Egetis Therapeutics AB (publ) (EGTX) Earnings Call Transcript & Summary

Welcome to Egetis' press conference regarding the FDA approval of EMCITATE. [Operator Instructions] Now, I will hand the conference over to CEO, Nicklas Westerholm. Please go ahead.

Thank you very much, operator, and thank you, everyone, for joining us today. For those I haven't had the privilege to meet before, my name is Nicklas Westerholm, and I'm the CEO of Egetis Therapeutics. Today is truly an historic and transformative day for Egetis with the approval of EMCITATE for patients with MCT8 deficiency in the United States. But with me also today, I have our Chief Medical Officer, Tiago Nunes, who will remind us about the severe condition of MCT8 deficiency. We also have Christian Sonesson, Vice President, Product Strategy and Development, who will elaborate about our robust data package that formed the basis on the NDA and the USPI, the so-called label. Last but not least, we have Anny Bedard, President of Egetis in North America, who will elaborate on our launch readiness. Next slide, please. We will also leave ample time for questions and answers at the end. So late last night, we announced that the U.S. Food and Drug Administration has approved EMCITATE for the treatment of peripheral thyrotoxicosis in adults and pediatric patients with MCT8 deficiency. This approval represents the first and only FDA-approved treatment for this rare, severe life-shortening genetic disorder that marks an important milestone for patients, families, clinicians and the broader MCT8 community. For families affected by this condition, the journey to diagnosis and care is often difficult and uncertain. Today changes that. For Egetis, this approval represents far more than a regulatory milestone. It is the culmination of a comprehensive development program that has evaluated EMCITATE across multiple clinical studies and patient populations. It's a validation of years of research and development together with our key collaborator, the Erasmus Medical Center, or EMC, from Rotterdam. This also marks the beginning of a new chapter for us as a company as we transition fully into a commercial stage rare disease company in the world's largest pharmaceutical market. So our focus now turns from approval to commercialization. We have been preparing for this moment and have established a commercial and medical affairs infrastructure necessary to support patients and health care providers from day 1. Our goal is simple, to help eligible patients to gain access to EMCITATE as quickly and seamlessly as possible following approval. We are also pleased that the FDA granted Egetis a rare pediatric disease priority review voucher in connection with the approval. The voucher represents a very important financial asset for the company and will provide additional flexibility as we continue to execute our mid- to long-term growth strategy, building a sustainable rare disease company. As outlined in today's press release, we expect to evaluate opportunities for the monetization of the voucher during the fourth quarter of this year. Today's achievement also reinforces the strength of Egetis' rare disease strategy. We remain focused on developing and commercializing therapies that address significant unmet medical need for small patient populations where meaningful innovation can have a profound impact on patients' lives. With that, I will now hand over the call to our Chief Medical Officer, Tiago Nunes, who will discuss the devastating condition of MCT8 deficiency.

