Q2 2026 PTC Therapeutics Inc Earnings Call

July 30, 2026

Speaker #1: question-and-answer session. Today's conference is being recorded. I would like to turn the conference over to Ellen Cavaleri, Head of Investor Relations. Please go ahead.

Speaker #2: Good afternoon, and thank you for joining us to discuss PTC THERAPEUTICS' second quarter 2026 corporate update and financial results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein.

Ellen Cavaleri: Good afternoon, thank you for joining us to discuss PTC Therapeutics' Q2 2026 corporate update and financial results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein, our Chief Business Officer, Eric Pauwels, and our Chief Financial Officer, Pierre Gravier. Today's call will include forward-looking statements based on our current expectations. These statements are subject to certain risks and uncertainties, actual results may differ materially. Please review the slide posted on our investor relations website in conjunction with the call, which contains information about our forward-looking statements and our most recent quarterly report on Form 10-Q and annual report on Form 10-K filed with the SEC, as well as our other SEC filings, for a detailed description of applicable risks and uncertainties that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements.

Ellen Cavaleri: Good afternoon, thank you for joining us to discuss PTC Therapeutics' Q2 2026 Corporate Update and Financial Results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein, our Chief Business Officer, Eric Pauwels, and our Chief Financial Officer, Pierre Gravier. Today's call will include forward-looking statements based on our current expectations. These statements are subject to certain risks and uncertainties, actual results may differ materially. Please review the slide posted on our investor relations website in conjunction with the call, which contains information about our forward-looking statements and our most recent quarterly report on Form 10-Q and annual report on Form 10-K filed with the SEC, as well as our other SEC filings, for a detailed description of applicable risks and uncertainties that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements.

Speaker #2: Our Chief Business Officer, Eric Pauwels, and our Chief Financial Officer, Pierre Gravier. Today's call will include forward-looking statements based on our current expectations. These statements are subject to certain risks and uncertainties, and actual results may differ materially.

Speaker #2: Please review the slide posted on our investor relations website in conjunction with the call, which contains information about our forward-looking statements and our most recent quarterly report on Form 10-Q and annual report on Form 10-K filed with the SEC, as well as our other SEC filings.

Speaker #2: For a detailed description of applicable risks and uncertainties, that could cause our actual performance and results, to differ materially from those expressed or implied in these forward-looking statements.

Speaker #2: Additionally, we will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures, and the reconciliation of GAAP to non-GAAP, are available in today's earnings release.

Ellen Cavaleri: Additionally, we will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures and reconciliation of GAAP to non-GAAP are available in today's earnings release. I will now pass the call over to our CEO, Dr. Matthew Klein.

Speaker #2: I will now pass the call over to our CEO, Dr. Matthew Klein.

Speaker #3: Thank you all for joining today. I'm excited to share the results of another quarter of outstanding execution across the company. Starting with revenue, we achieved another record quarter with total revenue of $361 million, including $239 million of product revenue driven by continued strong global suvinance sales.

Matthew Klein: Thank you all for joining today. I'm excited to share the results of another quarter of outstanding execution across the company. Starting with revenue, we achieved another record quarter with total revenue of $361 million, including $239 million of product revenue, driven by continued strong global tafamidis sales. Based on this performance, we are raising our full year 2026 product revenue guidance to $850 to 950 million and now expect total revenue of $1.18 to 1.28 billion. With our continued effective management of expenses, we remain in position to potentially reach the milestone of being cash flow breakeven in 2026. I'll begin with an update on tafamidis' global launch. Momentum remains strong in the quarter, with continued steady growth in the US and accelerating growth internationally.

Speaker #3: Based on this performance, we are raising our full-year 2026 product revenue guidance to $850 million to $950 million, and now expect total revenue of $1.18 billion to $1.28 billion.

Speaker #3: In addition, with our continued effective management of expenses, we remain in position to potentially reach the milestone of being cash-flow break-even in 2026. I'll begin with an update on the Suffisa global launch.

Speaker #3: Momentum remains strong in the quarter, with continued steady growth in the US and accelerating growth internationally. Second quarter global sepiapterin revenue was $151 million, up 21% quarter over quarter.

Matthew Klein: Second quarter global tafamidis revenue was $151 million, up 21% quarter-over-quarter, with the majority coming from the US and increasing contributions internationally. As of 30 June, we had 1,647 commercial patients on tafamidis globally. We continue to see broad uptake across all patient segments and age groups worldwide. There remains strong underlying demand for tafamidis, and our teams continue to effectively execute. In the US, we now have received prescriptions from 100% of the Centers of Excellence, as well as prescriptions from other centers not previously designated as Centers of Excellence. This breadth of penetration this early in the launch is impressive. We will now work to continue to penetrate deeper into these centers. We continue to see demand across disease severities and treatment histories, including treatment-naive patients, prior therapy failures, and those switching from existing treatments.

Speaker #3: With the majority coming from the US and increasing contributions internationally, as of June 30, we had 1,647 commercial patients on Suflianza globally. We continue to see broad uptake across all patient segments and age groups worldwide.

Speaker #3: There remains strong underlying demand for sefinaconazole, and our teams continue to effectively execute. In the US, we now have received prescriptions from 100% of the centers of excellence, as well as prescriptions from other centers not previously designated as centers of excellence.

Speaker #3: This breadth of penetration this early in the launch is impressive. And we will now work to continue to penetrate deeper into these centers. We continue to see demand across disease severities and treatment histories, including treatment naive patients, prior therapy failures, and those switching from existing treatments.

Speaker #3: Adherence rates remain strong, and we continue to hear reports, not only of meaningful reductions in fentanyl, alanine, and increasing evidence of dialytization, but also of significant benefits on mood, cognition, and quality of life.

Matthew Klein: Adherence rates remain strong. We continue to hear reports not only of meaningful reductions in phenylalanine and increasing evidence of diet liberalization, but also of tafamidis' benefits on mood, cognition, and quality of life. These dynamics of strong demand and reported patient benefit reinforce our confidence in SEPHIENCE's long-term commercial opportunity. In international markets, momentum for SEPHIENCE continues to build. Commercial sales in Japan began to ramp in Q2 following our first commercial sale in late March. We started expanded access programs in a number of European countries and have seen positive progress towards future revenue in Latin America, including Brazil, where SEPHIENCE recently received the highest classification for therapeutic benefit from the country's drug market regulation chamber. As we have previously shared, we expect international revenue to increasingly contribute in late 2026 and into 2027 as additional markets come on board.

Speaker #3: These dynamics of strong demand and reported patient benefit reinforce our confidence in Suffiance's long-term commercial opportunity. In international markets, momentum for Suffiance continues to build.

Speaker #3: Commercial sales in Japan began to ramp in Q2 following our first commercial sale in late March. We started to expand access programs in a number of European countries, and have seen positive progress towards future revenue in Latin America, including Brazil, where sepiapterin recently received the highest classification for therapeutic benefit from the country's drug market regulation chamber.

Speaker #3: As we have previously shared, we expect international revenue to increasingly contribute in late 2026 and into 2027 as additional markets come on board. Overall, based on the continued strong launch momentum and the persistent strong underlying demand, we remain confident in the $2 billion-plus global commercial opportunity for Suffiance.

Matthew Klein: Overall, based on the continued strong launch momentum and the persistent strong underlying demand, we remain confident in the $2 billion-plus global commercial opportunity for SEPHIENCE. Turning to the votoplam Huntington's disease program. In April, we reported positive top-line results from the 24-month interim analysis of the PIVOT-HD long-term extension study. At month 24, votoplam demonstrated dose-dependent slowing of disease progression on cUHDRS, including an average slowing of 52% relative to natural history in the 10-milligram stage 2 cohort. Importantly, we continue to observe a favorable safety profile across doses and disease stages. These data support the potential for votoplam to provide long-term, meaningful clinical benefit for individuals affected by Huntington's disease. We also shared that Novartis is initiating enrollment in the global phase III INVEST-HD study, which is being conducted and funded by Novartis.

Speaker #3: Turning to the voter plan Huntington's disease program, in April we reported positive top-line results from the 24-month interim analysis of the PIVOT-HD long-term extension study.

Speaker #3: At month 24, voter plan demonstrated dose-dependent slowing of disease progression on CUHDRS, including an average slowing of 52% relative to natural history in the 10 mg stage II cohort.

Speaker #3: Importantly, we continue to observe a favorable safety profile across doses and disease stages. These data support the potential for Vatiqan to provide long-term, meaningful clinical benefit for individuals affected by Huntington's disease.

Speaker #3: We also shared that Novartis has initiated enrollment in the global Phase III Invest-HD study, which is being conducted and funded by Novartis. The study is expected to enroll approximately 770 individuals with early symptomatic disease, randomized 3-to-2 to receive Votiplan 10 mg or placebo, and the study includes an interim analysis.

Matthew Klein: The study is expected to enroll approximately 770 individuals with early symptomatic disease, randomized 3 to 2 to receive votoplam 10 milligrams or placebo. The study includes an interim analysis. While the phase III study remains the base case for votoplam approval, the Novartis and PTC teams are finalizing a plan to engage with FDA in H2 2026 to discuss the 24-month results and potential accelerated paths. For the Friedreich's ataxia program, based on discussions with FDA, we have finalized a study protocol for the open-label trial with a natural history comparator arm to support NDA resubmission. We plan to initiate this study, PROVE-FA, in Q3 of this year. The trial will enroll approximately 120 individuals ages 7 to 21. The study primary endpoint is the change in mFARS from baseline to month 24.

Speaker #3: While the Phase III study remains the base case for voter plan approval, the Novartis and PTC teams are finalizing a plan to engage with the FDA in the second half of 2026 to discuss the 24-month results and potential accelerated paths.

Speaker #3: For the viticulinophagic ataxia program, based on discussions with the FDA, we have finalized a study protocol for the open-label trial with a natural history comparator arm to support NDA resubmission.

Speaker #3: We plan to initiate this study, PROVE FA, in the third quarter of this year. The trial will enroll approximately 120 individuals, ages 7 to 21, and the study's primary endpoint is the change in MFARS from baseline to month 24.

Speaker #3: The study design reflects the key learnings from our prior development work and has understandably generated enthusiasm within the FA community, particularly because it offers patients the opportunity to access therapy with the uncertainty of receiving placebo.

Matthew Klein: The study design reflects the key learnings from our prior development work and has understandably generated enthusiasm within the FA community, particularly because it offers patients the opportunity to access therapy without the uncertainty of receiving placebo. We believe the study design, coupled with our experience in FA therapy clinical development, meaningfully enhances the probability of success of the PROVE-FA study and the potential to deliver an important new therapy for children and adults affected by FA. Shifting to our other clinical pipeline programs, we have initiated the phase I study of PTC612, our oral NLRP3 inhibitor, and have completed several of the single and multiple ascending dose treatment cohorts. Notably, this healthy volunteer study will enroll a cohort of individuals with obesity and cardiovascular disease, which we expect will provide an early view of PK/PD effect.

Speaker #3: We believe the study design, coupled with our experience in FA therapy clinical development, meaningfully enhances the probability of success of the Prove FA study.

Speaker #3: And the potential to deliver an important new therapy for children and adults affected by FA. Shifting to our other clinical pipeline programs, we have initiated the Phase I study of PTC 612, our oral NLRP3 inhibitor, and have completed several of the single and multiple ascending dose treatment cohorts.

Speaker #3: Notably, this healthy volunteer study will enroll a cohort of individuals with obesity and cardiovascular disease, which we expect will provide an early view of PK/PD effect.

Speaker #3: As we have previously shared, PTC 612 is differentiated from other NLRP3 inhibitors in terms of potency, selectivity, and chemical structure. Later in the third quarter of this year, we expect to initiate a Phase IIa study of PTC 844, our next-generation DHODH inhibitor.

