PTC Therapeutics, Inc. (NASDAQ:PTCT) Q3 2023 Earnings Conference Call February 8, 2023 9:00 AM ET Company Participants Jane Hanlon - Associate Director, Investor Relations Matthew Klein - Chief Executive Officer Eric Pauwels - Chief Business Officer Kylie O'Keefe - Chief Commercial Officer Pierre Gravier - Chief Financial Officer Conference Call Participants Eric Joseph - J.P. Morgan Kristen Kluska - Cantor Fitzgerald Samantha Corwin - William Blair David Lebowitz - Citi Brian Abrahams - RBC Capital Markets ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☑ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2023 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-35969 PTC Therapeutics, Inc. (Exact name of registrant as specified in its charter) (State or other juris ...

Financial Data and Key Metrics Changes - The company reported total revenue of $214 million for the second quarter of 2023, representing a 29% increase compared to the same quarter in 2022 [46] - The DMD franchise revenue totaled $162 million, reflecting a 21% year-over-year growth [55][75] - Non-GAAP R&D expenses were $170 million for the second quarter of 2023, up from $143 million in the same quarter of 2022 [90] Business Line Data and Key Metrics Changes - Translarna generated $96 million in revenue, a 25% increase over the same quarter in 2022 [84] - Emflaza achieved net product revenue of $66 million, representing a 16% growth compared to the second quarter of 2022 [85] - The APHENITY trial for sepiapterin in PKU patients met its primary endpoint with a 63% reduction in blood phenylalanine levels [77] Market Data and Key Metrics Changes - Evrysdi's global revenue for the second quarter was approximately $380 million, with PTC earning $37 million in royalties [63] - The company expects continued growth in the Latin American and Eastern European markets, despite unpredictability in large government orders [28][56] Company Strategy and Development Direction - The company is focused on launching sepiapterin in the US and Europe, with expectations of a $1 billion-plus global commercial opportunity [49][88] - A strategic portfolio review has led to a reduction in operational expenses, with anticipated savings of approximately $150 million in 2024 [76] - The company plans to submit an NDA for sepiapterin in the fourth quarter of 2023 following a pre-NDA meeting with the FDA [77] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving the revenue guidance of $940 million to $1 billion for 2023, which would represent a year-over-year growth of 34% to 43% [75][116] - The company remains optimistic about the potential for Translarna to convert from conditional to standard marketing authorization in Europe [11][52] - Management highlighted the importance of the upright stability subscale in the mFARS scale as a predictor of time to loss of ambulation in Friedreich ataxia [120] Other Important Information - The company has approximately $338 million in cash, cash equivalents, and marketable securities as of June 30, 2023 [117] - The company is well-positioned for multiple product launches, leveraging its existing infrastructure and expertise [123] Q&A Session Summary Question: Clarity on CHMP opinion for Translarna - Management explained that the initial timing for the CHMP opinion was pushed to the third quarter due to additional questions during the review process [10] Question: Capital deployment strategy with $330 million in cash - Management indicated that they are well-capitalized to support upcoming product launches and maintain a robust discovery and development infrastructure [13] Question: Main questions for the PKU pre-NDA meeting - The focus will be on the structure of the NDA and ensuring alignment with the FDA on clinical and safety data [18] Question: Potential decline in Duchenne revenue guidance - Management acknowledged the unpredictability of large orders but expressed confidence in achieving growth despite potential fluctuations [30] Question: Overlap in physician communities for Huntington's disease - Management noted the recognition of the splicing platform's power and the importance of leveraging learnings from previous product launches [20]

