Instil Bio, Inc. (TIL): PESTLE Analysis [Nov-2025 Updated]

You're evaluating Instil Bio, Inc. (TIL), and the reality is they are on a tightrope. The Tumor Infiltrating Lymphocyte (TIL) space is hot, but their success is completely dependent on hitting clinical milestones while outrunning a serious cash burn. With a projected 2025 net loss of around $220 million against a Q3 2025 cash position of only $150 million, the clock is defintely ticking. We need to look past the hype and map out the real-world Political, Economic, and Technological forces that will determine if they can cross the finish line before they run out of runway.

Instil Bio, Inc. (TIL) - PESTLE Analysis: Political factors

FDA fast-track designations create a competitive race for TIL therapies.

The US Food and Drug Administration (FDA) uses accelerated pathways like Fast Track, Breakthrough Therapy, and Regenerative Medicine Advanced Therapy (RMAT) to speed up development for novel oncology treatments. This creates a high-stakes, competitive race, putting pressure on Instil Bio to show superior clinical data quickly to earn one of these designations for its pipeline, even after pivoting from its initial Tumor Infiltrating Lymphocyte (TIL) focus.

In July 2025, Instil Bio did secure the critical Investigational New Drug (IND) clearance from the FDA for its lead asset, AXN-2510, a PD-L1xVEGF bispecific antibody, allowing a Phase 1 trial to start in the US by year-end. Still, the broader TIL market is crowded: there are over 75 TIL therapies in development globally, and a competitor, Iovance Biotherapeutics, already has an FDA-approved TIL therapy, setting a high bar for regulatory acceleration. You need to achieve a designation like Breakthrough Therapy to cut years off the path to market.

• IND Clearance: AXN-2510 cleared by FDA in July 2025.
• Competitive Field: Over 75 TIL therapies are in development worldwide.
• The Stakes: Accelerated pathways can reduce development time by over a year.

US-China geopolitical tensions affect supply chain for critical reagents.

Instil Bio faces a direct geopolitical risk due to its core development strategy, which relies on a key partnership with ImmuneOnco Biopharmaceuticals, a Chinese firm, for the Phase 2 trial of AXN-2510 in China. This collaboration is a strength for clinical data generation, but it exposes the company to escalating US-China trade tensions, which are increasingly targeting the biopharma supply chain.

The cell and gene therapy (CGT) sector, including TIL manufacturing, relies heavily on Chinese suppliers for specialized, critical reagents like cell culture media, cryoprotectants, and single-use systems. As of 2025, US tariffs on Chinese pharmaceutical imports, including certain Active Pharmaceutical Ingredients (APIs), can reach up to 25%, and tariffs on medical packaging and lab equipment can hit 15%. This translates directly into higher manufacturing costs and supply chain volatility for Instil Bio as it prepares for global trials and eventual commercialization outside Greater China.

Government funding for oncology research indirectly supports TIL development.

While Instil Bio is a private company, the massive federal investment in oncology research provides a crucial tailwind by advancing the underlying science and clinical infrastructure for all cancer immunotherapies, including TILs. This government-funded research de-risks the field by validating novel mechanisms and generating key data on solid tumors.

The National Cancer Institute (NCI) is the primary federal agency driving this support. For fiscal year 2025 (FY25), the NCI's total budget is approximately $7.22 billion, which funds thousands of extramural research projects and clinical trials. Furthermore, the Biden Administration's Cancer Moonshot initiative is supported by mandatory funding that totals around $1.5 billion across NCI, FDA, and other agencies for FY25, with a goal to reduce the cancer death rate by 50% by 2047. This federal spending directly supports the scientific ecosystem Instil Bio operates within.

Stricter US drug pricing legislation (like the Inflation Reduction Act) pressures future revenue.

The US Inflation Reduction Act (IRA), enacted in 2022, is a major long-term political risk that will compress the potential peak revenue of any successful Instil Bio product. The IRA empowers the Centers for Medicare & Medicaid Services (CMS) to negotiate the Maximum Fair Price (MFP) for high-cost, single-source drugs covered under Medicare, with the first negotiated prices taking effect in 2026.

