Hypochondroplasia

First Quarter 2025 Total Revenues of $745 million (+15% Y/Y and +17% at Constant Currency Y/Y) First Quarter 2025 GAAP Diluted Earnings Per Share (EPS) of $0.95 (+107% Y/Y) First Quarter 2025 Non-GAAP Diluted EPS of $1.13 (+59% Y/Y) Conference Call and Webcast Scheduled Today at 4:30 p.m. ET SAN RAFAEL, Calif., May 1, 2025 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) today announced financial results for the first quarter ended March 31, 2025. "During the first quarter, we saw continued high demand for our innovative medicines resulting in strong revenue growth and profitability," said Alexander Hardy, President and Chief Executive Officer of BioMarin. "Products in our pipeline also advanced according to plan. In April, we shared positive top-line results from the Phase 3 PALYNZIQ® study for the treatment of adolescents with phenylketonuria between the ages of 12 and 17. Also in April, we were pleased to conclude enrollment in the pivotal study in hypochondroplasia with VOXZOGO, keeping us on track to launch in 2027, should data be supportive." Mr. Hardy continued, "For the remainder of 2025, we look forward to continued momentum in our global expansion of VOXZOGO® for achondroplasia. Across our Enzyme Therapies, we plan to build upon strong PALYNZIQ performance in the quarter, as well as initiatives to drive uptake of our other therapies to reach an even greater number of patients around the world. In addition to our strong financial outlook, we expect to advance multiple new indications with VOXZOGO in our CANOPY clinical program, share early clinical results from both BMN 351 for Duchenne Muscular dystrophy and BMN 333, our long-acting C-type natriuretic peptide, as well as execute on our business development strategy. We are delivering strong growth and profitability while we continue to implement BioMarin's new strategy and operating model. We look forward to seeing the benefits of this transformation flow through our results in the coming quarters and beyond." First Quarter 2025 Financial Highlights Total Revenues for the first quarter of 2025 were $745 million, an increase of 15% compared to the same period in 2024, driven by strong 40% year-over-year VOXZOGO revenue growth from new patients initiating therapy across all regions. In the quarter, revenues from BioMarin's Enzyme Therapies (ALDURAZYME®, BRINEURA®, NAGLAZYME®, PALYNZIQ and VIMIZIM®) increased 8% compared to the first quarter of 2024, driven by a combination of increased patient demand and the timing of large government orders in all regions. The increase was partially offset by lower KUVAN® product revenues attributed to continued generic competition as a result of the loss of market exclusivity. GAAP Net Incom e increased by $97 million to $186 million in the first quarter of 2025 compared to the same period in 2024, an increase of 109%, primarily attributed to higher gross profit driven by the factors noted above. The increase was also attributed to lower operating expenses following the termination of certain early stage development programs following the company's 2024 strategic portfolio review and focused ROCTAVIAN strategy announced in the second half of 2024. These increases were partially offset by higher tax provision primarily due to increase in taxable income. Non-GAAP Income increased by $81 million to $221 million in the first quarter of 2025 compared to the same period in 2024, representing 58% growth. The increase in Non-GAAP Income was primarily due to the factors noted above. First Quarter 2025 Business Highlights Innovation Skeletal Conditions: In March 2025, BioMarin presented new data demonstrating favorable safety and strong adherence in real-world clinical practice with VOXZOGO in children with achondroplasia under the age of 3 years old at the 2025 American College of Medical Genetics and Genomics (ACMG) Annual Meeting. No treatment-related adverse events nor any dose interruptions were reported among 63 children followed for up to 23.7 months. These real-world findings further validate VOXZOGO's established safety profile and reinforce the therapeutic benefit seen in clinical studies. The study's safety results, including in infants as young as 1 month old, add to the growing body of evidence supporting early treatment initiation with VOXZOGO, consistent with new international treatment guidelines published in the journal Nature Reviews Endocrinology earlier this year. In April 2025, BioMarin completed enrollment in its pivotal Phase 3 study with VOXZOGO in hypochondroplasia and the company is on track to share topline data in 2026, with a potential launch in 2027. BioMarin plans to leverage its multiyear track record treating children with achondroplasia, a related condition, to raise awareness and treat children with hypochondroplasia across the globe. The CANOPY clinical program is continuing to advance VOXZOGO in additional new indications, including idiopathic short stature, Noonan syndrome, Turner syndrome, and SHOX deficiency. With BMN 333, BioMarin's long-acting C-type natriuretic peptide (CNP), the company enrolled multiple cohorts of healthy volunteers in its first-in-human study, with initial pharmacokinetic (PK) data expected by year-end. Detailed data from this study is expected to be presented at a scientific forum in the first half of 2026. Pre-clinical data with BMN 333 demonstrated sustained 100 pM concentrations for free CNP, representing an approximate 2-3 fold increase versus published data in an analogous pre-clinical model for other long-acting CNP analogs. Additionally, BioMarin recently met with FDA and reached agreement on an overall clinical development plan for BMN 333 in achondroplasia. Assuming the Phase 1 data are supportive, the company plans to initiate a registration-enabling study in 2026, supporting a previously disclosed target for 2030 approval. BioMarin plans to seek similar agreements with additional global regulators in the coming months. The company announced in April that its pivotal study with PALYNZIQ for the treatment of adolescents between the ages of 12 and 17 met its primary efficacy endpoint, demonstrating a statistically significant lowering in blood Phe levels. These data will support the planned submission of applications in the second half of 2025 to expand PALYNZIQ age eligibility in the United States and Europe. Other Clinical Pipeline Programs: BMN 351, BioMarin's next generation oligonucleotide for Duchenne Muscular Dystrophy, and BMN 349, an oral therapeutic for Alpha-1 antitrypsin deficiency (AATD)-associated liver disease, continue to advance. Initial data for BMN 351 is anticipated to be presented at a scientific congress in the