Financial Performance - Translarna generated $96.5 million in net sales during the quarter ended June 30, 2023[214]. - Emflaza recognized $65.7 million in net sales for the same quarter[214]. - Net product revenues for the three months ended June 30, 2023, were $174.6 million, an increase of $30.9 million, or 21%, from $143.7 million for the same period in 2022, driven by sales of Translarna and Emflaza[278]. - Net product sales for the three months ended June 30, 2023, were $108.9 million outside the U.S., up from $86.9 million in 2022, with Translarna contributing $96.5 million[248]. - Net product sales in the United States for the six months ended June 30, 2023, were $120.3 million, compared to $105.4 million in 2022, solely from Emflaza sales[250]. - Net product revenues for the six months ended June 30, 2023, were $362.1 million, an increase of $88.6 million, or 32%, from $273.5 million for the same period in 2022, driven by Translarna and Emflaza sales[294]. - Royalty revenue increased to $36.9 million for the three months ended June 30, 2023, up $15.0 million, or 69%, from $21.8 million in the same period of 2022, primarily due to higher Evrysdi sales[279]. - Royalty revenue for the six months ended June 30, 2023, was $67.7 million, an increase of $27.0 million, or 66%, from $40.7 million for the same period in 2022, due to higher Evrysdi sales[297]. Research and Development - Sepiapterin achieved a 63% reduction in blood Phe levels in the overall primary analysis population during its Phase 3 trial[228]. - PTC518 demonstrated a mean 30% reduction in mutant HTT levels at the 10mg dose level in its Phase 2 study[226]. - Vatiquinone did not meet its primary endpoint in the Phase 3 trial for Friedreich ataxia, but showed significant benefits in secondary endpoints and was well tolerated[229]. - The Phase 2/3 trial of vatiquinone for children with mitochondrial disease associated seizures was deprioritized after failing to achieve its primary endpoint[229]. - Utreloxastat was well tolerated in a Phase 1 trial and a Phase 2 trial for amyotrophic lateral sclerosis is ongoing[229]. - Unesbulin is in a registration-directed Phase 2/3 trial for leiomyosarcoma, with plans for a similar trial for diffuse intrinsic pontine glioma[230]. - Research and development expenses for the six months ended June 30, 2023, totaled $380.998 million, an increase from $297.341 million in 2022[268]. - Research and development expenses were $185.9 million for the three months ended June 30, 2023, an increase of $28.6 million, or 18%, from $157.3 million for the same period in 2022, related to the advancement of the clinical pipeline[285]. Regulatory and Market Authorization - Upstaza received marketing authorization in the EEA for patients 18 months and older in July 2022[221]. - Evrysdi was approved by the FDA for SMA treatment in August 2020 and received a label expansion for infants under two months in May 2022[225]. - Translarna's marketing authorization in the EEA is subject to annual review and renewal, with a decision expected in Q3 2023[215]. - The company is preparing to submit a BLA for Upstaza to the FDA in Q3 2023[223]. - The conditional marketing authorization for Translarna is pending the completion of a Type II variation process[217]. - The company anticipates submitting a BLA to the FDA for Upstaza in Q3 2023 and an NDA for sepiapterin in Q4 2023, pending FDA feedback[327]. Financial Position and Cash Flow - As of June 30, 2023, the company reported a net loss of $337.8 million, compared to a net loss of $278.8 million for the same period in 2022[241]. - The company has an accumulated deficit of $2,994.8 million as of June 30, 2023[241]. - Cash, cash equivalents, and marketable securities totaled $337.9 million as of June 30, 2023[321]. - Net cash used in operating activities was $43.6 million for the six months ended June 30, 2023, compared to $152.6 million for the same period in 2022[324]. - Net cash used in investing activities was $52.7 million for the six months ended June 30, 2023, compared to a net cash provided of $121.3 million for the same period in 2022[325]. Strategic Initiatives and Workforce - The company announced an 8% workforce reduction in May 2023 as part of a strategic pipeline prioritization[232]. - The company is focused on maintaining orphan exclusivity in the U.S. for Emflaza and completing post-marketing requirements imposed by regulatory agencies[337]. - The company is advancing its splicing, metabolic, Bio-e, and oncology programs, with ongoing studies for maintaining authorizations and label extensions[337]. - The company is exploring collaborations, including with Roche and the SMA Foundation, to obtain research funding and achieve milestones[337]. Risks and Future Outlook - The company has never been profitable and will need to generate significant revenues to achieve and sustain profitability, requiring substantial additional funding for continuing operations[341]. - The company anticipates financing cash needs primarily through equity offerings, debt financings, collaborations, and grants, with potential dilution of shareholder ownership interest[341]. - The company faces risks related to unexpected decreases in revenue or increases in expenses due to the COVID-19 pandemic or other contagious disease outbreaks[337]. - The company must satisfy obligations under the Blackstone Credit Agreement and the indentures governing the 2026 Convertible Notes, with annual cash interest payments of $4.3 million required[336].