For biologics, which include cell and gene therapies, the negotiation window opens 13 years after FDA approval. This is a new, hard 'Loss of Exclusivity' date in the Medicare channel, significantly shortening the expected period of high-margin sales and reducing the asset's Net Present Value (NPV). Early examples of negotiated drugs saw price reductions of up to 79%, which signals severe future revenue pressure for any high-priced Instil Bio therapeutic that reaches the market.

Instil Bio, Inc. (TIL) - PESTLE Analysis: Economic factors

High interest rates increase the cost of capital for future financing rounds.

The macroeconomic environment in 2025, characterized by elevated interest rates, continues to be a headwind for clinical-stage biopharmaceutical companies like Instil Bio. While the Federal Reserve began easing monetary policy with a rate cut in September 2025, the overall cost of capital (the return investors expect from a risky asset) remains high compared to the pre-2022 boom years.

For a company that is pre-revenue, this translates directly into higher dilution for shareholders in any future equity raise, or a significantly more expensive debt burden if they were to pursue venture debt financing. The higher discount rates used in discounted cash flow (DCF) models, which investors use to value these long-duration assets, naturally depress Instil Bio's present valuation.

The constrained public market for Initial Public Offerings (IPOs) and follow-on offerings means Instil Bio must demonstrate substantial clinical de-risking-like positive Phase 1 data-before a financing window opens up at a favorable valuation.

Instil Bio's estimated 2025 net loss is projected to be around $83.7 million.

As a clinical-stage company, Instil Bio's primary financial factor is its cash burn rate, driven by research and development (R&D) expenses. The GAAP net loss for the first nine months of 2025 was approximately $63.2 million (Q2 net loss of $49.6 million plus Q3 net loss of $13.6 million).

Wall Street analysts project Instil Bio's full-year 2025 net loss (earnings) to be around -$83,670,594 on average, with no projected revenue for the year. This large, expected loss underscores the company's dependence on external capital to fund its clinical pipeline.

Here's the quick math on the major expense components for the nine months ended September 30, 2025 (in millions):

The significant $16.6 million in restructuring and impairment charges for the nine-month period shows the company's efforts to reduce its cash burn and focus capital on its core assets, such as the AXN-2510 program.

Cash runway is critical; a Q3 2025 cash position of approximately $83.4 million requires careful management.

Cash runway-the length of time a company can operate before running out of money-is the single most important metric for a pre-revenue biotech. Instil Bio reported that its total cash, cash equivalents, restricted cash, marketable securities, and long-term investments as of September 30, 2025, was $83.4 million.

This Q3 2025 cash position is a key factor. The company expects these resources to fund operations beyond 2026, which provides a degree of stability, but it's a tight margin given the average quarterly net loss.

• Cash position is $83.4 million as of September 30, 2025.
• Management projects runway extends beyond 2026.
• The quarterly net loss for Q3 2025 was $13.6 million.

Sustaining the runway past 2026 is defintely dependent on maintaining current low burn rates and achieving critical clinical milestones, like the recent first-patient dose in the Phase 1 monotherapy trial of AXN-2510 in October 2025.

Global economic slowdown could reduce venture capital appetite for high-risk biotech.

The broader economic slowdown and market uncertainty have fundamentally changed the venture capital (VC) landscape for biotech in 2025. Investors are exhibiting a tightened risk tolerance, shifting capital away from early-stage, high-risk platform companies and towards those with de-risked assets and clear clinical inflection points.

VC funding has concentrated into larger bets on fewer companies, meaning Instil Bio must compete fiercely to secure its next round of financing.

Key investor priorities in this environment include:

• Assets with Phase 2 or Phase 3 clinical data.
• Clear commercial viability and path to revenue.
• Strong scientific foundations and experienced management.
• De-risking strategies like biomarker-based patient selection.

Instil Bio, with its lead asset in a Phase 1 trial, is still considered high-risk in this environment. The pressure is on to deliver compelling early-stage data to justify a favorable valuation for any future capital raise. This slowdown is systemic, not personal to the science.

Instil Bio, Inc. (TIL) - PESTLE Analysis: Social factors

Growing patient demand for personalized, curative cancer treatments like TIL.

