing a broader pipeline of predosable genetic medicines for many of the other rare and serious diseases that lack adequate treatment options.

With respect to our B-VEC development, steady progress towards European and Japanese regulatory authorization has us on track for launches in both regions by 2025. In Europe, the EMA's review of our marketing authorization application continues. In February, manufacturing facility inspections were completed, and we expect to receive GMP certification in the second half of this year.

Based on recent discussions, we believe EMA like the FDA is also supportive of home dosing. We continue to expect a decision on our marketing authorization application before the end of the year. In Japan, we have now successfully completed the efficacy portion of our open-label bridging study in Japanese patients, enabling us to proceed with the Japanese new drug application, which we expect to file in the second half of the year.

Having previously received orphan drug designation by Japan's pharmaceuticals and medical device agency, a designation which confers specific benefits for orphan drug development, including priority review of application. We remain on a trajectory for both a decision by Japanese authorities as well as launch in 2025.

With respect to our broader clinical pipeline, there were two major themes in the first quarter expansion and acceleration. With an expanding pipeline and accelerating enrollment, we are setting up for a number of exciting data readouts starting later this year.

Our oncology program, KB707 has been progressing rapidly to start 2024. Recall that KB707 is a modified HSV-1 vector designed to deliver genes and putting both IL-12 and IL-2 to the tumor microenvironment and promote systemic immune-mediated tumor clearance. We have two formulations of KB707 in development. A liquid formulation for intra-tumoral injection and an inhaled formulation from nebulization and lung delivery.

Our Phase 1 study to evaluate intra-tumoral KB707 monotherapy is moving ahead well. Aince dosing our first patient in October of last year, we now have cleared the first two dose levels in our study and completed enrollment in the third.

KB707 has so far been generally well-tolerated across a diverse population that includes patients but sarcomas, colon, breast and cutaneous cancers. No patient as experienced dose-limiting toxicity or drug-related grade III or greater adverse events. Based on the current pace of enrollment, we expect to be able to report interim data before the end of this year.

We also recently dosed the first patient in our inhaled KB707 Phase 1 study, KYANITE-1, an open-label multi-center dose escalation and expansion study evaluating inhaled KB707 monotherapy in patients with advanced solid tumor malignancies affecting the lungs.

This is another exciting milestone as we look to extend the clinical utility of cytokine therapy and make a new class of medicines to treat a wide range of otherwise difficult to treat solid tumors. It is also gratifying to report that both intra-tumoral and inhaled formulations of KD707 have now received fast-track designation by the FDA after inhaled KB707 was granted fast-track earlier this year for treatment of patients with solid tumors, but pulmonary metastases that are relapse or refractive to standard of care therapy.

Turning to our respiratory program. We are pleased to report a pickup in enrollment here as well. On KB407, our redosing in the healthy gene therapy for the treatment of cystic fibrosis, we have now completed dosing in cohort 2 of the CORAL-1 study are on track to start dosing in the third and final cohort later this quarter.

Recall that this cohort is scheduled include bronchoscopies that will allow for evaluation of airway epithelial cell transactions and expression of CFTR Transcript and protein.

Cohort 3 also includes minimum enrollment thresholds for patients that are not eligible for modulators, an important patient population for which no effective disease-modifying therapies exist. Our KB408 are reusable inhaled therapy for Alpha-1 antitrypsin deficiency. We dosed the first patient in our SERPENTINE-1 study in February of this year.

SERPENTINE-1 is the Phase 1 open label single dose escalation study in adult patients with AATD to allow assessment of safety, tolerability, Alpha-1 antitrypsin levels and key pharmacodynamic biomarkers. With strong support from the Alpha-1 research community, we are on track for an interim data readout before the end of 2024.

Our development activities in ophthalmology are also ramping up, working towards our goal of treating DEB comprehensively. In February, we disclosed that we had reached alignment with the FDA on single-arm open-label study enabled approval of the B-VEC eyedrops for the treatment of lesions in the eye of DEB patients. We have since initiated clinical operations to enable a study start in the second half of the year.

And finally, we look forward to reporting results from cohort 3 and 4 of our KB301 Phase 1 study later this year. Both cohorts are running concurrently to evaluate KB301 in two potential target indications. Improvement of the lateral canthal lines at rest and improvement of dynamic wrinkles of the decollete.

Following readouts from cohort 3 and 4, we expect to select a single indication for Phase 2 development. Our HSV-1 platform has the potential to yield a large number of highly differentiated redosing gene therapies. We look forward to making continued progress in 2024 and sharing data updates on our clinical pipeline later this year.