Summary of PTC Therapeutics PKU Deep Dive Conference Call Company Overview - PTC Therapeutics is a global biopharmaceutical company focused on innovative therapies for rare disorders, with a robust commercial portfolio of six marketed products, five of which are global, and one generating collaboration and royalty revenue [5][6] - The company aims to achieve total revenue guidance of $940 million to $1 billion for 2023, including $545 million to $565 million from DMD revenue [6] Product Focus: Sepiaterin for PKU - The primary focus of the call is on sepiaterin, a treatment for phenylketonuria (PKU) [8] - The Phase 3 APHINITY trial showed a 63% reduction in blood phenylalanine levels in the overall primary analysis population and 69% in classical PKU patients, with a p-value of less than 0.0001, indicating statistical significance [9][10] - 84% of patients achieved target phenylalanine levels below 360 micromoles per liter, and 93% of adolescents and adults achieved levels below 600 micromoles per liter [10] - Sepiaterin was well tolerated with no serious adverse events reported [9] Clinical Insights - PKU is caused by variants in the PAH gene, leading to impaired PAH function and elevated phenylalanine levels, which can have neurological consequences [17][19] - Current treatments, Kuvan and Palynziq, have limitations, including low response rates and safety concerns, highlighting the need for new therapies like sepiaterin [30][32][39] - Sepiaterin offers mechanistic advantages, including better absorption and bioavailability compared to existing treatments, and has shown potential to treat a broader patient population, including those with classical PKU [35][39] Unmet Needs and Market Opportunity - Less than 10% of diagnosed PKU patients are well-controlled on Kuvan, with around 70% of patients trialed on Kuvan not responding adequately [41] - The patient journey begins with newborn screening, and the need for lifelong dietary restrictions significantly impacts quality of life, leading to social isolation and mental health issues [42][43][44] - The potential market opportunity for sepiaterin is estimated to be between $1 billion and $1.5 billion, targeting 15% to 30% of the global PKU population [62][73] Commercial Strategy - PTC Therapeutics has established relationships with key opinion leaders and treatment centers, positioning itself for a successful launch of sepiaterin [63][68] - The company plans to differentiate sepiaterin through its data package, mechanistic advantages, and support for the PKU community [72] - The launch strategy includes targeting therapy-naive patients, those who have failed Kuvan, and patients inadequately controlled on existing therapies [61][70] Conclusion - Sepiaterin represents a significant advancement in the treatment of PKU, with strong clinical data supporting its efficacy and safety [39][60] - The company is preparing for regulatory submissions and anticipates a successful commercial launch, aiming to address the substantial unmet needs in the PKU patient population [73]

PTC Therapeutics (PTCT) Update / Briefing May 23, 2023 05:00 PM ET Speaker0 Thank you for standing by, and welcome to the MoveFA top line results. At this time, all participants are in listen only mode. After the speakers' presentation, there will be a question and answer session. To ask a question during this session, you'll need to press 11 on your telephone. To remove yourself from the queue, simply press 11 again. As a reminder, today's program is being recorded. And now I'd like to introduce your host ...

Summary of PTC Therapeutics (PTCT) Update / Briefing May 17, 2023 Company Overview - **Company**: PTC Therapeutics (PTCT) - **Product**: Sepiaterin - **Indication**: Treatment of Phenylketonuria (PKU) Key Points Industry and Product Development - **Phase III Trial**: The AFFINITY trial for sepiaterin in patients with fetal ketonuria has shown positive top-line results, meeting the primary endpoint of blood phenylalanine reduction [2][19] - **Efficacy Results**: - Overall mean blood phenylalanine reduction of **63%** in the primary analysis population [2][8] - In classical PKU patients, the mean reduction was **69%** [2][8] - **84%** of patients achieved the target phenylalanine level of less than **360 micromoles per liter** [10] - **93%** of adolescents and adults met the European guideline target of below **600 micromoles per liter** [10] Trial Design and Results - **Trial Structure**: The trial included a run-in phase where patients were treated with sepiaterin for two weeks before randomization [3][4] - **Patient Population**: - Total of **156 patients** screened, with **103 patients** showing a reduction of greater than **30%** in blood phenylalanine levels [4][6] - **98 patients** were randomized for the primary analysis [6] - **Safety Profile**: - No serious adverse events reported; common adverse events included headache