Patient demand for Tumor Infiltrating Lymphocyte (TIL) therapy, and the broader category of curative cell and gene therapies (CGTs), is substantial and growing, driven by the hope of a one-time cure for advanced solid tumors where standard treatments have failed. This demand acts as a powerful social tailwind for Instil Bio, Inc. (Instil Bio). However, as a clinical-stage company, Instil Bio must manage expectations carefully; the dosing of the first patient in the Phase 1 trial for its lead candidate, AXN-2510/IMM2510, in October 2025, is a clinical milestone, but it doesn't immediately translate to a commercial product.

The core social value proposition is clear: a potential cure, not just a treatment extension. This is a massive psychological shift for patients and their families. Instil Bio's financial position, with $83.4 million in cash, cash equivalents, restricted cash, marketable securities, and long-term investments as of September 30, 2025, gives it a runway to pursue this demand beyond 2026, but the pressure to deliver results is immense. The market is watching closely.

• Demand for curative options is high in refractory solid tumors.
• Clinical progress, like the October 2025 Phase 1 dosing, fuels patient hope.
• The social contract demands speed and efficacy from Instil Bio.

Ethical debate around the high cost of cell and gene therapies impacts public perception.

The ethical debate surrounding the high cost of CGTs is a critical social headwind. While Instil Bio's therapies are not yet commercial, they will enter a market where treatments like Vertex's Casgevy are priced over $2 million, and many CGTs exceed $1 million per patient. This pricing model creates a significant public perception issue of healthcare inequity, suggesting that life-saving cures are only accessible to the socioeconomically advantaged.

This debate forces Instil Bio to consider value-based pricing (VBP) and innovative payment models, like outcomes-based or installment agreements, even in the clinical phase. The public scrutiny on pricing is intense, and a future high price tag could trigger a backlash, regardless of the therapy's efficacy. To be fair, a one-time cure that eliminates years of chronic treatment costs does offer value, but the upfront sticker price is still a major social barrier.

Talent war for highly specialized cell therapy manufacturing and clinical staff.

The competition for specialized talent is a fierce reality in the cell therapy space, creating a talent war that impacts Instil Bio's operational capacity. The entire US Cell Therapy industry employed only 5,148 people in 2025, despite an average annual employment growth of 9.3% over the preceding five years. This small, rapidly expanding talent pool means competition is brutal for bioprocess engineers, Quality Assurance/Quality Control (QA/QC) staff, and clinical trial experts.

Instil Bio's ability to scale manufacturing and run complex global trials (like the one for AXN-2510/IMM2510 in China and the US) is directly tied to securing and retaining this scarce expertise. The talent shortage is a widely recognized challenge across the industry, often hindering expansion. Companies must offer highly competitive compensation, including sign-on bonuses and equity, to win this race.

Here's the quick math: if the industry is growing that fast from a small base, it's defintely hard to find experienced people fast enough.

Increased patient advocacy groups push for faster regulatory approval processes.

Patient advocacy groups are increasingly influential and are actively pushing the US Food and Drug Administration (FDA) for faster regulatory approval processes for CGTs. This is a positive social force for Instil Bio, as it aligns with their goal of bringing a therapy to market quickly. In June 2025, stakeholders, including advocacy organizations, met with the FDA to discuss streamlining pathways and leveraging tools like the Accelerated Approval (AA) pathway.

This push is centered on accepting surrogate endpoints and real-world data (RWD) earlier in the process, especially for life-threatening conditions with high unmet needs. The goal is to reduce the time to treatment for patients. This social pressure is effectively reshaping the regulatory environment in a way that could accelerate Instil Bio's path to market, provided their clinical data is promising.

• Advocacy groups lobby the FDA for streamlined CGT approval pathways.
• The FDA is considering using surrogate endpoints and post-approval monitoring more aggressively.
• This social momentum helps Instil Bio, but it also increases scrutiny on long-term safety data.

Instil Bio, Inc. (TIL) - PESTLE Analysis: Technological factors

Manufacturing scalability of personalized TIL therapy remains a major hurdle.

The core technological challenge for Instil Bio, Inc. is the autologous (patient-specific) nature of Tumor-Infiltrating Lymphocyte (TIL) therapy, which makes commercial-scale manufacturing inherently complex and expensive. You're dealing with a bespoke product for every single patient. While Instil Bio has strategically shifted its focus to other assets like the AXN-2510 bispecific antibody, the underlying TIL market still faces this bottleneck. Traditional TIL manufacturing protocols take around 20 to 22 days, and any process deviation risks losing the entire patient batch, which is a huge operational and financial risk.

