PTC's Q3 2025: Contradictions Emerge on Sephience Launch, Payer Coverage, and FDA Strategy

Date of Call: November 4, 2025

Financials Results

• Revenue: $211.0M total Q3 revenue; includes Sephience net product revenue of $19.6M (US $14.4M; ex-US $5.2M) and DMD franchise $86M (Translarna $51M; Emflaza $35M); Evrysdi royalties $71M; company narrowed 2025 full-year revenue guidance to $750M–$800M (upper end of prior range).

Guidance:

• Full-year 2025 revenue narrowed to $750M–$800M (upper end of initial range).
• Expect OpEx to decline in 2026; 2026 guidance to be provided at JPMorgan.
• Payer mix anticipated to stabilize at ~65% commercial / 35% Medicaid/Medicare as policies finalize in Q4.
• Japan approval for Sephience anticipated in Q4 and Brazil approval expected this quarter; international rollouts and HTA processes continue into 2026.
• Cash position ~$1.688B supports path to cash-flow breakeven and further BD.

Business Commentary:

• Sephience Launch Success:
• PTC Therapeutics reported $19.6 million in revenue from SEPHIENCE in its first two months of launch, contributing to a total revenue of $211 million for Q3 2025.

• The strong launch was driven by significant enthusiasm from the physician and patient communities, with 521 patient start forms received in the U.S. and 341 patients on commercial therapy.

• Payer Engagement and Access:

• PTC Therapeutics has engaged with more than 35 payers covering approximately 250 million lives, resulting in favorable payer policies with broad access and no or limited step edits.

• This positive reception is attributed to the highly differentiated profile and strong value proposition of SEPHIENCE, as demonstrated by robust clinical data and rapid patient responses.

• Financial Performance and Cash Position:

• The company's cash, cash equivalents, and marketable securities totaled $1,688 million as of September 30, 2025, reflecting a strong financial position.

• This was due in part to the purchase of the annual global net sales payment obligation of SEPHIENCE, which is expected to create value based on current transaction terms.

• R&D and Portfolio Advancement:

• PTC Therapeutics is planning a Research & Development Day on December 2, sharing progress on its research programs, including those from its splicing platform.
• This investment in R&D is supported by the company's strong financial position, which enables it to pursue strategic business development opportunities and enhance its commercial portfolio.

Sentiment Analysis:

Overall Tone: Positive

• Management described an "outstanding" quarter and said "Sephience launch is off to a great start." Q3 revenue was $211M with Sephience contributing $19.6M; company narrowed FY guidance to $750M–$800M and reported $1.688B cash, citing ability to reach cash-flow breakeven.

Q&A:

• Question from Kristen Kluska (Cantor Fitzgerald & Co., Research Division): What's going to give you confidence that beyond this really strong out-of-the-gate launch, you're going to see maintained durability and that patients will be on therapy for a while?
  Response: Early real-world feedback across patient segments plus clinical trial durability (up to ~75% response rate) and social/physician reports of Phe lowering and diet liberalization support anticipated durable adherence.

• Question from Tazeen Ahmad (BofA Securities, Research Division): What magnitude of Phe reduction are doctors and payers looking for to keep a patient on treatment; what percent will stay on after initial trial; how are you thinking about guiding the Street on that dynamic?
  Response: No single Phe threshold—clinicians cite 15–30% (and patient-reported benefits); combined cognitive and Phe benefits and trial response rates (~66–75%) lead management to expect a majority will remain on therapy, but it's too early to give precise retention guidance.

• Question from Brian Abrahams (RBC Capital Markets, Research Division): Timeline from a new start form to a patient receiving drug and should we expect start-form patients to roll on to treatment in Q4?
  Response: PTC Cares shepherds patients; average PSF-to-fill about 2–4 weeks (commercial can be days); many should convert in Q4 though government plans may take longer.