With this, I would like to turn the call to Kate.

Thank you, Suma. We ended the first quarter with $359 million in cash on hand and $622.3 million in total cash and investments, an increase over year end cash and investments of about $28.1 million.

VYJUVEK net product revenue for the quarter was $45.3 million. As VYJUVEK was approved by the FDA in May of 2023, there was no comparative period revenue. Cost of goods sold was $2.4 million for the quarter or about 5% of net product revenue, making gross margin 95%.

In the first quarter of 2023, costs associated with the manufacturing of VYJUVEK were expensed as research and development costs prior to approval. And therefore, there are no comparative period costs in the first quarter of 2023.

Research and development expenses for the quarter were $11 million, inclusive of stock-based compensation of $1.9 million compared to $12.3 million for the prior year's first quarter, inclusive of $2.5 million of stock-based compensation.

Lower research and development expenses in the first quarter of 2024 for due to decreased VYJUVEK manufacturing and overhead costs as following FDA approval, those costs are now recorded as part of our cost of inventory.

This decrease was partially offset by additional clinical development costs and R&D related depreciation expenses. Selling, general and administrative expenses for the quarter were $26.1 million, inclusive of stock-based compensation of $7.4 million compared to $24 million for the prior year's first quarter, inclusive of stock-based compensation of $7.9 million.

Higher selling, general and administrative expenses in the first quarter of 2024 compared to the prior year's first quarter were primarily the result of increased selling expenses related to the launch of VYJUVEK, in particular, an increase of about $1.5 million related to the additional patient access program related costs that were incurred in light of the J-code transition that was previously discussed.

Other increases included higher professional services, payroll and other administrative costs, offset by lower marketing related expenses compared to the prior year's first quarter. This quarter, we also recorded litigation settlement expense of $12.5 million due to our anticipation of reaching the first milestone payment in the PeriphaGen settlement at $100 million in net product revenues.

Our net income for the quarter was $932,000, which represented $0.03 per basic and diluted share. We would also like to reiterate our previously issued guidance of between $150 million to $175 million in combined non-GAAP R&D and SG&A costs in 2024.

As a reminder, this projection excludes an estimate for stock-based compensation. We continue to expect higher research and development costs relating to our several active pipeline projects and higher selling, general and administrative costs relating to the continued launch of VYJUVEK across the United States and our pre-commercial activities in Europe and Japan.

And now I will turn the call back over to Krish.

Thanks, Kate. If there's one message that I hope you take away from today's call, it is our excitement for the path ahead at Krystal. Our US launch continues to progress very well with high compliance, broad access and a growing number of patient conversions, putting us on an excellent trajectory.

Momentum is also building outside of the US with the rapid completion of our Japan OLE and soon to be second regulatory filing in the major ex-US market. We look forward to further expanding access to VYJUVEK here and abroad, all while progressing and deep clinical pipeline addressing urgent unmet needs in rare and serious diseases.

Thanks for listening, and I'd like to now open the call for Q&A.

(Operator Instructions) Alec Stranahan, Bank of America.

Hey, guys. Thanks for the questions. Just two quick ones from me. First, could you maybe talk about patient compliance that you saw in the quarter? What has the feedback there from the field on this today? And then I didn't see any mention of new start forms, but any trends here that you would have highlight? I guess what else needs to happen to shorten that time to less than a month for conversion? Thanks.

Thanks, Alec. Hey, on your question on compliance, I'm going to turn it over to Jennifer.

Sure. Thanks, Alec. So what when it comes to compliance, we are just thrilled with the patient experience. Overall, patients continue to see the impact of VYJUVEK and because it's dosed weekly, they understand that it's important to keep up with those weekly doses. That's definitely what we're hearing.

With that, they continue -- the home dosing is important for them. And but with that in the time on therapies, our opportunities potentially miss a week here or there. So overall, patients are completely, I think, aligned with the idea that weekly is important that the dosing is important for wound healing.

They're thrilled with the outcomes that they're receiving with VYJUVEK, and we work with them for flexibility and understanding that life happens and then they may miss a week or two here or there. But overall, compliance has just been stellar.

Alec, on the start from question, look, we stopped talking about (inaudible) last quarter, we think reimbursement approvals is a much closer predictor of net revenue than PFSs at this stage of the launch.

But having said that, demand, it used to be really good with respect to patients coming on drug. And I'll turn it over to Christine to maybe say, a sentence or two, having come into the story over the last couple of months.

