A：Biomarin Pharmaceuticals achieved strategic goals for Ly in 2025 while experiencing outstanding growth. The specific strategic accomplishments were not detailed in the provided transcript excerpt, but the company is proud of the progress and is excited about the potential for further expansion with future product approvals.

A：Biomarin's recent acquisitions include Innerzone Me, which strengthened their Enzyme Therapies portfolio with the addition of bmn 401 for enzyme deficiencies, and Amicus, which could add treatments for Fabre disease and Pompei disease. The acquisition of Amicus is expected to close next quarter and could significantly expand their commercial portfolio. The potential addition of hypochondroplasia to their portfolio is also highlighted, supported by positive PK data for the bmn 333 therapy, which is in phase 2/3 study.

A：Anticipated pipeline highlights for 2026 include the potential addition of hypochondroplasia to their global skeletal condition treatment offerings by early 2026, based on upcoming pivotal results. Also, the bmn 333 phase 2/3 study is expected to begin enrollment, with potential for setting a new standard of care for patients with achondroplasia.

A：Biomarin expects enzyme therapies to deliver high single-digit growth and Voseco to continue its trajectory towards blockbuster status. Post-acquisition, the integration of Gallop Fold and probability and unfolded medicines is anticipated to enable both to reach more people around the world with habre and Pompeii, significantly enhancing the 2026 outlook and driving accelerated revenue growth through 2030. The company plans to provide updated guidance after the close of the Amicus acquisition.

A：For full year 2026, Biomarin provided initial guidance that excludes post-closure contributions from the Amicus acquisition. They expect enzyme therapies revenue between $2.225 billion to $2.275 billion and Voseco revenue of $975 million to $1.025 billion. The guidance also factors in significantly lower royalty revenues from Huan and roctavian, which will affect year-over-year comparisons of total revenue. After the acquisition, the company anticipates a meaningful uplift to their guidance, with a projected non-GAAP diluted earnings per share in the range of $4.95 to $5.15 per share, and an underlying organic operating margin expectation of approximately 40%.

A：The first quarter of 2026 is anticipated to be the lowest total revenue quarter with both total revenues and VoxelGo revenue expected to be on par with Q1 2025. It is also expected to have the lowest non-GAAP diluted earnings per share, influenced by the vast majority of pre-closed Amicus costs.

A：Enzyme therapies in 2025 delivered year-over-year revenue growth across every product in the portfolio, leading to a 9% growth. The primary growth driver in the enzyme therapy portfolio in 2026 is expected to be Palin Zeke, supported by an adolescent label expansion with a U.S. FDA action date of February 28 and anticipated European approval later that year.

A：The growth strategy for Voxgo in 2026 is focused on a multi-pronged approach, including driving new Sart globally across all ages with an emphasis on children under 2, expanding into incident markets, finding and starting treatment eligible infants, and increasing uptake in fast-growing newly launched markets.

A：Recent examples include Fox Sogo reaching approximately 40% penetration within 7 months in the Asia Pacific region and achieving approximately 70% penetration within 12 months in a mid-size European country. These successes were attributed to early engagement with clinicians, patient advocacy groups, and strong relationship building with stakeholders.

A：The company is planning to submit a full approval package for Vox Sogo in the U.S., which will present comprehensive data on final adult height, health and wellness outcomes, and quality of life impacts. With over 10,000 patient years of safety data, the submission aims to establish Vox Sogo as the standard of care for achondroplasia.

A：The Phase III study for bmn 333 will enroll 60 patients in each arm and aims to have 90% power to detect a 50% increase in annualized growth velocity versus Vox Sogo. This could translate into a growth increase of 2.25 cm per year over placebo. The study seeks to establish bmn 333 as the new standard of care for achondroplasia and potentially other skeletal conditions.

A：Anticipated highlights in 2026 include phase 3 data readouts for Vox Sogo in hypochondroplasia and for bmn 401 in enpp 1 deficiency, serving as key steps toward potential approvals as the first genetically targeted therapies for their respective indications. There is also the US FDA action date of February 28 for Palin Zeke for adolescent PKU, along with ongoing enrollment in a 12 mg per kilogram cohort for emn 351.

A：The recently released data for the Fgfr 3 inhibitor is comparable to other CNP class effects at one year, and while short-term data on durability and safety is available, long-term data and the read-through course will be important. The data supports the value proposition of Vaxago with its 10,000 patient years of safety information and evidence beyond height, including frame, function, and quality of life.

A：The preliminary market research suggests that the potential growth of the Fgfr 3 inhibitor is important not just as an outcome but also as a surrogate for the health and wellness of patients. It is believed that the increase in growth could lead to a best-in-disease profile valued by patients, payers, and physicians.

