Stoke Therapeutics, Inc. (STOK): PESTLE Analysis [Nov-2025 Updated]

Stoke Therapeutics, Inc. is a high-stakes biotech play, and you need to know that while their proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) platform and Orphan Drug status offer a clear path to potential peak sales over $1.5 billion annually, the company is still burning cash-projecting R&D near $170 million in 2025-and operates under the constant shadow of drug pricing politics and strict regulatory oversight. This isn't just about the science; it's about navigating a terrain where political headwinds and economic realities are just as critical as the clinical trial data. So, let's map out the external forces that will defintely determine if STOK hits that billion-dollar mark.

Stoke Therapeutics, Inc. (STOK) - PESTLE Analysis: Political factors

US FDA Fast Track and Orphan Drug Designation offer regulatory advantages

The political and regulatory environment is defintely a tailwind for Stoke Therapeutics, Inc., thanks to key designations for its lead candidate, zorevunersen (STK-001), which targets Dravet syndrome. This is one of the clearest political advantages you can get in biotech.

Specifically, zorevunersen has been granted Orphan Drug Designation (ODD) by the FDA, which is a major win. ODD provides a powerful set of incentives designed to offset the high cost of developing treatments for rare conditions affecting fewer than 200,000 people in the U.S.

Plus, the FDA gave zorevunersen Breakthrough Therapy Designation (BTD) in late 2024. This BTD status automatically grants the drug all the benefits of Fast Track designation, meaning the company gets intensive guidance from senior FDA managers and an expedited review process.

These designations translate into concrete financial and market benefits:

• Potential seven years of market exclusivity upon approval.
• Waiver of the New Drug Application (NDA) user fee, which is a substantial saving.
• Access to the 25% federal Orphan Drug Tax Credit (ODTC).

Government funding and tax incentives for rare disease research remain stable

The U.S. government continues to provide a stable, albeit complex, framework of financial support for rare disease R&D. The core incentive is the Orphan Drug Tax Credit (ODTC), which offers a 25% federal tax credit on qualified clinical testing expenses.

A significant, positive political change for the 2025 fiscal year is the tax treatment of research expenses. Starting in 2025, expenses under Section 174 of the tax code-which include the clinical trial costs eligible for the ODTC-can be fully deducted in the year they are incurred. This reverses the 2022-2024 requirement for capitalization and amortization, immediately improving Stoke Therapeutics' cash flow and tax efficiency in the near term.

Beyond tax breaks, direct funding remains available. The FDA's Orphan Products Grants Program continues to fund clinical trials and natural history studies. For example, the Clinical Studies of Orphan Products R01 grant has a receipt date of October 21, 2025, offering a clear, recurring path for external funding to support pipeline expansion beyond zorevunersen.

Global trade tensions could impact supply chain for specialized raw materials

While Stoke Therapeutics is a U.S.-based biotech, the global political climate is creating significant supply chain risk, especially for specialized raw materials like the active pharmaceutical ingredients (APIs) and other components needed for its antisense oligonucleotide (ASO) technology. This is a clear near-term headwind.

The Trump administration's trade policy in 2025 has introduced new tariffs that directly affect the life sciences sector. A 55% consolidated tariff on Chinese imports, for instance, took effect on June 11, 2025. This is a huge cost shock.

The pharmaceutical supply chain is highly exposed: approximately 82% of API 'building blocks' for vital drugs are sourced from China and India. Even if Stoke Therapeutics doesn't source directly from China, their contract manufacturers almost certainly rely on these upstream inputs. The threat of a 100% tariff on branded or patented drugs announced in September 2025, unless manufacturing is moved to the U.S., only heightens this risk and forces a costly re-evaluation of the entire manufacturing footprint.

Political pressure on drug pricing, especially for novel therapies, is a constant

The political focus on high drug prices is relentless and presents a long-term risk to Stoke Therapeutics' future revenue model. The company's novel, disease-modifying therapy, zorevunersen, will command a premium price, making it a target for political scrutiny.