Matthew Klein: As we have previously shared, PTC612 is differentiated from other NLRP3 inhibitors in terms of potency, selectivity, and chemical structure. Later in Q3 of this year, we expect to initiate a phase IIa study of PTC844, our next generation DHODH inhibitor. PTC844 is highly selective for the DHODH enzyme and benchmarks favorably to other DHODH inhibitors in preclinical potency models. The PTC844 study will be a 12-week PK/PD study in which we will assess treatment effect on biomarkers related to T-cell and B-cell immunity. The results of this study will help inform the ultimate target indications for PTC844. We have also made a number of advances in our splicing platform. We recently selected a development candidate for our MSH3 splicing program, PTC303. MSH3 is increasingly recognized as an important target for triplet repeat expansion diseases, including Huntington's disease and myotonic dystrophy.

Speaker #3: PTC 844 is highly selective for the DHODH enzyme and benchmarks favorably to other DHODH inhibitors in preclinical potency models. The PTC 844 study will be a 12-week PK/PD study in which we will assess treatment effect on biomarkers related to T-cell and B-cell immunity.

Speaker #3: The results of this study will help inform the ultimate target indications for PTC 844. We have also made a number of advances in our splicing platform.

Speaker #3: We recently selected a development candidate for our MSH3 splicing program, PTC 303. MSH3 is increasingly recognized as an important target for triplet repeat expansion diseases, including Huntington's disease and myotonic dystrophy.

Speaker #3: As we have discussed, targeting MSH3 provides a complementary approach to HTT lowering in addressing the key pathological causes of Huntington’s disease. The MSH3 program also further reinforces PTC’s leadership in the discovery and development of oral small-molecule splicing therapies.

Matthew Klein: As we have discussed, targeting MSH3 provides a complementary approach to HCT lowering in addressing the key pathological causes of Huntington's disease. The MSH3 program also further reinforces PTC's leadership in the discovery and development of oral small molecule splicing therapies. PTC303 is fully owned by PTC, and we expect it to be in the clinic in 2027. Overall, the company remains in a very strong financial position. In June, we strategically managed the 2026 convertible note liability with the refinancing of the majority of the existing notes at a 0% coupon and 40% conversion premium to the stock's closing price at the time of the deal. We closed the quarter with over $2.2 billion in cash and remain in position to achieve cash flow breakeven in 2026.

Speaker #3: PTC 303 is fully owned by PTC, and we expect it to be in the clinic in 2027. Overall, the company remains in a very strong financial position.

Speaker #3: In June, we strategically managed the 2026 convertible note liability with the refinancing of the majority of the existing notes at a 0% coupon and 40% conversion premium to the stocks closing price at the time of the deal.

Speaker #3: We closed the quarter with over $2.2 billion in cash and remain in position to achieve cash flow breakeven in 2026. In summary, I am proud of our team's outstanding performance in the first half of 2026, as we continue to make significant progress across the business.

Matthew Klein: In summary, I'm proud of our team's outstanding performance in H1 2026 as we continue to make significant progress across the business. I'll now turn the call over to Eric to provide a commercial update, including additional details on the SEPHIENCE launch. Eric?

Speaker #3: I will now turn the call over to Eric to provide a commercial update, including additional details on the Sufiance launch. Eric?

Speaker #2: Thanks, Matt. In the second quarter, our commercial team continued the strong global launch of Suflienza, driving solid product revenue and reinforcing confidence in our growth trajectory through 2026 and beyond.

Eric Pauwels: Thanks, Matt. In the Q2, our commercial team continued the strong global launch of SEPHIENCE, driving solid product revenue and reinforcing confidence in our growth trajectory through 2026 and beyond. Launch momentum remained strong, supported by sustained contributions in the US and increasing contributions from international markets. Now we have 1,647 patients on commercial therapy globally on SEPHIENCE. In the Q2, SEPHIENCE revenue was $151 million, representing 21% growth over the Q1 of 2026. In the US, launch execution remained strong, with steady demand. As Matt noted, all US centers of excellence are now prescribing SEPHIENCE, with adoption spanning the full spectrum of disease severity, all ages, including classical patients, and a broad mix of treatment backgrounds, including therapy-naive adults, prior treatment failures, and an increasing proportion of switches from existing therapies.

Speaker #2: Launch momentum remained strong, supported by sustained contributions in the US and increasing contributions from international markets. And now we have 1,647 patients on commercial therapy globally on Suflance.

Speaker #2: In the second quarter, Sutifance revenue was $151 million, representing 21% growth over the first quarter of 2026. In the US, launch execution remained strong, with steady demand.

Speaker #2: As Matt noted, all U.S. centers of excellence are now prescribing Suffiance, with adoption spanning the full spectrum—all ages, including classical patients, and a broad mix of treatment backgrounds.

Speaker #2: Including therapy-naive adults, prior treatment failures, and an increasing proportion of switches from existing therapies. We are pleased to see persistent, strong demand and to hear reports of the meaningful impact Suflience is providing children and adults on diet liberalization, as well as mood, cognitive improvements, and improvements in quality of life.

Eric Pauwels: We are pleased to see persistent strong demand and to hear reports of the meaningful impact SEPHIENCE is providing children and adults on diet liberalization, as well as mood, cognitive improvements, and improvements in quality of life. With our increasing base of commercial PKU patients being treated with SEPHIENCE in the US, our customer-facing teams are focused on rapidly filling new prescriptions and successfully managing reauthorizations, refills, and providing exceptional patient support. Our customer-facing teams are dedicated to work closely with healthcare providers and the patient community to facilitate access to SEPHIENCE. These efforts will help support continued momentum and growth as we move further into the launch. Turning to our patient advocacy support. We had a strong presence at the National PKU Alliance Conference in Chicago earlier this month, where we focused on connecting with patients and caregivers and understanding their unmet needs.

Speaker #2: With our increasing base of commercial PKU patients being treated with Suffiance in the US, our customer-facing teams are focused on rapidly filling new prescriptions and successfully managing reauthorizations, refills, and providing exceptional patient support.

Speaker #2: Our customer-facing teams are dedicated to working closely with healthcare providers and the patient community to facilitate access to Suflienza. These efforts will help support continued momentum and growth as we move further into the launch.

Speaker #2: Turning to our patient advocacy support, we had a strong presence at the National PKU Association Conference in Chicago earlier this month, where we focused on connecting with patients and caregivers and understanding their unmet needs.

Speaker #2: At this meeting, we presented data from the AMPLIFY study demonstrating the ability of sepiapterin to reduce blood Phe significantly more than BH4, as well as new data on patients switching to sepiapterin in both pediatric and adult PKU populations.

Eric Pauwels: At this meeting, we presented data from the AMPLIPHY study demonstrating the ability of SEPHIENCE to reduce blood Phe significantly more than BH4, as well as new data on patients switching to SEPHIENCE in both pediatric and adult PKU populations. We also held several engagement events with patient advocacy groups, including a symposium emphasizing the extensive real-world data and examples of patients who, in addition to seeing important reductions in blood Phe levels, have also experienced significant improvement in their day-to-day quality of life on SEPHIENCE treatment. Internationally, launch momentum continues to build. In Japan, the early launch results are exceeding our internal expectations, with rapid uptake across many Japanese centers of excellence. We have secured pricing in Japan on par with the US, and importantly, this price is locked in for 10 years.

Speaker #2: We also held several engagement events with patient advocacy groups, including a symposium emphasizing the extensive real-world data and examples of patients who in addition to seeing important reductions in blood fee levels have also experienced significant improvement in their day-to-day quality of life on suffiance treatment.

Speaker #2: Internationally, launch momentum continues to build. In Japan, the early launch results are exceeding our internal expectations with rapid uptake across many Japanese centers of excellence.

Speaker #2: We have secured pricing in Japan on par with the US, and importantly, this price is locked in for 10 years. As we observed in the early stages of the US launch, we are seeing broad uptake in Japan across disease severities and age groups, as well as treatment histories.

Eric Pauwels: As we observed in the early stages of the US launch, we are seeing broad uptake in Japan across disease severities and age groups, as well as treatment histories. In Germany, we continue to see strong momentum in the quarter, especially with an increase in newly prescribed adult and naive PKU patients, as our pricing and reimbursement discussions are continuing in the country. In other European markets, we are leveraging early access and name patient programs effectively and are seeing accelerated demand in France, Italy, and Spain. In other regions, including Latin America and the Middle East, we are similarly leveraging early access programs as we grow the SEPHIENCE global footprint and see important contributions to future commercial patients. While the US remains an important near-term growth driver, we expect global revenue to become an increasingly meaningful contributor in the H2 of this year and well into 2027.

Speaker #2: In Germany, we continue to see strong momentum in the quarter, especially with an increase in newly prescribed adult and naive PKU patients, as our pricing and reimbursement discussions are continuing in the country.

Speaker #2: In other European markets, we are leveraging early access and named patient programs effectively, and are seeing accelerated demand in France, Italy, and Spain. In other regions, including Latin America and the Middle East, we are similarly leveraging early access programs as we grow the Suffiance global footprint and see important contributions to future commercial patients.

Speaker #2: While the U.S. remains an important near-term growth driver, we expect global revenue to become an increasingly meaningful contributor in the second half of this year and well into 2027.

Speaker #2: As we discussed, there is a large addressable PKU population globally in markets where innovative treatments are reimbursed, and we expect to bring Sufficiency to as many of these countries as quickly as possible, reinforcing our confidence in achieving a multi-billion dollar peak revenue potential.

Eric Pauwels: As we discussed, there is a large addressable PKU population globally in markets where innovative treatments are reimbursed, and we expect to bring SEPHIENCE to as many of these countries as quickly as possible, reinforcing our confidence in achieving a $multibillion peak revenue potential. Looking ahead to our key event this summer, our team is preparing for a strong showing at the SSIEM meeting in Helsinki next month. This being the largest global metabolism meeting of the year, we have 17 oral and poster presentations planned that continue to showcase evidence of SEPHIENCE treatment benefit across the broad range of individuals with PKU based on new analyses of long-term trial data, as well as reports of real-world evidence.

Speaker #2: Looking ahead to our key event this summer, our team is preparing for a strong showing at the SSIEM meeting in Helsinki next month. This is the largest global metabolism meeting of the year.

Speaker #2: We have 17 oral and poster presentations planned that continue to showcase evidence of sustained treatment benefit across the broad range of individuals with PKU, based on new analyses of long-term trial data, as well as reports of real-world evidence.

Speaker #2: Many of these presentations will highlight the positive impact that sufficience has had on PKU patients in countries around the world, with lower fee levels leading to better diet, neurocognitive, and quality of life outcomes for these patients.

Eric Pauwels: Many of these presentations will highlight the positive impact that SEPHIENCE has had on PKU patients in countries around the world, with lower Phe levels leading to better diet, neurocognitive, and quality-of-life outcomes for these patients.

Matthew Klein: Importantly, we plan to present new data demonstrating that treatment with SEPHIENCE responders led to a substantial portion of participants achieving complete normalization of blood Phe levels of 120 micromoles per milliliter in a rapid timeframe, including those PKU patients who are classical and BH4 non-responsive. This impressive real-world data demonstrated that achieving Phe level normalization is an important key treatment goal for all potential PKU patients. Now, turning to our mature brands. In Q2, we continued to generate meaningful revenue despite challenges in the DMD franchise. For Translarna, we had continued sales in Europe and Latin America, as well as a government order from Russia. In the US, EMFLAZA continues to see new prescriptions and despite generic pressure, we see ongoing brand loyalty attributable in part to our programs and continued high touch, white glove services from our PTC Cares teams.