Yeah. Thank you, Krish. We continue to be very pleased by the volume of new starts we're seeing, and we are beginning to see that transition from and the COEs into the community base. But as that awareness continues to grow, the education, the clinical experiences we intend to build on that momentum that we're currently seeing.

Tim Lugo, William Blair.

Thank you for taking the question. Khris, I believe you mentioned that you're confident in hitting revenue projections in 2024 despite a disruption this quarter given the J-code switch, can you just talk a bit about that. I see consensus around $255 million this year. Is that just something we are generally comfortable with?

Look without getting into the specifics, what I think about is what I see the analysts projecting and the consensus estimate, but that would be average or median. I realize that 1Q was light on the revenue side, but not on the fundamentals of the commercial launch, right.

When the J-code issue surfaced, two things happened, I think our specialty pharmacy probably underestimated the time it would take to convert. We probably assume that that was right, but when the actual issue surfaced because the dosing is at a weekly level, we don't have time to think about what we could have done in the past.

We had to jump in quickly, provide access to free vials. And we ended up I'm spending about 400 free vials, as I mentioned in the call, but by the time we started to learn to figure out how to address such an issue, either now or in the future. The issue was well behind us. So it was a very transitory, resulted in about 400 free vials, which you can imagine is about -- slightly north of $8 million in net revenue. But we were really pleased.

So we keep the patients on drug and provided continuity without having to slip up on that front. That's more important to us, since patient experiences at the forefront of what -- of the launch over everything else in the story. But then coming back to your question, we feel good about generally where we think we're going to end up in 2024.

Understood. Thank you. And maybe switching to the pipeline a bit for KB407. The third cohort is about to begin enrollment. Can you narrow down when we should expect first data coming out of this study, given the first two cohorts are behind us now? And are there any trends maybe in the second cohort that make you more or less confident in the program?

This is Suma. I'm going to take that question. I mean, again, we are very excited about 407. We are working with two sites because remember, we need sites that have the capability to do bronchoscopy because this is a procedure that needs a lot of specific how do you biopsy the patient to make sure we increase the chances of getting the right tissues to show expression.

So yes, we are working on that. Also remember, that we are looking at now patients, potentially patients that are not on modulators or correctors. So we see I mean, there is no interference from that. So again, it's that kind of population that we're looking for. We have identified patients, we are actively working with the sites to get the study up and running.

Our goal is to try to enroll all of them by the end of the year. We're going to work hard at it. I mean, again, remember, we're looking for a specific patient population that is not on modulators or correctors. So there will -- I mean, again, we are working to get those patients enrolled.

(multiple speakers) complete that because we're outside the TDN. We're not guiding -- we have never guided on CF, we never know, but things are trending in a positive direction.

Ritu Baral, TD Cowen.

Thanks for taking the questions. I wanted to ask about on Europe and Japan on specifically what you guys are planning on commercial build-out for Europe right now. And if you can just give us an update on the MAA process, whether you're past the 180-day questions and whether you anticipate oral arguments there?

Thanks, Ritu. On the commercial side, we anticipate a first launch to be Germany either very late this year or early next year, depending on when we get approval. We do have German GM in place with -- coming from Shire. And so, we're super excited about the launch in Germany.

Meanwhile, we're setting up for named patient sales, expanded access, whatever, and the demand has been really good in Europe in terms of experience with the drug prior to actual launch and approval.

Japan is maybe a little bit behind relative to Europe, maybe six months or so. We do have a GM in Japan in place, and I'll now turn it over to Suma talk about where we are with respect to timelines and approval in both these countries.

Thanks, Krish. Yes, I mean, we have received the 120-day questions. We also have -- remember, we have had scientific discussions to them throughout the process, there were no surprises. In the questions, we also met with the EMA recently to go over some of the key questions that we needed for the clarification. I think the meeting went pretty well.

We have clear clarity on what the expectations are, and we expect to respond to the LOQ in the next couple of months. And I think the process -- the timeline is on track for an approval end of this year.

So overall, we're very pleased with the process and as you know, the inspection was also completed. I think we had a very successful inspection and based on the feedback looks like we should get GMP certification in a couple of months from now.

Got it.

And in Japan, we have, as Krish mentioned, we have completed the open-label Japanese patient population study. The data looks very promising. We are in the process of writing up the study report. We have a meeting scheduled with the PMDA to talk about the Japanese NDA, and we are on track for filing the Japanese application. We are working with the CRO, the process of converting the European and the US BLA to the Japanese NDA has begun, and we anticipate filing this application end of this year.