The administration in 2025 is aggressively pushing a 'most favored nation' (MFN) policy, aiming to force U.S. drug prices to match the lowest prices paid in developed foreign countries. This policy, if fully enacted and upheld against expected legal challenges, would dramatically cut the potential U.S. revenue for zorevunersen and other future TANGO platform drugs.

Also, the Inflation Reduction Act (IRA) drug negotiation program is in its second year of implementation in 2025. While orphan drugs for a single indication are currently excluded from Medicare price negotiation, there is constant political pressure and legislative efforts to amend this exclusion, which would immediately expose zorevunersen to price caps post-approval.

US election cycles defintely influence healthcare policy uncertainty

The political environment in 2025 is defined by policy volatility following the election cycle. The new administration and Congress are actively mobilizing their agendas, which creates a high degree of uncertainty for long-term strategic planning.

The drug pricing executive orders issued in May and September 2025, while signaling a clear intent to lower prices, have been criticized for lacking immediate, clear mechanisms and are expected to face significant legal challenges. This means the rules of the road for drug pricing are in flux, making it difficult to project long-term cash flows for a potential 2027/2028 drug launch.

Here's the quick math on the regulatory environment:

Stoke Therapeutics, Inc. (STOK) - PESTLE Analysis: Economic factors

High R&D expenditure continues, with 2025 projected to be near $170 million

You need to understand that Stoke Therapeutics is a clinical-stage company, meaning its entire economic model is built on burning cash now to generate massive revenue later. This is a capital-intensive business, so R&D spending is the key metric. For the nine months ending September 30, 2025, Research and Development expenses were already $96.2 million, a significant increase from the prior year as the zorevunersen (STK-001) Phase 3 EMPEROR trial ramps up.

The full-year 2025 R&D expenditure is projected to be near $170 million, reflecting the cost of advancing a first-in-class antisense oligonucleotide (ASO) into late-stage clinical development. This projection implies a substantial increase in Q4 spending, driven by clinical site initiation and increased manufacturing costs for the Phase 3 trial. You are defintely paying for a potential disease-modifying therapy.

Reliance on capital markets for funding operations until STK-001 commercialization

The company's reliance on capital markets is high but currently well-managed. As of September 30, 2025, Stoke Therapeutics had a strong cash position of $328.6 million in cash, cash equivalents, and marketable securities. This cash runway is anticipated to fund operations into mid-2028, which is beyond the expected Phase 3 data readout in the second half of 2027.

Still, the company maintains flexibility for future funding. They recently raised an additional $48.7 million after September 30, 2025, through an At-The-Market (ATM) offering, and have a mixed shelf offering on file, allowing them to issue up to $400 million in various securities as needed. This strategic financial planning buys them time and leverage.

• Cash as of Q3 2025: $328.6 million.
• Anticipated cash runway: Mid-2028.
• Post-Q3 ATM raise: $48.7 million.

Potential peak sales for STK-001 in Dravet Syndrome could exceed $1.5 billion annually

The economic opportunity for zorevunersen in Dravet Syndrome is substantial, which is why the R&D burn is justified. Dravet Syndrome is a rare genetic epilepsy affecting an estimated 38,000 patients across major markets (U.S., UK, EU-4, and Japan). Investment bank Jefferies initiated coverage in July 2025, projecting peak annual sales for zorevunersen in the range of $1 billion to $1.5 billion, with an upside scenario reaching $4 billion if the disease-modifying effects are profound.

This valuation is based on zorevunersen's potential to be a first-in-class, disease-modifying therapy, which commands premium pricing in the rare disease space (orphan drugs). The collaboration with Biogen for ex-North America rights, which included a $165 million upfront payment and up to $385 million in milestones, further validates this multi-billion-dollar market potential.

