Summary of Conference Call Company and Industry - **Company**: PTC Therapeutics - **Industry**: Biotechnology, specifically focusing on treatments for neurodegenerative diseases and metabolic disorders such as Huntington's disease and Phenylketonuria (PKU) Key Points and Arguments Huntington's Disease Program 1. **Phase II Study Results**: The Phase II study for Huntington's disease met primary endpoints, demonstrating target engagement and safety, which supports moving to Phase III trials [3][4][11] 2. **Biomarker Data**: Data showed dose-dependent lowering of neurofilament light chain (NfL), indicating neuroprotection, and early signs of clinical effect were observed at 24 months [4][11] 3. **Regulatory Discussions**: Ongoing discussions with the FDA regarding the potential for accelerated approval based on Huntington protein lowering as a surrogate marker [10][15] 4. **KOL Feedback**: Key opinion leaders (KOLs) have responded positively, indicating strong support for the drug's safety and efficacy in lowering Huntington's protein [5][6] 5. **Future Steps**: Plans to gather additional data from ongoing studies to support an accelerated approval application while preparing for an efficacy trial [12][16] PKU Market and Product Launch 1. **Regulatory Progress**: Product discussions with the FDA have been productive, with expectations for timely approval ahead of the PDUFA date [19][20] 2. **Commercial Infrastructure**: The company has redeployed its existing sales force and added case managers to support patient and physician engagement [22][23] 3. **Market Strategy**: Targeting specialty centers and understanding KOL prescribing habits to maximize market penetration [25][30] 4. **Patient Engagement**: High enthusiasm from the patient community for the new treatment, emphasizing diet liberalization benefits [28][37] 5. **Launch Dynamics**: Anticipated rapid uptake post-approval, although throughput at treatment centers may limit initial patient access [34][36] Vutiquinone Regulatory Process 1. **Mid-Cycle Meeting**: The FDA does not expect an advisory committee meeting, and the review process is progressing well [38][39] Capital Allocation and Business Development 1. **Strong Financial Position**: The company has a balance sheet of approximately $2 billion, allowing for strategic investments without immediate pressure [40][41] 2. **Business Development Opportunities**: Actively looking for late-stage commercial and development-stage assets to complement internal pipeline [42][45] 3. **European Market Strategy**: Plans to maintain a narrow price corridor and leverage early access programs in Germany to facilitate market entry [47][48] Other Important Content - **Regulatory Environment**: The current administration is perceived to be open to accelerated approval pathways for neurodegenerative diseases, which may benefit PTC's programs [14][15] - **Market Segmentation**: The company is aware of different patient segments and is prepared to address the needs of classical PKU patients who have not previously received treatment [31][32] - **Long-term Market Potential**: The European market is expected to represent about 50% of the overall opportunity, with strategic pricing and market entry plans in place [47][48]

Summary of PTC Therapeutics Conference Call Company Overview - **Company**: PTC Therapeutics (PTCT) - **Industry**: Biotechnology, focusing on rare diseases and gene therapies Key Points and Arguments Executive Order and Market Position - The recent executive order has unclear ramifications for companies, but PTC Therapeutics expects minimal impact due to its revenue being more international than domestic [4][5] - The company is preparing for the launch of its PKU product, emphasizing a global pricing corridor to maintain product value [5][6] FDA Interactions - PTC has three applications pending with the FDA, with no significant impact from recent agency changes noted [10][12] - The PKU New Drug Application (NDA) is progressing well, with confidence in approval by the PDUFA date [11][12] Translarna Sales in Europe - Despite a negative opinion from the CHMP, PTC is pursuing a country-by-country strategy to commercialize Translarna, with about 50% of countries showing interest [16][17] - The company anticipates achieving 25-30% of European revenue for the year from Translarna [18][20] PKU Launch Strategy - PTC is ready for a global launch of its PKU product, with an early access program initiated in Germany [33][34] - The company has built a robust infrastructure to support the launch, including a patient services team to assist with prior authorizations and patient engagement [38][39] Competitive Landscape for PKU - There are approximately 17,000 individuals with PKU in the US, with a significant unmet need as 85-90% are not on current therapies [44][45] - PTC's PKU therapy is positioned as a better option compared to existing treatments, with a focus on diet liberalization and improved tolerability [47][50] Pricing Strategy - PTC plans to price its PKU therapy at a premium to Palynziq, justified by strong efficacy data and a favorable safety profile [54][55] - The company believes it could achieve a billion-dollar opportunity in the US alone with low double-digit market penetration [57][58] PTC 518 and Huntington's Disease - PTC 518 is positioned as a potential first-ever disease-modifying therapy for Huntington's disease, with promising early data [63][64] - The company is focused on understanding the optimal patient population for this therapy, emphasizing the importance of early-stage patients [66][68] Competitive Landscape for Huntington's Disease - PTC believes that its oral therapy will be more attractive than gene therapies due to its safety, tolerability, and ability to be administered early in the disease process [78][79] - The partnership with Novartis is expected to enhance commercialization efforts for PTC 518 [76][79] Additional Important Content - The company is optimistic about the global opportunity for its therapies, with plans for launches in Japan and other markets [59][61] - PTC is committed to addressing unmet needs in rare diseases, which is a key focus for its product development strategy [32][33]