Eric Pauwels: Importantly, we plan to present new data demonstrating that treatment with SEPHIENCE responders led to a substantial portion of participants achieving complete normalization of blood Phe levels of 120 micromoles per milliliter in a rapid timeframe, including those PKU patients who are classical and BH4 non-responsive. This impressive real-world data demonstrated that achieving Phe level normalization is an important key treatment goal for all potential PKU patients. Now, turning to our mature brands. In Q2, we continued to generate meaningful revenue despite challenges in the DMD franchise. For Translarna, we had continued sales in Europe and Latin America, as well as a government order from Russia. In the US, EMFLAZA continues to see new prescriptions and despite generic pressure, we see ongoing brand loyalty attributable in part to our programs and continued high touch, white glove services from our PTC Cares teams.

Speaker #2: Importantly, we plan to present new data demonstrating that treatment with suffiancet responders led to a substantial portion of participants achieving complete normalization of blood Phe levels of 120 micromoles per liter, in a rapid timeframe.

Speaker #2: Including those PKU patients who are classical and BH4 non-responsive, this impressive real-world data demonstrated that achieving Phe level normalization is an important key treatment goal for all potential PKU patients.

Speaker #2: Now, turning to our mature brands—in the second quarter, we continued to generate meaningful revenue despite challenges in the DMD franchise. For Translarna, we had continued sales in Europe and Latin America, as well as a government order from Russia.

Speaker #2: In the US, in Plaza continues to see new prescriptions and despite generic pressure, we see ongoing brand loyalty attributable in part to our programs and continued high touch white glove services from our PTC Cares teams.

Speaker #2: In summary, our customer-facing teams delivered another strong quarter with another record revenue performance, once again demonstrating PTC's global rare disease commercial capabilities. We remain confident in our ability to grow and sustain our launch momentum of suffiance globally, and firmly establish it as the standard of care for PKU patients.

Matthew Klein: In summary, our customer-facing teams delivered another strong quarter with another record revenue performance, once again, demonstrating PTC's global rare disease commercial capabilities. We remain confident in our ability to grow and sustain our launch momentum of SEPHIENCE globally and firmly establish it as the standard of care for PKU patients. With that, I will now turn the call over to Pierre for a financial update. Pierre?

Eric Pauwels: In summary, our customer-facing teams delivered another strong quarter with another record revenue performance, once again, demonstrating PTC's global rare disease commercial capabilities. We remain confident in our ability to grow and sustain our launch momentum of SEPHIENCE globally and firmly establish it as the standard of care for PKU patients. With that, I will now turn the call over to Pierre for a financial update. Pierre?

Speaker #2: With that, I will now turn the call over to Pierre for a financial update. Pierre?

Speaker #3: Thank you, Eric. I will now share the financial highlights of our second quarter of 2026. Beginning with top-line results, total product and royalty revenue for the second quarter was $310 million, and total net product revenue across the commercial portfolio was $239 million, compared to $118 million for the second quarter of 2025, representing over 100% growth.

Pierre Gravier: Thank you, Eric. I will now share the financial highlights of our Q2 2026. Beginning with top-line results. Total products and royalty revenue for Q2 was $310 million, and total net product revenue across the commercial portfolio was $239 million, compared to $118 million for Q2 2025, representing over 100% growth. Q2 2026 product revenue includes SEPHIENCE's net product revenue of $161 million and DMD franchise revenue of $67 million. Translarna net product revenue was $42 million, including a government purchase order from Russia, and EMFLAZA net product revenue was $25 million. For Evrysdi, Roche achieved Q2 global revenue of approximately $628 million, resulting in royalty revenue of $71 million.

Speaker #3: Second quarter 2026 product revenue includes suffiance net product revenue of $161 million, and DMD franchise revenue of $67 million. Translarna net product revenue was $42 million, including a government purchase order from Russia, an M-Plaza net product revenue was $25 million.

Speaker #3: For everyday, Roche achieved second quarter global revenue of approximately $628 million US dollars, resulting in royalty revenue of $71 million. For the second quarter of 2026, non-GAAP R&D expense was $89 million, excluding $11 million in non-cash stocks-based compensation expense, compared to $104 million for the second quarter of 2025, excluding $9 million in non-cash stock-based compensation expense.

Pierre Gravier: For Q2 2026, non-GAAP R&D expense was $89 million, excluding $11 million in non-cash stock-based compensation expense, compared to $104 million for Q2 2025, excluding $9 million in non-cash stock-based compensation expense. Non-GAAP SG&A expense was $68 million for Q2 2026, excluding $13 million in non-cash stock-based compensation expense, compared to $76 million for Q2 2025, excluding $10 million in non-cash stock-based compensation expense. Cash, cash equivalents, and marketable securities totaled $2.23 billion as of 30 June 2026, compared to $1.95 billion as of 31 December 2025. In Q2 2026, we repurchased the majority of our existing 2026 convertible notes and issued new convertible notes due in 2031 at 0% interest rate and a conversion price representing a 40% premium over the stock's closing price at the time of the issue.

Speaker #3: Non-GAAP SG&A expense was $68 million for the second quarter of 2026, excluding $13 million in non-cash stock-based compensation expense, compared to $76 million for the second quarter of 2025, excluding $10 million in non-cash stock-based compensation expense.

Speaker #3: Cash, cash equivalents, and marketable securities totaled $2.23 billion as of June 30, 2026, compared to $1.95 billion as of December 31, 2025. In the second quarter of 2026, we repurchased the majority of our existing 2026 convertible notes and issued new convertible notes due in 2031 at a 0% interest rate, with a conversion price representing a 40% premium over the stock's closing price at the time of issuance.

Pierre Gravier: Our strong financial position gives us the flexibility to pursue business development opportunities that support future growth while advancing toward cash flow breakeven and future sustained profitability. I will now turn the call over to the operator for Q&A. Operator?

Speaker #3: Our strong financial position gives us the flexibility to pursue business development opportunities that support future growth. While advancing toward cash flow break-even and future sustained profitability.

Speaker #3: And I will now turn the call over to the operator for Q&A. Operator?

Speaker #1: Thank you. If you would like to ask a question, please press star one-one. If your question has been answered and you'd like to remove yourself from the queue, press star one-one again.

Operator: Thank you. If you would like to ask a question, please press star one. If your question has been answered and you'd like to remove yourself from the queue, press star one again. Our first question comes from Kristen Kluska with Cantor. Your line is open.

Speaker #1: Our first question comes from Kristen Kloska with Cancer. Your line is open.

Speaker #4: Hi, good afternoon everybody, and congrats on a really strong quarter. I have two sufficiency questions. The first is, based on the patients on therapy and accounting for potential dropouts, my math is getting to about 10% or so of the patient population in the US has tried the therapy.

Kristen Kluska: Hi. Good afternoon, everybody, and congrats on a really strong quarter. I have two SEPHIENCE questions. The first is, based on the patients on therapy and accounting for potential dropouts, my math is getting to about 10% or so of the patient population in the US has tried the therapy. Curious if that matches what you think, and also what % of patients you think may at least be open to trying a therapy, not saying we'll get on it and assume peak penetration there. Second, just thinking about the conference circuit. You just came off the biggest one for the patients in the US, and now you have a big medical focus. What are really the key drivers there? Is it awareness? Is it proving that the therapy works across a breadth of patients? What are the key goals you hope to learn? Thank you so much.

Speaker #4: Curious if that matches what you think, and also what percent of patients you think may at least be open to trying a therapy, not saying we'll get on it and assume peak penetration there.

Speaker #4: And then second, just thinking about the conference circuit, you just came off the biggest one for the patients in the US, and now you have a big medical focus.

Speaker #4: What are really the key drivers there? Is it awareness? Is it proving that the therapy works across a breadth of patients? What are the key goals you hope to learn?

Speaker #4: Thank you so much.

Speaker #3: Hi, Kristen. Thanks so much for the question. So, on the first question, look, I think the key takeaway that we see this early in the launch is we're incredibly excited about the demand and the uptake thus far.

Matthew Klein: Hi, Kristen. Thanks so much for the question. On the first question, look, I think the key take home that we see this early in launches, we're incredibly excited about the demand and the uptake thus far. As you highlight, we still have a very long way to go, given the size of the population in the US of 17,000 and the 58,000 patients we see in addressable markets worldwide. I think when we look to metrics thus far and we see penetration into 100% of the centers of excellence. That's really an incredible milestone this early, and it basically puts us in the position we want to be with a strong base of patients to now go deeper and deeper into those centers of excellence. Usually, at this stage of a launch, you're usually trying to get to all the centers of excellence.

Speaker #3: But as you highlight, we still have a very, very long way to go, given the size of the population in the US of 17,000 and the 58,000 patients we see in addressable markets worldwide.

Speaker #3: I think when we look at the metrics thus far, and we see penetration into 100% of the centers of excellence, that's really an incredible milestone this early, and it basically puts us in the position we want to be in—with a strong base of patients to now go deeper and deeper into those centers of excellence.

Speaker #3: Usually, at this stage of a launch, you're trying to get to all the centers of excellence. We're there, and now the task is to get deeper and deeper into those centers.

Matthew Klein: We're there, now the task is to get deeper and deeper into those centers. In terms of overall patients who may try the therapy, I think the number we had always had is about 70% of individuals tried KUVAN. That again suggests we have a very large number of patients who are yet to try SEPHIENCE, and we already know that we've seen patients who were therapy naive, that never tried KUVAN, that are in that other 30% bucket who are coming back to clinic. Again, it's hard to put an exact number on it other than to say, we're still very early in this launch.

Speaker #3: In terms of overall patients who may try the therapy, I think the number we have always had is about 70%. Seventy percent of individuals tried Cuvette.

Speaker #3: And that again suggests we have a very, very large number of patients who are yet to try suffiance, and we already know that we've seen patients who were at therapy naive that never tried Cuvette, that are in that other 30% bucket, who are coming back to clinic.

Speaker #3: So again, it's hard to put an exact number on it other than to say we're still very early in this launch. We've had strong momentum at the start, but we have a very, very long way to go in terms of continuing to get a much larger number of patients to try the therapy, and of course, to stay on the therapy and enjoy the benefits.

Matthew Klein: We've had strong momentum at the start, we have a very long way to go in terms of continuing to get much larger number of patients to try the therapy and, of course, to stay on the therapy and enjoy the benefits. Which I think goes into your second question about our goal at these conferences. It's multifold, right? Manyfold. One is, look, there's a lot of patients and there's a limited number of clinics. We know that means that it's going to be just this steady cadence over time, given the strong underlying demand. What we do at these conferences is continue to promote awareness of the drug for those who may have been not on therapies or remote to care and are starting to come back or are curious about being on a therapy.

Speaker #3: Which I think goes then into your second question about our goal at these conferences. It's multifold, right? Manifold. One is, look, there's a lot of patients, and there's a limited number of clinics.

Speaker #3: And we know that means it's going to be just a steady cadence over time, given the strong underlying demand. What we do at these conferences is continue to promote awareness of the drug.

Speaker #3: For those who may have been not on therapies or remote to care and are starting to come back, we're curious about being on a therapy.

Speaker #3: And then also continuing to let people understand the benefits we're seeing, that we're seeing benefits in patients who have classical BKU and non-BH4 mutations, and we've had an NPKUA one of the caregivers I'm sorry, one of the prescribers told stories about patients severe patients with classical PKU having significant responses.

Matthew Klein: Also continuing to let people understand the benefits we are seeing, that we are seeing benefits in patients who have classical PKU and non-BH4 mutations. We have had it in NPKUA. One of the prescribers told stories about severe patients with classical PKU having significant responses. That is really important for patients to hear that they can get an oral therapy that allows them to lower phenylalanine and liberalize diet. It is also really important to continue to reinforce the data and the messages around AMPLIPHY and patients who are on KUVAN, for example, or the brands that are generic, and to hear that 100% of those patients in our data have a much better response to SEPHIENCE and are able to get even lower in phenylalanine and liberalize their diet even more. I'd sum it up by saying we are early in the launch. The response has been strong.