Thank you, Nicklas. MCT8 deficiency is a rare, severely debilitating life-shortening condition. It is caused by mutations in the SLC16A2 gene located on the X chromosome, hence, its predominance in males. The MCT8 deficiency impaired transport of thyroid hormone leads to low T3 levels in the brain and high circulating T3 levels. This disease is characterized by impairment in neurodevelopment and systemic metabolic and cardiovascular disturbances with increased morbidity and mortality. There is a median overall survival of 35 years of age, and it is expected that 1 in 3 children with MCT8 deficiency will not survive to adulthood. Cellular differences in MCT8 dependence lead to simultaneous thyroid hormone insufficiency in the CNS, central nervous system, and persistent peripheral thyrotoxicosis. This is a clinical state in which tissues are exposed to and respond to excessive thyroid hormone. Thyroid hormone insufficiency in the central nervous system occurs because T3 cannot enter due to MCT8 dysfunction. Entry of T3 by alternative transporters leads to peripheral thyrotoxicosis in the periphery in organs like the heart and the muscle. In MCT8 deficiency, clinical presentation results from thyroid hormone insufficiency in the central nervous system and persistent peripheral thyrotoxicosis. These patients present high T3 levels, the active hormone; low to normal T4 levels, the storage hormone; and TSH, which is the control hormone, which is normal or slightly elevated, as our SLC16A2 genetic testing confirms the diagnosis. Impairment in neurodevelopment, hypotonia and failure to thrive are characteristic. Untreated persistent peripheral thyrotoxicosis that may include tachycardia, cardiac arrhythmias and hypertension are associated with elevated risk of major cardiovascular events and cardiovascular abnormalities. Sudden death has been reported as frequent cause of mortality and is likely linked to underlying cardiac abnormalities. The treatment of MCT8 deficiency is multidisciplinary, and one of the main focus of treatment is the management of failure to thrive. Most affected patients are underweight with body weight for age showing progressive decline over time. Undernourishment can weaken the immune system, leading to difficulties fighting infections. Failure to gain weight is associated with poor prognosis and increased risk of death in this population. Up to recently, there was no approved drug for the management of MCT8 deficiency. The approval of EMCITATE for the treatment of peripheral thyrotoxicosis in patients with MCT8 deficiency has changed that. EMCITATE is a thyroid hormone receptor agonist that enters MCT8-dependent cells independent of MCT8 transporter. EMCITATE replaces T3 in MCT8-dependent tissues and normalizes thyroid hormone activity across tissues. Clinical trials show that EMCITATE reduces serum T3 levels and improves clinical manifestations of thyrotoxicosis, which are associated with increased morbidity and cardiovascular mortality. I now want to present and introduce Christian Sonesson, Vice President, Product Strategy and Development, to take a closer look at the clinical data supporting EMCITATE treatment in MCT8 deficiency.

Thank you, Tiago. Next slide, please. So before I turn to the label itself, let me start with the clinical evidence submitted in the NDA. This package rests on 2 pillars. First, 3 clinical studies: Triac Trial I, which established the core effect of EMCITATE in lowering T3 and improving the clinical markers of thyrotoxicosis. ReTRIACt, the randomized withdrawal study that delivered confirmatory placebo-controlled evidence that this T3-lowering effect is directly attributable to EMCITATE. And Triac Trial II, which added safety data at high doses in the youngest patients. Together with 3 independent sources of real-world evidence, the Erasmus Medical Center cohort study following patients for up to 6 years, confirming that the effect on T3 and clinical markers of thyrotoxicosis are durable over the long term. The EMC survival study, which examined treated versus untreated patients in a cohort of more than 600 individuals. And the U.S. expanded access program showed that the real-world experience in the U.S. was consistent with everything we had seen in the clinical trials. From this clinical package, really 2 things stand out. First, the robustness of the data behind EMCITATE, which is unusually complete for an ultra-rare genetic disease. And second, the consistency of the results across different designs, different populations and different settings. And building on what you heard Tiago just described, the biological plausibility of the treatment effects seen in our clinical data has been key in the NDA package. Thyrotoxicosis is a well-characterized condition. It's linked to cardiovascular and metabolic harm, is extensively documented, and correcting the thyroid hormone excess is known to reverse it. With the EMCITATE lowering the elevated T3, we see the expected clinical benefits also in patients with MCT8 deficiency. So the clinical data in the NDA package don't stand alone. They sit on top of well-established biology. Every data we have moved in the same direction, and that coherence is what underpins our confidence in the clinical package. Next slide, please. So turning to the label itself. Key here is the broad indication statement covering all patients with MCT8 deficiency, saying that EMCITATE is a thyroid hormone receptor agonist indicated for the treatment of peripheral thyrotoxicosis in adults and pediatric patients with MCT8 deficiency. With this approval, EMCITATE becomes the first and only approved therapy for these patients in the United States. The remainder of this slide gives a brief overview of the highlights of the USPI, the class black box warning, how the medicine is dosed and individualized, the dosage forms, the warnings and precautions, the contraindication, most common adverse reactions and drug interactions. I won't go through each of these in details. Here, the full approved prescribing information is the definitive source, and it's linked on this slide for anyone who would like to see the complete safety and usage information. Next slide, please. Here, we see how the clinical data package translates into Section 14 of the USPI. In other words, which studies FDA considered adequate and well controlled to provide the primary support of effectiveness. Two studies are included. ReTRIACt is Study 1, the randomized withdrawal study. It gives us 2 findings. First, the rate of T3 change, where total T3 rose 1.5x faster on placebo than on EMCITATE during the randomized treatment period with a p-value of 0.034. Second, the need for rescue, where 4 out of 8 patients on placebo met the rescue criteria of total T3 above the upper limit of normal versus 1 out of 7 on EMCITATE. And I'd note the asterisks here that, that single case was a participant who discontinued prematurely for reasons not related to drug and was counted as having met the criteria. What is also worth emphasizing is the consistency. Every patient randomized to placebo had a larger increase in total T3 than any participant who continued EMCITATE. Triac Trial I is Study 2, a 12-month open-label study where we saw a reduction in mean total T3 from 323 to 118 nanograms per deciliter over a year, a change of -205 with a p-value below 0.0001. Alongside that, key clinical markers of thyrotoxicosis improved, systolic blood pressure down, heart rate down and body weight for age Z-score up. All 3 secondary endpoints moved in the direction of reduced peripheral thyrotoxicosis, which is positive to have acknowledged in labeling given the importance of improvement on thyrotoxicosis in this patient population as previously covered by Tiago. The EMC survival study was not included in labeling. It's important to remember that this study is a retrospective real-world cohort study, and the scientific and regulatory perspective on rigor is slightly different. And ultimately, FDA considered that given the limitations of the retrospective real-world design, the study did not meet the regulatory requirements for an adequate and well-controlled study. But certainly, from a scientific perspective, we are confident that the EMC survival study is unprecedented and the data have shown to be robust across a multitude of different sensitivity analyses. Instead, in the short term, we look forward to seeing the EMC survival study published so that the scientific and clinical community can be informed about the study. With that, I leave the word to Anny Bedard, our President of North America, to cover the U.S. launch readiness.