Core Viewpoint - Pomerantz LLP is investigating potential securities fraud or unlawful business practices involving PTC Therapeutics, Inc. and its officers or directors [1] Group 1: Company Developments - On May 5, 2025, PTC announced results from the Phase 2 PIVOT-HD study of PTC518 (votoplam) in Stage 2 and Stage 3 Huntington's disease patients, which met its primary endpoint of reducing blood Huntingtin protein levels with a p-value of less than 0.0001 at Week 12 [3] - Analysts suggest that PTC may need to conduct a Phase 3 study to confirm whether the treatment effectively slows Huntington's disease [3] Group 2: Market Reaction - Following the announcement of the study results, PTC's stock price dropped by $9.30 per share, or 18.62%, closing at $40.65 per share on May 5, 2025 [4]

Core Viewpoint - PTC Therapeutics, Inc. is under investigation for potential securities fraud and unlawful business practices following the announcement of Phase 2 study results for its treatment of Huntington's disease, which led to a significant drop in stock price [1][2][3]. Group 1: Company Developments - PTC announced results from the Phase 2 PIVOT-HD study of PTC518 (votoplam) in Stage 2 and Stage 3 Huntington's disease patients, achieving its primary endpoint of reducing blood Huntingtin protein levels with a p-value of less than 0.0001 at Week 12 [2]. - Despite meeting the primary endpoint, analysts suggest that a Phase 3 study may be necessary to confirm the treatment's efficacy in slowing the progression of Huntington's disease [2]. Group 2: Market Reaction - Following the announcement of the study results, PTC's stock price fell by $9.30 per share, representing an 18.62% decline, closing at $40.65 per share on May 5, 2025 [3].

Financial Data and Key Metrics Changes - The company reported total product and royalty revenue of $190 million for Q1 2025, with a narrowed full-year revenue guidance of $650 million to $800 million [5][6][20] - The cash position at the end of Q1 was over $2 billion, providing resources for commercial and R&D efforts [5][10][20] Business Line Data and Key Metrics Changes - The DMD franchise generated $134 million in revenue, with Translarna contributing $86 million and Emflaza $48 million [12][20] - The company is preparing for the launch of SUFIANCE, with a positive CHMP opinion and expected broad label for PKU patients [6][16] Market Data and Key Metrics Changes - The company anticipates revenue from SUFIANCE in 2025, leveraging early access programs in Germany and other markets [6][37] - Approximately 58,000 addressable patients with PKU are expected to be targeted in the global launch [16] Company Strategy and Development Direction - The company aims to achieve cash flow breakeven through ramping up PKU commercial sales and pending FDA approvals [10][11] - Strategic focus on business development opportunities while maintaining a strong financial position [38] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing FDA review processes, indicating no expected delays [28][29] - The company is well-positioned to navigate global macro uncertainties, with minimal expected impact from tariffs and regulatory changes [97][99] Other Important Information - The company is actively engaging with healthcare providers and patients to prepare for the launch of SUFIANCE, emphasizing the importance of diet liberalization for PKU patients [17][31] - The FDA is conducting inspections for the Pitiquinone NDA, with no AdCom meeting planned, indicating a smooth review process [9][78] Q&A Session Summary Question: On SUFIANCE, what is the dynamic of patient inquiries? - Management noted that inquiries are coming from both therapy-naive patients and those who have tried other therapies, driven by social media engagement [24][25][29] Question: Expectations for SUFIANCE sales in Europe? - Management confirmed expectations for revenue in 2025 from early access programs in Germany and other countries [35][37] Question: Feedback from the nutritionist community regarding SUFIANCE? - Management highlighted the involvement of nutritionists in the launch plan, emphasizing their role in patient management [41][42] Question: Insights on Friedreich's ataxia and potential patient access? - Management indicated a significant unmet need for patients under 16 and expressed confidence in rapid uptake post-approval [80][82] Question: Impact of global macro factors on financial guidance? - Management stated minimal expected impact from tariffs and regulatory changes, maintaining confidence in their pricing strategy [97][99]