Speaker #3: That's really important for patients to hear—that if they can get an oral therapy that allows them to lower phenylalanine and liberalize diet, it's also really important to continue to reinforce the data and the messages around AMPLYA, and patients who are on Kuvan, for example, or the brands that are generic, and to hear that 100% of those patients in our data have a much better response to sepiapterin and are able to get even lower in phenylalanine and liberalize their diet even more.

Speaker #3: So I'd sum it up by saying we're early in the launch, the response has been strong, the demand is really strong, but our teams still have work to do in continuing to reinforce the message, continuing to engage with patients, family members, caregivers, prescribers, letting them understand the benefits that they could enjoy with suffiance so we can continue to get those trying numbers up to 70%, 80%, or even higher.

Matthew Klein: The demand is really strong, our teams still have work to do in continuing to reinforce the message, continuing to engage with patients, family members, caregivers, prescribers, letting them understand the benefits that they could enjoy with SEPHIENCE so we can continue to get those trying numbers up to 70%, 80% or even higher.

Kristen Kluska: Thanks, Matt.

Speaker #4: Thanks, Matt.

Speaker #1: Thank you. Our next question comes from Tazeena Maud with Bank of America. Your line is open.

Operator: Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open.

Tazeen Ahmad: Hi. Good afternoon. Thanks for taking my questions. Matt, you've been really clear about defining how this launch is proceeding as very steady and consistent. You have in the past talked about roughly adding about 140 new scripts per month. Can you just talk about whether or not you expect that to continue to be the cadence for the rest of the year? If not, maybe just talk to us about anything that's changed. Then can you just give us a little bit more color about what you're seeing in discontinuation rates so far? Thanks.

Speaker #5: Hi, good afternoon. Thanks for taking my questions. Matt, you've been really clear about defining how this launch is proceeding as very steady and consistent.

Speaker #5: So, you have in the past talked about roughly adding about 140 new scripts per month. Can you just talk about whether or not you expect that to continue to be the cadence for the rest of the year?

Speaker #5: And if not, maybe just talk to us about anything that's changed. And then can you just give us a little bit more color about what you're seeing in discontinuation rates so far?

Speaker #5: Thanks.

Speaker #3: Yeah, absolutely. So, Tazeena, I think we've now moved towards really highlighting revenue and patients on drug, because at this stage in the launch, you're starting to hear that global contributions and prescriptions mean different things in different locations.

Matthew Klein: Yeah, absolutely. Tazeen, I think we've moved now towards just really highlighting revenue in patients on drug because at this stage in the launch that you're starting to hear the global contributions and prescriptions mean different things in different locations. I'll characterize things this way. I think we're continuing to see consistent demand. We believe in the potential for there to be steady growth, continued growth in the US based on that demand and continue to expect accelerated demand outside of the US. A lot of that is what underpinned our confidence in raising guidance to $850 million to $950 million, that we believe that we can continue to have steady growth in the US and accelerating growth outside of the US. In terms of discontinuations, we continue to see very high compliance and very high adherence rates.

Speaker #3: I'll characterize things this way. I think we're continuing to see consistent demand. We believe in the potential for there to be steady growth, continued growth in the US based on that demand.

Speaker #3: And we continue to expect accelerated demand outside of the US. A lot of that is what underpinned our confidence in raising guidance to 850 to 950. We believe that we can continue to have steady growth in the US and accelerate growth outside of the US.

Speaker #3: In terms of discontinuations, we continue to see very high compliance and very high adherence rates. I think discontinuations now remain low at about 20%, which is really impressive at this point in the launch, given the fact that a lot of the early patients who came on drug were those more severe patients.

Matthew Klein: I think discontinuations now remain low at about 20%, which is really impressive at this point in the launch given the fact that a lot of the early patients who came on drug were those more severe patients. We also feel at this level that we're getting pretty close to steady state based on what we have seen from the clinical studies. Importantly, the renewal rates on prescriptions is super high. It's over 90%. Overall, all these metrics look really good and again support our confidence not only in our ability to raise guidance for this year, but in the long-term significant revenue potential for SEPHIENCE.

Speaker #3: And we also feel at this level that we're getting pretty close to steady state based on what we had seen from the clinical studies.

Speaker #3: Importantly, the renewal rates on prescriptions are super high—it's over 90%. So overall, all these metrics look really, really good and, again, support our confidence not only in our ability to raise guidance for this year but also in the long-term, significant revenue potential for sepiance.

Speaker #1: Thank you. Our next question comes from Joseph Han with Barclays. Your line is open.

Operator: Thank you. Our next question comes from Joseph Han with Barclays. Your line is open.

Matthew Klein: Hey, it's Ellie from Barclays. Thanks for taking the question. You mentioned several early access programs ex-US. Just to clarify, are you recognizing revenues from these programs yet? I think you mentioned seeing accelerated demand in France, Italy, Spain, LATAM, and Middle East. Can you maybe give some color or characterize the number of patients on all of these early access programs and how that might compare to the 1,600 patients on commercial therapy globally? Lastly, I think you've mentioned being launched in about 30 countries by the end of this year. How should we think about which countries and when will contribute to revenues over the course of Q3 and Q4? Thanks. Hi, Ellie. I'll give just some general comments, then I'll let Eric give a little bit more detail on early access. All those early access patients are contributing to revenue.

Ellie Merle: Hey, it's Ellie from Barclays. Thanks for taking the question. You mentioned several early access programs ex-US. Just to clarify, are you recognizing revenues from these programs yet? I think you mentioned seeing accelerated demand in France, Italy, Spain, LATAM, and Middle East. Can you maybe give some color or characterize the number of patients on all of these early access programs and how that might compare to the 1,600 patients on commercial therapy globally? Lastly, I think you've mentioned being launched in about 30 countries by the end of this year. How should we think about which countries and when will contribute to revenues over the course of Q3 and Q4? Thanks.

Speaker #6: Hey, it's Ellie from Barclays. Thanks for taking the question. You mentioned several early access programs ex-US. Just to clarify, are you recognizing revenues from these programs yet?

Speaker #6: I think you mentioned seeing accelerated demand in France, Italy, Spain, Latvia, and Middle East. Can you maybe give some color or characterize the number of patients on all of these early access programs?

Speaker #6: And how might that compare to the 1,600 patients on commercial therapy globally? And then, lastly, I think you've mentioned being launched in about 30 countries by the end of this year.

Speaker #6: So, how should we think about which countries, and when, will contribute to revenues over the course of Q3 and Q4? Thanks.

Speaker #3: Hi, Ellie. I'll give just some general comments, then I'll let Eric give a little bit more detail on early access. So, all those early access patients are contributing to revenue.

Matthew Klein: Hi, Ellie. I'll give just some general comments, then I'll let Eric give a little bit more detail on early access. All those early access patients are contributing to revenue.

Speaker #3: And what's important to know is that this whole approach we're taking in the global launch is really a well-thought-out plan. First, we had global commercial infrastructure in place, had already been commercializing in 50 countries, and a lot of this was about understanding different markets, understanding sequencing of launch, understanding how we can maintain a rigid pricing corridor, which is more important now than ever.

Matthew Klein: What's important to note is that this whole approach we're taking in the global launch is really a well-thought-out plan. First, we had the global commercial infrastructure in place, had already been commercializing in 50 countries, and a lot of this was about understanding different markets, understanding sequencing of launch, understanding how we can maintain a rigid pricing corridor, which is more important now than ever. Also with early access programs, it allows us to get drug into patients in countries. It also tends to be a lot of those prescribers who are the leading KOLs in certain countries. That's super important because this allows those physicians to have positive experiences with SEPHIENCE, and those are going to be the same physicians that will be called upon when HTAs are making assessments about access and pricing.

Speaker #3: And also, with early access programs, it allows us to get drug into patients in countries. It also tends to be a lot of those prescribers who are the leading KOLs in certain countries.

Speaker #3: That's super important, because this allows those physicians to have positive experience with seficien, and those are going to be the same physicians that will be called upon when HTAs are making assessments about access and pricing.

Matthew Klein: They then can go to these physicians who will have had firsthand positive experiences with the drug, which has obvious benefits in terms of access and reimbursement. I'll let Eric talk a little bit more about just overall number of countries and how we're thinking about sequence and launch and revenue contribution. Eric?

Speaker #3: They then can go to these physicians who will have had firsthand positive experiences with the drug, which has obvious benefits in terms of access and reimbursement.

Speaker #3: I'll let Eric talk a little bit more about the overall number of countries and how we're thinking about sequence and launch, as well as revenue contribution.

Speaker #3: Eric?

Speaker #2: Yeah, thanks, Ellie, for the question. As Matt said, the strategic plan was laid out many, many years ago, actually, because we are leveraging this infrastructure, which has had a portfolio of products for over 12 years.

Eric Pauwels: Yes, thanks, Ellie, for the question. As Matt said, the strategic plan was laid out many years ago, actually, because we are leveraging this infrastructure, which had a portfolio of products for over 12 years. When we mapped out the sequence of this, we knew exactly that the US, Germany, and Japan would be commercial launches. We've also mapped out very carefully where early access programs would actually be implemented. We knew that there would be large addressable populations in Europe, the Middle East, and Latin America, places where we could get innovative pricing and reimbursement and maintain, if you will, a price for that innovation and maintain a narrow pricing corridor. We've actually implemented programs in France right now and key major markets.

Speaker #2: So, when we mapped out the sequence of this, we knew exactly that the US, Germany, and Japan would be commercial launches. But we've also mapped out very carefully where early access programs would actually be implemented.

Speaker #2: We knew that there would be large addressable populations in Europe, the Middle East, and Latin America—places where we could get innovative pricing and reimbursement and maintain, if you will, a price for that innovation and maintain a narrow pricing corridor.

Speaker #2: So we've actually implemented programs in France right now. In key major markets, France has already given us an HTA assessment, and that's completed. And they've approved our early access program.

Eric Pauwels: France has already given us an HTA assessment, and that's completed, and they've approved our early access program, and we've seen an accelerated demand rapidly in France. We've also seen accelerated demand both in Italy and Spain and a number of southern European markets, as well as central and eastern European markets. We're just in that process of beginning and implementing those in Latin America and the Middle East, where they will be meaningful contributors. We've said that there's up to 30 markets that could potentially provide revenue. Keep in mind, as Matt said, over the last 10, 15, 12 years or so, we have actually been commercializing products in over 50 countries, and we have extensive experience. We're going to bring SEPHIENCE to as many of these markets and as quickly as effectively as possible.

Speaker #2: And we've seen an accelerated demand rapidly in France. We've also seen accelerated demand both in Italy and Spain. And a number of southern European markets, as well as Central and Eastern European markets.

Speaker #2: We're just in that process of beginning and implementing those in Latin America, and the Middle East, where there will be meaningful contributors. We've said that there's up to 30 markets that could potentially provide revenue.

Speaker #2: Keep in mind, as Matt said, over the last 10, 15, 12 years or so, we have actually been commercializing products in over 50 countries, and we have extensive experience.

Speaker #2: So we're going to bring suffiance to as many of these markets and as quickly as effectively as possible.

Speaker #6: Great.

[Analyst] (Barclays): Great.

Ellie Merle: Great.

Speaker #1: Thank you. Our next question comes from Eric Joseph with Citi. Your line is open.

Operator: Thank you. Our next question comes from Eric Joseph with Citi. Your line is open.

Speaker #5: Oh, thanks for taking the questions, and congrats on all the progress. Maybe just to pick up on the XUS outlook, can you talk a little bit about, of the 30 global markets that you're pursuing, which are likely to have their own HTA review processes versus referencing other geographies to arrive at a pricing decision, and also what HTA review timelines might look like?