Got it. And then moving back to the US, can you tell us what is current conversion time to commercial? Jen, if you mentioned that it was -- sorry, I think it was Christine, who mentioned that it was getting a little longer than expected. Can you discuss what's some of the headwinds on to shorten that to the target 30 days has been? Thanks.

Let me start and I'll turn it over to Jen to provide specifics. Look, there are three pieces, right, first the part in the middle is access. Once you get access, it's about how quickly can you get a nurse into the home that you like and get treatment going.

The piece before access is once the doctor thinks about writing a prescription is the genetic information in place, whether you're in the community setting or in a COE setting, getting all the paperwork and genetic information in place. I'll start by saying the access part is fairly quick, maybe less than a week.

So anytime we're spending is either on the front end, depending on the type of the patient or on the back end where the caregiver is being pretty picky on the nurse that comes home and scheduling of the nurse to come home. But that said, in terms of turnaround time, Jen, maybe you can weigh in?

And just like Krish explained, there are several dynamics when it comes to getting that patient on their first treatment working with the payer, assuming those clinicals definitely takes time as we move into the community setting, some of those offices, they don't have the staffing. Some of that chart worker and the lab work is maybe potentially in the center. So that takes some time. So we continue to work our team. And we have a great field team is working with the offices supporting providing the education at the payer level.

So we expect that to kind of shorten as we continue that education. Once we submitted to the payer, as Krish said, that really is very positive process. For the most part, our payers are well aligned. We have a great policy. We understand what they need to be able to provide the approval. So that kind of turnaround time on determination seems to be shortening for sure the payers are much more on understanding of what's needed.

And then that third part scheduling with the family, part of that, of course, is getting the nurses, making sure we have a trained VYJUVEK nurse and that we have the schedule and the flexibility that the family needs and that just takes a little bit of time.

But once we are -- the exciting part is once we get a patient on, their routines established, they have a great experience, and we'll continue to kind of shorten that up. We understand it needs to be as short as possible. We need to get these patients on therapy as fast as possible, that's our goal.

Benazir Ali, Stifel.

Hi, this is Benazir on for Dae Gon. Can you guys hear me? Okay.

Yep.

Okay. Just a couple of questions. First Christine, based on your experience with [the full story], which one of those three priorities have you find most impactful and onboarding patients? And any sense of what kind of growth we can envision going forward?

Thanks for the question. So really, all three of those pillars continue to be very important into this launch. And I find there's some uniqueness certainly in the DEB space, but there's also some consistency that you see in the rare space. And so, they're all three of those priorities continue to be important, the education of the HCP, the patient outreach and activation.

So when you take a look across this right, where our focus is in the three pillars that we talked about previously. And we want to make sure that only -- not only are we educating the HCPs, but that we're really working with the patient population to share that education with them to make sure that we're building on the momentum that has been created thus far.

Okay. And then just one more question for either you or Krish, I think you mentioned about like 5,000 HCPs are aware of VYJUVEK, what's the geographic distribution? What areas you're going to focus on in the rest of 2024?

Yeah, I can take that question. I mean, really what's exciting is that we are starting to identify patients, not just in the COEs but outside the community. And really, we are seeing those patients all across the country.

This DEB population really can set in some more rural locations. And it also sets obviously in our COE setting. So that's the exciting, I think, evolution of this launch that we're really starting to understand that the alerts are helping us with really identify patients across the country, but also across different specialties we're starting to see as well.

Andrea Tan, Goldman Sachs.

Good morning. Thanks for taking our question. Krish, maybe one for you, just as patients have been on commercial drug now for quite a bit of time. Just wondering if you could provide an update on what you're hearing on the experience of these patients with respect to wound closure.

Curious if you're starting to hear of any patient starting to come off therapy as their wounds closure. Do you still believe the induction phase that previously you had projected at two years is still intact? Thanks so much.

Yeah. So to start with your last question, I think we continue to see a very high level of compliance. It has been what almost a year. Actually, August was the first time a patient gone on VYJUVEK in a commercial setting, but compliance seems to be high, and with our continuing to say for the induction period, we expect induction to last maybe 15 to 18 months afterwards, you should expect patients to consume less number of vials going forward as the wounds heal.

Now look at 91% or 93% on a high over 90% compliance, if you think about 200, 300 patients on drug on a weekly administration to get to 91%, we're talking a handful of patients maybe missing a week here and there. So for all practical purposes, most of the patients are still on drug.