PART I—FINANCIAL INFORMATION [Item 1. Financial Statements (unaudited)](index=4&type=section&id=Item%201.%20Financial%20Statements) This section presents the company's unaudited consolidated financial statements and accompanying detailed notes [Consolidated Balance Sheets (unaudited)](index=9&type=section&id=Consolidated%20Balance%20Sheets) Consolidated Balance Sheet Highlights (in thousands) | Metric | March 31, 2025 | December 31, 2024 | Change ($k) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Cash and cash equivalents | $1,480,231 | $779,709 | $700,522 | 89.8% | | Marketable securities | $546,950 | $359,987 | $186,963 | 51.9% | | Total current assets | $2,316,406 | $1,365,531 | $950,875 | 69.6% | | Total assets | $2,655,387 | $1,705,024 | $950,363 | 55.7% | | Total liabilities | $2,841,147 | $2,803,095 | $38,052 | 1.4% | | Total stockholders' deficit | $(185,760) | $(1,098,071) | $912,311 | (83.1%) | [Consolidated Statements of Operations (unaudited)](index=10&type=section&id=Consolidated%20Statements%20of%20Operations) Consolidated Statements of Operations Highlights (Three Months Ended March 31, in thousands) | Metric | 2025 | 2024 | Change ($k) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Net product revenue | $153,426 | $177,604 | $(24,178) | (13.6%) | | Collaboration and license revenue | $986,231 | $— | $986,231 | 100% | | Royalty revenue | $36,439 | $31,154 | $5,285 | 17.0% | | Total revenues | $1,176,096 | $210,118 | $965,978 | 459.7% | | Total operating expenses | $205,871 | $255,571 | $(49,700) | (19.4%) | | Research and development | $108,973 | $116,129 | $(7,156) | (6.2%) | | Selling, general and administrative | $80,961 | $73,272 | $7,689 | 10.5% | | Net income (loss) attributable to common stockholders | $866,562 | $(91,576) | $958,138 | (1046.2%) | | Net income (loss) per share—diluted | $10.04 | $(1.20) | $11.24 | (936.7%) | [Consolidated Statements of Comprehensive Income (Loss) (unaudited)](index=11&type=section&id=Consolidated%20Statements%20of%20Comprehensive%20Income%20(Loss)) Consolidated Statements of Comprehensive Income (Loss) Highlights (Three Months Ended March 31, in thousands) | Metric | 2025 | 2024 | Change ($k) | | :--- | :--- | :--- | :--- | | Net income (loss) | $866,562 | $(91,576) | $958,138 | | Foreign currency translation gain (loss), net of tax | $12,025 | $(3,831) | $15,856 | | Comprehensive income (loss) | $878,499 | $(95,851) | $974,350 | [Consolidated Statements of Stockholders' Deficit (unaudited)](index=12&type=section&id=Consolidated%20Statements%20of%20Stockholders'%20Deficit) Consolidated Statements of Stockholders' Deficit Highlights (in thousands) | Metric | March 31, 2025 | December 31, 2024 | Change ($k) | | :--- | :--- | :--- | :--- | | Total stockholders' deficit | $(185,760) | $(1,098,071) | $912,311 | | Net income | $866,562 | — | $866,562 | | Share-based compensation expense | $18,060 | — | $18,060 | [Consolidated Statements of Cash Flows (unaudited)](index=13&type=section&id=Consolidated%20Statements%20of%20Cash%20Flows) Consolidated Statements of Cash Flows Highlights (Three Months Ended March 31, in thousands) | Metric | 2025 | 2024 | Change ($k) | | :--- | :--- | :--- | :--- | | Net cash provided by operating activities | $870,103 | $70,761 | $799,342 | | Net cash used in investing activities | $(184,360) | $(114,932) | $(69,428) | | Net cash provided by financing activities | $9,410 | $540 | $8,870 | | Net increase (decrease) in cash and cash equivalents | $700,546 | $(45,661) | $746,207 | | Cash and cash equivalents, and restricted cash end of period | $1,495,862 | $564,623 | $931,239 | [Notes to Consolidated Financial Statements (unaudited)](index=14&type=section&id=Notes%20to%20Consolidated%20Financial%20Statements) [1. The Company](index=14&type=section&id=1.%20The%20Company) - PTC Therapeutics is a global biopharmaceutical company focused on rare disorders, with a mission to provide access to best-in-class treatments for patients with limited options[28](index=28&type=chunk) - **Translarna** (nmDMD) marketing authorization in the EEA was not renewed as of March 28, 2025, but individual EU countries may allow continued commercial use; an NDA resubmitted to the FDA in July 2024 was accepted for review in October 2024[30](index=30&type=chunk)[31](index=31&type=chunk)[33](index=33&type=chunk) - **Emflaza** (DMD) orphan drug exclusivity for patients aged five years and older **expired in February 2024**, potentially impacting net product revenue, while exclusivity for patients aged two to less than five expires in June 2026[29](index=29&type=chunk)[195](index=195&type=chunk) - **Upstaza/Kebilidi** (AADC deficiency) received **FDA accelerated approval** in November 2024 and is marketed as Kebilidi in the United States[34](index=34&type=chunk)[196](index=196&type=chunk) - **Sepiapterin** (PKU) achieved its primary endpoint in a Phase 3 trial, received a **positive CHMP opinion** in April 2025, and has an FDA target action date of July 29, 2025[37](index=37&type=chunk)[201](index=201&type=chunk) - **PTC518** (Huntington's disease) Phase 2 study met primary endpoints, received **FDA Fast Track designation**, and a collaboration with Novartis closed in January 2025, including a **$1.0 billion upfront cash payment**[39](index=39&type=chunk)[40](index=40&type=chunk)[204](index=204&type=chunk) - **Vatiquinone** (Friedreich's ataxia) showed durable treatment benefit in long-term studies, and its NDA was granted **priority review** by the FDA with a target action date of August 19, 2025[41](index=41&type=chunk)[205](index=205&type=chunk) - The Company had an **accumulated deficit of approximately $2.8 billion** as of March 31, 2025, but expects to fund operations for at least the next twelve months[43](index=43&type=chunk) [2. Summary of significant accounting policies](index=18&type=section&id=2.