second half of 2025 (including muscle dystrophin levels from the 6 mg/kg cohort after 25 weeks of dosing). During a recent strategic portfolio assessment of R&D programs, BioMarin determined that the evolving profile for BMN 370, a pre-clinical candidate for the treatment of von Willebrand disease, did not meet its threshold for further development and commercialization. The program has been discontinued and impacted employees have been redeployed within BioMarin. Growth Total VOXZOGO revenue in the first quarter increased 40% compared to the same period in 2024, representing continued strong global demand since its commercial launch in 2021. As of the end of the quarter, children with achondroplasia in 49 countries around the world were being treated with VOXZOGO. In the U.S., BioMarin is investing in focused initiatives to drive continued expansion. These efforts include increasing field personnel to broaden the prescriber base and adding awareness platforms to drive adoption of VOXZOGO treatment. This is expected to begin increasing the rate of U.S. expansion in the second half of the year. Outside of the U.S. (OUS), from where the majority of VOXZOGO revenue is generated, uneven ordering patterns, consistent with BioMarin's other brands, were observed. This OUS dynamic is expected to result in VOXZOGO full-year revenues being more weighted towards the second half of 2025. Enzyme Therapies revenues grew 8% in the first quarter Y/Y, driven by strong continued demand for PALYNZIQ. Strong PALYNZIQ performance as well as solid growth from BioMarin's other enzyme treatments are expected to continue throughout 2025. Value Commitment In the first quarter of 2025, BioMarin delivered strong results across the business. Total revenues for the first quarter grew 15% Y/Y. First quarter GAAP Operating Margin of 30.0% expanded 16.4 percentage points Y/Y while GAAP Diluted EPS of $0.95 increased 107% Y/Y. First quarter Non-GAAP Operating Margin of 35.7% expanded 11.9 percentage points Y/Y while Non-GAAP Diluted EPS of $1.13 increased 59% Y/Y. These measures of profitability increased at rates faster than revenue growth, representing the company's focus on operational efficiency. During the quarter, BioMarin continued to realize the benefits of cost transformation initiatives implemented in 2024, resulting in a decrease in GAAP and Non-GAAP R&D and SG&A expenses Y/Y. Throughout the remainder of 2025, BioMarin expects to increase investments in VOXZOGO indication expansion, clinical pipeline development, and commercialization initiatives supporting the company's Skeletal Conditions and Enzyme Therapies business units. The company generated operating cash flows totaling $174 million in first quarter 2025, an increase of 271% compared to first quarter 2024. Total cash and investments at the end of the first quarter were approximately $1.8 billion, and with anticipated increasing profitability, BioMarin is positioned to generate increasing operating cash flow into the future. Today, the company reaffirmed its previously communicated 2025 full-year financial guidance, which reflects the impact of tariffs that have already been enacted but does not reflect the impact of potential future pharmaceutical tariffs. BioMarin has immaterial exposure to U.S. tariffs for China, Mexico and Canada across its global supply chain operations and product sales. Forward-Looking Non-GAAP Financial Information BioMarin does not provide guidance for GAAP reported financial measures (other than revenue) or a reconciliation of forward-looking Non-GAAP financial measures to the most directly comparable GAAP reported financial measures because the company is unable to predict with reasonable certainty the financial impact of changes resulting from its strategic portfolio and business operating model reviews; potential future asset impairments; gains and losses on investments; and other unusual gains and losses without unreasonable effort. These items are uncertain, depend on various factors, and could have a material impact on GAAP reported results for the guidance period. As such, any reconciliations provided would imply a degree of precision that could be confusing or misleading to investors. 2025 Full-Year Financial Guidance (in millions, except % and EPS amounts) BioMarin will host a conference call and webcast to discuss first quarter 2025 financial results today, Thursday, May 1, 2025, at 4:30 p.m. ET. This event can be accessed through this link or on the investor section of the BioMarin website at . About BioMarin BioMarin is a global biotechnology company dedicated to translating the promise of genetic discovery into medicines that make a profound impact on the life of each patient. The San Rafael, California-based company, founded in 1997, has a proven track record of innovation with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin pursues treatments that offer new possibilities for patients and families around the world navigating rare or difficult to treat genetic conditions. To learn more, please visit .  Forward-Looking Statements This press release and the associated conference call and webcast contain forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including, without limitation, statements about: future financial performance, including the expectations of Total Revenues, Non-GAAP Operating Margin percentage, Non-GAAP Diluted EPS and Operating Cash Flow for, in certain instances, the full-year 2025 and future periods, as well as profitability growth in 2025, and the underlying drivers of those results, such as the revenue opportunity represented by treatments for Skeletal Conditions, namely VOXZOGO, the expected demand and continued growth of BioMarin's Enzyme Therapies portfolio, including PALYNZIQ, and the expectation regarding the full realization of the benefits of BioMarin's cost transformation program; plans regarding BioMarin's revamped corporate strategy and operating model in 2025 and beyond, including expected growth in the Skeletal Conditions business unit and execution of BioMarin's business development strategy, and its anticipated benefits; the timing of orders for commercial products; BioMarin's ability to meet product demand; the timing of BioMarin's clinical development and commercial prospects, including announcements of data from clinical studies and trials; the clinical development and commercialization of BioMarin's product candidates and commercial products, including (i) expected advancements of pipeline candidates, including BMN 333, BMN 349 and BMN 351, the anticipated initial data read-out for BMN 351 in the second half of 2025, the expected data and data presentation for BMN 333 in the first half of 2026 and plans to initiate a registration-enabling study for BMN 333 in 2026, as well as plans to seek similar agreements with additional global regulators in the coming months; (ii) plans to submit applications to expand PALYNZIQ age eligibility for the treatment of adolescents with phenylketonuria between the ages of 12 and 17 in the U.S. and Europe in the second half of 2025; (iii) expected topline data from the pivotal study in hypochondroplasia in 2026 and launch in 2027; (iv) the expectations regarding global expansion of VOXZOGO for achondroplasia and expected increase in the rate of U.S. expansion in the second half of 2025; (v) plans to advance five new VOXZOGO indications with BioMarin's CANOPY clinical program; and (vi) plans to reach greater number of patients around the world across BioMarin's Enzyme Therapies; the expected benefits and availability of BioMarin's commercial products and product candidates; and potential growth opportunities and trends. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: BioMarin's success in the commercialization of its commercial products; impacts of macroeconomic and other external factors on BioMarin's operations, such as trade wars and potential future pharmaceutical tariffs; results and timing of current and planned preclinical studies and clinical trials and the release of data from those trials; BioMarin's ability to successfully manufacture its commercial products and product candidates; the content and timing of decisions by the U.S. Food and Drug Administration, the European Commission and other regulatory authorities concerning each of the described products and product candidates; the market for each of these products; actual sales of BioMarin's commercial products; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the fiscal year ended December 31, 2024, as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin®, BRINEURA®, KUVAN®, NAGLAZYME®, PALYNZIQ®, ROCTAVIAN®, VIMIZIM® and VOXZOGO® are registered trademarks of BioMarin Pharmaceutical Inc., or its affiliates. ALDURAZYME® is a registered trademark of BioMarin/Genzyme LLC. All other brand names and service marks, trademarks and other trade names appearing in this release are the property of their respective owners. Non-GAAP Information The results presented in this press release include both GAAP information and Non-GAAP information. Non-GAAP Income is defined by the company as GAAP Net Income excluding amortization of intangible assets, stock-based compensation expense and, in certain periods, certain other specified items, as detailed below when applicable. The company also includes a Non-GAAP adjustment for the estimated tax impact of the reconciling items. Non-GAAP R&D expenses and Non-GAAP SG&A expenses are defined by the company as GAAP R&D expenses and GAAP SG&A expenses, respectively, excluding stock-based compensation expense and, in certain periods, certain other specified items, as detailed below when applicable. Non-GAAP Operating Margin percentage is defined by the company as GAAP Income from Operations, excluding amortization of intangible assets, stock-based compensation expense and, in certain periods, certain other specified items, divided by GAAP Total Revenues. Non-GAAP Diluted EPS is defined by the company as Non-GAAP Income divided by Non-GAAP Weighted-Average Diluted Shares Outstanding. Non-GAAP Weighted-Average Diluted Shares Outstanding is defined by the company as GAAP Weighted-Average Diluted Shares Outstanding, adjusted to include any common shares issuable under the company's equity plans and convertible debt in periods when they are dilutive under Non-GAAP. The company's presentation of percentage changes in total revenues at Constant Currency rates, which is computed using current period local currency sales at the prior period's foreign exchange rates, is also a Non-GAAP financial measure. This measure provides information about growth (or declines) in the company's total revenue as if foreign currency exchange rates had not changed between the prior period and the current period. BioMarin regularly uses both GAAP and Non-GAAP results and expectations internally to assess its financial operating performance and evaluate key business decisions related to its principal business activities: the discovery, development, manufacture, marketing and sale of innovative biologic therapies. Because Non-GAAP Income, Non-GAAP R&D expenses, Non-GAAP SG&A expenses, Non-GAAP Operating Margin percentage, Non-GAAP Diluted EPS, Non-GAAP Weighted-Average Diluted Shares Outstanding and Constant Currency are important internal measurements for BioMarin, the company believes that providing this information in conjunction with BioMarin's GAAP information enhances investors' and analysts' ability to meaningfully compare the company's results from period to period and to its forward-looking guidance, and to identify operating trends in the company's principal business. BioMarin also uses Non-GAAP Income internally to understand, manage and evaluate its business and to make operating decisions, and compensation of executives is based in part on this measure. Non-GAAP financial measures are not meant to be considered in isolation or as a substitute for, or superior to comparable GAAP measures and should be read in conjunction with the consolidated financial information prepared in accordance with GAAP. Investors should note that the Non-GAAP information is not prepared under any comprehensive set of accounting rules or principles and does not reflect all of the amounts associated with the company's results of operations as determined in accordance with GAAP. Investors should also note that these Non-GAAP financial measures have no standardized meaning prescribed by GAAP and, therefore, have limits in their usefulness to investors. In addition, from time to time in the future there may be other items that the company may exclude for purposes of its Non-GAAP financial measures; likewise, the company may in the future cease to exclude items that it has historically excluded for purposes of its Non-GAAP financial measures. Because of the non-standardized definitions, the Non-GAAP financial measure as used by BioMarin in this press release and the accompanying tables may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. The following tables present the reconciliation of GAAP reported to Non-GAAP adjusted financial information: SOURCE BioMarin Pharmaceutical Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