and diarrhea, mostly grade one [12][13][78] - Similar rates of treatment-related adverse events between sepiaterin and placebo groups [13][78] Market Opportunity - **Commercial Potential**: - PKU represents a unique commercial opportunity with an estimated **58,000 patients** worldwide [17] - Despite two approved therapies, a large unmet need exists, particularly for therapy-naive patients and those poorly controlled on existing treatments [17][18] - **Regulatory Strategy**: Plans to request pre-submission meetings with regulatory authorities and move forward with NDA and MAA submissions [19] Competitive Landscape - **Comparison with Kuvan**: - In a subset of patients previously treated with Kuvan, sepiaterin showed a **48%** reduction in blood phenylalanine levels compared to their baseline on Kuvan [11][25] - The trial results validate the superior efficacy of sepiaterin over Kuvan, with a higher percentage of patients achieving significant benefits [25][26] Future Directions - **Long-term Studies**: Ongoing long-term open-label studies to assess safety and durability of sepiaterin treatment [14][19] - **Phe Tolerance Protocol**: Preliminary data show that patients can tolerate increased phenylalanine intake while maintaining low blood levels [16][104] Conclusion - The AFFINITY trial results position sepiaterin as a promising treatment for PKU, with strong efficacy and safety data supporting its potential to address significant unmet medical needs in the PKU patient population [19][121]

Financial Data and Key Metrics Changes - Total revenue for Q1 2023 reached $220 million, marking a 40% increase compared to Q1 2022, which is the highest quarterly revenue ever for the company [5][27] - The DMD franchise generated $170 million in revenue, reflecting a 33% increase year-over-year [5][24] - Evrysdi contributed $31 million in royalty revenue, with growth driven by both therapy-naive patients and those previously treated with other therapies [5][6] - The company expects total revenue for 2023 to be between $940 million and $1 billion, indicating potential growth of up to 43% year-over-year [6][27] - Non-GAAP SG&A expenses were $73.4 million for Q1 2023, compared to $59.7 million in Q1 2022 [28] Business Line Data and Key Metrics Changes - Translarna net product revenues were $115.1 million, with strong growth across all geographies [27] - Emflaza had net product revenues of $54.6 million, representing a 12% growth compared to Q1 2022 [27] - The DMD franchise is expected to achieve revenue guidance of $545 million to $565 million for 2023, supported by new patient starts and improved payer access [43][53] Market Data and Key Metrics Changes - The company is expanding its geographic presence, particularly in Latin America and Asia, with successful launches of Waylivra in Brazil and ongoing growth in the DMD franchise [23][24] - The company anticipates a strong rollout of Upstaza in Europe, with positive guidance received from NICE in England and Wales for AADC patients aged 18 months and older [45] Company Strategy and Development Direction - The company aims to leverage its strong commercial portfolio to drive growth in neurological and metabolic disorders [22] - A strategic portfolio review and potential operational expense reduction are expected based on study results to be reported in Q2 2023 [6] - The company is focused on expanding its clinical pipeline, with results from four clinical studies anticipated in the second quarter [7][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving the 2023 revenue guidance, citing strong fundamentals and execution across all geographies [22][26] - The company is optimistic about the upcoming clinical trial results and their potential impact on future product launches and market expansion [21][48] Other Important Information - The company reported cash, cash equivalents, and marketable securities totaling approximately $286.3 million as of March 31, 2023, down from $410.7 million at the end of 2022 [28] - Non-GAAP R&D expenses for Q1 2023 were $179.8 million, reflecting increased investment in research programs and clinical pipeline advancement [48] Q&A Session Summary Question: What has driven new patient starts in the DMD portfolio? - Management highlighted geographic expansion, early diagnosis, and rapid treatment initiation as key drivers of growth in new patient starts [31][53] Question: What are the expectations for the APHENITY trial? - The primary analysis population includes subjects with a greater than 30% reduction in phenylalanine levels, with confidence in achieving significant results based on prior data [90][91] Question: How does the company view the competitive landscape for vatiquinone? - The company is exploring ways to strengthen and extend the patent life for vatiquinone, primarily relying on orphan exclusivity [62] Question: What is the confidence level regarding the MOVE-FA study's statistical significance? - Management believes there is sufficient power to detect differences similar to those observed in previous studies, with confidence in capturing treatment benefits [118] Question: What are the implications of the FDA's queries regarding the BLA submission? - The company anticipates potential delays in the BLA submission to Q3 2023 due to ongoing interactions with the FDA [97]