%20Summary%20of%20significant%20accounting%20policies) - The Company operates as a single 'life science' operating and reporting segment, focusing on medicines for rare disorders[52](index=52&type=chunk)[53](index=53&type=chunk) - Collaboration and license revenue for Q1 2025 included **$989.8 million from the Novartis Agreement**, partially offset by a $3.6 million refund for a prior collaboration[177](index=177&type=chunk) - Inventory write-downs of **$3.5 million** and **$3.7 million** were recorded for the three months ended March 31, 2025 and 2024, respectively[59](index=59&type=chunk) - The liability for sale of future royalties is amortized using the effective interest method, with an effective interest rate of **9.3%** as of March 31, 2025[142](index=142&type=chunk) - Changes to IRC Section 174 requiring R&D capitalization are anticipated to increase current taxable income by **$45.3 million** for the year ending December 31, 2025[77](index=77&type=chunk)[78](index=78&type=chunk) Restricted Cash (in thousands) | Metric | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Restricted cash included in deposits and other assets | $15,631 | $15,607 | [3. Leases](index=32&type=section&id=3.%20Leases) Lease Liabilities (in thousands) | Metric | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Finance lease liabilities- current | $5,047 | $3,000 | | Finance lease liabilities- noncurrent | $13,833 | $15,574 | Operating Lease Costs (Three Months Ended March 31, in thousands) | Metric | 2025 | 2024 | | :--- | :--- | :--- | | Total operating lease cost | $5,041 | $6,858 | Weighted-Average Lease Terms and Discount Rates (as of March 31, 2025) | Metric | Value | | :--- | :--- | | Weighted-average remaining lease terms - operating leases (years) | 11.48 | | Weighted-average discount rate - operating leases | 7.60% | | Weighted-average remaining lease terms - finance lease (years) | 7.76 | | Weighted-average discount rate - finance lease | 7.80% | [4. Fair value of financial instruments and marketable securities](index=34&type=section&id=4.%20Fair%20value%20of%20financial%20instruments%20and%20marketable%20securities) - The fair value of the 2026 Convertible Notes was **$340.6 million** as of March 31, 2025, and **$321.3 million** as of December 31, 2024[111](index=111&type=chunk) - Contingent consideration payable was **written down to zero** as of March 31, 2025, as the probability of triggering the remaining consideration was determined to be remote[112](index=112&type=chunk) Fair Value of Financial Assets (March 31, 2025, in thousands) | Asset Category | Total Fair Value | Level 1 | Level 2 | Level 3 | | :--- | :--- | :--- | :--- | :--- | | Marketable securities - available for sale | $518,763 | $— | $518,763 | $— | | Marketable securities - equity investments | $28,187 | $28,187 | $— | $— | | ClearPoint Equity Investments | $10,637 | $10,637 | $— | $— | [5. Accounts payable and accrued expenses](index=41&type=section&id=5.%20Accounts%20payable%20and%20accrued%20expenses) - Bad debt expense for the three months ended March 31, 2025, was **$1.9 million**, compared to an immaterial amount for the same period in 2024[72](index=72&type=chunk) Accounts Payable and Accrued Expenses (in thousands) | Category | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Total Accounts payable and accrued expenses | $317,807 | $304,292 | | Income tax payable | $64,622 | $4,701 | | Milestone payable | $— | $11,025 | [6. Capitalization](index=41&type=section&id=6.%20Capitalization) - As of March 31, 2025, **$93.0 million of common stock remains available** for issuance under the At the Market Offering Sales Agreement, with no shares sold in Q1 2025 or Q1 2024[114](index=114&type=chunk) [7. Net income (loss) per share](index=41&type=section&id=7.%20Net%20income%20(loss)%20per%20share) Net Income (Loss) Per Share (Three Months Ended March 31) | Metric | 2025 | 2024 | | :--- | :--- | :--- | | Net income (loss) per common share, basic | $11.09 | $(1.20) | | Net income (loss) per common share, diluted | $10.04 | $(1.20) | | Weighted-average common shares outstanding, diluted | 86,385,922 | 76,496,127 | [8. Stock award plan](index=43&type=section&id=8.%20Stock%20award%20plan) - As of March 31, 2025, **4,984,677 shares** were available under the Amended 2013 LTIP, and **1,894,422 shares** under the 2020 Inducement Stock Incentive Plan[120](index=120&type=chunk)[124](index=124&type=chunk) - During Q1 2025, **802,745 stock options** were issued with a weighted average grant date fair value of **$25.24 per share**[126](index=126&type=chunk)[127](index=127&type=chunk) - During Q1 2025, **1,537,675 restricted stock units** were issued[129](index=129&type=chunk) - Approximately **$170.3 million of total unrecognized compensation cost** remains, expected to be recognized over approximately 2.9 years[132](index=132&type=chunk) Share-Based Compensation Expense (Three Months Ended March 31, in thousands) | Category | 2025 | 2024 | | :--- | :--- | :--- | | Research and development | $8,663 | $8,967 | | Selling, general and administrative | $9,397 | $9,411 | | **Total** | **$18,060** | **$18,378** | [9. Debt](index=48&type=section&id=9.