Inflationary pressures increase costs for clinical trials and specialized personnel

General macroeconomic inflation is directly impacting the cost of running clinical trials, a critical factor for Stoke. The average per-patient trial costs in the U.S. rose by approximately 12% compared to 2023, according to a June 2025 EvaluatePharma report. This increase is compounded by rising costs for specialized personnel and supply chain issues.

Specifically, the company's Q3 2025 financial reports cited that the increase in operating expenses was driven by higher personnel expenses and launch readiness expenses. Geopolitical issues and US tariffs on pharmaceutical ingredients and medical supplies (ranging from 15% to 25% on some inputs) are also inflating the cost of reagents and consumables for the Phase 3 trial.

Interest rate environment affects the cost of future debt financing

The Federal Reserve's shift to an easing cycle in 2025 is a positive economic tailwind for growth-stage biotechs. Following a quarter-percentage point cut, the federal funds rate is now in the 4.00-4.25% range as of September 2025. This environment directly influences the cost of capital.

Lower interest rates reduce the discount rate used in valuing future cash flows, which is crucial for a company like Stoke that is valued on projected 2030+ revenues from zorevunersen. Also, should Stoke decide to tap into its mixed shelf offering for debt financing, the lower interest rate environment makes borrowing cheaper and more accessible. This improves the appeal of the sector to risk-on investors, which is good for equity raises too.

Stoke Therapeutics, Inc. (STOK) - PESTLE Analysis: Social factors

High unmet medical need for a disease with significant morbidity and mortality

The social imperative for Stoke Therapeutics, Inc.'s zorevunersen (STK-001) is driven by the profound and enduring burden of Dravet Syndrome (DS), a severe developmental and epileptic encephalopathy. This is not just a seizure disorder; it is a life-altering condition with high morbidity and mortality. In the U.S., the patient population is estimated at approximately 16,000 people living with Dravet Syndrome.

The severity of the disease creates an urgent social need. Despite treatment with standard-of-care anti-seizure medicines, children with DS experience a high seizure burden, and a November 2025 study showed their neurodevelopment often plateaus at a developmental age of approximately two years old, causing a widening developmental gap over time. The mortality rate is tragically high, estimated at 15% to 20% by adulthood, primarily due to sudden unexpected death in epilepsy (SUDEP) and status epilepticus (prolonged seizures).

Here's the quick math on the patient need:

Strong, organized patient advocacy groups for Dravet Syndrome drive adoption

The Dravet Syndrome Foundation (DSF) and other advocacy groups are highly organized, acting as a powerful social force that directly influences research, policy, and treatment adoption. This community engagement is defintely a tailwind for Stoke Therapeutics, Inc. The DSF actively engages in legislative advocacy, including participation in Rare Disease Week on Capitol Hill in 2025, to champion policies that support the community.

Their financial support and collaboration are critical. For example, the Dravet Syndrome Foundation announced $1.4 million in new grant awards in 2024, demonstrating their commitment to funding high-impact research. This level of organization ensures that, upon regulatory approval, there will be an immediate, informed, and vocal patient base pushing for rapid access and reimbursement for zorevunersen. They are already actively encouraging patient participation in clinical trials, which streamlines the development process.

Growing demand for non-curative, disease-modifying treatments like STK-001

The market is shifting from purely symptomatic control to disease-modifying treatments (DMTs), a trend that STK-001, or zorevunersen, is positioned to capitalize on. Zorevunersen is an antisense oligonucleotide (ASO) designed to address the underlying genetic cause-the haploinsufficiency of the SCN1A gene-by increasing the functional NaV1.1 protein.

This approach, which aims to improve cognition and behavior alongside seizure reduction, is exactly what the patient community is demanding. Early results from open-label extension studies, presented in October 2025, showed continuing improvements in cognition and behavior at two years, which contrasts sharply with the minimal changes seen in natural history studies with standard-of-care. This clinical benefit beyond just seizures is the key social differentiator for Stoke Therapeutics, Inc. The rare epilepsy syndromes therapeutics market is projected to grow to $2.25 billion in 2025, with growth supported by greater adoption of gene therapies and precision medicine.

