Executive Summary / Key Takeaways

• Amicus Therapeutics is transitioning from a development-stage company to a profitable commercial entity, driven by strong growth from its two rare disease therapies, Galafold for Fabry disease and Pombiliti + Opfolda for Pompe disease.
• Galafold continues to demonstrate robust demand, particularly from newly diagnosed patients, supported by strong IP protection extending to 2037 and high patient adherence rates, positioning it for sustained double-digit growth and a path to $1 billion in sales.
• Pombiliti + Opfolda is gaining significant traction in its global launch, capturing market share from existing therapies and expanding into new geographies, with management anticipating accelerating sales in the latter half of 2025 despite initial timing shifts and rebate impacts.
• The recent U.S. licensing of DMX-200 for FSGS strategically expands Amicus's late-stage pipeline into a rare kidney disease with synergistic call points, leveraging existing infrastructure and adding a potential blockbuster opportunity with success-based financial terms.
• The company achieved non-GAAP profitability in 2024 and is on track for GAAP profitability in the second half of 2025, underpinned by disciplined expense management and the leverageability of its global rare disease organization, providing a solid financial foundation for future growth and potential portfolio expansion.

The Foundation of a Rare Disease Leader

Amicus Therapeutics, Inc. has evolved significantly since its incorporation in 2002, transforming from a research-focused entity into a global, patient-dedicated biotechnology company with two commercial therapies for devastating rare diseases. The company's journey has been marked by a strategic focus on discovering, developing, and delivering high-quality medicines, initially funding operations through various financing arrangements while incurring operating losses. This history laid the groundwork for building the specialized infrastructure required to serve niche patient populations.

The company's core strategy revolves around providing first- or best-in-class therapies that offer significant benefits over existing treatments. This strategy is embodied by its two marketed products: Galafold for Fabry disease and Pombiliti + Opfolda for Pompe disease. These therapies operate within the competitive landscape of lysosomal storage disorders, where established players like Sanofi (SNY) have historically held significant market share with enzyme replacement therapies (ERTs) like Fabrazyme and Myozyme/Lumizyme, and newer entrants like Ultragenyx Pharmaceutical (RARE) and BioMarin Pharmaceutical (BMRN) also compete with specialized therapies and gene therapy approaches.

Amicus differentiates itself through precision medicine and novel therapeutic designs. Galafold, an oral pharmacological chaperone, represents a distinct approach for Fabry patients with amenable genetic variants, offering the convenience of oral administration compared to intravenous ERTs. Pombiliti + Opfolda, a two-component system combining an engineered enzyme (cipaglucosidase alfa-atga) with an oral stabilizer (miglustat), is designed to enhance enzyme uptake and stability, aiming to improve outcomes for late-onset Pompe disease patients, including those previously treated with other ERTs. This focus on differentiated mechanisms and patient-friendly administration forms a key part of Amicus's competitive moat.

Technological Edge and Innovation Pipeline

Amicus's competitive position is significantly shaped by its technological differentiators. Galafold's oral administration for amenable Fabry patients offers a tangible benefit over traditional intravenous ERTs, potentially reducing the burden of frequent infusions. While specific quantitative data on reduced clinic visits or cost savings per patient compared to intravenous therapies is not readily available, the convenience of an oral therapy is a clear advantage for patient quality of life and adherence. Galafold works by stabilizing the patient's own dysfunctional alpha-Gal A enzyme, a precision approach targeting the underlying genetic defect in a subset of Fabry patients.

Pombiliti + Opfolda employs a novel two-component system. Pombiliti is an engineered enzyme with an optimized carbohydrate structure designed for enhanced cellular uptake via the M6P receptor, while Opfolda (miglustat) acts as an oral stabilizer to reduce enzyme inactivation in circulation. This combination aims to improve the delivery and activity of the enzyme in key disease-relevant tissues. Clinical data, particularly from the PROPEL study, has shown improvement in ERT-experienced patients, a critical point of differentiation against therapies that may primarily focus on stabilizing or slowing decline. Management highlights that this therapy is challenging therapeutic expectations and providing a real choice for patients. While specific quantitative metrics on enhanced uptake or stability versus competitor enzymes are not readily available, the clinical outcomes observed in trials support the functional benefits of this design.