• Question from Lut Ming Cheng (JPMorgan Chase & Co, Research Division): On the 521 start form number, how should we think about the rate of start forms and what specifically is driving the October sustained momentum?
  Response: Start-form inflow and patient starts have been fairly consistent month-to-month; 'sustained momentum' refers to steady start-form rates and continued patient initiations.

• Question from Judah Frommer (Morgan Stanley, Research Division): Help us with the narrowing of the full-year guide—is that solely tied to Sephience and any other moving pieces; how penetrated are centers of excellence?
  Response: Guidance narrowed to the upper end mainly due to stronger-than-expected Emflaza performance plus the Sephience launch; all centers of excellence are aware and have prescribed, with ~2/3 of centers prescribing more than one patient.

• Question from Yuxi Dong (Jefferies LLC, Research Division): Can you share details on patient profile for new prescribers and whether uptake is concentrated in any group; updated thoughts on overall opportunity given strong early momentum?
  Response: Initial uptake spans all segments and ages (treatment-naive, switches, broad age range from infants to elderly); supports opportunity within estimated ~17,000 US PKU patients, but it's too early for detailed segment revenue projections.

• Question from Kyuwon Choi (Goldman Sachs Group, Inc., Research Division): Any additional coverage updates in Germany/major European markets and comment on OpEx trajectory for '26 relative to expectations?
  Response: Germany currently in free-pricing period with MNOG/HTA process extending into 2026; HTA dossiers submitted in multiple countries; management expects OpEx to decline in 2026 and will provide guidance at JPMorgan.

• Question from Joon Lee (Truist Securities, Inc., Research Division): Why are you seeing switches from Palynziq and timeline/peak opportunity for Japan post-approval?
  Response: Early switches reflect Sephience's once-daily oral, tolerability and ability to treat severe genotypes; Japan approval anticipated before year-end, ~1,000 patients with expected premium pricing and rapid launch preparations.

• Question from Huidong Wang (Barclays Bank PLC, Research Division): Based on $19.6M revenue and 341 patients, is net price ~$350k and what's average time on drug/retention and how is revenue booked?
  Response: Management says the simple math is misleading; WAC guidance around ~$490k with avg patient ~45kg gives similar ballpark; revenue is recognized at shipment (immediate in Germany), gross-to-net driven by payer mix which should stabilize at ~65% commercial; early refill rates are strong.

• Question from Samantha Corwin (William Blair & Company L.L.C., Research Division): Are initial patients skewing pediatric or adult; update on Huntington's registrational plan and FDA meeting goals?
  Response: Initial patients show a broad age mix with average around late adolescence (~17 years); for votoplam (Huntington's) Q4 FDA meeting aims to align on an accelerated-approval pathway and the design/requirements for the next efficacy/confirmatory study.

• Question from Joseph Schwartz (Leerink Partners LLC, Research Division): Can you quantify real-world response rate for Sephience based on refills or other metrics versus APHENITY?
  Response: Too early to provide quantified real-world response rates; management reports encouraging refill momentum and positive signals but no concrete comparative numbers yet.

• Question from John Peyton Bohnsack (TD Cowen, Research Division): Quantify the Sephience opportunity in Brazil, differences in patient population, and steps from approval to launch?
  Response: Brazil approval expected this quarter; after registration pricing via ANVISA-CMED will reference Germany/Japan/US within a narrow pricing corridor; Brazilian prevalence (~6,000+ patients) presents significant opportunity and revenue expected to begin in 2026 as access processes complete.

• Question from Luke Herrmann (Robert W. Baird & Co., Research Division): Could diet liberalization drive patient weight over time, especially for poorly controlled patients?
  Response: Management does not expect uniform weight effects; diet liberalization is being managed via center dietitians and protocols to ensure gradual, medically supervised changes to set patients up for success.

Contradiction Point 1

Sephience Launch Dynamics and Market Access

It involves the expectations and actual outcomes of the Sephience launch, impacting the company's performance and market reception.

