Dwarfism

– Study met all primary endpoints, including 79.2% sensitivity for colorectal cancer (CRC) and 91.5% specificity for non-advanced colorectal neoplasia – – PREEMPT CRC, the largest study of a blood-based test for CRC, enrolled 48,995 participants, which reflects the real-world diversity of average-risk adults in the U.S. – – As part of its planned test versioning strategy, the company will continue to optimize for CRC sensitivity and advanced adenoma (AA) detection in 2024 to meet guideline and policy milestones – SOUTH SAN FRANCISCO, Calif., April 2, 2024 /PRNewswire/ -- Freenome, a biotechnology company pioneering an early cancer detection platform, today announced topline results from PREEMPT CRC, a prospective, registrational clinical study to validate its blood-based test for the early detection of colorectal cancer (CRC) among average-risk adults. In a prespecified analysis, the Freenome blood test for CRC screening demonstrated 79.2% sensitivity in detecting colorectal cancer (Stage I: 57.1%, Stage II: 100%, Stage III: 82.4%, Stage IV: 100%) with 91.5% specificity for non-advanced colorectal neoplasia. The test also showed 12.5% sensitivity in detecting advanced adenomas (AA), with a sensitivity of 29% for AAs with high-grade dysplasia, also referred to as Stage 0. All endpoints were powered at 96% or greater. When specificity was adjusted to the Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD) cut-off of 90%, there was a corresponding increase in the sensitivity for AA (14.8%) while maintaining CRC sensitivity. With the addition of proteins, an improved sensitivity for both AA (16.4%) and CRC (80.5%) at the 90% cut-off was observed. Additional study findings will be presented at a future scientific meeting. "These results advance our early cancer detection programs toward mainstream clinical use, and we are grateful to the participants, partners and communities who helped accomplish this study," said Lance Baldo, M.D., chief medical officer at Freenome. "PREEMPT CRC was designed and executed with high scientific rigor and generated valuable data and insights that enable near- and long-term test improvements. These clinical performance metrics set a standard from which Freenome will continue to innovate, including the evaluation of prespecified test versioning." PREEMPT CRC was a prospective, registrational study designed to validate the Freenome blood test for CRC screening. Conducted at more than 200 sites, the study enrolled 48,995 asymptomatic, average-risk adults between the ages of 45 and 85 scheduled to undergo a screening colonoscopy. The results were based on data from the 27,010 eligible participants who enrolled consecutively in the study after a predetermined cut-off date. The retained samples from these participants, along with samples from over 16,000 additional participants not utilized in the present analysis, remain available to support future test improvements. The study leveraged a hybrid model involving virtual and traditional recruitment methods to reach underserved communities and ensure a representative population that includes people from all 48 states in the continental U.S. In addition, real-world data (RWD) collection through tokenization was integrated into the trial to complement the molecular data with longitudinal clinical outcomes that can be applied to CRC and other early cancer detection applications as part of the company's platform and test versioning roadmap. "While physicians have screening tools available for colorectal cancer, the associated inconvenience and discomfort of these methods deter many from getting recommended screenings," said Aasma Shaukat, M.D., M.P.H., professor of medicine at the NYU Grossman School of Medicine and a principal investigator for the PREEMPT CRC study. "By providing a more convenient option, Freenome's blood test for the early detection of CRC has the potential to boost screening adherence rates and improve accessibility for people in all communities." "In the PREEMPT CRC study, we brought communities together to confront a common enemy – cancer," said Mike Nolan, chief executive officer at Freenome. "We built Freenome to be able to integrate many analytes and computational methods into one test to implement a 'staircase' of increasing performance for the benefit of patient care. The performance of this initial version establishes a strong foundation and we expect to broaden it to other cancers. Our platform uniquely enables our team to efficiently iterate as we consistently push to achieve what is possible for patients." About PREEMPT CRC PREEMPT CRC (NCT04369053) was a prospective, registrational clinical study to validate Freenome's blood test for the early detection of colorectal cancer (CRC) among average-risk adults. Initiated in 2020, the study was conducted at more than 200 sites and enrolled 48,995 asymptomatic, average-risk participants between the ages of 45 and 85 scheduled to undergo a screening colonoscopy. Freenome and the U.S. Food and Drug Administration agreed upon a predetermined cut-off date for the period most affected by the COVID-19 pandemic. Of the 48,995 participants enrolled, 27,010 were evaluated. The study leveraged a novel hybrid model involving virtual and traditional recruitment methods to reach underserved communities and ensure a representative population. The decentralized recruitment strategy