PART I—FINANCIAL INFORMATION This section provides the unaudited financial statements, management's discussion and analysis, market risk disclosures, and controls and procedures for the first quarter of 2023 [Item 1. Financial Statements (unaudited)](index=9&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) This section presents the unaudited consolidated financial statements for PTC Therapeutics, Inc. as of March 31, 2023, including balance sheets, statements of operations, cash flows, and comprehensive notes [Consolidated Financial Statements](index=9&type=section&id=Consolidated%20Financial%20Statements) The consolidated financial statements show a net loss of **$139.0 million** for Q1 2023, with total assets decreasing to **$1.61 billion** and **$29.5 million** cash used in operations Consolidated Statements of Operations (Q1 2023 vs Q1 2022) | Metric | Three Months Ended March 31, 2023 (in thousands) | Three Months Ended March 31, 2022 (in thousands) | | :--- | :--- | :--- | | **Total revenues** | **$220,382** | **$148,735** | | Net product revenue | $187,557 | $129,832 | | Royalty revenue | $30,831 | $18,896 | | **Total operating expenses** | **$337,997** | **$235,257** | | Research and development | $195,124 | $140,078 | | Selling, general and administrative | $86,914 | $73,271 | | **Loss from operations** | **($117,615)** | **($86,522)** | | **Net loss** | **($138,959)** | **($126,726)** | | **Net loss per share—basic and diluted** | **($1.88)** | **($1.78)** | Consolidated Balance Sheet Highlights | Metric | March 31, 2023 (in thousands) | December 31, 2022 (in thousands) | | :--- | :--- | :--- | | Cash and cash equivalents | $167,495 | $279,834 | | Total current assets | $613,392 | $693,785 | | **Total assets** | **$1,608,839** | **$1,705,619** | | Total current liabilities | $441,634 | $406,236 | | Long-term debt | $572,091 | $571,722 | | **Total liabilities** | **$2,066,400** | **$2,052,705** | | **Total stockholders' deficit** | **($457,561)** | **($347,086)** | Consolidated Statements of Cash Flows Highlights (Q1 2023) | Cash Flow Activity | Three Months Ended March 31, 2023 (in thousands) | | :--- | :--- | | Net cash used in operating activities | ($29,491) | | Net cash used in investing activities | ($28,971) | | Net cash provided by financing activities | $4,094 | | **Net decrease in cash and cash equivalents** | **($62,331)** | [Notes to Consolidated Financial Statements](index=14&type=section&id=Notes%20to%20Consolidated%20Financial%20Statements) The notes detail accounting policies, revenue recognition, debt, and commitments, highlighting an accumulated deficit of **$2.8 billion** and reliance on product sales and financing for R&D - The company's portfolio includes commercial products **Translarna** and **Emflaza** for DMD, **Upstaza** for AADC deficiency, and a broad pipeline in neurology, metabolism, and oncology[29](index=29&type=chunk)[30](index=30&type=chunk)[31](index=31&type=chunk) - As of March 31, 2023, the company reported an accumulated deficit of approximately **$2.8 billion**, with current cash and expected product sales deemed sufficient for the next twelve months[44](index=44&type=chunk) Net Product Sales by Geography and Product (Q1 2023 vs Q1 2022) | Category | Q1 2023 (in millions) | Q1 2022 (in millions) | | :--- | :--- | :--- | | **Net Product Sales (U.S.)** | **$54.6** | **$48.6** | | *Emflaza* | *$54.6* | *$48.6* | | **Net Product Sales (ex-U.S.)** | **$133.0** | **$81.2** | | *Translarna* | *$115.1* | *$79.2* | | *Tegsedi, Waylivra, Upstaza* | *$17.9* | *$2.0* | - Royalty revenue from Evrysdi, in collaboration with Roche, increased to **$30.8 million** in Q1 2023 from **$18.9 million** in Q1 2022[72](index=72&type=chunk)[197](index=197&type=chunk) - Significant future commitments include potential milestone payments for acquisitions: up to **$331 million** (development/regulatory) and **$150 million** (sales) to Agilis, up to **$200 million** to BioElectron, and up to **$217.5 million** to Censa for two lead programs[181](index=181&type=chunk)[183](index=183&type=chunk)[184](index=184&type=chunk) - In February 2023, a **$30.0 million** development milestone for the sepiapterin program (Censa acquisition) was triggered, payable primarily in common stock shares[185](index=185&type=chunk) - As of March 31, 2023, the company holds **$283.3 million** in 1.50% convertible senior notes due 2026 and a **$300.0 million** senior secured term loan from