Eric Joseph: Oh, thanks for taking the questions, and congrats on all the progress. Maybe just to pick up on the ex-US outlook, can you talk a little bit about sort of of the 30 global markets that you're pursuing, which are likely to have their own HTA review processes versus referencing other geographies to arrive at a pricing decision, and also what HTA review timelines might look like? If I could just squeeze in a pipeline question, I'd be curious to kind of get a sense of timeline as it relates to the NLRP3 inhibitor program and what kind of profile might support later-stage development as those data read out. Thank you.

Speaker #5: And if I could just squeeze in a pipeline question, I'd be curious to kind of get a sense of timeline as it relates to the NLRP3 inhibitor program and what kind of profile might support later stage development as those data read out.

Speaker #5: Thank you.

Speaker #3: Hi, Eric. I'll take the second question first. Make a comment on the first one and turn it over to Eric. So we're excited about the NLRP3 program, as we talked about.

Matthew Klein: Hi, Eric. I'll take the second question first, make a comment on the first, and then turn it over to Eric. We're excited about the NLRP3 program, as we've talked about. We've done a lot of work preclinically demonstrating that this molecule is highly differentiated in terms of potency. We've been able to benchmark it against others. It has specificity for the target, and we talked a bit about how its chemical backbone was a bit different than others that have been in development that were, and that others had some potential toxicity concerns that we don't think will apply here. We've designed the phase I study to answer the typical phase I pharmacology, biodistribution, and safety questions.

Speaker #3: We've done a lot of work preclinically demonstrating that this molecule is highly differentiated in terms of potency. We've been able to benchmark it against others.

Speaker #3: It has specificity for the target, and we talked a bit about how it's chemical backbone is a bit different than others that have been in development that were and that others had some potential toxicity concerns that we don't think will apply here.

Speaker #3: We've designed the phase one study to answer the typical phase one pharmacology biodistribution and safety questions, but also we're including a cohort of patients with sort of metabolic syndrome phenotype and inflammatory biomarkers so that we can get early confidence that the at the exposures that we're able to get, exposures we can get safely, the level of inhibition we're seeing is associated with favorable biomarker.

Matthew Klein: Also we're including a cohort of patients with sort of metabolic syndrome phenotype and inflammatory biomarkers so that we can get early confidence that with the exposures that we're able to get, exposures we can get safely, the level of inhibition we're seeing is associated with favorable biomarker effects. We could have those data as early as the end of this year into early next year. That would really put us in place then to move quickly into phase II. Again, we're super excited about this program. We've talked about focusing on rare pulmonary disorders as a first set of indications. That was based on the understood overlap between NLRP3 inflammasome and a number of pulmonary inflammation and fibrotic pathologies.

Speaker #3: Effects. And we could have those data as early as the end of this year into early next year. And that would really put us in place then to move quickly into phase two.

Speaker #3: And so again, we're super excited about this program. We've talked about focusing on rare pulmonary disorders as a first set of indications and that was based on the understood overlap between NLRP3 and flavazone and a number of pulmonary inflammation and fibrotic pathologies.

Matthew Klein: In the first question, let me just make a general comment that number of 30 countries, we had said between 20 and 30, that was just in 2026. I just want to make clear that we expect this to be, as the launch moves forward into 2027 and beyond, there's many more countries we seek to get to and target that 58,000 global adjustable market. Eric, do you want to talk a little bit about HTA processes? Yeah, Eric, thanks for the question again. HTA assessments are primarily in large southern European markets, and I'll just give you a little color for that because those are the markets that are referenced pretty much around the world in international markets. For France, the HTA assessment is complete.

Speaker #3: In the first question, let me just take a general comment. That number of 30 countries, we had said between 20 and 30, that was just in 2026.

Speaker #3: I just want to make clear that we expect this to be as a launch moves forward into 27 and beyond, there's many more countries we seek to get to and target that 58,000 global adjustable market.

Speaker #3: Eric, do you want to talk a little bit about HTA processes?

Speaker #2: Yeah, Eric, thanks for the question again. HTA assessments are primarily in large Southern European markets, and I'll just give you a little color on that.

Eric Pauwels: Yeah, Eric, thanks for the question again. HTA assessments are primarily in large southern European markets, and I'll just give you a little color for that because those are the markets that are referenced pretty much around the world in international markets. For France, the HTA assessment is complete.

Speaker #2: Because those are the markets that are referenced pretty much around the world in international markets. So, for France, the HTA assessment is complete. We've completed that.

Eric Pauwels: We've completed that, the early access program has been approved in Q2, as I mentioned, there's been a very accelerated demand by healthcare professionals for the early access program, we're recognizing revenue there. The price is actually the German price. In terms of timing, pricing and reimbursement discussions are now ongoing, we would expect that to conclude sometime next year in France. In Italy and Spain, again, key markets, HTA process is still ongoing, that's going to be going on for probably into Q3 and Q4. However, we do have early access programs, again, being leveraged. Those are priced at the German price at this point in time. Then pricing and reimbursement discussions will be conducted with the authorities likely in Q4 and we're expecting that to conclude sometime in early 2027.

Speaker #2: And the early access program is been approved in Q2. And as I very accelerated demand by healthcare professionals for the early access program, and we're recognizing revenue there.

Speaker #2: The price is actually the German price. But in terms of timing, pricing and reimbursement discussions are now ongoing, and we would expect that to conclude sometime next year in France.

Speaker #2: In Italy and Spain—again, key markets—the HTA process is still ongoing, and that's going to be going on probably into the third and fourth quarters.

Speaker #2: However, we do have early access programs, again, being leveraged. Those are priced at the German price at this point in time. Pricing and reimbursement discussions will be conducted with the authorities, likely in the fourth quarter, and we’re expecting that to conclude sometime in early 2027.

Speaker #2: And as you already know, Germany, the HTA assessment was completed at the beginning of the year. And right now, from a GKV discussion, this is still ongoing.

Matthew Klein: As you already know, Germany, the HTA assessment was completed at the beginning of the year, right now from a GKV discussion, this is still ongoing. Pricing and reimbursement should be finalized before the end of this year in Germany.

Speaker #2: Pricing and reimbursement should be finalized before the end of this year in Germany.

Speaker #5: Excellent. Thanks for all the color.

Eric Joseph: Excellent. Thanks for all the color.

Speaker #2: Sure.

Matthew Klein: Sure.

Speaker #1: Thank you. Our next question comes from Ben Burnett with Wells Fargo. Your line is open.

Operator: Thank you. Our next question comes from Ben Burnett with Wells Fargo. Your line is open.

Speaker #3: Hey, thanks very much. I was wondering if you could maybe just talk to the revenue guidance. Great to see that increase just want to know what's considered in the increase.

Ben Burnett: Hey, thanks very much. I was wondering if you could maybe just talk to the revenue guidance. Great to see that increase. Just want to know what's considered in the increase. Is this mostly SEPHIENCE confidence, or is this from sort of broader confidence with other programs? Then just one clarification on the discontinuation rate. How was that defined?

Speaker #3: Is this mostly suffiance, confidence, or is this from sort of broader confidence with other programs? And then just one clarification on the discontinuation rate.

Speaker #3: How is that defined? Hi, Ben. So, in your first question on the revenue guidance—look, when we came into this year, we said we had a lot of unknowns that we were dealing with.

Matthew Klein: Hi, Ben. On your first question on the revenue guidance, look, when we came into this year, we said we had a lot of unknowns that we were dealing with. We were still very early in the SEPHIENCE launch. We also, in terms of the Duchenne franchise, had significant headwinds with a significant number of generics now from EMFLAZA and headwinds in some of the larger countries where we get group purchase orders as well as the fact that we're still selling product in Europe without a license. Clearly, the Duchenne franchise has had a bit more durability than expected, and the SEPHIENCE growth has been terrific.

Speaker #3: We were still very early in the Sufficiency launch. And we also, in terms of the Duchenne franchise, had significant headwinds with a significant number of generics now from Plaza.

Speaker #3: And headwinds in some of the larger countries where we get good purchase orders, as well as the fact that we were still selling product in Europe without a license.

Speaker #3: Clearly, the Duchenne franchise has had a bit more durability than expected, and the suffiance growth has been terrific. So as we went and looked at revising the guidance, as we did after the first quarter, and now again after second quarter, it's based in large part on our confidence with suffiance.

Matthew Klein: As we went and looked at revising the guidance as we did after Q1 and now again after Q2, it's based in large part on our confidence with SEPHIENCE and the ability for it to continue to grow in the way that we have seen it growing. Some of the widespread of the guidance range incorporates the fact that we could still see some contributions from the Duchenne franchise if EMFLAZA is able to withstand the continued generics, for example. A lot of it is our confidence in SEPHIENCE with some confidence that we may get still some more life out of the Duchenne franchise. In terms of the discontinuation numbers, we define that as going basically 60 days or two months without prescription renewal.

Speaker #3: And the ability for it to continue to grow in the way that we have seen it growing and some of the widespread of the guidance range incorporates the fact that we could still see some contributions from the Duchenne franchise if Plaza is able to withstand the continued generics, for example.

Speaker #3: But a lot of it is our confidence and sufficiency, with some confidence that we may still get some more life out of the Duchenne franchise.

Speaker #3: In terms of the discontinuation numbers, we define that as going basically 60 days or two months without prescription renewal. Great. Thank you.

Ben Burnett: Great. Thank you.

Speaker #1: Thank you. Our next question comes from Brian Cheng with JP Morgan, your line is open.

Operator: Thank you. Our next question comes from Brian Chang with J.P. Morgan. Your line is open.

Operator: Thank you. Our next question comes from Brian Cheng with JPMorgan. Your line is open.

Speaker #4: Hey, guys. I'm glad it's on a quarter. Maybe just first, heading into the discussion with the agency on the VYDERA plan later this year, is the discussion going to enable you to talk about the ability to file for an accelerated approval based on the 24-month data?

Brian Chang: Hey, guys. Congrats on the quarter. Maybe just first, heading into the discussion with the agency on votoplam later this year. Is the discussion going to enable you to talk about the ability to file for an accelerated approval based on the 24-month data? Is that one of the primary goals here? Secondly, we're seeing new patient add accelerated this specific quarter, and the revenue is not catching up as fast. I'm curious if you can help us, how do we best reconcile these two numbers? Thank you.

Brian Cheng: Hey, guys. Congrats on the quarter. Maybe just first, heading into the discussion with the agency on votoplam later this year. Is the discussion going to enable you to talk about the ability to file for an accelerated approval based on the 24-month data? Is that one of the primary goals here? Secondly, we're seeing new patient add accelerated this specific quarter, and the revenue is not catching up as fast. I'm curious if you can help us, how do we best reconcile these two numbers? Thank you.

Speaker #4: Is that one of the primary goals here? And then secondly, we're seeing new patient add accelerated this specific quarter. And the revenue is not catching up as fast.

Speaker #4: So I'm curious if you can help us, how do we best reconcile these two numbers? Thank you.

Speaker #3: Yep. Brian, in terms of voter plan, as we had said after we shared the data, that we and our team and Navarre’s team would discuss whether we would review those data with the FDA.

Matthew Klein: Yeah. Brian, in terms of the votoplam, as we had said after we shared the data that our team and the Novartis team would discuss whether we would review those data with FDA. Clearly, the FDA's seeming agreement to accept a filing for the gene therapy on cUHDRS as an intermediate clinical endpoint was an important data point in our consideration of whether to talk to the FDA. I think the belief is that it's important to go and talk to them, talk to them about the data. Obviously one of the important topics is going to be if there is a precedent for applications based on ICE in HD.