- Three INDs cleared by US FDA for TYRA's proprietary precision small molecules - - TYRA-300 to be evaluated in three Phase 2 studies: SURF302 for Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR NMIBC), BEACH301 for pediatric achondroplasia (ACH) and SURF301 for metastatic urothelial cancer (mUC) - - Cash, cash equivalents, and marketable securities of $341.4 million at YE 2024; runway through at least 2027 - CARLSBAD, Calif., March 27, 2025 /PRNewswire/ -- Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, today reported financial results for the fourth quarter and full year ended December 31, 2024, and highlighted recent corporate progress. "2024 was a momentous year for TYRA and the patient communities we serve, highlighted by the positive interim results from our SURF301 study, which demonstrated a combination of high anti-tumor activity with favorable tolerability results in very sick, heavily pre-treated cancer patients. Importantly, the oncology doses tested in SURF301 are significantly higher than those to be tested in BEACH301, giving us confidence as we advance TYRA-300 in ACH," said Todd Harris, CEO of TYRA. "Our conviction in TYRA-300 has never been stronger and we are working diligently to advance this potential best-in-class agent for multiple high-value indications in oncology and skeletal dysplasia into three Phase 2 studies in NMIBC, ACH and mUC." Fourth Quarter and Full Year 2024 and Recent Corporate Highlights TYRA-300 Advanced Clinical Evaluation of TYRA-300 into Three Phase 2 Studies. During 2024, TYRA progressed TYRA-300, an oral, investigational FGFR3-selective inhibitor, for the treatment of IR NMIBC, mUC and ACH, and achieved the following milestones: Cleared Phase 2 NMIBC IND with US FDA – SURF302. TYRA expanded the clinical development of TYRA-300 into NMIBC to address the unmet needs in this cancer population for an efficacious, orally available therapy. SURF302 is an open-label Phase 2 clinical study evaluating the efficacy and safety of TYRA-300 in participants with FGFR3-altered low-grade, IR NMIBC. The study will enroll up to 90 participants at multiple sites primarily in the United States. Participants will be randomized initially to treatment with TYRA-300 at 50 mg once-daily (QD) (Cohort 1) or treatment with TYRA-300 at 60 mg QD (Cohort 2). Following a review of efficacy and safety, an additional dosing cohort may be evaluated. The primary endpoint is complete response (CR) rate at three months. Secondary endpoints include time to recurrence, the median duration of response, recurrence free survival (RFS), progression free survival (PFS), safety and tolerability. Cleared Phase 2 ACH IND with US FDA - BEACH301. The study is a Phase 2, multicenter, open-label, dose-escalation/dose-expansion study evaluating TYRA-300 in children ages 3 to 10 with achondroplasia with open growth plates. The study will enroll children who are treatment-naïve (Cohort 1) and those who have received prior growth-accelerating therapy (Cohort 2) at multiple sites across the globe. Each of these cohorts is expected to enroll up to 10 participants per dose level (0.125, 0.25, 0.375, 0.50 mg/kg) for up to 12 months. The study will initially enroll a safety sentinel cohort of up to 3 treatment-naïve participants per dose level in children ages 5 to 10. Reported Interim Clinical Proof-of-Concept Results in mUC Patients – SURF301. TYRA-300 demonstrated encouraging preliminary anti-tumor activity in a heavily pre-treated population: at ≥ 90 mg QD, 6 out of 11 (54.5%) patients with FGFR3+ mUC achieved a confirmed partial response (PR), with 100% disease control rate and sustained duration of activity; positive safety results were reported across all QD doses, with infrequent FGFR2/FGFR1-associated toxicities (data cutoff of August 15, 2024). TYRA-300 is being evaluated in Part B of SURF301 (NCT05544552) at potentially therapeutic QD doses in preparation for potential future Phase 2 studies. TYRA-200 Advanced Phase 1 SURF201 Study. TYRA-200 is an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752) is a multi-center, open label study designed to evaluate the safety, tolerability, and pharmacokinetics of TYRA-200 and determine the optimal and maximum tolerated dose and recommended Phase 2 dose, as well as evaluate the preliminary antitumor activity of TYRA-200. The SURF201 study is currently enrolling and dosing adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations. TYRA-430 Cleared Phase 1 IND with US FDA – SURF431. TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431). We believe TYRA-430 has the potential to address a significant unmet need in HCC, where there are no approved biomarker-driven, targeted therapies. Corporate Strengthened Leadership Team and Board of Directors. In 2024, TYRA appointed Doug Warner, MD, as Chief Medical Officer, and Erik Goluboff, MD, as SVP, Clinical Development to lead the Company's oncology strategy and clinical development plans. In 2025, TYRA appointed accomplished drug developer Adele Gulfo to its Board of Directors, Sinette Heys as SVP, Clinical Operations to lead the Company's clinical operations team, and Will Charlton, MD, as SVP, Clinical Development to lead the Company's skeletal dysplasia clinical development group. SNÅP Platform and Pipeline TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions. Fourth Quarter and Full-Year 2024 Financial Results Cash, Cash Equivalents and Short-Term Investments. As of December 31, 2024, TYRA had cash, cash equivalents, and marketable securities of $341.4 million, compared to $203.5 million at the end of 2023. The increase was primarily due to the completion of a private placement financing for net proceeds of $199.6 million in the first quarter of 2024. The Company's current cash, cash equivalents and marketable securities are expected to allow TYRA to execute on its plans through at least 2027. Research and Development (R&D) Expenses. Research and development expenses for the three months ended December 31, 2024 were $22.2 million compared to $20.7 million for the same period in 2023, and $80.1 million for the full year 2024 compared to $62.5 million for the same period in 2023. The increases were primarily driven by increased expenses incurred in connection with our ongoing and planned clinical trials and personnel-related costs, including stock-based compensation, partially offset by decreased drug manufacturing and preclinical costs. General and Administrative (G&A) Expenses. General and administrative expenses for the three months ended December 31, 2024 were $7.6 million compared to $5.0 million for the same period in 2023, and $24.1 million for the full year 2024 compared to $17.4 million for the same period in 2023. The increases were primarily driven by increased personnel-related costs, including stock-based compensation. Net Loss. Fourth quarter 2024 net loss was $25.6 million compared