Krystal Biotech Q4 2024 Earnings Call Transcript

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Provided by Quartr
February 19, 2025
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Operator

Thank you for standing by, and welcome to the Crystal Biotech Q4 twenty twenty four Earnings Call. At this time, all participants are on a listen only mode. After the speakers' presentations, there will be a question and answer session. As a reminder, today's conference is being recorded. I would now like to hand the conference over to your host, Stephan Paquette, Vice President of Corporate Development.

Operator

You may begin.

Stéphane Paquette
Stéphane Paquette
Vice President, Corporate Development at Krystal Biotech

Good morning, and thank you all for joining today's call. Earlier today, we released our financial results for the fourth quarter and full year of 2024. The press release is available on our website at www.crystalbio.com. We also filed our earnings eight K and 10 K with the SEC earlier today. Joining me today 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 U.

Stéphane Paquette
Stéphane Paquette
Vice President, Corporate Development at Krystal Biotech

S. 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.

Stéphane Paquette
Stéphane Paquette
Vice President, Corporate Development at Krystal Biotech

With that, I will turn the call over to Krish.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Stefan, thank you. Good morning and welcome to the call. 2024 was a strong year for Cristal. ViseuVec U. S.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Launch continue to progress well and tracks in the top tier of rare disease launches. The strength of the launch speaks to the robust efficacy and safety profile of ViseuVec and our relentless focus on patient and physician experience. In addition, in 2024, we demonstrated that we can safely and repeatedly deliver genes to the lung with a nebulizer across our cystic fibrosis, alpha-one antitrypsin and MSCLC programs, clearly validating the lung as a second target tissue for our platform. There were also strong early signs of efficacy in our readouts and we fully expect the data to mature later this year. Looking ahead at 2025, we have three primary things to accomplish.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

First, a successful VizaVec launch in EU and Japan. Second, to translate the early signs of efficacy into strong results across our CF and A180 programs. And the third is to prepare for the anticipated launch of BVAC to treat lesions in the eye of dDeP patients. If we do this right, we believe the company will be in a much stronger place with respect to revenue, net income and market cap going into 2026. For the year, net income per share was $3.12 per share, up sequentially from $0.4 per share in 2023.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

This is our sixth straight quarter of positive EPS and fourth straight quarter of sequential earnings growth. In addition to operational success, we have also put ourselves in a strong financial position for future growth. In aesthetics, June Aesthetics reported a strong KB301 Phase one data for the treatment of DECLITA and we plan to start a Phase two study later this year. We're in the process of building out a seasoned management team at Genesthetics with more to come on this later in 2025. '3 '40 '1 million dollars in net revenue within eighteen months of launch and sequential revenue growth for six straight quarters is a tremendous achievement and a testament to the tireless contributions by our commercial and patient support teams on behalf of patients with DEB.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Net Visovac revenue for the queue came in at $91,100,000 bringing revenue for 2024 to $290,500,000 Gross margins and GTN were consistent with prior Qs. I'll now turn it over to Jen and Christine to share more details on The U. S. Launch.

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

Thank you, Krish. Looking back on 2024 and now the early days of 2025, I'm incredibly proud of what our team has been able to accomplish. With steady progress over the entire year and a strong access landscape carrying over from 2024 into 2025, a growing number of dead patients have or will soon benefit from fundamentally corrective BijuVec therapy. I'm also happy to share a major milestone achievement for our United States team as we recently crossed 500 reimbursement approvals nationwide. As of February, the number of patients with reimbursement approvals exceeds five ten.

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

This is in spite of losing a few weeks to holidays in the fourth quarter. With a good pickup of the pace of approvals to start 2025, as well as strong underlying demand trends, we remain confident in our ability to hit our ambitious pre launch penetration targets. Reimbursement approval splits were again largely in line with recent quarters and roughly evenly split between commercial and government plans. Approvals continue to come across the entire debt population, including patients of all ages and with either dominant or recessive forms of the disease. With effectively full nationwide commercial and Medicaid coverage, the access landscape for VIGUVEC remains strong.

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

Reauthorizations are getting processed smoothly. All have either been approved or are in process. In the community, we are still seeing a lag from prescription to approval dictated primarily by the availability of genetic test results and prescriber familiarity with access pathways. As always, our CRISSTL Connect team is working closely with home healthcare providers to meet patient needs and preferences. It is this infrastructure and patient centric approach that has allowed us to navigate scheduling constraints and holidays to ensure patients can get on and stay on treatment.