Beyond its marketed products, Amicus is investing in next-generation therapies for Fabry and Pompe diseases. This includes focused discovery work on novel technologies, such as genetic medicines and alternative delivery approaches. The stated goal is to develop more active, potent, and stable enzymes or gene constructs. This R&D aims to address patient populations not currently treatable with Galafold (e.g., non-amenable Fabry patients) and potentially offer improved outcomes for Pompe patients. While specific target metrics or timelines for these early-stage programs are not detailed, this ongoing innovation demonstrates a commitment to maintaining scientific leadership and expanding the potential patient reach in its core franchises, which is a key "so what" for investors looking at long-term growth drivers beyond the current portfolio.

Commercial Momentum and Financial Trajectory

Amicus has demonstrated consistent commercial execution, delivering its eleventh consecutive quarter of double-digit sales growth in Q1 2025 from its core Fabry and Pompe businesses. Total net product sales reached $125.2 million in Q1 2025, a 13% increase (15% at CER) compared to $110.4 million in Q1 2024. This builds on a strong FY 2024 performance, where total revenue hit $528 million, representing 32% growth (33% at CER) over FY 2023.

Galafold remains a foundational growth driver, with Q1 2025 sales of $104.2 million, up from $99.4 million in Q1 2024. Underlying patient demand remains strong, with new patient starts globally up 14% in Q1 2025, putting the company on track for the highest level of new patient starts this year. Galafold ended Q1 2025 with over 69% global market share of treated amenable Fabry patients, with mature markets showing potential to reach 85-90% share. Growth is driven by penetrating the diagnosed untreated population, expanding into new geographies, increasing market share, and maintaining high compliance and adherence rates (>90%). The long-term outlook is bolstered by the IP settlement with Teva (TEVA), securing U.S. market exclusivity until at least January 30, 2037, supporting the company's confidence in Galafold surpassing $1 billion in revenue over its lifecycle.

Pombiliti + Opfolda is rapidly contributing to growth, with Q1 2025 revenue of $21.0 million, a significant increase from $11.0 million in Q1 2024 (92% growth at CER). The launch is gaining momentum, driven by initial markets like the U.S., Germany, and Spain. The U.S. represented approximately 45% of Q1 revenue and contributed 65% of the growth for the Pompe franchise. The company is seeing patients switching proportionally from existing therapies (Myozyme/Lumizyme and Nexviazyme) based on market share, as well as increasing the breadth and depth of prescribers. Geographic expansion is a key driver, with launches in 7 countries in Q1 2025 and anticipated first patients in four more countries in Q2. Recent successes include selection as the preferred treatment in the Netherlands. Regulatory approvals in Australia and Canada have been secured, and a submission is under review in Japan.

While Q1 2025 revenues for both products were impacted by some unexpected factors, including non-linear ex-U.S. ordering patterns and higher-than-anticipated UK VPAG rebates (22% vs. expected max 15%), management is highly confident in sales acceleration through the remainder of the year. The revised 2025 Pombiliti + Opfolda revenue growth guidance (50-65% at CER, down from 65-85%) reflects the timing shift of new patient starts in newly reimbursed markets towards the second half of the year and the UK rebate impact, but still implies a healthy exit rate.

Financially, Amicus is progressing towards profitability. The company achieved non-GAAP profitability in 2024 and reiterated its target of achieving positive GAAP net income during the second half of 2025. Gross margins were approximately 90% in FY 2024 but are expected to be in the mid-80s range for FY 2025, which management describes as a "hybrid year" due to working through previously expensed Pombiliti + Opfolda inventory in the first half. Operating expenses are being managed disciplinedly, with non-GAAP OpEx guidance for 2025 set at $380 million to $400 million, including the $30 million upfront payment for the Dimerix deal. Liquidity remains solid, with $250.6 million in cash, cash equivalents, and marketable securities as of March 31, 2025. Net cash provided by operating activities improved significantly in Q1 2025 ($7.8 million) compared to Q1 2024 (net cash used of $29.7 million), reflecting improved operational cash flow generation.

Strategic Portfolio Expansion and Competitive Dynamics

A significant strategic move occurred on April 30, 2025, with the exclusive U.S. licensing agreement for DMX-200 from Dimerix Limited (DMX). This Phase 3 drug candidate targets Focal Segmental Glomerulosclerosis (FSGS), a rare kidney disease with no specifically approved therapies in the U.S. This collaboration represents a deliberate step to expand Amicus's pipeline with a late-stage, de-risked asset in a disease area that offers significant synergies with its existing capabilities, particularly the nephrologist call points and established regulatory and commercial infrastructure.