to $22.8 million for the same period in 2023, and $86.5 million for the full year 2024 compared to $69.1 million for the same period in 2023. Upcoming Anticipated Milestones and Events BEACH301: dose first child with achondroplasia with TYRA-300 – Q2 2025 SURF302: dose first NMIBC patient with TYRA-300 – Q2 2025 SURF431: dose first HCC patient with TYRA-430 – Q2 2025 About TYRA-300 TYRA-300 is the Company's lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasia, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in mUC and IR NMIBC. In mUC, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552). The study is designed to determine the optimal and the recommended Phase 2 dose of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. In October 2024, TYRA reported interim clinical proof-of-concept data in mUC from SURF301. TYRA has received IND clearance from the US FDA to proceed with its SURF302 clinical trial in patients with IR NMIBC. In skeletal dysplasia, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia, and its BEACH301 clinical trial in children with achondroplasia is now recruiting. About TYRA-200 TYRA-200 is an oral, investigational, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The Phase 1 clinical study of TYRA-200, SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752), is a multi-center, open label study designed to evaluate the maximum tolerated dose (MTD) and the recommended Phase 2 dose of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling and dosing adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2. About TYRA-430 TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The US FDA has cleared Tyra's IND to proceed with a Phase 1 clinical study of TYRA-430. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced HCC and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431). About Tyra Biosciences Tyra Biosciences, Inc. (Nasdaq: TYRA) is a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in FGFR biology. The Company's in-house precision medicine platform, SNÅP, enables rapid and precise drug design through iterative molecular SNÅPshots that help predict genetic alterations most likely to cause acquired resistance to existing therapies. TYRA's expertise in FGFR biology has created a differentiated pipeline with three product candidates in clinical development in targeted oncology and genetically defined conditions. The Company's lead precision medicine stemming from SNÅP, TYRA-300, is a potential first-in-class selective FGFR3 inhibitor that is designed to avoid the toxicities associated with inhibition of FGFR1, FGFR2 and FGFR4, while being agnostic for the FGFR3 gatekeeper mutations. TYRA-300 is expected to be evaluated in three Phase 2 studies: SURF302 for IR NMIBC, BEACH301 for pediatric achondroplasia and SURF301 for metastatic urothelial cancer. TYRA is also developing TYRA-200, an oral, investigational, FGFR1/2/3 inhibitor, in the SURF201 study for metastatic intrahepatic cholangiocarcinoma, and TYRA-430, an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. TYRA is based in Carlsbad, CA. For more information about our science, pipeline and people, please visit and engage with us on LinkedIn. Forward-Looking Statements TYRA cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: the expected advancement of our pipeline and our growth; the potential to develop next-generation precision medicines and their potential to be first-in-class and/or best-in-class; the potential safety and therapeutic benefits of, and market opportunities for, our product candidates; the expected trial design, timing and phase of development of our product candidates, including timing for patient dosing; the potential for SNÅP to develop therapies; and our expected cash runway. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: interim results of a clinical trial are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues and as more patient or final data becomes available, including the risk that unconfirmed responses may not ultimately result in confirmed responses to treatment after follow-up evaluations; the potential for proof-of-concept results to fail to result in successful subsequent development of TYRA-300; later developments with the FDA may be inconsistent with prior feedback from the FDA; we are early in our development efforts, and the approach we are taking to discover and develop drugs based on our SNÅP platform is novel and unproven and it may never lead to product candidates that are successful in clinical development or approved products of commercial value; potential delays in the commencement, recruitment, enrollment, data readouts and completion of preclinical studies and clinical trials; results from preclinical studies or early clinical trials not necessarily being predictive of future results; our dependence on third parties in connection with manufacturing, research and preclinical testing; we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; acceptance by the FDA of INDs or of similar regulatory submissions by comparable foreign regulatory authorities for the conduct of clinical trials of our product candidates; an accelerated development or approval pathway may not be available for TYRA-300 or other product candidates and any such pathway may not lead to a faster development process; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization; the potential for our programs and prospects to be negatively impacted by developments relating to our competitors, including the results of studies or regulatory determinations relating to our competitors; unfavorable results from preclinical studies; regulatory developments in the United States and foreign countries; our ability to obtain and maintain intellectual property protection for our product candidates and proprietary technologies; we may use our capital resources sooner than we expect; unstable market and economic conditions may adversely affect our business and financial condition and the broader economy and biotechnology industry; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our annual report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact: Amy Conrad [email protected] SOURCE Tyra Biosciences WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