Speaker #3: Clearly, the FDA's seeming agreement to accept a filing from for the gene therapy on COHDRS is an intermediate clinical endpoint, was an important data point in our consideration of whether to talk to the FDA.

Speaker #3: So I think the belief is that it's important to go and talk to them, talk to them about the data. And obviously, one of the important topics is going to be if there is a precedent for applications based on ICE in HD, we believe our data compare quite favorably when you consider just a number of patients exposed to dose-dependent effect, seen in the stage two patients, the fact that we have objective data of target engagement and mechanism of action with the dose-dependent durable lowering of blood Huntington protein, as well as safety exposure in a large number of patients in a drug that's titratable, reversible, and we have a phase three study that's up and going and enrollment's underway.

Matthew Klein: We believe our data compare quite favorably when you consider just the number of patients exposed, the dose-dependent effect seen in the stage 2 patients, the fact that we have objective data of target engagement and mechanism of action with the dose-dependent durable lowering of blood huntingtin protein, as well as safety exposure in a larger number of patients in a drug that's titratable, reversible, and we have a phase III study that's up and going, and enrollment's underway. We think all of those things allow for a really good discussion with FDA. Obviously Novartis has made the comment that they're still operating under the assumption that phase III is the base case.

Speaker #3: So, we think all of those things allow for a really good discussion with the FDA. Obviously, Novartis has made the comment that they're still operating under the assumption that Phase 3 is the base case.

Matthew Klein: Importantly, that study has an interim analysis, they have also commented, as we have, that we would look for any chance we have to accelerate access to a potential disease-modifying therapy, given a significant unmet need for Huntington's disease patients. In terms of patient adds, look, I think what we're seeing, again, is what we said is consistent demand and consistent adds in the US and increasing contributions now globally. Obviously, patient numbers coming different. Patient numbers and revenue may be different in terms of that. Patient weights may be different. There's a lot of variables that actually go into the amount of reimbursement and obviously, all patients don't enter in a quarter at one time. Some can come in a lot early, some can come in a bit later. I think there's a lot of variables that go into it.

Speaker #3: Importantly, that study has an interim analysis, but they have also commented—as we have—on accelerating access to a potential disease-modifying therapy, given the significant unmet need for Huntington's disease patients.

Speaker #3: In terms of patient ads, look, I think what you're seeing again is what we said is consistent demand and consistent ads in the US and increasing contributions now globally.

Speaker #3: Obviously, patient numbers come in different patient numbers and revenue may be different in terms of that patient weights may be different. There's a lot of variables that actually go into the amount of reimbursement and obviously all patients don't enter in a quarter at one time.

Speaker #3: Some can come in, you can have a lot early, then some can come in a bit later. So I think there's a lot of variables that go into it.

Speaker #3: I think importantly to your point, we see consistent demand, we see growth in patient numbers that we saw your early note is more than folks expected.

Matthew Klein: I think importantly to your point, we see consistent demand. We see growth in patient numbers that, we saw in your early note, is more than folks expected. We expect that to continue, we expect the revenue also to continue to grow over time, as we said, given the large number of patients, and again, what we've consistently said is a significant $2 billion-plus, multi-billion dollar opportunity.

Speaker #3: We expect that to continue, and we expect the revenue also to continue to grow over time as we said, given the large number of patients. And again, what we've consistently said is a significant, $2 billion-plus, multi-billion-dollar opportunity.

Speaker #4: Thank you, Matt. Thank you.

Brian Chang: Thank you, Matthew Klein. Thank you.

Brian Cheng: Thank you, Matt. Thank you.

Speaker #1: Thank you. Our next question comes from Judah Fromer with MS, your line is open.

Operator: Thank you. Our next question comes from Judah Frommer with Morgan Stanley. Your line is open.

Speaker #5: Yeah. Hi, guys. Congrats on the quarter, and thanks for taking the questions. Are you able to add any guidance or detail on switching dynamics?

Judah Frommer: Yeah. Hi, guys. Congrats on the quarter and thanks for taking the questions. Are you able to add any guidance or detail on switching dynamics, patients that are switching from standard of care therapy to SEPHIENCE? Are there particular sales efforts that are generating success there? Is it word of mouth amongst patients? Anything anecdotal or tangible there would be helpful. Just on the peak sales opportunity for SEPHIENCE, any change in speed to peak as you're now through several quarters of the launch? Or do you expect things to be in line with your original expectations as of now? Thanks.

Speaker #5: Patients that are switching from standard-of-care therapy to sefinace, are there particular sales efforts that are generating success there? Is it word of mouth amongst patients?

Speaker #5: Anything anecdotal or tangible that would be helpful? And then just on the peak sales opportunity for suffiance, any change in speed to peak as you're now through several quarters of the launch or do you expect things to kind of be in line with your original expectations as of now?

Speaker #5: Thanks.

Speaker #3: Thanks for the questions, Judah. Let me take the second one first, and then I'll ask Eric to comment a little bit on what we're seeing in the switching dynamics, some of the data that's driving that, and some of the dynamics of those patients.

Matthew Klein: Thanks for the questions, Judah. Let me take the second one first and then I'll ask Eric Pauwels to comment a little bit on what we're seeing in the switching dynamic and some of the data that's driving that and some of the dynamics of those patients. Look, I think we've talked just generally about this being, call it $2 billion-plus, multi-billion dollar, not in terms of specific guidance, but just to help people understand what we believe is the magnitude of this opportunity. Recalling that when we started the launch, we were getting ready for the launch, a lot of people were benchmarking this to previous therapies. I think we are now at a full year run rate that exceeds what many people thought the initial opportunity was for this product.

Speaker #3: Look, I think we've talked just generally about this being, call it, $2 billion-plus, multi-billion dollar—not in terms of specific guidance, but just to help people understand what we believe is the magnitude of this opportunity.

Speaker #3: Recalling that when we started the launch, we were getting ready for the launch. A lot of people were benchmarking this to previous therapies. I mean, I think we are now at a full-year run rate that exceeds what people initially many people thought the initial opportunity was for this product.

Speaker #3: So we've thought it's really important to really explain that there's no precedent, there's no benchmarking this in terms of previous PKU therapies, but rather to benchmark in terms of what a differentiated rare disease therapy with a population of 17,000 US and 58,000 in markets where we could access patients and get reimbursed for drug could bring.

Matthew Klein: We thought it's really important to really say that there's no benchmarking this in terms of previous PKU therapies, rather it should be benchmarked in terms of what a differentiated rare disease therapy with a population of 17,000 in the US and 58,000 in markets where we could access patients and get reimbursed for drug could bring. I think as we get further into this year and into next year, we'll be in a better position to talk more about formal guidance. Again, we just have that number and have stuck to that number now just to hold out the fact that, one, it's a much larger opportunity, I think, than many have initially imagined. Two, what we're seeing thus far in the launch does nothing but increase our confidence that this is the magnitude of this opportunity.

Speaker #3: I think as we get closer, as we get further into this year and into next year, we've been in a better position to talk more about formal guidance.

Speaker #3: But again, we just have that number, and it's stuck at a number now, just to hold out the fact that, one, it's a much larger opportunity.

Speaker #3: I think that many have initial imagined. Two, what we're seeing thus far in the launch does nothing but increase our confidence that this is the magnitude of this opportunity.

Speaker #3: Eric, do you want to talk a little bit about the switching dynamics, some of the data, and what that's looking like?

Matthew Klein: Eric, do you want to talk a little bit about the switching dynamics, some of the data, and what that's looking like?

Speaker #2: Yeah, Judah. Thanks for the question again. I think the first thing that we said is we're really impressed after 12 months in the launch, that we were able to see a lot of the dynamics of those patients who are actually failed or poorly controlled and we also saw that adults and naive have been coming in.

Eric Pauwels: Yeah, Judah. Thanks for the question again. I think the first thing is that we said is we're really impressed after 12 months in the launch that we were able to see a lot of the dynamics of those patients who are actually failed or poorly controlled, and we also saw that adults and naive have been coming in. What we thought may have been the case was that patients and physicians who were the highest unmet need would be the first ones treated. Now we have all centers of excellence who are prescribing, and we're also seeing now a significant movement to change what patients are seeing in terms of Phe reduction. I think we have a number of key programs that our sales teams, our medical teams are communicating about not just Phe reduction, but how lower Phe reduction is more important.

Speaker #2: When what at we thought may have been the case with was that patients and physicians who are the highest unmet need would be the first ones treated.

Speaker #2: Now we have all centers of excellence who are prescribing. And we're also seeing now a significant movement to change what patients are seeing in terms of fee reduction.

Speaker #2: And I think we have a number of key programs that are sales teams or medical teams are communicating about not just fee reduction, but how lower fee reduction is more important.

Speaker #2: And what we'll be showing at SSIEM will be some very important data that talks about normalization, patients at 120 micrometers per milliliter, and when you think about normalization, that's incredibly important because we know patients who already respond to BH4 will have a much better response to suffiance and are likely to not only reach goal, but to reach normalization.

Eric Pauwels: What we'll be showing at SSIEM will be some very important data that talks about normalization, patients at 120 micromoles per milliliter. When you think about normalization, that's incredibly important because we know patients who already respond to BH4 will have a much better response to SEPHIENCE and are likely to not only reach goal, but to reach normalization. That's going to be a very, very important part of our communication and messaging as we go forward, and that's going to be supported by data as soon as next month at SSIEM. We have tailored programs from the medical perspective, and we're working with these centers. As we thought, these patients who are the most severe were the first ones to come onto therapy. Now we're seeing more and more benefits from patients who are switching, and that dynamic will continue over time.

Speaker #2: And that's going to be a very, very important part of our communication and messaging as we go forward. And that's going to be supported by data as soon as next month at SSIEM.

Speaker #2: So we have tailored programs from medical perspective, and we're working with these centers and as we thought, these patients who are the most severe were the first ones to come onto therapy.

Speaker #2: But now we're seeing more and more benefits from patients who are switching, and that dynamic will continue over time.

Speaker #5: Thanks.

Speaker #1: Thank you. Our next question comes from Joseph Tone with TD Cowen. Your line is open.

Judah Frommer: Thanks.

Operator: Thank you. Our next question comes from Joseph Thome with TD Cowen. Your line is open.

Speaker #6: Hi there. Good afternoon and thank you for taking my questions. Maybe the first one, I guess in that upside scenario that the FDA is amenable to a filing for Huntington's, can you talk a little bit about where you are from a CMC perspective with VotaPlan and your readiness there?

Joseph Thome: Hi there. Good afternoon, and thank you for taking my questions. Maybe the first one, I guess, in that upside scenario that the FDA is amenable to a filing for Huntington's, can you talk a little bit about where you are from a CMC perspective with votaplam and your readiness there? Second, maybe on the DHODH inhibitor program, I know it's been a while, but you also had PTC299. Can you talk a little bit about the differences between that older agent and your next gen compound? Thank you.

Speaker #6: And then second, maybe on the DHODH inhibitor program, I know it's been a while, but you also had PTC 299. Can you talk a little bit about the differences between that older agent and your next-gen compound?

Speaker #6: Thank you.

Speaker #3: Yeah, absolutely, Joe. So on the HD, look, I think these are the benefits: one, it's a small molecule; and two, having a partner like Novartis who's well equipped to move all of these things forward as quickly as needed.

Matthew Klein: Yeah, absolutely, Joe. On the HD, look, I think this is the benefits of one, it's a small molecule and two, having a partner like Novartis, who's well-equipped to move all of these things forward as quickly as needed. I think when we did the partnership back in 2024, then once we did the official handover in early 2025, it's very clear that their teams are all over every aspect of getting things exactly in order for FDA approval. If we were given the opportunity based on the clinical data, I think we'd be very confident that that application could get there. Of course, obviously, the confirmatory study is already up and running.