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

Patient preference for at home administration is again effectively unchanged with ninety seven percent of the weekly treatments occurring in the home setting. Patient applies to weekly treatments while on drug with eighty five percent as of the end of the fourth quarter and in the third quarter it was at eighty seven percent. As we progress our U. S. Launch, we are thrilled to see that patients are achieving durable wound closure and getting to live fuller more active lives.

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

This of course is the whole point of VIGUVAC. As patients enjoy their first positive therapy and then settle into a more regular maintenance regimen, we do expect to see compliance to continue to trend towards the rates that we guided at launch. We are learning from real world experience that the treatment journey for each patient is unique and dynamic. A 21 year old initiating therapy after decades of blistering and wounding may have a very different journey than a very active toddler. The time to wound closure and durability are dependent on a myriad of inputs, including nutritional status and iron levels, as well as the patient's age, their mobility and activity levels, and of course the location and the age of the specific wound treated.

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

Because each patient and each wound area is unique, the length and frequency of treatment pauses are personalized to the patient. Critically, patients and their prescribers understand the importance of treatment persistence. And patients that have benefited from APPLAUSE due to full wound closure are now transitioning into an ongoing wound maintenance routine with BIJUVEC helped by our CristalConnect team. As always, our team will be with them every step of the way to ensure they have a steady access and can continue to enjoy the benefits of regular VIJUVEC treatment. I will now hand it off to Christine to discuss recent sales and marketing activities, which are keeping us on our top tier launch trajectory.

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

Christine?

Christine Wilson
Christine Wilson
Head of U.S. Sales and Marketing at Krystal Biotech

Thank you, Jen. As we enter 2025, it is my pleasure to report that tactics that we developed in 2024 continue to pay dividends, driving significant growth in reimbursement approvals and strong patient demand across the country. Prescribing trends, claims analytics and patient engagement all point to strong and sustained underlying demand. Education and patient activation remain core focus areas for our field team as we look to further penetrate into the identified patient pool.

Christine Wilson
Christine Wilson
Head of U.S. Sales and Marketing at Krystal Biotech

We partnered with multiple advocacy groups in EB in the fourth quarter to host live webinars led by prescribing physicians and patients who shared their experience with BIJUVEC and positive progress that they've experienced since starting on therapy in 2023. In addition, and in honor of EB Awareness Week, we hosted a national broadcast led by Doctor. John Browning. The virtual platform allowed us to reach healthcare professionals across The United States and showcase our clinical trial data, longer term safety and efficacy data and case studies of patients on BIJUVEC. This event also included a patient ambassador on BIJUVEC sharing their firsthand experience.

Christine Wilson
Christine Wilson
Head of U.S. Sales and Marketing at Krystal Biotech

This comprehensive showcase of trial data and real world insights emphasized the clear and durable benefits of therapy and critically demonstrated the significant impact it can have for patients. We also equipped our sales team with new promotional material that emphasizes the long term safety and efficacy of IGVEC. These materials not only reinforce the durable wound healing benefits that can be achieved only with a corrective therapy like IGVEC. They also underscore that all dep patients can benefit from therapy with actual patient images demonstrating healing in both the RDEB and DDEB subtypes across both the adult and pediatric spectrum. Most importantly, these efforts have yielded tangible results.

Christine Wilson
Christine Wilson
Head of U.S. Sales and Marketing at Krystal Biotech

Not only did we achieve significant reimbursement approval growth over the past few months, we also continue to expand our prescriber base. Over 65% of prescribers in the fourth quarter were new writers. With each new prescriber, awareness of deb and BIJUVA grows, extending our reach into new communities. As the number of patients on therapy grows, I would also like to highlight that we have personalized and ongoing communication with patients and their caregivers to ensure they are supported throughout their journey. These communications are via phone call, email or text, all based on the preferences of patients and their families.

Christine Wilson
Christine Wilson
Head of U.S. Sales and Marketing at Krystal Biotech

These touch points are another part of our commitment to patients, allowing us to move proactively to meet their needs with practical resources and EB community connections, while also gaining valuable insights to support new patient starts. With strong underlying demand, growing awareness and a broadening prescriber base, we are excited to continue growing the number of patients on BIJUVICA across The U. S. Now I will hand it back to Krish to share an overview of our global expansion plans for 2025.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Thanks, Kristine. We expect a positive CHMP opinion on our application later this month. And based on this timeline, we expect our first EU launch in Germany around mid year along with commencing an access per course AP2 program in France. The opportunity that exists in Europe is significant with many already identified deaf patients in urgent need of fundamentally corrective therapy. In Germany and France alone, there are over one thousand identified death patients.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