%20Debt) - The Company has sold **90.49%** of its right to receive Evrysdi royalties to Royalty Pharma for a total of **$1.9 billion** in upfront cash consideration[141](index=141&type=chunk) - The Company retains **9.51%** of the Evrysdi royalty, which increases to **16.67%** after the assigned royalty cap is met[141](index=141&type=chunk) - The 2026 Convertible Notes bear cash interest at **1.50% per year** and mature on September 15, 2026[143](index=143&type=chunk)[151](index=151&type=chunk) Liability for Sale of Future Royalties (in thousands) | Metric | March 31, 2025 | | :--- | :--- | | Beginning balance as of December 31, 2024 | $2,081,776 | | Less: Non-cash royalty revenue payable to Royalty Pharma | $(32,974) | | Plus: Non-cash interest expense recognized | $49,661 | | **Ending balance** | **$2,098,463** | | Effective interest rate as of March 31, 2025 | 9.3% | 2026 Convertible Notes (in thousands) | Metric | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Principal | $287,500 | $287,500 | | Net carrying amount | $285,712 | $285,412 | [10. Commitments and contingencies](index=54&type=section&id=10.%20Commitments%20and%20contingencies) - Potential sales milestones for **Upstaza/Kebilidi of $50.0 million** are deemed remote, and contingent consideration for FA and Angelman syndrome is not expected to be achieved[155](index=155&type=chunk) - Under the Censa Merger Agreement, **$95.0 million** of development and regulatory milestones for sepiapterin have been paid, with up to **$109.0 million** for new indications and **$160.0 million** in sales milestones remaining[158](index=158&type=chunk) - The Company is not currently aware of any material legal proceedings against it[161](index=161&type=chunk) [11. Revenue recognition](index=56&type=section&id=11.%20Revenue%20recognition) - **Translarna** net revenues outside the US were **$86.2 million** in Q1 2025, down from $103.6 million in Q1 2024, primarily due to the timing of bulk patient orders[164](index=164&type=chunk)[254](index=254&type=chunk) - **Collaboration and license revenue increased by $986.2 million** in Q1 2025, driven by the **$1.0 billion upfront payment** from the Novartis Agreement for the PTC518 HD program[171](index=171&type=chunk)[177](index=177&type=chunk)[255](index=255&type=chunk) - **Royalty revenue from Evrysdi sales increased by 17%** to $36.4 million in Q1 2025 from $31.2 million in Q1 2024[170](index=170&type=chunk)[256](index=256&type=chunk) - Manufacturing revenue was **$0** in Q1 2025, down from $1.4 million in Q1 2024, as the gene therapy manufacturing business was sold in June 2024[178](index=178&type=chunk)[179](index=179&type=chunk)[257](index=257&type=chunk)[258](index=258&type=chunk) Net Product Sales (Three Months Ended March 31, in millions) | Region | 2025 | 2024 | | :--- | :--- | :--- | | Outside United States | $105.6 | $120.1 | | United States (Emflaza) | $47.8 | $57.5 | [12. Intangible assets and goodwill](index=60&type=section&id=12.%20Intangible%20assets%20and%20goodwill) - Amortization expense **decreased significantly to $3.8 million** in Q1 2025 from $51.5 million in Q1 2024, as the Emflaza rights intangible asset was fully amortized as of February 2024[182](index=182&type=chunk)[260](index=260&type=chunk) - The weighted average remaining amortization period for definite-lived intangibles was **8.9 years** as of March 31, 2025[182](index=182&type=chunk) - Goodwill remained unchanged at **$82.3 million** as of March 31, 2025[183](index=183&type=chunk) Definite-Lived Intangible Assets, Net (in thousands) | Metric | March 31, 2025 | | :--- | :--- | | Total definite-lived intangibles, net | $118,448 | [13. Segment information](index=62&type=section&id=13.%20Segment%20information) - The Company operates as a single 'life science' segment[185](index=185&type=chunk) Segment Net Income (Loss) (Three Months Ended March 31, in thousands) | Metric | 2025 | 2024 | | :--- | :--- | :--- | | Total revenues | $1,176,096 | $210,118 | | Segment Net Income (Loss) | $866,562 | $(91,576) | [14. Subsequent events](index=62&type=section&id=14.%20Subsequent%20events) - No material subsequent events impacting the consolidated financial statements or disclosures were identified through the filing date[186](index=186&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=63&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's financial condition, operational results, liquidity, and key corporate updates [Our Company](index=63&type=section&id=Our%20Company) - PTC Therapeutics is a global biopharmaceutical company focused on discovering, developing, and commercializing clinically differentiated medicines for rare disorders[189](index=189&type=chunk) [Corporate Updates](index=63&type=section&id=Corporate%20Updates) - **Translarna's** conditional marketing authorization in the EEA was **not renewed** by the European Commission on March 28, 2025[193](index=193&type=chunk) - The FDA accepted the resubmission of the New Drug Application for **Translarna** for nmDMD in October 2024[194](index=194&type=chunk) - **Emflaza's** orphan drug exclusivity for patients five years and older **expired in February 2024**, which is expected to have a significant negative impact on net product revenue[195](index=195&type=chunk) - The FDA granted **accelerated approval** for the gene therapy for AADC deficiency in November 2024, marketed as **Kebilidi** in the United States[196](index=196&type=chunk) - The CHMP issued a **positive