Public perception of genetic therapies is generally positive but sensitive to safety events

Public sentiment toward genetic therapies is broadly positive for therapeutic uses, especially for severe, life-threatening rare diseases with few options. This is a huge benefit for a company like Stoke Therapeutics, Inc.

However, the field is highly sensitive to safety issues. A significant risk factor is the public scrutiny following adverse events in other gene therapy products. For instance, in November 2025, the FDA approved a Boxed Warning for Elevidys, a gene therapy for Duchenne muscular dystrophy, following two reports of fatal acute liver failure in pediatric patients in June 2025. While zorevunersen is an ASO, not a viral vector gene therapy, any high-profile safety event in the broader genetic medicine space can negatively impact patient and payer confidence, increasing the social pressure on Stoke Therapeutics, Inc. to maintain a clean safety profile in its Phase 3 EMPEROR study, which is expected to initiate in mid-2025.

Scrutiny over the high cost of rare disease treatments (e.g., potential price point)

The high cost of rare disease treatments, particularly one-time or disease-modifying therapies, is a major social and political flashpoint. This scrutiny will absolutely apply to zorevunersen upon its potential approval.

The current market sets a high benchmark for genetic therapies, with one-time treatments for other rare genetic disorders priced at or near $4 million. For example, Lenmeldy, a gene therapy for metachromatic leukodystrophy, is priced at $4.25 million per dose. Even existing non-gene rare epilepsy treatments are expensive; Fintepla, a current Dravet Syndrome drug, has a list price of $1,650.39 per 30 mL bottle as of January 2025, which translates to a high annual cost.

The social challenge for Stoke Therapeutics, Inc. will be justifying its price point based on the durable, disease-modifying nature of zorevunersen, particularly the cognitive and behavioral improvements. Payers, guided by organizations like the Institute for Clinical and Economic Review (ICER), are looking for at least five years of demonstrated clinical benefit to justify these high, one-time prices.

• Lenmeldy (Gene Therapy): $4.25 million (one-time dose).
• Kebilidi (Gene Therapy): $3.95 million (one-time dose).
• Fintepla (Current Dravet Drug): List price of $1,650.39 per 30 mL bottle.

Stoke Therapeutics, Inc. (STOK) - PESTLE Analysis: Technological factors

Proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) platform is a core asset

The TANGO platform is Stoke Therapeutics' most valuable technological asset, a proprietary approach that uses Antisense Oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. This is a highly differentiated mechanism of action focused on treating severe genetic diseases caused by haploinsufficiency-a condition where a patient produces only about 50% of the normal protein level.

The platform's commercial potential was significantly validated in 2025 by the collaboration with Biogen for zorevunersen (STK-001), the lead asset for Dravet syndrome. That deal provided Stoke with a substantial $165 million upfront payment and the potential for up to $385 million in future milestones, de-risking the late-stage development.

Still, the technology's broad applicability saw a recent setback when Acadia Pharmaceuticals discontinued two TANGO programs in May 2025, including one for Rett syndrome. This shifts the immediate technological focus and pipeline risk heavily onto the success of zorevunersen, which is currently in the pivotal Phase 3 EMPEROR study.

Advancements in Antisense Oligonucleotide (ASO) delivery systems improve efficacy

ASOs face a fundamental technical challenge in crossing biological barriers, especially the blood-brain barrier for Central Nervous System (CNS) disorders. Stoke's lead candidate, zorevunersen, is a third-generation ASO delivered via an intrathecal (ASO-IT) injection into the cerebrospinal fluid, a delivery method that is becoming the standard for CNS ASO therapies.

The broader ASO market is seeing rapid innovation, which is both an opportunity and a competitive threat. New advancements focus on improving systemic delivery to avoid the need for spinal injections. You should track these emerging technologies:

• Synthetic Polymer Systems: Enhance ASO stability and cellular uptake.
• Nanoparticle Formulations: Engineered to improve tissue specificity, especially for systemic delivery to organs outside the CNS.
• Exosome Carriers: Naturally occurring vesicles being explored to transport ASOs more efficiently across biological barriers.