Thank you very much, Christian. Today marks an important milestone for the MCT8 deficiency community and for Egetis. For this community, EMCITATE is the first and only approved treatment in the United States. And for Egetis, it marks our transition from a development stage company to a commercial rare disease organization. This is a pivotal moment with our focus now shifting to execution, enabling access and supporting physicians and families to treatment initiation. Next slide, please. Our commercial readiness is grounded in real-world experience, extensive pre-approval preparation and stakeholder insight. We identified more than 100 genetically confirmed patients, of which more than 60 have been treated with EMCITATE across 17 sites in our early access program, evidence of an identified patient base, confidence in therapeutic effectiveness, early adoption and physician motivation to prescribe following approval. Our work with patient advocacy organization has raised the patient voice, built disease awareness and shaped the caregiver education and support we're rolling out at launch. The community is informed and ready to act, which we expect will translate into faster identification and referral of patients. We engaged payer well ahead of approval, including the 3 largest pharmacy benefit managers, representing more than 80% of U.S. prescription claims and more than 1/3 of state Medicaid plans. Feedback has been constructive with payers recognizing the burden of the disease and the importance of appropriate access for eligible patients. We're confident in the team we've built. Their rare disease expertise, multi-launch experience and disciplined execution gives us conviction in our ability to deliver. Next slide. More than 65% of early access patients are managed across 6 centers, which gives us a concentrated place to start. Supporting continuity of care is our top priority. Our team is prepared to work with physicians and where they determine continued treatment is appropriate, help patients transition from early access to commercial supply. The same preparation applies to the remaining early access site. Every investigator and care team has been engaged multiple times by our medical team ahead of approval, and account level activation plans are ready to go. Next slide. Persistent peripheral thyrotoxicosis is a central feature of MCT8 deficiency and is associated with systemic burden, medical fragility and increased mortality risk. Until now, no approved treatment has been available. The price of EMCITATE balances 4 principles: access, affordability, the value of the medicine and sustaining innovation. It reflects the severity and life-shortening nature of MCT8 deficiency, the absence of approved alternatives, EMCITATE's potential to address the modifiable systemic driver of morbidity and mortality and the need to reliably supply and support an ultra-rare patient population. We've set the wholesaler acquisition cost at $74,026 per pack of 60 scorable tablets of 350 micrograms. Based on the average daily dose of approximately 740 micrograms observed in Triac Trial I and as described in the U.S. prescribing information, this equates to an annualized wholesaler acquisition cost of approximately $950,000. Broad and equitable access remains our commitment, and our work with payers will continue through launch and beyond. This gives Egetis a strong foundation for commercialization and sustainable growth. Next slide. To support access to therapy, we built Egetis RareLink, a fit-for-purpose patient support program developed in partnership with PantherRx Rare Pharmacy. Egetis RareLink brings treatment education, access support and specialty pharmacy coordination into one connected experience. The program offers personalized support through a patient support liaison, dedicated care managers who help coordinate insurance requirements and financial support options and resources for families and providers. Our goal is to help families and providers move through the access process efficiently. Next slide. Commercial product is expected to be available in approximately 8 to 10 weeks. In the meantime, prescription, enrollment and access preparation begins now. Through Egetis RareLink, we will support physicians through that process, so the necessary steps are completed before product availability, allowing eligible patients to move toward treatment efficiently once supply is available. And as stated, this is an exciting and defining moment for the patients, for the MCT8 deficiency community and for Egetis. So from here, it's execution, disciplined delivery, appropriate patient access and establishing EMCITATE as the standard of care for peripheral thyrotoxicosis in MCT8 deficiency, and we're ready. With that, I'll turn it back to Nick.