As in The U. S, our initial focus will be to penetrate the identified patient pool. We're also on track for the regulatory decision in Japan later this year, enabling launch into another market with hundreds of already identified death patients. In support of this filing and our launch, we have established our head office team in Tokyo and have started hiring our field force. It has always been our goal to treat death globally and comprehensively.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

And thanks to the continued efforts of our development team, we're also working steadily towards treating lesions in the eye of deaf patients. Suma will now share more detail on both our ophthalmic Vivek program and our broader pipeline.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

Thank you, Krish. As Krish just noted, we are committed to treating deb comprehensively and are very excited to be progressing our second product, KB-eight zero three, towards a potential approval to address the ocular complications associated with death. In support of this goal, we initiated a natural history study last year to prospectively collect data on the frequency of corneal abrasion in death patients. This study is providing valuable information on the burden of disease and is helping us refine endpoint selection for our Phase three study. The natural history study may also serve as a run-in to our registrational trial adding more baseline data to contextualize our Phase three results.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

The high rate of enrollment in the study with approximately 50 patients enrolled underscores the unmet need and demand for a corrective therapy for the eye and given the run-in options should provide us an opportunity to rapidly enroll our Phase three once initiated. We are finalizing the study design and statistical analysis plan with the agency and remain on track to initiate our registrational Phase three, which we refer to as our IO Light study in the first half of the year. Assuming rapid enrollment, given the run-in option, we continue to expect top line data before year end. We look forward to sharing updates on IO light and our natural history study in the coming months. We also announced a series of updates on our inhaled programs last quarter that in our view validate the lung as a second target tissue for our HSV-one based gene delivery platform.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

Included in these updates was a first look at safety and gene delivery data for our KB-four zero eight program, which collectively demonstrated that we could safely deliver functional genetic cargo to the lung. KB-four zero eight is our redosable inhale therapy for the treatment of AATD, a serious disease linked to the absence of functional AAT in the lung. KB-four zero eight is designed to deliver two copies of the SERPAN1 TENS gene, which encodes for normal human AAT protein to enable local AAT production in the lung itself. KB-four zero eight is currently being evaluated in our first in human Phase one SERPENTIME I study, an open label single dose escalation study in adult patients with AATD. SERPENTIME I is designed to include up to three dose escalation cohorts evaluating single administration of ten thousand and nine, ten thousand and ten and ten thousand and eleven PFU of KB-four zero eight via inhalation.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

In December of last year, we announced an interim clinical data update including safety data for seven patients enrolled in the first two dose escalation cohort of SERPENTAN1 as well as molecular data from two patients in the second cohort that had consented to bronchoscopy. KB-four zero eight was found to be well tolerated at both tested dose levels with only mild to moderate and transient adverse events observed. No serious adverse events or dose limiting toxicities were reported. In addition, clear evidence of successful gene delivery was observed in both patients that underwent bronchoscopies with the proportion of conducting airway epithelial cells positive for AAT increasing from zero percent to thirty nine percent in one patient and from three percent to thirty five percent in the other. Secretion and functionality of encoded AAT was also demonstrated in the patient with available LAVAGE samples, with AAT levels in epithelial lining fluid reaching seven twenty nine nanomolar and the proportion of free neutrophil elastase dropping from ninety seven point two percent to forty point two percent after a single KB-four zero eight dose.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

Following this data update, we simultaneously expanded the second SERPENTIME I cohort and opened enrollment in the third for more comprehensive molecular assessment at both dose levels. We are working closely with the ALPHA-one Foundation and their therapeutic development network on the SERPENTINE one study and expect to announce complete study results later this year. Our second rare respiratory disease program, KB-four zero seven is also progressing well. KB-four zero seven is a redosable inhaled therapy designed to deliver two copies of full length CFTR transgene for the mutation agnostic treatment of cystic fibrosis. As summarized on this slide, we have built out a robust preclinical data package that demonstrates that KB-four zero seven efficiently transduces target airway epithelial cells, leading to the expression of full length properly localized glycosylated and functional CFTR.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

On the back of this data, a growing clinical data set, I'm pleased to report that we recently received full sanctioning of our KB-four zero seven Phase one protocol, providing further validation of our program and opening up access to network trial sites for future clinical development efforts. We also recently announced an initial safety update on cystic fibrosis patients treated with KB-four zero seven in the first two dose escalation cohorts of CORAL-one, our ongoing first in human Phase one study, both single and repeat inhaled administration of KB-four zero seven was well tolerated with early mild to moderate and transient adverse events. Again, there were no reports of serious adverse events or dose limiting toxicities reinforcing the attractive safety profile of our vector when delivered via inhalation. With the first two cohorts successfully cleared and KV-four zero seven well tolerated, we have progressed to our third cohort and expect to report top line results including molecular data around the middle of this year. These are just a few of the recent highlights from our clinical stage pipeline.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