This evolving landscape means Stoke must defintely continue to enhance its ASO chemistry and delivery to maintain a competitive edge against next-generation systemic ASO and siRNA therapies. One clean one-liner: Delivery is the new chemistry in RNA medicine.

Competition from gene therapy and other ASO developers targeting similar pathways

Stoke operates in a highly competitive and rapidly evolving genomic medicine space. The ASO therapeutics pipeline is vast, with over 70 companies and more than 75 pipeline drugs globally in 2025, including major players like Ionis Pharmaceuticals, Novartis, and Biogen.

The primary technological threats come from two areas:

• Other ASO/RNAi Developers: Companies are constantly improving ASO chemistry and delivery to achieve better safety and efficacy profiles, often targeting the same or similar neurological pathways.
• Gene Therapy and Gene Editing: Disruptive technologies like in vivo gene editing and gene-modified cell therapies offer the potential for a single, curative dose, which could eventually supersede the need for chronic ASO treatments.

Stoke's TANGO approach, which restores protein function rather than just silencing a gene, offers a unique value proposition, but it must be proven durable and safe over a long-term treatment horizon to compete with the promise of a one-time cure. The global ASO drug market is estimated at $2.5 billion in 2025, underscoring the high-stakes environment.

Data analytics and AI are increasingly used to accelerate clinical trial design

The financial and time pressure of late-stage clinical trials for rare diseases makes the adoption of Artificial Intelligence (AI) and advanced data analytics a necessity, not an option. The global AI in clinical trials market is projected to reach $7.60 billion by 2034, growing at a CAGR of 14.0% from a $2.05 billion valuation in 2024.

For Stoke, this technology is crucial for the success of its ongoing Phase 3 EMPEROR study for zorevunersen, a CNS-focused trial-a therapeutic area that accounts for 686 planned trials in 2025.

Key AI applications that Stoke must be using or integrating to manage its complex, global trial include:

• Patient Recruitment: Using AI algorithms to mine Electronic Medical Records (EMR) for precise patient matching in rare diseases like Dravet syndrome.
• Adaptive Trial Design: Employing predictive analytics to allow for real-time dose adjustments and streamlined protocols based on emerging safety and efficacy data.
• Data Processing: Accelerating the sifting and analysis of the massive, complex datasets generated in long-term open-label extension studies.

Manufacturing scalability of ASO drugs presents a technical hurdle

While ASO synthesis is generally more scalable than cell or gene therapy manufacturing, scaling up for commercial launch still poses significant technical and cost hurdles. The complexity and high cost of legacy manufacturing processes in the advanced therapy sector are a leading driver of high therapeutic costs.

Stoke's financial data for the nine months ended September 30, 2025, shows a clear commitment to overcoming this, with Research and Development expenses rising to $96.2 million, an increase of $30.5 million over the same period in 2024. This increase is largely driven by activities to support the advancement of zorevunersen, which includes manufacturing scale-up and process optimization for a potential commercial product.

The challenge is ensuring a robust, repeatable, and cost-effective process that meets global regulatory standards as the company transitions from clinical supply to commercial-scale production. The ultimate goal is to leverage ASO's inherent advantage-the ability to easily modify sequences-to achieve low-cost, high-speed manufacturing that can meet the demand for a rare, chronic disease treatment.

Stoke Therapeutics, Inc. (STOK) - PESTLE Analysis: Legal factors

Intellectual property protection for the TANGO platform and zorevunersen (STK-001) is critical

For a biotech like Stoke Therapeutics, the strength of its intellectual property (IP) is the core asset, and the legal framework protecting the TANGO (Targeted Augmentation of Nuclear Gene Output) platform is paramount. The company relies on a combination of licensed and internally developed patents to maintain its competitive moat, which is defintely a high-stakes legal area.