Thank you very much, Anny. And let me now close on how we see the value drivers for the company. EMCITATE addresses a devastating rare disease with severe lifelong morbidity, shortening life expectancy and substantial caregiver burden. It's now the first and only approved therapy in the United States for patients with MCT8 deficiency following the EU approval in February last year. This truly marks the transition for Egetis into a fully commercial stage rare disease company. As you have heard from Anny, we're ready to launch in the U.S., the world's largest pharmaceutical market. Around 60 U.S. patients are already on expanded access, and the identified 100-plus patient pool keeps growing. We see EMCITATE's clinical profile and disease severity supporting orphan premium pricing. For exclusivity, we have 7 years orphan exclusivity in the U.S., 10 years in Europe and Japan with patents expected to protect to roughly 2045. Furthermore, we see that indication expansion into RTH-beta represents a meaningful additional growth opportunity in a larger nonoverlapping patient population with cardiovascular morbidity, where the ambition is to start a pivotal study next year. Last but not least, I would like to acknowledge and thank the people who made this achievement possible. We're deeply grateful to the patients, caregivers, investigators, clinicians and advocacy organizations whose partnership and determination made this achievement possible. Finally, I would like to thank everyone at Egetis. This approval reflects years of dedication, persistence and unwavering focus on our mission to bring innovative therapies to patients with rare diseases. So with that, thank you, and we're now happy to take questions. Operator, over to you.

The next question comes from Kristen Kluska from Cantor Fitzgerald.

Congratulations on this approval. You should be very proud of all the work you've done for this rare disease community. So a few questions from me. First, how should we be thinking about gross to net pricing? And then second, I know you mentioned that there were over 100 patients identified in the U.S. I believe when you really first started this mission, there was far fewer that you had identified in the U.S...

Yes. We can hear you, Kristen.

We can hear you, Kristen.

Yes, we can.

Okay. Perfect. Congratulations on this approval. You should be very proud of all the work you've done for this patient community. So -- okay, great. So just 2 questions for me. First, how should we be thinking about gross to net pricing? And then second, of the identified pool of 100-plus patients, I believe that this number has grown substantially since you started working in the U.S. Can you give us a sense of the most successful ways you've been able to identify these patients? And how you plan to use that going forward to further that pool?

Nick, would you want me to take that answer? Can you hear me, Kristen?

We seem to have a problem with the speaker line. They are logging on again.

Yes. I can hear you.

This is -- yes, the call is logging on. So now they're back again.

Can anybody hear us?

Yes. Perfect.

Now, we can hear you.

We can hear you, Nicklas. Maybe I can try and dial out from the system to Karl, and we can continue on the phone if they have problem with the Internet in the room or if you can try to reconnect. Maybe you can start, Anny.