Now there have been one or two instances with dominant patients where we've actually heard look, all the ones appear to be healed, especially in really young patient and calling us to ask, hey, can we take a pause and resume if we see some kind of disruption in the wound, hasn't happened a lot. It just happens with young kids predominantly on dominant or DDEB, but it does have happened.

Anything else Jen, you want to add to that question?

No. I think again, I think real world experience, we continue to hear very, very positive feedback from patients and pictures that we're seeing from our patient showing the improvement in the skin, the durability of the skin, just the skin feeling different all over. So the patients are very excited and we're happy that they are where they're at.

Perfect. Just to confirm the majority of your patients, you are still seeing receive about one vial per week portfolio.

Absolutely. Yes.

(Operator Instructions) Gavin Clark-Gartner, Evercore ISI.

Hey, thanks for taking my questions. I have a few, so I'll just go one by one. First, for the reimbursement approvals. Are all these patients going on to receive paid drug? Or is there any leakage along the way?

Sure. So while the definitely the majority are going on therapy. We continue to work with those that are -- as we go through the process, but for the most part, they are all going on therapy. Yes.

Okay. And you noted -- I believe you noted that the Change Healthcare hack resulted in a lower number of reimbursement approvals in the quarter. Can you help us quantify what that impact is?

Yeah, I don't have -- quantifying it in most part, it slowed it down a bit as you're aware that when it came to change some of that claim adjudication and some of the benefit verification had to pause because our partner relied on change exclusively, I think. They definitely had a pause there. So it's back to normal and we're back expediting those approvals as fast as possible.

Hey Gavin, I would say, look, if you do track something at reimbursement approvals on a weekly basis, the disruption can be quantified as a week to two weeks of disruption.

Okay, that helps. Thanks. And I wanted to just clarify on the compliance metric, that 91% that you provided. I think you noted it was 91% of patients who were on once weekly therapy, is the other 90 -- is the other 9%, are they on less frequent therapy? Or is there a different group of patients who have discontinued treatment altogether?

No, that measurement is actually compliance two weekly therapy. How many patients receive their treatments weekly, if they miss a dose and that would negatively impact it. But in general, 91% of patients receive it weekly. And then if they miss a dose, again, it could take a down a bit, but does not mean that patients are getting at any alternative way. It's weekly. That's how it's prescribed. That's how it dosed.

Okay. Like is there a different group of patients who have discontinued?

No. It's just the balance of that, as I said, just missed a dose.

Yigal Nochomovitz, Citigroup.

Hi, Krish and team. Thank you for taking the question. I just had a question on the ophthalmic study, this small open-label study in 10 patients. Could you just explain are this patients, ones that are existing VYJUVEK patients or could they have been -- or use of VYJUVEK on exclusion criteria for those 10 patients.

And then regarding your inhaled technology, I don't think you've talked a lot about the delivery system there. Could you just explain or using a nebulizer, how long is the inhalation session per dose? Could you just explain a little bit more about the way that's delivered? Thank you.

Yes, this is Suma, I'll answer the first part of your question. With regarding to the eye, yes, a good chunk of the patients that are in a Phase 3 study also have manifestation impact on their eye. They have severe blistering or wounding. As a result, they can't open the eye and it's very painful. So we already have a good chunk of patients who know about this study and are actually proactively want to enroll in the study.

So we feel pretty good which we should be able to enroll these patients pretty rapidly. Again, as I said, we discussed with the agency seven to eight patients, a small number of patients that we need to show wound-healing compared to their natural history (technical difficulty) straightforward study, and we anticipate enrolling with this study pretty rapidly because we already know patients that are lining up for the study.

With regarding to your second question with the inhalation, yes, it's a standard nebulizer that is off the shelf, that's available. The beauty of our product is unlike some of the mRNA deliveries because of the viscous nature of the material you have to dilute it a lot for it to go through the mash.

In our case, I mean, this is -- you can nebulize the product in less than 15 minutes. So it's a pretty rapid fast nebulization time for these patients.

Okay, thanks. And just one quick follow-up on Japan and Europe, I assume that those approvals would be for the skin application first and then the ophthalmic application later? Or is there any possibility that the data from the ophthalmic product could be included with those submissions?

I mean, obviously at the moment, it's all for the skin, it's the same. But once we complete the US study, we may use the same strategy to go into these two countries. We can use the US data to seek approval in those regions.

Thank you. And there were no other questions at this time, and this does conclude today's conference call.

At this time. Thank you, all participants, for joining the Krystal Biotech first quarter 2024 earnings conference call. You may now disconnect.