DMX-200 is a small molecule inhibitor of CCR2, differentiated from previous failed CCR2 inhibitors by targeting downstream signaling from the A1TR CCR2 heteromer on damaged kidney tissue, rather than direct binding. This mechanism is designed to address the inflammatory component of FSGS. The pivotal Phase 3 ACTION3 study is enrolling patients (185 of 286 target as of Q1 2025 filing), with full enrollment expected around the end of 2025. Positive early interim data showed DMX-200 outperforming placebo in reducing proteinuria, and the FDA has aligned on proteinuria as an appropriate primary endpoint for traditional approval. The deal structure, with a $30 million upfront and significant success-based milestones (up to $75M development/regulatory, $35M first sale, $410M commercial, $40M future indications) and tiered royalties, aligns financial commitment with clinical and commercial success. Amicus will handle U.S. regulatory and commercial activities, leveraging its established rare disease expertise. This asset adds a potential blockbuster opportunity to the portfolio, diversifying revenue streams beyond Fabry and Pompe.

In the broader competitive landscape, Amicus competes with larger, more diversified pharmaceutical companies like Sanofi, which has established ERT franchises in Fabry and Pompe. While Sanofi benefits from scale, broader global distribution, and higher profitability margins (e.g., Sanofi's 2024 gross margin ~70% vs. FOLD's ~90% in FY24, expected mid-80s in FY25), Amicus is demonstrating its ability to take market share, as evidenced by Sanofi's global Pompe franchise decline in Q1 2025. Amicus's focus on differentiated technology and patient-centricity provides a competitive edge, particularly for amenable Fabry patients with Galafold and for Pompe patients seeking improved outcomes with Pombiliti + Opfolda. Compared to smaller biotech focused on rare diseases like Ultragenyx and BioMarin, Amicus's current strength lies in its growing commercial revenue and clear path to GAAP profitability, contrasting with some peers who remain in earlier stages of commercialization or profitability. However, peers like BioMarin exhibit higher gross margins (e.g., BioMarin's 2024 gross margin ~80%) and potentially broader R&D pipelines in genetic medicines. Amicus's strategy to in-license late-stage assets like DMX-200 is a response to leverage its commercial infrastructure and accelerate portfolio expansion, complementing its internal, earlier-stage R&D efforts.

Outlook and Risks

Amicus's outlook is centered on continued strong commercial growth and achieving profitability. The company guides for total revenue growth of 15% to 22% at CER in 2025. This is driven by Galafold growth of 10% to 15% at CER and Pombiliti + Opfolda growth of 50% to 65% at CER. Management remains confident in reaching combined sales of $1 billion by the end of 2028. The path to GAAP profitability in the second half of 2025 is supported by disciplined non-GAAP OpEx management, despite the Dimerix upfront payment and ongoing R&D investments.

Key risks to this outlook include the potential for unexpected impacts on revenue, such as the higher UK VPAG rebates or non-linear ordering patterns experienced in Q1 2025. The timing and success of Pombiliti + Opfolda launches and reimbursement in new countries are critical to achieving growth targets. While management does not expect a material impact from potential tariffs in 2025 due to proactive supply chain planning, this remains an evolving risk. Fluctuations in foreign currency exchange rates can also impact reported revenues. The success of the DMX-200 program is contingent on positive Phase 3 data and regulatory approval, although the deal structure mitigates some financial risk through success-based milestones. Ongoing litigation related to Galafold IP, while bolstered by the Teva settlement, continues against other parties.

Conclusion

Amicus Therapeutics is executing a clear strategy focused on leveraging its established commercial success in rare diseases to drive profitability and fund future growth. The strong performance of Galafold, underpinned by its differentiated oral technology and robust IP, provides a stable foundation and significant long-term revenue potential. The global launch of Pombiliti + Opfolda is gaining critical momentum, capturing market share and expanding geographic reach, positioning it as a major growth driver. The strategic in-licensing of DMX-200 represents a prudent expansion into a synergistic rare kidney disease, adding a potential blockbuster opportunity and leveraging Amicus's existing infrastructure. With a clear path to GAAP profitability in the second half of 2025 and a disciplined approach to expense management, Amicus is building the financial strength necessary to support its growth trajectory and potentially expand its portfolio further. While facing competitive pressures and inherent risks in the rare disease market, Amicus's focus on differentiated therapies, commercial execution, and strategic expansion presents a compelling narrative for investors looking for growth in the biotechnology sector.