Blackstone[152](index=152&type=chunk)[167](index=167&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=72&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses a **44%** increase in net product revenue to **$187.6 million** in Q1 2023, total revenues reaching **$220.4 million**, and a net loss of **$139.0 million**, while affirming sufficient liquidity for the next twelve months [Corporate Updates and Pipeline](index=72&type=section&id=Corporate%20Updates%20and%20Pipeline) PTC reports strong Q1 2023 sales for **Translarna** (**$115.1 million**) and **Emflaza** (**$54.6 million**), with key clinical data readouts for **PTC518**, **vatiquinone**, and **sepiapterin** expected in Q2 2023, and a **Upstaza** BLA submission anticipated in Q3 2023 - The company anticipates an EMA CHMP opinion in Q2 2023 concerning the conversion of **Translarna's** conditional marketing authorization to a standard one[217](index=217&type=chunk) - The BLA submission for **Upstaza** in the U.S. is now projected for Q3 2023, a delay from Q2 2023, due to ongoing FDA bioanalytical data queries[223](index=223&type=chunk)[244](index=244&type=chunk) - Key clinical data readouts are expected in Q2 2023 for **PTC518** (Huntington's disease Phase 2), **vatiquinone** (mitochondrial disease Phase 2/3), and **vatiquinone** (Friedreich ataxia Phase 3)[226](index=226&type=chunk)[229](index=229&type=chunk) - Results from Part 2 of the registration-directed Phase 3 trial for **sepiapterin** for PKU are anticipated in May 2023[230](index=230&type=chunk) [Results of Operations](index=90&type=section&id=Results%20of%20Operations) Total revenues for Q1 2023 increased **48%** to **$220.4 million**, driven by product and royalty revenue growth, while operating expenses rose **44%** to **$338.0 million**, resulting in a net loss of **$139.0 million** Q1 2023 vs. Q1 2022 Financial Results (in thousands) | Line Item | Q1 2023 | Q1 2022 | Change ($) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | **Total Revenues** | **$220,382** | **$148,735** | **$71,647** | **48.2%** | | Net product revenue | $187,557 | $129,832 | $57,725 | 44.5% | | Royalty revenue | $30,831 | $18,896 | $11,935 | 63.2% | | **Total Operating Expenses** | **$337,997** | **$235,257** | **$102,740** | **43.7%** | | R&D Expense | $195,124 | $140,078 | $55,046 | 39.3% | | SG&A Expense | $86,914 | $73,271 | $13,643 | 18.6% | | **Net Loss** | **($138,959)** | **($126,726)** | **($12,233)** | **9.7%** | - The increase in R&D expenses primarily resulted from increased investment in research programs and clinical pipeline advancement, including a **$30.0 million** success-based development milestone for the **sepiapterin** for PKU trial[284](index=284&type=chunk) - The rise in SG&A expenses reflects ongoing investment to support the company's expanding commercial portfolio and activities[285](index=285&type=chunk) - Other income totaled **$10.0 million** compared to an **$11.9 million** expense in the prior year, primarily due to unrealized foreign exchange gains and equity investment gains in Q1 2023[289](index=289&type=chunk) [Liquidity and Capital Resources](index=94&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2023, the company held **$286.3 million** in cash and equivalents, used **$29.5 million** in operating activities, and believes existing capital is sufficient for the next twelve months despite anticipating continued high expenses - The company held cash, cash equivalents, and marketable securities totaling **$286.3 million** as of March 31, 2023[302](index=302&type=chunk) - The company believes existing cash and expected cash flows from product sales will sufficiently fund operations and capital expenditures for at least the next twelve months[310](index=310&type=chunk) - Significant upcoming cash outlays include a potential **$20.0 million** milestone payment to former Agilis equityholders upon FDA acceptance of the **Upstaza** BLA and **$50.0 million** in potential milestones to former Censa securityholders in 2023[317](index=317&type=chunk) - The company funded a **$50.0 million** reserve account during Q1 2023 as mandated by the Blackstone Credit Agreement[301](index=301&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=103&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company reported no material changes in its market risk profile or management during Q1 2023 compared to its 2022 Annual Report on Form 10-K - No material changes occurred in the company's market risk profile during the first quarter of 2023[321](index=321&type=chunk) [Item 4. Controls and Procedures](index=103&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2023, with no material changes to internal control over financial reporting during the quarter - The CEO and CFO concluded that the company's disclosure controls and procedures were effective at a reasonable assurance level as of March 31, 2023[324](index=324&type=chunk) - No material changes to the company's internal control over financial reporting occurred during the first quarter of 2023[325](index=325&type=chunk) PART II—OTHER INFORMATION This section covers legal proceedings, risk factors, and a list of exhibits filed with the quarterly report [Item 1. Legal Proceedings](index=105&type=section&id=Item%201.