opinion** on the Marketing Authorization Application for **Sephience™ (sepiapterin)** for PKU in April 2025[201](index=201&type=chunk) - The Phase 2 study of **PTC518** for Huntington's disease met its primary endpoints, and the collaboration with Novartis closed in January 2025, providing a **$1.0 billion upfront payment**[204](index=204&type=chunk)[210](index=210&type=chunk) - The FDA accepted the NDA for **vatiquinone** for Friedreich's ataxia in February 2025, granting **priority review** with a target action date of August 19, 2025[205](index=205&type=chunk) [Financial operations overview](index=73&type=section&id=Financial%20operations%20overview) - Net product revenues primarily consist of sales of **Translarna** outside the U.S. and **Emflaza** in the U.S[221](index=221&type=chunk)[222](index=222&type=chunk) - Collaboration and license revenue for Q1 2025 included **$989.8 million from the Novartis Agreement**[231](index=231&type=chunk) - Research and development expenses **decreased by $7.2 million (6%)** to $109.0 million in Q1 2025[238](index=238&type=chunk)[239](index=239&type=chunk)[261](index=261&type=chunk) - Selling, general and administrative expenses **increased by $7.7 million (10%)** to $81.0 million in Q1 2025[248](index=248&type=chunk)[262](index=262&type=chunk) - Interest expense, net **decreased by $6.7 million (17%)** to $34.1 million in Q1 2025, primarily due to increased investment income[249](index=249&type=chunk)[265](index=265&type=chunk) - No material changes to critical accounting policies were reported during the three months ended March 31, 2025[251](index=251&type=chunk) [Results of operations](index=81&type=section&id=Results%20of%20operations) - The decrease in net product revenue was primarily due to a **17% decrease in Emflaza sales ($9.7 million)** and a **17% decrease in Translarna sales ($17.4 million)**[254](index=254&type=chunk) - Amortization of acquired intangible assets **decreased significantly by 93%** due to the Emflaza rights intangible asset being fully amortized as of February 2024[260](index=260&type=chunk) - The increase in income tax expense was attributable to the recognition of revenue associated with the **Novartis Agreement**[267](index=267&type=chunk) Revenue Comparison (Three Months Ended March 31, in thousands) | Metric | 2025 | 2024 | Change ($k) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Net product revenue | $153,426 | $177,604 | $(24,178) | (13.6%) | | Collaboration and license revenue | $986,231 | $— | $986,231 | 100% | | Royalty revenue | $36,439 | $31,154 | $5,285 | 17.0% | | Manufacturing revenue | $— | $1,360 | $(1,360) | (100%) | | **Total revenues** | **$1,176,096** | **$210,118** | **$965,978** | **459.7%** | Expense Comparison (Three Months Ended March 31, in thousands) | Metric | 2025 | 2024 | Change ($k) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Cost of product, collaboration and license sales (excl. amortization) | $12,862 | $14,740 | $(1,878) | (12.7%) | | Amortization of acquired intangible assets | $3,798 | $51,530 | $(47,732) | (92.6%) | | Research and development expense | $108,973 | $116,129 | $(7,156) | (6.2%) | | Selling, general and administrative expense | $80,961 | $73,272 | $7,689 | 10.5% | | Change in the fair value of contingent consideration | $(800) | $(100) | $(700) | (700%) | | Tangible asset impairment and losses on transactions, net | $77 | $— | $77 | 100% | | Interest expense, net | $(34,092) | $(40,834) | $6,742 | 16.5% | | Other (expense) income, net | $(6,305) | $1,591 | $(7,896) | (496.3%) | | Income tax expense | $(63,266) | $(6,880) | $(56,386) | (819.6%) | [Liquidity and capital resources](index=85&type=section&id=Liquidity%20and%20capital%20resources) - As of March 31, 2025, the Company had **$2.03 billion in cash, cash equivalents, and marketable securities**[277](index=277&type=chunk) - Net cash provided by operating activities was **$870.1 million** for Q1 2025, primarily driven by the **$1.0 billion upfront payment** from the Novartis Agreement[278](index=278&type=chunk) - The Company expects existing cash and cash flows to be **sufficient to fund operations for at least the next twelve months**[282](index=282&type=chunk) - Future funding requirements include significant expenses for commercialization, ongoing R&D, and potential milestone payments[281](index=281&type=chunk)[284](index=284&type=chunk)[285](index=285&type=chunk) - Expected milestone payments include **$57.5 million in 2025** for sepiapterin and **$75.0 million in 2026** for vatiquinone[288](index=288&type=chunk)[289](index=289&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=93&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) No material changes in market risk or its management were reported for the period ended March 31, 2025 - No material changes in market risk or how market risk is managed were reported during the three months ended March 31, 2025[293](index=293&type=chunk) [Item 4. Controls and Procedures](index=95&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls were effective and no material changes to internal controls occurred - The Chief Executive Officer and Chief Financial Officer concluded that the company's **disclosure controls and procedures were effective** at the reasonable assurance level as of March 31, 2025[296](index=296&type=chunk) - **No change in internal control over financial reporting** occurred during the quarter ended March 31, 2025, that materially affected, or is reasonably likely to materially affect, internal control over financial reporting[297](index=297&type=chunk) PART II—OTHER INFORMATION [Item 1. Legal Proceedings](index=95&type=section&id=Item%201.