underscores Freenome's commitment to promoting equity and diversity in clinical studies, ensuring its tests are designed for everyone. Freenome's partners in PREEMPT CRC included the Colorectal Cancer Alliance, Dia de la Mujer Latina, the Intercultural Center for Health Research and Wellness, and historically Black colleges and universities (HBCUs), including Morehouse School of Medicine. Freenome also worked with CVS Health Clinical Trial Services to help drive study enrollment through coordinated communication efforts targeting patients with already scheduled colonoscopies. About Colorectal Cancer Though colorectal cancer (CRC) is curable if detected early, sub-optimal screening rates mean CRC is often detected too late for successful treatment, making it the second cause of cancer deaths in the U.S.2 Nearly twice as many people under the age of 55 are diagnosed with CRC than a decade ago, and more people are dying from the disease each year.3 In response, the U.S. Preventive Services Task Force lowered the screening guidelines for average-risk adults from 50 to 45 years old.4 Following screening guidelines can improve detection rates, and catching CRC early can lead to better outcomes.4 Despite the effectiveness of screenings in reducing CRC mortality, only 59% of U.S. adults adhere to screening guidelines.5 Recent data show that providing a blood test as a screening option to individuals who previously declined a colonoscopy or stool test increased screening rates.6 About Freenome Freenome is breaking barriers to early cancer detection with a suite of blood tests built on its multiomics platform. The company recognizes that no single technology can identify every cancer due to the inherent heterogeneity of the disease. Freenome's multimodal approach combines molecular biology and assays with computational biology, machine learning and multiple data types to tune into cancer's subtlest cues, even at the earliest stages of the disease. With the convenience of a standard blood draw, Freenome aims to empower everyone to access recommended cancer screenings. The company is partnering with healthcare organizations and population health decision-makers to integrate its technology and software platform, making cancer detection easier and more accessible. Freenome is headquartered in South San Francisco, California. Find out more at and visit us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the topline results from PREEMPT CRC, the use of information from such study, and Freenome's plans and expectations regarding future versions of PREEMPT CRC, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts, and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors. The forward-looking statements in this press release are based on information available to Freenome as of the date hereof, and Freenome disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Freenome's views as of any date subsequent to the date of this press release. References Xi & Xu. Transl Oncol. 2021;14(10):101174 American Cancer Society. How Common Is Colorectal Cancer? (2023). Cancer.org. American Cancer Society Colorectal Cancer Statistics, 2023 U.S. Preventive Services Task Force. Colorectal Cancer: Screening (2023) Colorectal cancer statistics, 2023. Siegel RL et al. CA: A Cancer J for Clinicians. 2023. doi: 10.3322/caac.21772 Liang, Peter S. et al. "Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial." Clinical Gastroenterology and Hepatology. April 2023 SOURCE Freenome Holdings, Inc.

- Advanced SURF301 Phase 1 oncology study; Initial Phase 1 results to be reported in 2H 2024 - - TYRA-300 Phase 2 ACH IND submission on track for 2H 2024 - - Initiated SURF201 Phase 1 study and dosed first patient with TYRA-200 - - Strengthened balance sheet with approximately $200 million PIPE in Q1 2024; pro-forma cash, cash equivalents, and marketable securities of approximately $403.5 million - CARLSBAD, Calif., March 19, 2024 /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, 2023 and highlighted recent corporate progress. "2023 was an outstanding year for TYRA and we are pleased to have positive momentum at the start of 2024," said Todd Harris, CEO of TYRA. "We have strong conviction in our pipeline and believe our lead program TYRA-300 has the potential to become a best-in-class agent for multiple high-value indications. TYRA-300 remains our top priority and we are focused on submitting our Phase 2 IND for achondroplasia, while optimizing dose in SURF301 in preparation for Phase 2 studies in NMIBC and metastatic urothelial carcinoma." "TYRA is in our strongest financial position to date, with a pro-forma cash position of over $400 million following our PIPE last month. Our ability to retain and attract high quality investors reflects the excitement around our pipeline to deliver value for both shareholders and patient communities," added Alan Fuhrman, Chief Financial Officer of TYRA. "Our current cash, cash equivalents and marketable securities on hand allow us to execute on our plans through at least 2026." Fourth Quarter 2023 and Recent Corporate Highlights Closed a $200M Private Placement Financing. In February 2024, TYRA entered into a securities purchase agreement with new and existing institutional and accredited investors to sell securities in a private placement financing (the PIPE) for gross proceeds of approximately $200 million. The