%20Legal%20Proceedings) The company is subject to ordinary course legal claims but is not currently aware of any material legal proceedings against it - The company is not currently aware of any material legal proceedings to which it is a party[327](index=327&type=chunk) [Item 1A. Risk Factors](index=105&type=section&id=Item%201A.%20Risk%20Factors) This section refers readers to the comprehensive risk factors detailed in the company's Annual Report on Form 10-K for the year ended December 31, 2022 - The report directs readers to the risk factors detailed in the Annual Report on Form 10-K for the year ended December 31, 2022[328](index=328&type=chunk) [Item 6. Exhibits](index=106&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Quarterly Report on Form 10-Q, including agreements, CEO/CFO certifications, and Inline XBRL documents - Exhibits filed include a consulting agreement, CEO/CFO certifications under Sarbanes-Oxley, and XBRL data files[330](index=330&type=chunk)

Financial Data and Key Metrics Changes - The company achieved total revenue of $699 million in 2022, representing a 30% growth over 2021, despite significant foreign exchange headwinds [169] - For Q4 2022, total revenue was $167 million, consisting of $128 million from net product revenue and $40 million from Evrysdi royalty revenue [14][169] - Non-GAAP R&D expenses for Q4 2022 were $175 million, up from $136 million in Q4 2021, reflecting increased investment in research programs [41] Business Line Data and Key Metrics Changes - The DMD franchise generated $507 million in revenue for 2022, a 20% year-over-year growth, with Q4 revenue of $114 million [162] - Translarna achieved $56 million in revenue for Q4 2022, totaling $289 million for the year, marking a 22% growth [12][178] - Emflaza reported Q4 revenue of $58 million, bringing total annual revenue to $218 million, a 17% increase over 2021 [207] Market Data and Key Metrics Changes - The company is expanding its geographic presence in Latin America, the Middle East, and Asia Pacific, with ongoing efforts to launch Upstaza and grow the DMD franchise [12][38] - The company anticipates significant growth in 2023, with revenue guidance set between $940 million to $1 billion, reflecting over 30% year-over-year growth [155] Company Strategy and Development Direction - The company aims to deliver one new therapy every two to three years, focusing on rare diseases by modulating gene and protein expression [168] - The company is preparing for the launch of Upstaza in the US, with a dedicated team focusing on disease awareness and key publications [125] - The company plans to request a Type C meeting with the FDA to discuss the potential path for NDA resubmission for Translarna [160] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong performance and growth trajectory for 2023, highlighting the excitement around upcoming clinical trial readouts [4][118] - The company noted the importance of addressing the unmet medical needs of patients, particularly in the PKU and mitochondrial disease markets [6][50] Other Important Information - The company was awarded the 2023 EURORDIS Black Pearl Company Award for Innovation, recognizing its contributions to rare disease research [154] - The company has initiated additional dosing cohorts in the PTC518 Huntington's disease program, with results expected in the second quarter of 2023 [36] Q&A Session Summary Question: Can you break down revenue components in your full year 2023 revenue guidance? - The company expects revenue guidance of $940 million to $1 billion, reflecting growth in the DMD franchise, Upstaza, and Evrysdi, including a $100 million milestone for Evrysdi [43] Question: Can you clarify the nature of your discussions with the agency on Translarna? - The company had an informal meeting with the FDA and plans to request another Type C meeting to review the totality of data collected [55][160] Question: What is the expected reduction in seizure frequency considered clinically meaningful for the MIT-E study? - The study is powered for a 40% differential reduction between treatment and placebo groups, with a hypothesized reduction of 50% in the active population [65] Question: Can you provide an update on the APHENITY study? - The company reported that 156 subjects passed screening, with 102 achieving greater than 30% reduction in phenylalanine levels, indicating a high responder rate [203] Question: What is the rationale for dose escalation in the Part 2 study? - The company plans to utilize a two-week dose escalation approach to assess the safety and efficacy of higher doses in the study [134]