Speaker #3: I think when we did the partnership back in '24 and then once we did the official handover in early '25, it's very clear that their teams were all over every aspect of getting things exactly in order for FDA approval.

Speaker #3: So we have, if we were given the opportunity based on the clinical data, I think we'd be very confident that that application could get there and of course, obviously, the confirmatory study is already up and running.

Speaker #3: In terms of DHODH inhibitor, yeah, I think PTC9 299 was really a legacy product and as one would expect from when you go from Gen 1.0 to, I would say, this is, I guess, technically 2.0, but it's more like a 3.0 or 4.0 in terms of how much more potent and specific it really is.

Matthew Klein: In terms of DHODH inhibitor, yeah, I think PTC299 was really a legacy product, as one would expect from a, when you go from gen 1.0 to, I would say this is just technically 2.0, but it's more like a 3.0 or 4.0 in terms of how much more potent and specific it really is. I think we had a lot of conversations internally about bringing this molecule forward, when we saw how differentiated it is and understanding that there have been other DHODH inhibitors that have been approved, that have been viable commercial products.

Speaker #3: And I think we had a lot of conversations internally about bringing this molecule forward, but when we saw how differentiated it is and understanding that there have been other DHODH inhibitors that have been approved, that have been viable commercial products, and to be able to benchmark PTCA44 to those and we showed those data at our research day as well as 299 and show the superiority in terms of in vitro potency as well as specificity for the DHODH target, tells us that we're now able to target a mechanism known to be important and do so in a very selective, specific, and potent way.

Matthew Klein: To be able to benchmark PTC-844 to those, and we showed those data at our research day, as well as 299, and showed the superiority in terms of in vitro potency as well as specificity for the DHODH target, tells us that we're now able to target a mechanism known to be important and do so in a very selective, specific, and potent way. We look forward to the phase IIa study. We're going to be doing that in a population of patients with significant inflammation with rheumatoid arthritis.

Speaker #3: So we look forward to the phase two A study. We're going to be doing that in a population of patients with significant inflammation with rheumatoid arthritis.

Matthew Klein: That's not our intended indication, but rather what we want to do is take a population in whom we knew would have a biomarker profile of inflammation that would allow us to establish the relationship between DHO levels, and effects on biomarkers of T-cell and B-cell immunity that can then help us inform where we would go from there in terms of specific target population.

Speaker #3: That's not our intended indication, but rather what we want to do is take a population and in whom we knew would have a biomarker profile of inflammation that would allow us to establish the relationship between DHO levels and effects on biomarkers of T-cell and B-cell immunity that can then help us inform where we would go from there in terms of specific target populations.

Speaker #6: Great. Thank you.

Joseph Thome: Great. Thank you.

Speaker #1: Thank you. Our next question comes from Faisal Khurshid with Jeffries, your line is open.

Operator: Thank you. Our next question comes from Faisal Khurshid with Jefferies. Your line is open.

Speaker #4: Hey, guys. Thanks for taking the question. I'm just going to ask a couple of nitty-gritty commercial things, if you don't mind. Could you comment if there were any inventory effects for sefiens in the second quarter?

Faisal Khurshid: Hey, guys. Thank you for taking the question. Just going to ask a couple of nitty-gritty commercial things, if you don't mind. Could you comment if there were any inventory effects for SEPHIENCE in Q2? Can you also comment on how we should be thinking about and modeling things like gross to net and net pricing and average patient weight? Have your assumptions there changed at all? Thank you.

Speaker #4: And then, can you also comment on how we should be thinking about and modeling things like gross to net, net pricing, and average patient weight?

Speaker #4: Have your assumptions that are changed at all? Thank you.

Speaker #3: Yeah, I would. Thank you for the questions. I would simply say, Faisal, we've had no inventory effects to think about. Things have been fairly constant in that regard.

Matthew Klein: Yeah. Thank you for the question. I would simply say, Faisal, we've had no inventory effects to think about. Things have been fairly constant in that regard. I would say as well in terms of patient weight, patient age, gross to net, all those things have been consistent. We haven't seen any real changes there.

Speaker #3: I would say as well, in terms of patient weight, patient age, gross to net—all those things have been consistent. We haven't seen any real changes there.

Speaker #4: Thank you.

Faisal Khurshid: Thank you.

Speaker #1: Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.

Operator: Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.

Speaker #6: Hi, everyone. This is Navin on for Brian. Thank you so much for taking our questions. Just one more on sepiapterin. How are you kind of thinking about the split of revenues over the long term, especially just given that the ex-US is progressing so well and you seem to be getting pretty good reimbursement and pricing there? And just given that there's kind of a larger population outside the US as well?

[Analyst] (RBC Capital Markets): Hi, everyone. This is Nevan on for Brian. Thank you so much for taking our questions. Just one more on SEPHIENCE. How are you kind of thinking about the split of revenues over the long term, especially just given that the ex-US is progressing so well and you seem to be getting pretty good reimbursement and pricing there, and just given that there's a kind of a larger population outside the US as well? I'm also wondering if you could talk about your updated thoughts on BD and if your kind of appetite has changed there, if you're looking at any specific programs or therapeutic areas, and what the size of any potential deals that you might be able to do is.

Nevin Varghese: Hi, everyone. This is Nevan on for Brian. Thank you so much for taking our questions. Just one more on SEPHIENCE. How are you kind of thinking about the split of revenues over the long term, especially just given that the ex-US is progressing so well and you seem to be getting pretty good reimbursement and pricing there, and just given that there's a kind of a larger population outside the US as well? I'm also wondering if you could talk about your updated thoughts on BD and if your kind of appetite has changed there, if you're looking at any specific programs or therapeutic areas, and what the size of any potential deals that you might be able to do is.

Speaker #6: And then I'm also wondering if you could talk about your updated thoughts on BD and if your appetite has changed there—if you're looking at any specific programs or therapeutic areas, and what the size of any potential deals that you might be able to do would be.

Speaker #3: Sure. First on the split, look, I think it may be a little early to give an exact breakout. I think we think that international can be a significant contributor here, but still the majority will likely always be driven by the US.

Matthew Klein: Sure. First on the split, look, I think it may be a little early to give an exact breakout. I think we think that international can be a significant contributor here, still the vast majority will likely always be driven by the US. I think there could be a significant contribution ex-US when you start looking at that number of patients, and what we believe we're going to be able to achieve in terms of reimbursement. It's a little early for us to give an exact breakdown there. I'd say, for example, what we're seeing thus far in Japan has been really impressive. There's maybe 1,000, 1,100 patients there with PKU, we're seeing a lot like the US. There's early demand. There's patients not on therapy who are coming back in and getting on therapy.

Speaker #3: But I think there could be a significant contribution XUS when you start looking at that number of patients and what we believe are going to be able to achieve in terms of reimbursement.

Speaker #3: But it's a little early for us to give an exact breakdown there. I'd say, for example, what we're seeing thus far in Japan has been really impressive.

Speaker #3: There are maybe 1,000 or 1,100 patients there at PKU, but we're seeing a lot like the US. There's early demand; there are patients not on therapy who are coming back in and getting on therapy.

Speaker #3: There's centers of excellence and as Eric mentioned, the prepared comments, there we have a price on par with the US. Price is set for 10 years.

Matthew Klein: There's centers of excellence and as Eric mentioned in the prepared comments, there we have a price on par with the US. Price is set for 10 years. It's very easy for patients to get on drugs. Again, there's a lot of these kinds of stories out there where we're seeing international markets be able to start to make an impact that we expect will continue to grow in the latter part of 2026 into 2027, and beyond. Pierre, do you want to talk a little bit about how we've been thinking about BD?

Speaker #3: It's very easy for patients to get on drugs. So again, there are a lot of these kinds of stories out there where we've seen international markets be able to start to make an impact that we expect will continue to grow in the latter part of ’26 into ’27 and beyond.

Speaker #3: Pierre, do you want to talk a little bit about how we've been thinking about BD?

Speaker #5: Yes, happy to. So first of all, I would say we closed the quarter with very strong cash position of 2.2 billion dollars. We work really hard to get there.

Pierre Gravier: Yes, happy to. First of all, I will say we closed the quarter with very strong cash position of $2.2 billion. We worked really hard to get there. As we said, our team has demonstrated their ability to launch products globally. That's a key strength of ours. They have capacity. We're looking at BD in a number of ways. One, obviously, we're still laser-focused on SEPHIENCE. We don't want to distract the momentum at all. Are there ways to complement that very strong franchise for us? That's one bucket. We're also looking at other areas in the rare disease space, late stage or commercial, again, to leverage that global infrastructure

Speaker #5: And as we said, our team has demonstrated their ability to launch products globally. That's a key strength of ours. They have capacity. So we're looking at BD in a number of ways.

Speaker #5: One, obviously, we're still laser focused on suffiance. We don't want to distract the momentum at all. Other ways to complement that very strong franchise for us, that's one bucket.

Speaker #5: We're also looking at other areas in a rare disease space, late stage, or commercial, again, to leverage that global infrastructure that we have. So that's how we're thinking about it.

Pierre Gravier: That we have. That's how we're thinking about it. Again, we want to make sure we are very disciplined in any potential transaction to make sure that we create value for shareholders. You mentioned size. Again, we are not going to do anything where we will lever up and use all our cash in one go. That's how we think about it.

Speaker #5: Again, we want to make sure we're very disciplined in any potential transaction to ensure that we create value for shareholders. You mentioned size.

Speaker #5: Again, we're not going to do anything where we would lever up and use all our cash in one go. So that's how we think about it.

Speaker #6: Great. Thank you so much.

Eric Pauwels: Great. Thank you so much.

Nevin Varghese: Great. Thank you so much.

Speaker #1: Thank you. Our next question comes from Luke Herman with Baird. Your line is open.

Operator: Thank you. Our next question comes from Luke Herrmann with Baird. Your line is open.

Speaker #7: Hey, thanks for the question, team. So now that you're established in all the centers of excellence, for suffiance, has there been any shift in the proportion of new starts stemming from sort of a proactive visit as compared to a more typical checkup schedule?

Luke Herrmann: Hey, thanks for the question, team. Now that you're established in all the centers of excellence for SEPHIENCE, has there been any shift in the proportion of new starts stemming from sort of a proactive visit as compared to a more typical checkup schedule? Sorry if you've already covered this, but to the extent you're able to qualify, how have new starts tracked into July? Thanks.

Speaker #7: And sorry if you've already covered this, but to the extent you're able to qualify, how have new starts tracked into July? Thanks.

Matthew Klein: Yep. Thanks for the questions, Luke. I would say that what we've been hearing from a lot of the KOLs is that most of the prescriptions are coming now as part of regular visits. Early on, we said the first couple of months of the launch, there were a lot of folks coming in, waiting lists, and a lot of attention in the first part. Most of the KOLs and prescribers have told us that somewhere late November or so, we saw a shift, and it's really as patients are coming in, they're looking to either start them on therapy or switch them, for example. Now, that being said, we still note that one of the questions earlier asked about what the effects of us going to conferences and the work that our customer-facing teams do in the field and our patient support and patient engagement work does.

Speaker #3: Yep. Thanks for the questions, Luke. I would say that what we've been hearing from a lot of the KOLs is that most of the prescriptions are coming now as part of regular visits.

Speaker #3: Early on, we said the first couple of months of launch, there were a lot of folks coming in waiting lists and a lot of attention in the first part, but most of the KOLs and prescribers have told us that somewhere late November or so, we saw a shift and it's really as patients are coming in, they're looking to either start them on therapy, or switch them.

Speaker #3: For example, now that being said, we still note that one of the questions earlier asked about what the effects of us going to conferences and the team work that our customer-facing teams do in the field and our patient support and patient engagement work does.