What gives you confidence that the initial success will translate into long-term durability and patients will remain on therapy? - Kristen Kluska(Cantor Fitzgerald & Co., Research Division)

2025Q3: We are excited with the start and the broad interest in trying patients, including classical PKU patients. - Matthew Klein(CEO)

What metrics should we expect for the Sephience launch during Q3? Have you started receiving prescriptions, and which patient types are prioritized? - Tazeen Ahmad(BofA Securities, Research Division)

2025Q2: It's early days for the Sephience launch, but we're seeing positive feedback from healthcare providers and patients. - Matthew Klein(CEO)

Contradiction Point 2

Payer Coverage and Commercialization Strategy

It involves the company's strategic decisions around payer coverage and commercialization, impacting market access and revenue projections.

What is the timeline from initiation to patient access? - Brian Abrahams(RBC Capital Markets, Research Division)

2025Q3: We're seeing favorable payer policies, with timely fill times, averaging between 2 to 4 weeks, and no significant denials. - Eric Pauwels(CBO)

What is the current contracting status for Sephience and commercial payer coverage? Is a significant inventory build planned for the product launch? - Lut Ming Cheng(JPMorgan Chase & Co, Research Division)

2025Q2: Our meetings with payers have been productive, with minimal restrictions and few implementing step edits. - Eric Pauwels(CBO)

Contradiction Point 3

Pipeline and Clinical Trial Discussions with FDA

It involves the company's strategic discussions and alignment with the FDA on clinical trials and pipeline development, which can impact future product approvals and timelines.

Can you provide an update on coverage changes in Europe and the outlook for Japan? - Kyuwon Choi(Goldman Sachs Group, Inc., Research Division)

2025Q3: We're interested in CBER's interactions with AMT-130. There's potential alignment in rare disease understanding between CDER and CBER. We're encouraged by the possibility of alignment on our Huntington's disease program. - Matthew Klein(CEO)

What are your priorities for the trial design in discussions with the FDA for Huntington's disease? Will you have additional data to share at that time? - Kristen Kluska(Cantor Fitzgerald)

2025Q2: Our wish list for the trial design includes engaging with the FDA to discuss the design of the efficacy trial based on key learnings from the PIVOT-HD study. - Matthew B. Klein(CEO)

Contradiction Point 4

Launch and Market Response for SUFIANCE/PKU

It highlights differing perspectives on the market response and launch strategy for SUFIANCE/PKU, which is crucial for revenue projections and market positioning.

What is the timeline from a new start form to a patient receiving the drug? - Brian Abrahams (RBC Capital Markets, Research Division)

2025Q3: Our experienced PTC Cares team is processing start forms quickly. Eric Pauwels: We're seeing favorable payer policies, with timely fill times, averaging between 2 to 4 weeks, and no significant denials. - Matthew Klein(CEO), Eric Pauwels(CBO)

Can you discuss your progress in FDA discussions for SUFIANCE, and are patients inquiring about it ahead of a potential launch? What's driving this interest? - Kristen Kluska (Cantor Fitzgerald)

2025Q1: Eric Pauwels: Activity is through social media and the patient awareness website. Patients of all types, including those not on therapy, are reaching out. Social media activity and information updates drive interest. - Eric Pauwels(CBO)

Contradiction Point 5

Payer Engagement and Pricing Strategy for Sephience

It involves discrepancies in the company's communication regarding payer engagement and pricing strategy for Sephience, which impacts revenue and market positioning.

Is $350,000 per patient the correct net price benchmark? - Huidong Wang (Barclays Bank PLC, Research Division)

2025Q3: Eric Pauwels: The math is slightly off, as we’re in the early days, with various patient weights. We're within the expected range of $350,000 to $490,000. - Eric Pauwels(CBO)

Can you discuss the status of SUFIANCE's FDA discussions and whether patients are contacting doctors for information before a potential launch, and what's driving this interest? - Kristen Kluska (Cantor Fitzgerald)

2025Q1: Matthew Klein: We are through several rounds of legal negotiations and have gone through package insert discussions. We believe we are near the end and are confident that the FDA review is on track with no impact from recent changes. - Matthew Klein(CEO)