We also recently reported early evidence of monotherapy activity with inhaled KB707 in heavily pretreated patients with advanced lung cancer and earlier in the year shared positive safety and efficacy results of our aesthetic candidate KB301, which we are progressing into Phase two. As we look forward, 2025 is shaping up to be another busy year. Some of the key development milestones for our team are laid out here. In addition to the initiation and completion of our registrational study evaluating KB-eight zero three for ocular complications of death, we are also expecting to provide molecular data updates for our rare risk for disease program, KB-four zero eight and KB-four zero seven as well as first in human data for a second aesthetic product candidate, KB-three zero four, which encodes both Type three collagen and elastin. Our oncology programs will continue to progress with potential of interim updates later in the year.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

As our recent data announcement have demonstrated the potential HSV-one based gene delivery goes well beyond the skin. We are looking forward to making rapid progress of our pipeline in 2025 and further validating the breadth of the opportunities in front of us targeting the skin, lung and eye. With that, I would like to turn the call to Kate.

Kathryn Romano
Kathryn Romano
Executive VP & Chief Accounting Officer at Krystal Biotech

Thank you, Souma. In the fourth quarter, Cristal saw continued VizaVec revenue growth with net product revenue of $91,100,000 representing an increase of approximately $49,000,000 over the fourth quarter of twenty twenty three, which was the first full quarter that Cristal had revenue after our approval in May of twenty twenty three. Cost of goods sold for the quarter was $4,900,000 resulting in a gross margin of 95%. In the fourth quarter of twenty twenty three, cost of goods sold was $2,900,000 resulting in a 93% gross margin. Research and development expenses for the quarter were $13,500,000 inclusive of stock based compensation of 2,300,000 compared to $11,400,000 for the prior year's fourth quarter inclusive of $2,400,000 of stock based compensation.

Kathryn Romano
Kathryn Romano
Executive VP & Chief Accounting Officer at Krystal Biotech

Higher research and development expenses in the fourth quarter of twenty twenty four were mainly due to increased clinical trial related costs, increased R and D manufacturing costs for our pipeline candidates and increased license and regulatory fees. Selling, general and administrative expenses for the quarter were $31,300,000 inclusive of stock based compensation of $11,000,000 compared to $24,800,000 for the prior year's fourth quarter, which was inclusive of stock based compensation of $7,500,000 Higher selling, general and administrative expenses in the fourth quarter of twenty twenty four were primarily the result of increased personnel related costs, increased professional service fees and increased ViseVax sales and marketing costs as compared to the prior year's fourth quarter. Net income for the quarter was $45,500,000 which represented $1.58 per basic and $1.52 per diluted share. I'd also like to provide some perspective on our forecast for operating expenses in 2025. We expect to incur between $150,000,000 and $175,000,000 in combined non GAAP R and D and SG and A costs this year.

Kathryn Romano
Kathryn Romano
Executive VP & Chief Accounting Officer at Krystal Biotech

This projection excludes stock based compensation. This expected increase in operating expenses compared to 2024 is driven primarily by increased SG and A costs for our planned commercial launches outside of The United States and increased R and D costs from our continued clinical and regulatory costs associated with our expanded pipeline programs. In closing, we ended the fourth quarter with $344,900,000 in cash on hand and $749,600,000 in total cash plus short term and long term investments, noting quarterly growth in our overall cash and investments position with an increase over our third quarter of twenty twenty four cash and investments balance by about $55,000,000 And now I will turn the call back over to Krish.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Thanks, Kate. As you heard from Christine and Jan, patients are achieving profound benefits with VIZUREVAC and getting to live fuller, more active lives. We're steadily expanding our prescriber base and further penetration into the community setting. With one full calendar year of launch in The U. S.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Behind us and increasing presence in key European markets in Japan, our conviction in the global peak sales estimate of over $1,000,000,000 for VizaVac has only strengthened. As we look forward, I'd like to share a few key lessons we have learned since launch, so we're aligned on how we get to realize the opportunity in front of us. The first lesson has to do with timing from initial patient interest to starting treatment. As Jen mentioned earlier, patients and prescribers in the community often need more support to navigate the path to success. Our turnaround time on average is still between forty five and sixty days with respect to these patients.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

The second lesson is a realization that we never really get a full quarter when we are talking about VYJAVECT. VYJAVECT is a weekly therapy administered at home by HCP and life gets in the way for these patients in each quarter. In the first quarter, many families will be changing insurance. In the second, we have to work through summer holidays. In the third, Labor Day and back to school for families and in the fourth, we navigate around major U.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