New data also to be presented for PALYNZIQ® (pegvaliaise-pqpz), reinforcing its value in sustaining blood Phe level reduction and improving health-related quality of life for adults with phenylketonuria SAN RAFAEL, Calif., March 20, 2025 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced positive new data from studies of VOXZOGO® (vosoritide) in children with achondroplasia and in ongoing clinical trials investigating other skeletal conditions, as well as PALYNZIQ® (pegvaliase-pqpz) in adults with phenylketonuria (PKU). The latest findings further validate the long-term benefit and established safety profiles of both medicines, which continue to play a pivotal role for people living with these genetically defined conditions. The data will be presented at the 2025 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting in Los Angeles. Data Highlight VOXZOGO Treatment Adherence and Favorable Safety Profile in Infants New data from a study in Japan showed strong treatment adherence with VOXZOGO in children with achondroplasia under the age of 3, with no reported treatment-related adverse events nor any dose interruptions among 63 children followed for up to 23.7 months. These real-world findings validate VOXZOGO's established safety profile and reinforce the therapeutic benefit seen in clinical studies. The study's safety results, including in infants as young as 1 month old, add to the growing body of evidence supporting early treatment initiation. "VOXZOGO is the first and only approved treatment for children with achondroplasia, and it is encouraging to see favorable safety and strong adherence in very young children receiving the medicine in real-world clinical practice. As the effects of restricted growth are apparent from birth in children with achondroplasia, we expect that earlier treatment should translate to greater benefits," said Greg Friberg, M.D., executive vice president and chief research & development officer at BioMarin. "In addition to data in achondroplasia, scientific research at ACMG furthers our genetic understanding of skeletal conditions like hypochondroplasia, in which we hope to complete enrollment for our pivotal study with VOXZOGO in the first half of 2025." PALYNZIQ Data Show Importance of Sustained Blood Phe Level Reduction and Improvement in Quality of Life in Adults with PKU New data from the OPAL study, a post-marketing observational trial to assess the real-world safety and efficacy of PALYNZIQ, showed lowered blood Phe levels following treatment and positive health-related quality of life (HRQoL) outcomes. Mean blood Phe level was 1029 μmol/L at baseline (n=51) and lowered to 293 μmol/L at week 96 (n=16), representing a 67.8% reduction. Improvements in HRQoL were also observed, as measured by the PKU quality of life questionnaire (PKU-QOL) and the PKU Symptom Severity and Impacts Scale (PKU-SSIS), which use a scale of 1-100, with lower scores indicating better HRQoL. Mean change from baseline of -12.4 and -11.8 respectively were observed over the same time period. Additionally, secondary data analyses from the Phase 3 PRISM clinical trial program demonstrated that sustaining lowered blood Phe levels with PALYNZIQ led to improvements in attention and mood. Most notably, scores for sustained Phe levels ≤120 were significantly better than those at sustained levels of ≤600 or ≤360, suggesting blood Phe in the normal range may provide additional benefit for adults living with PKU. Real-world data from the Assessment of the Treatment and management LAndScape of PKU (ATLAS) study also highlighted a shift in the treatment landscape in part attributable to PALYNZIQ, with an increased proportion of people with PKU treated across 19 U.S. clinics achieving blood Phe levels ≤360 μmol/L and a reduction in the proportion of individuals with blood Phe levels >1200 μmol/L. These findings demonstrate PALYNZIQ's efficacy in treating PKU, as the company works to advance this option for younger people living with the genetically defined condition, with results from a Phase 3 study in adolescents expected later this year. Below are BioMarin's key presentations at ACMG, all listed in Pacific Time: Interdisciplinary Variant Re-Classification: FGFR3 as an Example of Genotypic Investigation in Suspected Skeletal Dysplasia Population Poster #P213 Thursday, March 20, 10:30 – 11:30 a.m. How Helpful are Sleep Studies in Determining Surgical Need in Infants with Achondroplasia? Poster #P313 Thursday, March 20, 10:30 – 11:30 a.m. Beyond Boundaries: The Continuous Spectrum in FGFR3-Related Conditions Poster #P373 Thursday, March 20, 10:30 – 11:30 a.m. Index of Sustained Phe Response and Improvements in PKU Clinical Outcome Assessments in Patients Receiving Pegvaliase Poster #P009 Thursday, March 20, 10:30 – 11:30 a.m. Initial Psychometric Evaluation of the Adult Symptom Severity and Impacts Scale (PKU-SSIS) Using Interim Data from the OPAL Study Poster #P029 Thursday, March 20, 10:30 – 11:30 a.m. The Assessment of the Treatment and Management Landscape of Phenylketonuria Survey Study: Findings from 19 Clinics in the United States Poster #P045 Thursday, March 20, 10:30 – 11:30 a.m. Safety Profile and Adherence of Vosoritide in Young Children with Achondroplasia in Japan Poster #P208 Friday, March 21, 10:30 – 11:30 a.m. Vosoritide as a Targeted Therapy for FGFR3-Related Thanatophoric Dysplasia Poster #P354 Friday, March 21, 10:30 – 11:30 a.m. Improvements in Blood Phenylalanine and Health-Related Quality of Life Outcomes Among Adults with PKU Receiving Pegvaliase in the OPAL Study Poster #P002 Friday, March 21, 10:30 – 11:30 a.m. Occurrence of Anaphylaxis in Adult Incident Pegvaliase-Treated PKU Patients in a Post-Marketing Safety Analysis in the United States Poster #P046 Friday, March 21, 10:30 – 11:30 a.m. About Achondroplasia Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face and base of the skull. This condition is caused by a change in the FGFR3 gene, a negative regulator of bone growth. More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation. The worldwide incidence rate of achondroplasia is about one in 25,000 live births. VOXZOGO is being tested in children whose growth plates are still "open," typically those under 18 years of age. Approximately 25% of people with achondroplasia fall into this category. About Phenylketonuria PKU, or phenylalanine hydroxylase (PAH) deficiency, is a genetic condition affecting approximately 70,000 people in the regions of the world where BioMarin operates. This enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If functional enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems and psychiatric symptoms. As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU born after this period in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after. PKU can be managed with a severe Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most individuals to adhere to the lifelong strict diet to the extent needed to achieve adequate control of blood Phe levels. Dietary control of Phe in childhood can prevent major developmental neurological toxicities, but poor control of Phe in adolescence and