Here's the quick math on their key IP runway, based on filings as of December 31, 2024:

The long-term patent protection, extending out to 2045 for the compounds, gives the company a substantial period of market exclusivity, but they must consistently defend these rights against potential infringement claims, which is a costly and ongoing legal risk.

Orphan Drug Exclusivity provides 7 years of market protection post-approval

The regulatory designations for zorevunersen (STK-001) in Dravet syndrome are a massive legal and commercial advantage. The drug has been granted Orphan Drug Designation (ODD) by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This designation is critical because, upon final marketing approval in the U.S., it automatically grants seven years of market exclusivity, regardless of the patent status.

This exclusivity prevents the FDA from approving a competitor's drug for the same indication during that period. Also, the FDA has granted zorevunersen both Rare Pediatric Disease Designation and Breakthrough Therapy Designation. The latter helps streamline the regulatory process, but the seven-year ODD is the true legal shield for the initial post-launch period.

Strict compliance with global clinical trial regulations (e.g., FDA, EMA)

Operating globally means navigating a complex web of regulatory bodies. Stoke Therapeutics demonstrated strong compliance in early 2025 by achieving alignment with the FDA, the EMA, and Japan's Pharmaceuticals and Medical Devices Agency (PMDA) on the design of the global Phase 3 EMPEROR study for zorevunersen. This regulatory consensus is a major de-risking event.

The FDA also removed the Partial Clinical Hold on zorevunersen (STK-001), which had been a regulatory hurdle, clearing the path to initiate the Phase 3 study in mid-2025. Maintaining this compliance is non-negotiable, especially as the trial moves into its registrational phase and involves multiple jurisdictions.

Potential for product liability litigation related to long-term safety data

As a developer of a novel, disease-modifying therapy delivered intrathecally (into the spinal fluid), the long-term safety profile of zorevunersen (STK-001) is the primary source of future product liability risk. While the company reported positive 3-year Open-Label Extension (OLE) data as of August 2025, noting the drug was 'generally well tolerated', any unforeseen long-term adverse events could trigger significant litigation.

Biotech companies must carry substantial product liability insurance to cover this risk. The company's cash position, which stood at $355.0 million as of June 30, 2025, and is anticipated to fund operations to mid-2028, provides a buffer, but a major safety issue could quickly erode investor confidence and trigger legal claims that exceed insurance limits. Also, the company did settle a shareholder derivative lawsuit in 2024 for up to $415,000 in attorney's fees, underscoring the ongoing reality of corporate litigation risk.

Evolving data privacy laws (e.g., HIPAA) impact patient data management

The collection and processing of Protected Health Information (PHI) from clinical trial participants subjects Stoke Therapeutics to stringent data privacy laws, primarily the Health Insurance Portability and Accountability Act (HIPAA) in the U.S. and the General Data Protection Regulation (GDPR) in Europe. The trend in 2025 is toward stricter enforcement and expanded scope, with significant fines being levied across the healthcare sector.

Key legal compliance actions required in this environment include:

• Mandatory implementation of multi-factor authentication and enhanced encryption standards for electronic PHI.
• Establishing and maintaining robust Business Associate Agreements (BAAs) with all vendors handling patient data.
• Adopting a 'privacy by design' approach to clinical data systems to mitigate the risk of a breach.

Given the global nature of the Phase 3 trial, the company must ensure its data collection practices satisfy the highest common denominator of global privacy standards, or risk facing penalties that can reach millions of dollars for willful neglect.

Stoke Therapeutics, Inc. (STOK) - PESTLE Analysis: Environmental factors

Minimal direct environmental impact from non-manufacturing R&D operations

As a pre-commercial biotechnology company primarily focused on research and development (R&D) of its TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke Therapeutics' direct environmental footprint is significantly lower than that of a fully integrated pharmaceutical manufacturer. This is a common characteristic for companies in the clinical-stage biotech sector. The main environmental impact stems from laboratory operations, not large-scale production. For the six months ended June 30, 2025, the company reported Research and Development expenses of $58.5 million, which indicates the scale of its lab-intensive activities.