S. Holidays. In spite of that, I'm pleased and proud to report sequential net Visovac revenue growth and continue to have strong conviction in our global visor vec peak sales estimates. The third lesson has to do with high compliance, which has been well above what we estimated at the time of launch. That said, we are entering a phase where some patients are now able to take initial pauses, enjoy the benefits of durable wound closure and come back on drug when there is a wound disruption.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

This is a fantastic outcome for patients and their families. Our Crystl Connect team remains in close contact with all of our patients and when new wounds emerge, reinitiation of treatment is seamless. Our relationship with our patients is for the long term and we want them to feel the freedom of being able to live their lives as they choose independently, actively with the confidence of knowing that they can now control their wounds with VIJUVEC. Finally, we've done a terrific job of accruing for the price cap of VIJUVEC. We've had no volatility in net revenues in 2024 and we do not expect to have any going forward.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Finally, in closing, as you can see from the slide, we have several important clinical and regulatory milestones in 2025 to demonstrate the full breadth of our platform and we're excited for 2025 with what we can deliver to patients and shareholders. I'd like to thank my Cristal colleagues for their dedication and perseverance that underscore our excitement in the long term outlook for Cristal and the patients we aim to serve. Thanks for listening and I'd like to open the call for Q and A.

Operator

Certainly. At this time, we will be conducting a question and answer session. Your first question for today is from Alec Stranahan with Bank of America.

Alec Stranahan
Alec Stranahan
Vice President - Equity Research at Bank of America

Hey guys, thanks for taking our questions and congrats on the continued progress. Just two from us. First on VYJUVEC, wondering if you saw any year end stocking in 4Q and maybe you could just remind us how accounting for patient annual cap fed into the 4Q results and sequentially into 1Q twenty twenty five as this is reset?

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Thanks, Alex. Thanks for your question. Nothing substantially different in Q4 versus any other quarters. So there was no any change in stocking or inventory with respect to Q4 as compared to Q3 or Q2 or Q1. And in terms of price cap, I think I've gone through this many times.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

At the end of every quarter, we look back starting at the beginning of twenty twenty four, see how we're going to how patients are doing. We revisit that calculation at the end of Q2, Q3 and Q4. So we actually believe, as I said in my speech, that we do a really good job of making sure there's no volatility in revenue. Of course, cap calculation is complicated, because it is at a payer level and has a lot to do with the mix within each payer, the number of patients and when they start during the year. But we've done a pretty good job of maintaining, taking volatility out of the equation.

Alec Stranahan
Alec Stranahan
Vice President - Equity Research at Bank of America

Okay. That makes sense. And maybe one quick one on the CF study. I guess how is enrollment going? Is cohort three maybe accruing faster or in line with cohorts one and two?

Alec Stranahan
Alec Stranahan
Vice President - Equity Research at Bank of America

And maybe walk us through how the CFF TDN sanctioning maybe helps with this? Thank you.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

No, it's definitely super helpful, but we just got started. So there's always a time lag when you just get started, it takes a few months to get a few patients on drug. But enrollment in Cohort three has already begun and I'll let Suma add some more color to this story.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

Absolutely. I mean, obviously, getting TDN fractioning was very important because all of these academic major sites that can do bronch and have expertise in CF and have these patients now are very excited. In fact, many of them reached out to us directly to participate. We have seven to eight sites active. We are in the process of doing all of the administrative stuff, so there's contracts, budgets, as Krish mentioned.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

But we have two sites that are part of TDN that are up and running and we have already enrolled patients for this cohort. So it's moving pretty well.

Alec Stranahan
Alec Stranahan
Vice President - Equity Research at Bank of America

All right. Thank you.

Operator

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

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Good morning guys. Thanks for taking the question. I wanted to ask a little bit about what you guys are expecting from Europe in the second half of the year. Krish, I believe you mentioned that there are about one thousand patients total between Germany and France that are identified. Can you give any additional breakdown of that one thousand between the two geographies?

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Are they treated at centers of excellence like in The U. S? And if so, is there a number between the two geographies? And then I have my second question, my follow-up question is on pricing. How right now are you thinking about the initial sort of German free price range and the French at least expanded access price?

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

And how should we be thinking about modeling longer term price in Europe?