%20Legal%20Proceedings) The company reports no material legal proceedings to which it is currently a party - The Company is not currently aware of any material legal proceedings to which it is a party or of which any of its property is subject[299](index=299&type=chunk) [Item 1A. Risk Factors](index=95&type=section&id=Item%201A.%20Risk%20Factors) This section refers to the comprehensive risk factors detailed in the company's 2024 Annual Report - Readers are referred to Item 1A of the Annual Report on Form 10-K for the year ended December 31, 2024, for a more complete understanding of risks concerning the Company[300](index=300&type=chunk) [Item 5. Other Information](index=95&type=section&id=Item%205.%20Other%20Information) This section details the adoption of Rule 10b5-1 trading arrangements by two company directors Director and Officer Trading Arrangements (Q1 2025) | Name (Title) | Action Taken (Date) | Type of Trading Arrangement | Nature of Trading Arrangement | Aggregate Number of Securities | | :--- | :--- | :--- | :--- | :--- | | Allan Jacobson (Director) | Adoption (March 12, 2025) | Rule 10b5-1 trading arrangement | Sale | Up to 38,000 shares | | Emma Reeve (Director) | Adoption (March 4, 2025) | Rule 10b5-1 trading arrangement | Sale | Up to 85,733 shares | [Item 6. Exhibits](index=98&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Quarterly Report, including certifications and XBRL data - Exhibits include certifications from the Principal Executive Officer and Principal Financial Officer (31.1, 31.2, 32.1, 32.2) and Inline XBRL documents (101.INS, SCH, CAL, LAB, PRE, DEF, 104)[305](index=305&type=chunk)

Financial Data and Key Metrics Changes - The company reported total product and royalty revenue of $190 million for Q1 2025, with a narrowed full-year revenue guidance of $650 million to $800 million [4][5][20] - Cash, cash equivalents, and marketable securities totaled over $2 billion as of March 31, 2025, providing resources for commercial and R&D efforts [10][20] Business Line Data and Key Metrics Changes - The DMD franchise generated $134 million in revenue, with Translarna contributing $86 million and Emflaza contributing $48 million [12][20] - The company expects to see revenue from the SUFIANCE launch in 2025, with preparations underway for its European launch following a positive CHMP opinion [5][15] Market Data and Key Metrics Changes - The company is prioritizing launches in Germany, the US, and Japan for SUFIANCE, with an addressable patient population of approximately 58,000 for PKU [16][17] - The company continues to receive orders for Translarna in Latin America, the Commonwealth of Independent States, and the Middle East and North Africa regions [13] Company Strategy and Development Direction - The company aims to achieve cash flow breakeven through ramping up PKU commercial sales and pending FDA approval applications [10][11] - The company is actively exploring business development opportunities while maintaining a strong financial position [39][40] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing FDA review processes for SUFIANCE and other applications, noting no impact from recent FDA changes [7][28] - The company highlighted strong patient interest and engagement through social media, indicating a positive environment for upcoming product launches [29][30] Other Important Information - The company reported positive top-line results for the PIVOT HT Phase 2 study for Huntington's disease, meeting primary endpoints [9] - The company is preparing for potential accelerated approval for PTC518 based on favorable data [10] Q&A Session Summary Question: On SUFIANCE, what is the dynamic of patient inquiries? - Management noted that inquiries are coming from both therapy-naive patients and those who have tried other therapies, driven by social media engagement [24][30] Question: Expectations for SUFIANCE revenue in Europe? - Management confirmed expectations for revenue in 2025 from early access programs in Germany and other European countries [36][38] Question: Feedback from the nutritionist community regarding SUFIANCE? - Management indicated that nutritionists are closely involved in the launch plan, emphasizing the importance of diet management for PKU patients [42][43] Question: Impact of global macro factors on financial guidance? - Management stated minimal expected impact from tariffs and other macro factors, maintaining confidence in their pricing strategy [95][100] Question: Patient population breakdown for Vetiquinone? - Management estimated that about one-third of the 6,000 patients with Friedreich's ataxia in the US would be pediatric patients [104]