A：Early treatment with Vaux Sogo is considered critical by international guidelines and the data presented, with the treatment providing the longest-term benefit. The data has shown this to be true across 1,000 patient years of data across all age groups, including the pediatric space.

A：Market research and field interactions indicate that patients who are doing well on Vaux Sogo are reluctant to switch to another therapy. The decision to switch is driven more by the performance of the patients, caregivers, and healthcare professionals (HCPs) rather than by HCPs themselves. Long-term safety and efficacy data will play an essential role in this decision process.

A：The plans for communicating the differentiation and superiority of bmn 351 involve presenting full data at the MDA conference next month. There will also be an opportunity to share 6 and 9 mg per kilogram data at the Shanes Muscular Dystrophy Association meeting in March. The company is encouraged by the data and wants to gather more chronic safety data and functional data before making further comments on bmn 351.

A：Patients, physicians, and caretakers are being provided with a wealth of data for Vaux Sogo that will be presented in the full evidence package for FDA approval. This data is particularly relevant for very young infants. The considerations include the ability to understand the data in the context of the medicine they are prescribed, which Vaux Sogo has demonstrated through long-term safety and efficacy data, and durability of effect over time.

A：Market dynamics differ between hypochondroplasia and achondroplasia as hypochondroplasia is seen as a faster-growing market. The upcoming results are expected to measure an effect size similar to what was seen for chondroplasty in achondroplasia patients, with the goal of not only measuring AGV but also looking at measures of health and wellness. The company is excited about reaching endpoints and seeing data in this area.

A：To enhance diagnosis and shorten the journey to diagnosis for hypochondroplasia, the company is educating on signs and symptoms requiring further evaluation and genetic testing, as well as establishing and disseminating guidelines for when to refer and test patients.

A：It is estimated that there are around 14,000 patients with hypochondroplasia in the market.

A：The targeted patient profile for the clinical trial includes those patients who are more negatively affected in terms of standard deviations for growth deficit.

A：The full approval for a product will provide an opportunity to present the totality of data, including measures of health and wellness, to regulators. This can enhance patient confidence in the product, build on the existing confidence in its safety and efficacy, and present a chance to differentiate the product as a leading evidence package in the market.

A：The guidance for the current year's growth reflects a range of scenarios, including potential competitive impact from new entrants in 2027 and being guarded on a couple of routine market access renegotiations. The guidance implies the company's cautious approach to the market's response to competition and its efforts to ensure product access.

A：The anticipated timeline for data readouts from the Phase 2 canopy basket study for the product is in the 2027 timeframe.

A：The projected growth rate for the product in the upcoming year is a single-digit rate, indicating that the product is expected to maintain its position as a blockbuster, with the infant market remaining 100% covered by the product.

A：The company anticipates that formal reimbursement processes will lead to broader access in established markets. They expect to negotiate potentially lower prices but have the opportunity to reach many more patients, suggesting an overall positive impact on the product's market access.

A：Based on preclinical data, there are no meaningful differences expected in safety profiles between the new drug and the existing treatment, with the new drug allowing higher exposures and potentially a better therapeutic window.

A：The two products are expected to seamlessly integrate into the enzyme therapy business unit post-close, leveraging the same go-to-market model as the current portfolio, which is anticipated to drive significant synergies on both the top line and in operational efficiencies.

A：The intention behind the comment was to clarify that some analysts had post-closure Amicus revenues included in their biomarin models, while others did not. This confusion was addressed to ensure there was clarity on the company's position and expectations for the deal impact.

A：Amicus is currently analyzing ongoing pilot programs and determining how they can be integrated with existing company operations. The company is running as an independent business at present, and pilots are continuing. The focus is on increasing diagnosis rates for both Fabry and Pompe diseases and driving the switch to enzyme therapy treatments.

A：The impact of a new market entrant on quarterly revenue patterns is discussed in terms of potential order patterns and the weighting of revenue towards the fourth quarter. The timing of the hypochondroplasia launch is set for the second half of the year with an expected immediate revenue impact upon approval in 2027, following top line data presentation in the first half.

A：The phase 3 clinical trial for bMN 33 is not based on a threshold effect but on the statistical significance and clinical relevance of the sample size outlined. The company aims to achieve a trajectory of improvement that meets both statistical and clinical standards. While a Bayesian approach will be used to evaluate the totality of the data, the company is confident that the planned study will achieve meaningful improvement over the established treatment, and the protocol may be modified if necessary based on Phase I data.