financing was led by RA Capital Management, with participation by new and existing institutional investors, including Boxer Capital, BVF Partners, Nextech Invest Ltd (on behalf of one or more funds managed by it), OrbiMed, 5AM Ventures, a large investment management firm and a life-sciences focused institutional investor. TYRA-300 Received FDA Rare Pediatric Disease Designation for the Treatment of Achondroplasia. In January 2024, TYRA-300 was granted Rare Pediatric Disease (RPD) Designation for the treatment of achondroplasia from the U.S. Food and Drug Administration (FDA). TYRA-300 has also received Orphan Drug Designation (ODD) for the treatment of achondroplasia from the FDA. SURF301 Phase 1/2 Study for Oncology Continued to Advance. The SURF301 Phase 1 study for oncology ( Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552) continues to advance. The study is a multi-center, open label study designed to determine the optimal and maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. TYRA expects that the Phase 1 portion of SURF301 will provide data to inform multiple doses and schedules of TYRA-300 in future studies in metastatic urothelial carcinoma (mUC), non-muscle invasive bladder cancer (NMIBC) and achondroplasia. As of March 2024, the Part A Phase 1 portion of SURF301 has completed dose escalation, and the current expansion cohorts in Part B are evaluating potentially therapeutic once daily and twice daily doses. TYRA expects to submit initial results from its SURF301 Phase 1 portion for presentation at a scientific congress in the second half of 2024. Phase 2 Achondroplasia (ACH) Study On Track. TYRA is planning to initiate a Phase 2 clinical trial testing multiple doses of TYRA-300 to support children with achondroplasia. TYRA expects that the primary objective of this study will be to assess safety and tolerability in children with achondroplasia and determine the dose(s) for further development. TYRA also expects that secondary objectives will include evaluating change in growth velocity, growth proportionality and pharmacokinetics (PK). TYRA is also planning exploratory assessments of clinical outcomes and quality of life measures, and an evaluation of biomarkers to determine dose-response relationships to TYRA-300. TYRA's current expectation is that the study will initially evaluate treatment naïve children ages 5-12 to determine optimal dose ranges and will also include a separate cohort and analysis of children ages 5-12 with achondroplasia who have received and did not tolerate or respond to a prior growth accelerating therapy. TYRA plans to submit an Investigational New Drug (IND) application to the FDA in the second half of 2024 for the initiation of the Phase 2 study. TYRA-200 Phase 1 SURF201 Study Initiated. SURF201 ( Study in Previo Usly 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 PK of TYRA-200 and determine the optimal and MTD and RP2D, as well as evaluate the preliminary antitumor activity of TYRA-200. TYRA-200 is an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. 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. 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 including FGF19+/FGFR4-driven cancers and others. Fourth Quarter and Full Year 2023 Financial Results Fourth quarter 2023 net loss was $22.8 million compared to $12.9 million for the same period in 2022. Fourth quarter 2023 research and development expenses were $20.7 million compared to $10.4 million for the same period in 2022. Fourth quarter 2023 general and administrative expenses were $5.0 million compared to $4.6 million for the same period in 2022. Full year 2023 net loss was $69.1 million compared to $55.3 million for the same period in 2022. Full year 2023 research and development expenses were $62.5 million compared to $43.0 million for the same period in 2022. Full year 2023 general and administrative expenses were $17.4 million compared to $15.9 million for the same period in 2022. As of December 31, 2023, TYRA had cash, cash equivalents, and marketable securities of $203.5 million. Following completion of the approximately $200 million PIPE in February 2024, TYRA's pro-forma cash position of approximately $403.5 million is expected to support the Company's important clinical and operational milestones through at least 2026. 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 dysplasias, including achondroplasia. In oncology, 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). SURF301 (NCT05544552) was designed to determine the optimal and MTD and the RP2D of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. SURF301 is currently enrolling adults with advanced urothelial carcinoma and other solid tumors with FGFR3 gene alterations. In skeletal dysplasias, TYRA-300 has demonstrated positive preclinical results, and the Company expects to submit an IND in the second half of 2024 for the initiation of a Phase 2 clinical study in pediatric achondroplasia. In July 2023 and January 2024, the FDA granted ODD and RPD Designation to TYRA-300, respectively, for the treatment of achondroplasia. About TYRA-200 TYRA-200 is an investigational, oral, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations currently in development for the treatment of cancer. TYRA-200 is being evaluated in a multi-center, open label Phase 1 clinical study, SURF201 ( Study in Previo Usly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors). SURF201 (NCT06160752) was designed to determine the optimal and MTD and the RP2D of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2. 