The core challenge here is managing energy use in R&D facilities, especially for climate-controlled labs. Though the company aims to operate with an environmentally-conscious mindset, the industry as a whole still struggles with energy intensity. For context, while the pharmaceutical industry's overall emissions are not the largest by sector, its carbon intensity is significant; per revenue dollar, it is approximately 55% more carbon-intensive than the automotive industry. This is the hidden cost of R&D-heavy operations.

Increasing investor focus on ESG (Environmental, Social, Governance) reporting

Investor scrutiny, particularly from large asset managers, on Environmental, Social, and Governance (ESG) factors is defintely rising in 2025, even for smaller-cap biotechs like Stoke Therapeutics. While the company's net impact ratio is generally positive due to its core mission (Creating Knowledge and Physical Diseases), it has been flagged for negative impact in the category of Waste. This highlights a clear area of risk and opportunity.

The market is setting high standards: over 65% of biotech companies are now integrating sustainability metrics into their corporate reporting, and 60% of industry leaders believe sustainability strategies will significantly influence investor decisions in the coming years. Simply stating an aim to be environmentally-conscious, as Stoke Therapeutics does, will soon be insufficient for institutional investors seeking alignment with a 1.5 °C pathway, a target now adopted by 31% of companies in a recent study.

Need for responsible disposal of biological and chemical waste from lab work

The most immediate and critical environmental risk for Stoke Therapeutics' lab-based operations is the proper handling and disposal of hazardous waste. This is a non-negotiable compliance area, and regulations are tightening in 2025.

The key regulatory changes to monitor include:

• EPA Subpart P Enforcement: The nationwide ban on sewering (flushing down the drain) all hazardous waste pharmaceuticals, a part of the EPA's 40 CFR Part 266 Subpart P, is being enforced in many states in early 2025.
• e-Manifest Compliance: Changes to the Resource Conservation and Recovery Act (RCRA) e-manifest system will take effect on December 1, 2025, requiring all generators, including small ones, to register electronically.
• SQG Re-Notification: Small Quantity Generators (SQGs) of hazardous waste must confirm re-notification with the EPA by September 1, 2025.

Failure to comply with these rules can result in significant fines and reputational damage. The average biotech firm has already reported a 25% decrease in waste generation in labs due to sustainability initiatives, so there is a clear industry benchmark to hit.

Supply chain resilience to climate-related disruptions for specialized reagents

While Stoke Therapeutics is not yet a commercial-stage company, its R&D pipeline, including the Phase 3 study for zorevunersen, relies on a complex global supply chain for specialized reagents, oligonucleotides, and other raw materials. This supply chain is highly vulnerable to climate-related and geopolitical disruptions.

The pharmaceutical industry's supply chain is the source of approximately 71% of the healthcare sector's total emissions (Scope 3), making it the single largest environmental and operational risk factor. The concentration risk is substantial: as of 2025, nearly 65% to 70% of Active Pharmaceutical Ingredients (APIs) used globally are sourced from China and India. Climate events like floods or extreme heat can shut down manufacturing in these regions, leading to shortages. The US experienced over 323 active drug shortages in early 2025, the highest in a decade, underscoring this vulnerability.

Pressure to reduce carbon footprint in drug transport and logistics

The pressure to reduce the carbon footprint of drug transport will intensify as Stoke Therapeutics moves closer to commercialization, especially for a product like zorevunersen, which may require temperature-controlled logistics. The majority of the pharmaceutical industry's emissions are Scope 3 (indirect emissions from the value chain, including transport).

Here is a snapshot of the logistics-related carbon intensity:

Moving forward, the company must proactively map its Scope 3 emissions, focusing on the carbon intensity of its contract manufacturing and cold chain logistics partners. This transparency is what investors and regulators will demand, and it is a key differentiator for long-term supply chain resilience.