adulthood is associated with a range of neurocognitive disabilities with significant functional impact. About VOXZOGO In children with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in FGFR3. VOXZOGO, a C-type natriuretic peptide (CNP) analog, acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth. VOXZOGO is approved in the U.S., Japan and Australia to increase linear growth in children of all ages with achondroplasia with open epiphyses, and VOXZOGO is indicated in the EU for the treatment of achondroplasia in children 4 months of age and older whose epiphyses are not closed, as confirmed by appropriate genetic testing. In the U.S., this indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s). To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history. Patient Support Accessing VOXZOGO To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-833-VOXZOGO (1-833-869-9646) or e-mail VOXZOGOSupport@biomarin-rareconnections.com. For more information about VOXZOGO, please visit www.voxzogo.com. For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com. About PALYNZIQ PALYNZIQ substitutes the deficient phenylalanine hydroxylase (PAH) enzyme in PKU with a PEGylated version of the enzyme phenylalanine ammonia lyase to break down Phe. PALYNZIQ is administered using a dosing regimen designed to facilitate tolerability; PALYNZIQ's safety profile consists primarily of immune-mediated responses, which can include anaphylaxis, for which robust risk management measures effective in clinical trials are in place. PALYNZIQ is approved to reduce blood Phe concentrations for adults in the U.S., for people 16 and older in the EU, Canada and Brazil, and for people 15 and older in Japan to reduce blood Phe concentrations in individuals with PKU who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management. Patient Support Accessing PALYNZIQ To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-866-906-6100 or e-mail support@biomarin-rareconnections.com. For more information about PALYNZIQ, please visit www.palynziq.com. For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com. VOXZOGO U.S. Important Safety Information What is VOXZOGO used for? VOXZOGO is a prescription medicine used to increase linear growth in children with achondroplasia and open growth plates (epiphyses). VOXZOGO is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. What is the most important safety information about VOXZOGO? VOXZOGO may cause serious side effects including a temporary decrease in blood pressure in some patients. To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, feeling tired, or nausea), patients should eat a meal and drink 8 to 10 ounces of fluid within 1 hour before receiving VOXZOGO. What are the most common side effects of VOXZOGO? The most common side effects of VOXZOGO include injection site reactions (including redness, itching, swelling, bruising, rash, hives, and injection site pain), high levels of blood alkaline phosphatase shown in blood tests, vomiting, joint pain, decreased blood pressure, and stomachache. These are not all the possible side effects of VOXZOGO. Ask your healthcare provider for medical advice about side effects, and about any side effects that bother the patient or that do not go away. How is VOXZOGO taken? VOXZOGO is taken daily as an injection given under the skin, administered by a caregiver after a healthcare provider determines the caregiver is able to administer VOXZOGO. Do not try to inject VOXZOGO until you have been shown the right way by your healthcare provider. VOXZOGO is supplied with Instructions for Use that describe the steps for preparing, injecting, and disposing VOXZOGO. Caregivers should review the Instructions for Use for guidance and any time they receive a refill of VOXZOGO in case any changes have been made. Inject VOXZOGO 1 time every day, at about the same time each day. If a dose of VOXZOGO is missed, it can be given within 12 hours from the missed dose. After 12 hours, skip the missed dose and administer the next daily dose as usual. The dose of VOXZOGO is based on body weight. Your healthcare provider will adjust the dose based on changes in weight following regular check-ups. Your healthcare provider will monitor the patient's growth and tell you when to stop taking VOXZOGO if they determine the patient is no longer able to grow. Stop administering VOXZOGO if instructed by your healthcare provider. What should you tell the doctor before or during taking VOXZOGO? Tell your doctor about all of the patient's medical conditions includingIf the patient has heart disease (cardiac or vascular disease), or if the patient is on blood pressure medicine (anti-hypertensive medicine). If the patient has kidney problems or renal impairment. If the patient is pregnant or plans to become pregnant. It is not known if VOXZOGO will harm the unborn baby. If the patient is breastfeeding or plans to breastfeed. It is not known if VOXZOGO passes into breast milk. Tell your doctor about all of the medicines the patient takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. If the patient has heart disease (cardiac or vascular disease), or if the patient is on blood pressure medicine (anti-hypertensive medicine). If the patient has kidney problems or renal impairment. If the patient is pregnant or plans to become pregnant. It is not known if VOXZOGO will harm the unborn baby. If the patient is breastfeeding or plans to breastfeed. It is not known if VOXZOGO passes into breast milk. You may report side effects to BioMarin at 1-866-906-6100. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see additional safety information in the full Prescribing Information and Patient Information. PALYNZIQ U.S. Indication and Important Safety Information PALYNZIQ® (pegvaliase-pqpz) is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe levels in adult patients with phenylketonuria who have uncontrolled blood Phe levels greater than 600 micromol/L on existing management. BOXED WARNING: RISK OF ANAPHYLAXIS Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient's and observer's (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable epinephrine, if needed Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use Prescribe auto-injectable epinephrine. Prior to the first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment PALYNZIQ is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Further information, including a list of qualified pharmacies, is available at www.PALYNZIQREMS.com or by telephone at 1-855-758-REMS (1-855-758-7367) WARNINGS AND PRECAUTIONS Anaphylaxis Signs and symptoms of anaphylaxis reported include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat tightness, skin flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea) Anaphylaxis generally occurred within 1 hour after injection; however, delayed episodes occurred up to 48 hours after PALYNZIQ administration Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use Anaphylaxis requires immediate treatment with auto-injectable epinephrine. Prescribe auto-injectable epinephrine to all patients receiving PALYNZIQ and instruct patients to carry auto-injectable epinephrine with them at all times during PALYNZIQ treatment. Prior to the first dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, how to properly administer auto-injectable epinephrine, and to seek immediate medical care upon its use. Consider the risks associated with auto-injectable epinephrine use when prescribing PALYNZIQ. Refer to the auto-injectable epinephrine prescribing information for complete information Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. Subsequent PALYNZIQ dose titration should be based on patient tolerability and therapeutic response Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to PALYNZIQ administration based upon individual patient tolerability Other Hypersensitivity Reactions Hypersensitivity reactions other than anaphylaxis have been reported in 204 of 285 (72%) patients treated with PALYNZIQ in clinical trials Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgment of the healthcare provider, and may include dosage adjustment, temporary drug interruption, or treatment with antihistamines, antipyretics, and/or corticosteroids ADVERSE REACTIONS The most common adverse reactions (at least 20% of patients in either treatment phase) were injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety Of the 285 patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. The most common adverse reactions leading to treatment discontinuation were hypersensitivity reactions (6% of patients) including anaphylaxis (3% of patients), angioedema (1% of patients), arthralgia (4% of patients), generalized skin reactions lasting at least 14 days (2% of patients), and injection site reactions (1% of patients) The most common adverse reactions leading to dosage reduction were arthralgia (15% of patients), hypersensitivity reactions (9% of patients), injection site reactions (4% of patients), alopecia (3% of patients), and generalized skin reactions lasting at least 14 days (2% of patients) The most common adverse reactions leading to temporary drug interruption were hypersensitivity reactions (14% of patients), arthralgia (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients) Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema, and face edema) occurring independent of anaphylaxis. In clinical trials, serum sickness was reported in 7 out of 285 (2%) patients Blood Phenylalanine Monitoring and Diet Obtain blood Phe levels every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe levels during maintenance therapy Counsel patients to monitor dietary protein and Phe intake, and adjust as directed by their healthcare provider DRUG INTERACTIONS Effect of PALYNZIQ on Other PEGylated Products In a single-dose study of PALYNZIQ in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced a hypersensitivity reaction. One of the two patients experienced anaphylaxis The clinical effects of concomitant treatment with different PEGylated products is unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis USE IN SPECIFIC POPULATIONS Pregnancy and Lactation PALYNZIQ may cause fetal harm when administered to a pregnant woman Advise women who are exposed to PALYNZIQ during pregnancy or who become pregnant within one month following the last dose of PALYNZIQ that there is a pregnancy surveillance program that monitors pregnancy outcomes. Healthcare providers should report PALYNZIQ exposure and encourage these patients to report their pregnancy to BioMarin (1-866-906-6100) Monitor blood Phe levels in breastfeeding women treated with PALYNZIQ Pediatric Use The safety and effectiveness of PALYNZIQ in pediatric patients have not been established Geriatric Use Clinical studies of PALYNZIQ did not include patients aged 65 years and older You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see accompanying full Prescribing Information, including Boxed Warning. About BioMarin BioMarin is a global biotechnology company dedicated to translating the promise of genetic discovery into medicines that make a profound impact on the life of each patient. The San Rafael, California-based company, founded in 1997, has a proven track record of innovation with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that offer new possibilities for people living with genetically defined conditions around the world. To learn more, please visit www.biomarin.com. Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: data to be presented at the 2025 American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, including the ten poster presentations; the development of BioMarin's VOXZOGO program generally, including expectation to complete enrollment of the pivotal study with VOXZOGO in hypochondroplasia in the first half of 2025; the safety profile and potential benefits of VOXZOGO for children with achondroplasia, including the expectation that earlier treatment should lead to potentially greater benefits; the development of BioMarin's PALYNZIQ program generally; BioMarin's plans to advance PALYNZIQ for the treatment of adolescents with phenylketonuria (PKU), including expectation that results from a Phase 3 study will be available later this year; the benefits of PALYNZIQ for adults with PKU, including potential improvement in health-related quality of life; and the continued clinical development of VOXZOGO and PALYNZIQ. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials of VOXZOGO and PALYNZIQ; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the U.S. Food and Drug Administration, the European Medicines Agency, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the year ended December 31, 2024, as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin®, BioMarin RareConnections®, VOXZOGO® and PALYNZIQ® are registered trademarks of BioMarin Pharmaceutical Inc. Contacts: Investors Media Traci McCarty Andrew Villani BioMarin Pharmaceutical Inc. BioMarin Pharmaceutical Inc. (415) 455-7558 (628) 269-7393 View original content to download multimedia:https://www.prnewswire.com/news-releases/biomarin-presents-new-data-demonstrating-favorable-safety-and-strong-adherence-in-real-world-clinical-practice-with-voxzogo-vosoritide-in-children-under-3-with-achondroplasia-at-2025-american-college-of-medical-genetics-and-gen-302406448.html SOURCE BioMarin Pharmaceutical Inc.