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Thanks, Ritu. At a high level, both Germany and France are a bit more concentrated than The United States. That said, Germany is closer to The U. S. And France is much more concentrated among centers of excellence and the spread of the 1,000 is about 600 in Germany at a very high level, 400 in France.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

In terms of pricing, in Germany, for the first six months, we get to launch with The U. S. Price as we put the dossier in place and start the negotiations. At the end of six months, depending on how we feel, how the negotiations are going, we start accruing for the next six months. And the expectation is in twelve months, we would get an actual German price and be steady state from that point on.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

In France, we're under the AP2 program and it kind of forces us to start accruing from day one. So the expectation, I mean, so the AP2 program should start maybe slightly after the German launch, but not too far out. And in France, maybe in about fifteen, eighteen months from approval, we expect to get a price in France and that's how they're laid out.

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Got it. Very quick follow-up, should we be thinking about home dosing in Europe as well?

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Yes, you should, for sure.

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Okay. Thanks for taking all the questions.

Operator

Your next question is from Gavin Clark Gartner with Evercore ISI.

Gavin Clark-Gartner
Director - Biotechnology Equity Research at Evercore ISI

Good morning. Thanks for taking the questions. Just on the reimbursement approvals first, if I'm doing my math correctly, last quarter about fifty percent of new patients coming on were dominant patients and this quarter that seems to be about up to seventy five percent dominant patients. Is that math correct? Do you think this trend will continue?

Gavin Clark-Gartner
Director - Biotechnology Equity Research at Evercore ISI

And how do you account for that in your compliance assumptions?

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Gavin, look, the percentage of dominant and recessive varies quarter by quarter. As we go into that community, I mean, your math is right, that we did see more dominant in Q4 than we saw in Q3 as we go into the community. But although at a high level, people think about recessive being more severe than dominant, there are a lot of patients who are in the cusp. That are dominant patients with just as severe as recessive and recessive patients who are just as mild as dominant. So I would not I mean, in terms of compliance going forward, I do not expect a material change in the way, I do not expect a big change based on the percentage of dominant in the study.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

But it is true. But that said, we don't like when we report Q1, our expectation is not that dominant will continue to go up. It could easily shift back to what it was in Q3 or Q2.

Gavin Clark-Gartner
Director - Biotechnology Equity Research at Evercore ISI

Very helpful. And then just one bigger picture question. So you have about $750,000,000 cash on the balance sheet. Consensus has you doing around $250,000,000 cash flow this year, ballpark $300,000,000 next year, depending on how exactly ex U. S.

Gavin Clark-Gartner
Director - Biotechnology Equity Research at Evercore ISI

Launch goes. So even if you did want to allocate a good chunk of capital to additional R and D, you still have a lot of financial flexibility. So how are you thinking about buybacks, capital allocation overall as you kind of progress to the next phase here? Thank you.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Look, I mean, it's a valid point. It's definitely a discussion point within Cristo. We're just figuring out the timing of such a buyback and the extent that is meaningful and measurable. So definitely a valid question, Gavin, and we're thinking about it pretty seriously going forward.

Gavin Clark-Gartner
Director - Biotechnology Equity Research at Evercore ISI

Got it. Thank you.

Operator

Your next question for today is from Sami Corwin with William Blair.

Sami Corwin
Biotech Equity Research Analyst at William Blair

Hey, good morning. Thanks for taking my question and congrats on the progress. I was wondering if you could provide a high level update on the EU regulatory process. I think we initially expected to hear a decision from CHMP in late twenty twenty four. So I was curious if you had any insight into the reason behind the delay.

Sami Corwin
Biotech Equity Research Analyst at William Blair

And then my second question is, given you could face DEB commercial competition as early as 2Q, just how you're kind of thinking about maintaining and expanding market share in the face of that competition? Thank you.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

Yes.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

I can address the first question. Obviously, the delay was because we were trying to get the best label. I mean, we have a very favorable label as the SMPC. So obviously, the home dosing and caregiver administrations, all of those nuances needed to be ironed out. So there were training materials that needed to be prepared to support that on the label.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

So that was the reason for the delay. And I think the two months helped us get all of those documentations and training materials in place to achieve that to get a favorable label.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Hey, Andy. Competition,

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

look, at a high level, it's tough to beat the value proposition of ViseuVec, both in terms of and if you look at how ninety eight percent of our patients are opting for home dosing and not even going to the local physician office, we have learned that the profile of VYJAVAC is well aligned with the expectations of the patients. But that said, we are putting in we are not ignoring

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

that the

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

market could potentially become more competitive later in the year. And our medical affairs team is having the right kind of conversations with the physicians. Our patient services team having the right kind of conversation with patients and we feel pretty good about our ability to hit the two year target and the overall peak sales in spite of the competitive nature of the market.

Sami Corwin
Biotech Equity Research Analyst at William Blair

Got it. Thank you.