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 initial focus is on applying its accelerated small molecule drug discovery engine to develop therapies in targeted oncology and genetically defined conditions. 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 potential to develop next-generation precision medicines, the potential for TYRA-300 to become a best-in-class agent, and the potential safety and therapeutic benefits of TYRA-300, TYRA-200 and other product candidates; the ability to deliver value for shareholders and patient communities; the sufficiency of our cash position to support clinical and operational milestones; expected cash runway; the potential benefits of regulatory designations; the expected timing and phase of clinical development of TYRA-300 and TYRA-200, including timing of a submission of an IND for TYRA-300 in pediatric achondroplasia, design of our planned Phase 2 study in achondroplasia, and the presentation of SURF301 clinical data at a scientific congress; and the potential for SNÅP to develop therapies in targeted oncology and genetically defined conditions. 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: we are early in our development efforts, have only recently begun testing TYRA-300 and TYRA-200 for oncology in clinical trials 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, enrollment, 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 TYRA-300 in pediatric achondroplasia; 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; later developments with the FDA may be inconsistent with the minutes from our prior meetings, including with respect to the design of our planned Phase 2 study of TYRA-300 in ACH; 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; we may not realize the benefits associated with ODD, including that orphan drug exclusivity may not effectively protect a product from competition and that such exclusivity may not be maintained, or from the RPD Designation, including receipt of a Priority Review Voucher (PRV) or any value therefrom; 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 and adverse developments with respect to financial institutions and associated liquidity risk 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

Investigator-Sponsored Phase 2 Study Demonstrated Positive Results for VOXZOGO in Children with Hypochondroplasia New Analyses Highlight VOXZOGO 7-year Data and Improvement on Quality of Life in Children with Achondroplasia SAN RAFAEL, Calif., March 12, 2024 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced that positive early results from an investigator-sponsored Phase 2 study of VOXZOGO® (vosoritide) in children with hypochondroplasia, will be presented at the 2024 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting in Toronto, Canada, March 12-16, 2024. Researchers will also present data from Phase 2 and Phase 3 studies of the medicine in children with achondroplasia, including results that demonstrate VOXZOGO's positive impact on quality of life. Results in Hypochondroplasia Andrew Dauber, M.D., will present positive results from his investigator-sponsored Phase 2 study of VOXZOGO in children with hypochondroplasia. The annualized growth velocity (AGV) increased from 5.12 cm/year during the observation period to 6.93 cm/year during the treatment period (mean difference: 1.81 cm/year, p<0.0001). No new safety signals were reported. "We are encouraged by preliminary results from the first study evaluating VOXZOGO in children with hypochondroplasia, suggesting the medicine has the potential to impact growth outcomes for this group of patients," said Dr. Dauber, who is the lead study author and Chief of Endocrinology at Children's National Hospital in Washington, D.C. "There are currently no approved medicines for children with hypochondroplasia, so we look forward to gathering additional data to deepen our understanding of VOXZOGO in hypochondroplasia and other growth-related conditions." In late 2023, BioMarin launched the pivotal clinical trial program studying the safety and efficacy of VOXZOGO in children with hypochondroplasia. A multinational observational study in children with hypochondroplasia (111-902) is currently recruiting participants, and the company plans to enter the treatment phase (Phase 3 trial) later this year. New Data Highlights VOXZOGO Long-Term Efficacy, Safety and Quality of Life in Achondroplasia 7-year Phase 2 Results in Achondroplasia Data from two studies of VOXZOGO in children ≥5 years of age with achondroplasia demonstrated a sustained improvement in AGV for each year that the participants were treated. In the Phase 2 study with more than 7 years of follow up, the mean increase in growth across each year of age up to 16 years compared with untreated participants was 1.63 cm/year for boys and 1.33 cm/year for girls. Separate cross-sectional comparative analysis assessing increase in height over a 7-year period showed an additional height gain of 11.03 cm with use of VOXZOGO compared to matched untreated children over the same period. 