Revenue and Financial Performance - Total net product and royalty revenue for Q1 2025 was $190 million, compared to $208.8 million in Q1 2024[8]. - Revenue from the DMD franchise in Q1 2025 was $134 million, with Translarna™ generating $86 million and Emflaza® generating $48 million[4]. - Net income for Q1 2025 was $866.6 million, compared to a net loss of $91.6 million in Q1 2024[8]. - PTC anticipates full-year 2025 revenue to be between $650 million and $800 million, including in-line products and potential new product launches[8]. - Cash, cash equivalents, and marketable securities totaled $2.03 billion as of March 31, 2025, up from $1.14 billion at the end of 2024[8]. - Full-year 2025 GAAP R&D and SG&A expenses are projected to be between $805 million and $835 million[8]. Research and Development - GAAP R&D expenses for Q1 2025 were $109 million, down from $116 million in Q1 2024[8]. - PTC518 Phase 2 study met primary endpoint of dose-dependent blood HTT lowering at Week 12, with favorable safety and tolerability[4]. - The NDA for pediatric and adult patients with Friedreich's ataxia has been accepted and granted Priority Review by the FDA, with a target action date of August 19, 2025[4]. Regulatory and Market Approvals - Positive CHMP opinion for Sephience™ received on April 25, 2025, with an expected EC adoption in approximately two months[4]. - PTC's marketing authorization for Translarna in Brazil, Russia, and other regions is under scrutiny due to potential risks in pricing and reimbursement negotiations[21]. - The company is relying on results from Study 041, an 18-month clinical trial, to support marketing approval for Translarna in the United States[21]. Collaborations and Commercialization - PTC has a collaboration agreement with Novartis, which includes development, regulatory, and sales milestone payments, as well as profit sharing and royalties[21]. - Expectations for Upstaza/Kebilidi include commercialization and achieving sales milestones, with potential contingent payments[21]. - The commercialization of Evrysdi under PTC's SMA collaboration is anticipated, along with Tegsedi and Waylivra[21]. Risks and Strategic Considerations - PTC faces significant risks in the development and regulatory approval of its products, including Translarna, Emflaza, and vatiquinone[23]. - The company emphasizes the importance of considering various risk factors that could impact its business and financial performance[21]. - PTC's ability to secure adequate financing for operating expenses and capital expenditures is critical for its future operations[21]. - The eligible patient base and commercial potential of PTC's products are key considerations for the company's growth strategy[21]. - PTC does not guarantee that any of its products will achieve commercial success or maintain regulatory approval[23].

Core Insights - PTC Therapeutics reported strong revenue performance of $190 million for the first quarter of 2025, with a significant cash position exceeding $2 billion as of March 31, 2025, supporting ongoing commercial and R&D activities [1][8]. Financial Performance - Total net product and royalty revenue for Q1 2025 was $190 million, a decrease from $208.8 million in Q1 2024 [5]. - Revenue from the DMD franchise was $134 million, with Translarna™ contributing $86 million and Emflaza® contributing $48 million [5]. - Collaboration and license revenue included $986.2 million from the PTC518 agreement with Novartis, which closed in January 2025 [5][7]. - Net income for Q1 2025 was $866.6 million, compared to a net loss of $91.6 million in Q1 2024 [8]. Regulatory and Clinical Updates - Positive CHMP opinion for Sephience™ (sepiapterin) received on April 25, 2025, with an expected European Commission adoption in approximately two months [5]. - NDA for Sephience is under review by the FDA, with a target action date of July 29, 2025 [5]. - NDA for vatiquinone accepted and granted Priority Review by the FDA, with a target action date of August 19, 2025 [5]. - Phase 2 PIVOT-HD study for PTC518 met primary endpoint of dose-dependent blood HTT lowering at Week 12, with favorable safety and tolerability [5]. Guidance and Future Outlook - PTC anticipates full-year 2025 revenue between $650 million and $800 million, including in-line products and potential new launches [8]. - Full-year 2025 GAAP R&D and SG&A expenses are projected to be between $805 million and $835 million [8]. - Non-GAAP R&D and SG&A expenses are expected to be between $730 million and $760 million, excluding estimated non-cash, stock-based compensation of $75 million [8].

Core Insights - PTC Therapeutics announced results from the Phase 2 PIVOT-HD study of PTC518 (votoplam) for Huntington's disease, achieving its primary endpoint of reducing blood HTT protein levels with significant statistical significance [1][2] Study Results - The study demonstrated a reduction in blood HTT protein levels of 23% at the 5mg dose and 39% at the 10mg dose for Stage 2 patients, while Stage 3 patients showed a 36% reduction at the 10mg dose [4] - The treatment exhibited favorable safety and tolerability across all dose levels and disease stages, with no serious adverse events reported [5] Clinical Implications - There were observed dose-dependent trends in clinical scales for Stage 2 patients, including improvements in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) and Total Motor Score (TMS) [4] - For Stage 3 patients, the 5mg dose showed favorable trends compared to placebo, indicating potential differences in treatment effects between stages [5] Long-term Data - 24-month treatment data indicated dose-dependent trends on cUHDRS, Total Function Capacity (TFC), and Symbol Digit Modalities Test (SDMT) subscales, with a notable lowering of plasma NfL levels at both 5mg and 10mg doses [6] Market Reaction - Following the announcement, PTC Therapeutics' stock fell by 18.60% to $40.65, reflecting investor concerns regarding the differing treatment effects observed in Stage 3 patients [5][7]