Operator

Your next question for today is from Ry Forsyth with Guggenheim.

Ry Forseth
Vice President at Guggenheim Securities

Hi, this is Ry from DevJits team. For four zero seven, how are you thinking about FEV1 in terms of the bar for advancing the program? And is that bar sort of consistent across genotypes?

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Look, we're just starting to dose our patients in the efficacy cohort, realized that the long term direction for Cristal is to target the null population, which is a complete unmet medical need. There have been comments made in press from other competing companies that in null patients, any kind of FEV improvement over three percent, four percent, five percent all the way up to ten percent is considered a very positive outcome for these patients. But please realize we are a redosing paradigm. So no matter where we start with these patients, we have the opportunity to build upon the FEV levels over time. And so we feel really good about our focus strategy on going after the null mutation.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

And then as a secondary effort, maybe as Suma mentioned in her speech, become mutation agnostic.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

Yes. I mean, there's null patients and there's also subset of population where they are they don't get correct those or these kind of therapies, they're not conducive to it. So it's both these populations that we're targeting. And obviously, as Krish mentioned, we are redosable, so we have that flexibility. We will look at improvements in FAD1.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

There's flexibility from a regulatory strategy for us to go just like we did in the eye to do a single label, open label study with some sort of natural history. So I think from a regulatory perspective, if we have any improvements in I mean, we show functionality, we show some expression and we show even slight improvement in FEV1, I think we have a very favorable regulatory environment and a pathway to move this program very rapidly into the into clinic and into an approval path, just like we did with DI.

Ry Forseth
Vice President at Guggenheim Securities

Thanks for that.

Operator

Your next question for today is from Josh Schimmer with Cantor.

Josh Schimmer
Managing Director at Cantor Fitzgerald

Great. Thanks for taking the questions. Two quick ones. First, can you help quantify the impact of the annual cap on BIJEVEC in 2024? And how you think that might impact in 2025?

Josh Schimmer
Managing Director at Cantor Fitzgerald

And whether you're planning any changes to that cap? And then second, the 10 has some new language around VIGEVEC manufacturing process changes and some risks around that at least theoretical. Have there been any changes to the VIGEVEC manufacturing process? And if so, can you explain why?

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Go ahead, Budd.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

So for the cap, we have been seeing about eight percent of commercial patients on the cap consistently from the beginning?

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

For the manufacturing process, we just scaled up. And so we have gone to the higher level bioreactor level. And we have we filed the PS and we got approval for it. So again, so we have a scale up process that is approved by the FDA. And the beauty about it is this process is can be adaptable across our pipeline.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

So if you see four zero seven, I mean the limitation is not going to be CNC anymore. We can scale up, we can make the material, the processes pretty much have been paced across all of our pipeline products. So CMC, we de risk CMC from for these other products that may need more commercial material. So I think that was very positive for us getting that scale up approved by the FDA.

Josh Schimmer
Managing Director at Cantor Fitzgerald

Thank you.

Operator

Your next question is from Yigal Nochilovitz with Citi.

Reena Patel
Reena Patel
Biotech Equity Research Analyst at Citi

Hi, this is Reena on for Yigal. Thanks for taking my question. I just wanted to ask on ATD, could you give us a little bit more color on what we should expect to see from the EXPANDE CORE2 and CORE3 data? What are more comprehensive molecular assessments that you're considering beyond ATD levels? And what therapeutic effect do you hope to see that you would consider clinically meaningful for these patients?

Reena Patel
Reena Patel
Biotech Equity Research Analyst at Citi

And I have a follow-up.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Yes. So on Cohort two, pretty much not much of a change than what we reported previously. We're just adding more patients to confirm what we saw. We were pretty pleased with what we saw and we just want to add one or two patients more to confirm both the levels in the lung, the increase in the levels in the systemic circulation and to quantify in terms of at a molecular level what they are. So Cohort two and Cohort three is simply exactly Cohort two, but at a higher dose.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

So do not expect anything dramatically different between the two.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

And obviously, we are looking for dose response. I mean, we know cohort two. We didn't even expect that the cohort dose level to see this level of AAT in the lung. So we're very pleased to see that. I mean, obviously, we can it was a very safe and we feel it's a dose that showed functional AAT expression at a pretty decent level.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

So we do want to see what we get at the third dose because again it's safe. So we want to see that's an increase and what does that correlate to levels in the serum too. So it's lung and serum. If you see a good correlation and increase, then maybe that's the dose we will move forward or repeat dose administration and beyond.