Speaker #3: We know that the more messages, the more patients hear about this, there still is a lot of patient pull and market pull to get into clinics and get on the drug.

Matthew Klein: We know that the more messages, the more patients hear about this, there still is a lot of patient pull and market pull to get into clinics and get on the drug. In terms of starts into July, what we've said is that overall we continue to see strong underlying demand. We expect it to be consistent growth in the US, accelerating growth outside of the US. A lot of that is what underpinned or prompted our confidence in our ability to raise guidance $50 to 950.

Speaker #3: In terms of starts into July, what we've said is that overall, we continue to expected to be consistent growth in the US, accelerating growth outside of the US.

Speaker #3: And a lot of that is what underpinned our or prompted our confidence and our ability to raise guidance to 850 to 950.

Speaker #1: Thank you. Our next question comes from Joe Schwartz with Lyric Partners. Your line is open.

Operator: Thank you. Our next question comes from Joseph Schwartz with Leerink Partners. Your line is open.

Speaker #7: Great, thanks very much. I guess I have a question on Germany first. I think the pricing and reimbursement for seficiane was this summer, with other European negotiations advancing behind that.

Joseph Schwartz: Great. Thanks very much. I guess I have a question on Germany first. I think the pricing and reimbursement for SEPHIENCE was previously expected to be finalized this summer with other European negotiations advancing behind that. Why is it seeming to take longer? Are you getting the traction you expected? Will it hold up any of the discussions with other European countries in any way? Thanks.

Speaker #7: Why does it seem to be taking longer? Are you getting the traction you expected? And will this hold up any of the discussions with other European countries in any way?

Speaker #7: Thanks.

Speaker #3: Thanks a lot, Eric. Do you want to talk a little about the negotiations globally and particularly Germany?

Matthew Klein: Thanks, Joe. Eric, do you want to talk a little about the negotiations globally and particularly Germany?

Speaker #7: Yeah. And in fact, keep in mind, thanks, Joe, for the question. Keep in mind that we've launched in Germany and it has been just barely on the 12-month cycle.

Eric Pauwels: Yeah. Thanks, Joe, for the question. Keep in mind that we've launched in Germany, and it has been just barely on the 12-month cycle. We have a number of what we call mandatory negotiation sessions, and then there are informal ones with GKV. Clearly, those discussions have been productive. They've been cordial. We've been working on that. We've just now hit the summer months. Those discussions will continue throughout the summer. It's likely that our pricing and reimbursement will be finalized sometime in Q3, but it could go into Q4. The list price right now that we have listed in the Lauer-Taxe is very similar to the US price. It has not affected any of the other markets.

Speaker #7: We have a number of what we call sort of mandatory negotiation sessions, and then they're informal ones with GKV. Clearly, those discussions have been productive.

Speaker #7: They've been cordial. We've been working on that. We've just now hit the summer months, so those discussions will continue throughout the summer. It's likely that our pricing and reimbursement will be finalized sometime in the third quarter, but it could go into the fourth quarter.

Speaker #7: The list price right now that we have listed in the LARTX is very similar to the US price. It has not affected any of the other markets.

Speaker #7: And in fact, Brazil, which CMED has referenced in terms of innovation status, the current Brazilian price is linked to the German price. So essentially, everything is going according to schedule.

Eric Pauwels: Brazil, which CMED has referenced in terms of innovation status, the current Brazilian price is linked to the German price. Everything is going according to schedule, and we anticipate to have the final decisions sometime in H2 of this year.

Speaker #7: And we anticipate to have the final decisions sometime in the second half of this year.

Speaker #3: Thank you.

Joseph Schwartz: Thank you.

Speaker #1: Thank you. Our next question comes from Paul Choi with Goldman Sachs. Your line is open.

Operator: Thank you. Our next question comes from Paul Choi with Goldman Sachs. Your line is open.

Speaker #7: Hi. Congratulations on the progress, and thanks for taking the questions. I have two on Huntington's. Matt, I was wondering if you could maybe offer your preliminary thoughts on development of PTC303 as a monotherapy in Huntington's versus potential combination use with Vodoplan. Any early thoughts there would be great.

Paul Choi: Hi. Congratulations on the progress, thanks for taking the questions. I have two on Huntington's. Matt, I was wondering if you maybe offer your preliminary thoughts on development of PTC303 as a monotherapy in Huntington's versus potential combination use with votaplam. Any early thoughts there would be great. My second one is, Roche recently discontinued its tominersen studies in Huntington's, caveating for the usual cross-trial and cross-drug differences. Any thoughts there just on the implications just given what was early and promising biomarker changes versus what looks like less success on clinical endpoints and any thoughts on potential read-throughs there? Thank you very much.

Speaker #7: And my second one is, Gross recently discontinued its tominersen studies in Huntington's. And, caveating for the usual cross-trial and cross-drug differences, any thoughts there just on the implications, just given what was early and promising biomarker changes versus what looks like less success on clinical endpoints, and just any thoughts on potential read-throughs there?

Speaker #7: Thank you very much.

Speaker #3: Yeah, absolutely. So first, look, we're super excited about PTC303. We talked about it at R&D Day, and I think, again, this shows PTC's ability to leverage splicing to bring forward potentially valuable and impactful therapies.

Matthew Klein: Yeah, absolutely. First, look, we're super excited about PTC303. We talked about it at R&D Day, I think, again, this shows PTC's ability to leverage splicing to bring forward potentially valuable and impactful therapies. PTC303 is one that can target several diseases characterized by somatic expansion. This is one that I think from conception to getting to a development candidate took our team probably a little less than three years, which is phenomenal. Really, I think is an example of how we're getting smarter and using the tools we have to facilitate and accelerate small molecule splicing development. As you pointed out, Paul, we talked about on the call, HD is a disease of somatic expansion. Targeting MSH3 is probably now the hottest target in Huntington's disease drug development. We're very excited about votaplam. We think they could work together.

Speaker #3: And PTC 303 is one that can target several diseases characterized by somatic expansion. This is one that I think, from conception to getting to a development candidate, took our team probably a little less than three years, which is phenomenal.

Speaker #3: And really, I think it is an example of how we're getting smarter and using the tools we have to facilitate and accelerate small molecule splicing development.

Speaker #3: As you pointed out, Paul, and we talked about on the call, HD is a disease of somatic expansion, targeting MSH3 is probably now the hottest target in Huntington's disease drug development.

Speaker #3: We're very excited about Vodoplan. We think they could work together, and also it could serve as a monotherapy, particularly in, for example, juvenile HD. Juvenile HD is a setting where there's a large number of triplet repeats, and it's characterized by rapid progression.

Matthew Klein: Also it could serve as a monotherapy, particularly in, for example, juvenile HD. Juvenile HD is a setting where there's a large number of triplet repeats, and it's characterized by rapid progression. Well, what does that mean? There's rapid somatic expansion. You would think that something targeting somatic expansion, you could see a signal sooner and maybe louder, in a short amount of time in, say, a juvenile HD population. We're very excited to be able to have this as a potential therapeutic option. We look forward to getting all of the IND-enabling studies done and getting this into the clinic as quickly as we can in 2027.

Speaker #3: What does that mean? There's rapid somatic expansion. So, you would think that something targeting somatic expansion—you could see a signal sooner, and maybe louder, in a short amount of time.

Speaker #3: In, say, a juvenile HD population. But we're very excited to be able to have this as a potential therapeutic option. We look forward to getting all of the IMD enabling studies done and getting this into the clinic as quickly as we can in 2027.

Speaker #3: In terms of Tomirson, I think it's been quite clear for a bit of time now, probably ever since the Generation HD1 data were presented.

Matthew Klein: In terms of tominersen, I think it's been quite clear for a bit of time now, probably ever since the GENERATION HD1 data were presented, and probably even before that, when some of the earlier stage data were presented, that a lot of the challenges with tominersen were not really a mandate or reflection of the potential of HTT lowering, but a lot of it was associated with the limitations of the ASO modality here. As was noted in earlier studies of tominersen, particularly when there was a 4-week dosing arm, it had to be discontinued because of the significant amount of inflammation created in the CSF by the ASO. In fact, in the doses used in GENERATION HD1 as well as GENERATION HD2, you still saw white blood cells and protein markers of immunoinflammatory response in the CSF of patients who received it.

Speaker #3: And probably even before that, when some of the earlier stage data were presented, a lot of the challenges of Tomirson were not really a mandate or a reflection of the potential of HCT lowering, but a lot of it was associated with the limitations of the ASL modality here.

Speaker #3: As was noted in earlier studies of Tomirson, particularly when there was a four-week dosing arm, it had to be discontinued because of the significant amount of inflammation created in the CSF by the ASL.

Speaker #3: And in fact, in the doses used in Generation HD1 as well as Generation saw white blood cells and protein markers of immunoinflammatory response in the CSF of patients who received it.

Speaker #3: That's been noted—that's something that has always been a concern. If you think about it, you're taking Huntington's disease patients, and a lot of those patients were later-stage patients.

Matthew Klein: That's been noted. That's something that has always been a concern. If you think about it, you're taking eight Huntington's disease patients, and a lot of those patients were later-stage patients. These are individuals who had brain inflammation and oxidative stress for decades, and you are dropping an inflammatory stimulus into their CSF. What ends up happening is you can't actually, I think, readily or easily detect a favorable Huntington-lowering response because it's confounded by a significant inflammatory response in that population. Again, that's corroborated by the protein and white blood cells in the CSF, as well as by some of the other issues with the CSF that were observed in that study. Of course, the association of certain points of NFL spikes following treatment.

Speaker #3: So these are individuals who had brain inflammation and oxidative stress for decades, and you are dropping an inflammatory stimulus into their CSF. And so what ends up happening is you can't actually, I think, readily or easily detect a favorable Huntington lowering response because it's confounded by a significant inflammatory response in that population.

Speaker #3: And again, that's corroborated by the protein and white blood cells in the CSF as well as by some of the other issues with the CSF that were observed in that study.

Speaker #3: And of course, the association at certain points of NFL spikes following treatment. All of that put together is really why I think a lot of people view the Tomirson experience as really a reflection of that drug and not HD lowering.

Matthew Klein: All of that put together is really why I think a lot of people view the tominersen experience as really a reflection of that drug and not HTT lowering. We think that the Evrysdi paradigm is probably a better way to think about votoplam, right? Oral small molecule splicing agent, gets full brain biodistribution, allow for titratability, allow to use the peripheral blood cells as a marker for target engagement and change of protein of interest, really allow you then to identify a therapeutic window so that you can deliver benefit along with safety. That's how we think about it.

Speaker #3: We think that Avisity is probably a better way to think about Vodoplan, right? Oral small molecule splicing agent, gets full brain biodistribution, allows for titratability, and allows us to use the peripheral blood cells as a marker.

Speaker #3: For target engagement and change of protein of interest and then really allow you then to identify a therapeutic window so that you can deliver benefit along with safety.

Speaker #3: So that's how we think about it.

Speaker #7: Great. Thank you.

Paul Choi: Great. Thank you.

Speaker #1: Thank you. I'm showing no further questions. I'd like to turn the call over to Dr. Matthew Klein for closing remarks.

Operator: Thank you. I am showing no further questions. I would like to turn the call over to Dr. Matthew Klein for closing remarks.

Speaker #3: Thank you again for joining the call. This afternoon, we are incredibly excited about our performance so far in 2026. And we look forward to continued outstanding performance not only with Sefiance, but across the entire company.

Matthew Klein: Thank you again for joining the call this afternoon. We are incredibly excited about our performance so far in 2026. We look forward to continued outstanding performance, not only with SEPHIENCE, but across the entire company. Thank you all again for joining the call.

Speaker #3: Thank you all again for joining the call.

Operator: Thank you for your participation. You may now disconnect. Everyone, enjoy the rest of your day.

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