4-year Phase 3 Results in Achondroplasia The same analyses were produced for the Phase 3 trial in which children with achondroplasia have a mean treatment follow-up of 4 years. The mean increase in growth across each year of age up to 17 years was 1.73 cm/year for boys and 1.46 cm/year for girls. A separate cross-sectional comparative analysis assessing increase in height over a 3-year period showed an additional height gain of 5.75 cm with use of VOXZOGO compared to matched untreated children over the same period. 3-year Phase 3 Quality of Life Results in Achondroplasia Results from a separate analysis of the Phase 3 study showed that VOXZOGO improved health-related quality of life (HRQoL) among children with achondroplasia, particularly those associated with physical activities. After 3 years, the mean increase in Quality of Life in Short Stature Youth (QoLISSY) physical domain score was 6.0 as reported by caregivers and 6.3 as reported by children. These improvements were even more pronounced in children who grew more (for those with ≥ 1 SD increase in height z-score, the mean increase in physical domain score was 11.4 as reported by caregivers and 8.5 as reported by children). "The clinical results at ACMG reinforce the long-term benefit we are seeing in children treated with VOXZOGO, with a meaningful median height gain of more than 11 cm in children with achondroplasia following 7 years of treatment," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "We are particularly encouraged by new data demonstrating the potential impact height gains from VOXZOGO can have on quality of life, an outcome of incredible importance for children and families impacted by achondroplasia." "Achondroplasia can have a negative effect on a child's quality of life, including physical, social and emotional aspects," said Melita Irving, M.D., study investigator and consultant clinical geneticist at Guy's and St. Thomas' NHS Foundation Trust in London. "Our studies showed that increasing height with long-term administration of VOXZOGO can result in meaningful improvements in quality-of-life measures for children with achondroplasia." BioMarin's full list of presentations at ACMG includes: BioMarin Poster Presentations Persistence of Growth-Promoting Effects in Children with Achondroplasia Up to 7 Years: Update from a Phase 2 Extension Study with Vosoritide Poster #: P144 Friday, March 15, 2024, 10:30 a.m. – 12 p.m. ET Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia for Up to 4 Years: Update from Phase 3 Extension Study Poster #: P139 Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia is Accompanied by Improvement in Physical Aspects of Quality of Life Poster #: P141 Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET Persistence of Growth-Promoting Effects in Infants and Toddlers with Achondroplasia: Results from a Phase 2 Extension Study with Vosoritide Poster #: P131 Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET Exploring the Landscape of Phenylketonuria Education and Learning Needs of Genetics Trainees Poster #: P049 Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET Reduction of Blood Phenylalanine in Participants Enrolled in OPAL, an Observational Study, Mirror Findings from the U.S.-based PRISM Population Poster #: P034 Friday, March 15, 2024, 10:30 a.m. – 12 p.m. ET Investigator-Sponsored Oral Presentation Vosoritide Increases Growth Velocity in Hypochondroplasia: Phase 2 Trial Results Oral Session: O03 Thursday, March 14, 2024, 1:30 – 3 p.m. ET 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. and indicated to increase linear growth in children with achondroplasia with open epiphyses. 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 . For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com. 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. 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 including 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. Tell your doctor about all of the medicines the patient takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. 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 , or call 1-800-FDA-1088. Please see additional safety information in the full Prescribing Information and Patient Information. About BioMarin Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of the genetic conditions. BioMarin's unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options. For additional information, please visit . 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 2024 American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, including the six poster presentations and the investor-sponsored oral presentation; the development of BioMarin's VOXZOGO program generally; the potential benefits of VOXZOGO for children with achondroplasia, including the duration of such benefits, potential improvement in annualized growth velocity (AGV), and potential improvement in health-related quality of life; the potential efficacy of VOXZOGO for children with hypochondroplasia, including potential to impact growth outcomes; and the continued clinical development of VOXZOGO, including BioMarin's plans for launching the treatment phase of the Phase 3 trial studying the safety and efficacy of VOXZOGO in children with hypochondroplasia. 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; 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, 2023 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® and VOXZOGO® are registered trademarks of BioMarin Pharmaceutical Inc. Company Codes: NASDAQ-NMS:BMRN