Reena Patel
Reena Patel
Biotech Equity Research Analyst at Citi

Okay, great. Thanks. And just as a quick follow-up, we understand that plasma ATD should be sort of a relevant benchmark if synthesis were to occur in the liver because of the need to transport into the circulatory system to get to the lung. But since you're already synthesizing in the lung to start with, shouldn't we maybe not put too much weight on plasma ATD since it's not as relevant to the therapeutic goals? I guess if you could give more color on that, how we should be thinking about that or?

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

Yes. I think what you're going to look is core relationship of a dose response of how much level are we seeing in the lung and what levels are we seeing in the plasma. So we want to see that core relationship that's increasing and going to the next dose, we want to see what that increases. So once we have that core relationship, then we can go to the FDA and let them know that a biomarker approach, we can say, yes, we see this level of lung and the plasma levels to this level in the lung based on the kind of dose that we are giving these patients. This is the ratio.

Suma Krishnan
Suma Krishnan
President, Research & Development at Krystal Biotech

So I think that will help us to go into from a regulatory pathway to sit down with the agency and discuss about biomarker path where we don't have to bronch these patients, but can use serum levels that is meaningful for lung administration for this patient population.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Yes. I do want to repeat what she just said. We do not care fundamentally, you're right. We do not care about levels in the lung levels in the systemic circulation, I apologize. We look for levels in the lung and maybe a correlation between the two, so we could avoid potentially bronching for molecular approval.

Reena Patel
Reena Patel
Biotech Equity Research Analyst at Citi

Thanks. Super helpful. Thanks so much.

Operator

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

Andrea Newkirk
Andrea Newkirk
Biotechnolgy Equity Research at Goldman Sachs

Good morning. Thanks for taking our question. For Jen and Christine, I'm just curious here based off of what you're seeing right now in terms of the rate of reimbursement approvals, what is needed to reaccelerate patients coming on to drug in order to reach your 60% penetration goal within two years of launch?

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

Yes, I can start that. I mean, I think we definitely, as I said in the speech, saw some slowdown over the holidays virtually with physician offices and payers sort of delaying and not answering the phone during those times. So we feel like we've increased our trajectory already. We have a healthy pipeline right now of potential patients and we're right on path for that. So we already started seeing that comp.

Jennifer McDonough
Jennifer McDonough
SVP of Patient Access, Analytics & Operations at Krystal Biotech

Obviously, the first few weeks of January, the same thing was occurring with reverification season and payers being sort of distracted at that point. So there were delays happening there as well.

Andrea Newkirk
Andrea Newkirk
Biotechnolgy Equity Research at Goldman Sachs

Okay. And Krish, just when you think about that $1,000,000,000 plus peak sales opportunity globally, just curious if you could provide a little bit more granularity on how The U. S. Versus the EU opportunity breaks down across that $1,000,000,000 plus or even with Japan as well?

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Look, there are 3,000 patients in The U. S, Three Thousand patients in Europe at a high level and about 3,000 worldwide. The pricing in U. S. Versus the pricing in Europe makes accounts for the ratio.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

The expectation on pricing in Europe is anywhere at the high end at 60%, seventy % discount 60%, seventy % of The U. S. Price to maybe 50%, sixty % of The U. S. Price.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

But that said, if you look at our drug, it was a blinded Phase three study. The efficacy results were very powerful. The convenience is amazing. It is a loud disease, right? Meaning, very visible, loud disease, unmet medical need, some chances of getting squamous cell carcinoma in a handful in a certain percentage of these patients.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

So we have a compelling case to make in the dossier with respect to pricing in Europe. And so we feel good about going into the negotiations. So to answer your question at a high level, the way you split the $1,000,000,000 plus across the nation is purely a function of the ratio of the pricing between across these nations. And so your assumption is 70% of The U. S.

Krish Krishnan
Krish Krishnan
Chairman & CEO at Krystal Biotech

Price and that's how they split because the prevalence is pretty identical across the three segments.

Operator

Thank you. This does conclude today's conference call. You may disconnect your phone lines at this time and have a wonderful day. Thank you for your participation.

Executives
    • Stéphane Paquette
      Stéphane Paquette
      Vice President, Corporate Development
    • Krish Krishnan
      Krish Krishnan
      Chairman & CEO
    • Jennifer McDonough
      Jennifer McDonough
      SVP of Patient Access, Analytics & Operations
    • Christine Wilson
      Christine Wilson
      Head of U.S. Sales and Marketing
    • Suma Krishnan
      Suma Krishnan
      President, Research & Development
    • Kathryn Romano
      Kathryn Romano
      Executive VP & Chief Accounting Officer
Analysts
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Earnings Conference Call
Krystal Biotech Q4 2024
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