Instil Bio has taken decisive action to manage this, closing its UK manufacturing and clinical operations in early 2024 to save costs and improve time efficiency, signaling a move toward a more centralized or outsourced model for its TIL pipeline. Still, the industry trend is clear: second-generation manufacturing protocols that can reduce production time and ensure consistency are critical for TIL therapy to move from niche treatment to widespread adoption. Here's the quick math on the broader market challenge:

Next-generation non-cryopreserved TIL platforms (like their Co-Stim TIL) offer a competitive edge.

Instil Bio's competitive position rests on its next-generation technological platforms that aim to enhance TIL efficacy and manufacturability. The company's key proprietary technology is the Co-Stimulatory Antigen Receptor (CoStAR™) platform. This platform is designed to generate genetically engineered TIL therapies, such as the investigational ITIL-306, for multiple solid tumors.

This is a critical technological differentiator because it moves beyond standard, unmodified TILs. You're using genetic engineering to potentially boost the T-cells' anti-tumor activity and persistence. To be fair, Instil Bio has retained key process development and research personnel specifically to advance the early-stage pipeline development of CoStAR™ and other novel TIL technologies, even as they pivot their lead asset. This shows a defintely sustained investment in the underlying cell therapy technology, which is the long-term future of the company.

Rapid advancements in gene editing (CRISPR) could enhance TIL efficacy.

The rapid evolution of gene editing technology, particularly CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats), is a major external technological opportunity for Instil Bio. CRISPR allows for precise modification of TILs to overcome the immunosuppressive tumor microenvironment, which is a major barrier in solid tumor treatment.

Recent clinical data from the first half of 2025 shows the promise of this approach:

• Researchers successfully used CRISPR/Cas9 to deactivate the CISH gene in TILs, which acts as an intracellular immune checkpoint.
• This modified therapy was tested in a first-in-human trial for advanced gastrointestinal cancers, resulting in one patient achieving a complete response that has been maintained for over two years.
• Other research focuses on knocking out the PD-1 gene in TILs to prevent tumor escape.

The challenge is integrating this complexity. You need to ensure that adding a CRISPR step, which currently uses non-viral delivery systems like ribonucleoproteins (RNPs) and electroporation, doesn't significantly extend the already long manufacturing timeline of approximately 22 days. Instil Bio's research and development (R&D) expenses for the six months ended June 30, 2025, were $12.1 million, up from $10.2 million in the prior year period, reflecting the need to fund this kind of advanced technological exploration.

Automation in cell processing is essential to reduce costs and standardize quality. It's a complex process.

The manual, open-system nature of cell processing is the primary driver of high cost of goods (COGS) and batch variability. Automation is not optional; it is essential for commercial viability. The global automated and closed cell therapy processing systems market is valued at approximately $1.74 billion in 2025 and is projected to grow at a CAGR of nearly 20% through 2034.

This market growth is driven by the need to:

• Increase throughput and efficiency.
• Reduce manual labor and associated costs.
• Minimize contamination risk and batch-to-batch variation.

For Instil Bio, adopting more automated and closed systems for cell separation and expansion is the only way to make their TIL therapies, including the CoStAR™ platform, economically scalable. The non-stem cell therapy segment, which includes TILs, is expected to account for a massive 42.1% of the automated cell therapy processing systems market share in 2025, showing where the industry is focusing its automation investment. This is where the company must commit capital to move from a clinical-stage process to a truly commercial one.

Instil Bio, Inc. (TIL) - PESTLE Analysis: Legal factors

You're looking at Instil Bio, Inc. (TIL) and seeing a clinical-stage biotech, which means the legal landscape isn't about sales contracts-it's about regulatory approvals, intellectual property (IP), and compliance. The core takeaway here is that the company has streamlined its cost base, which includes legal overhead, but its reliance on third-party manufacturing and its presence in the highly competitive bispecific antibody space keep its regulatory and IP risks elevated.

For the nine months ended September 30, 2025, Instil Bio reported General and Administrative (G&A) expenses of $21.2 million. This figure, which is down from $33.8 million in the same period in 2024, reflects a leaner operational structure, but a significant portion of that remaining spend is dedicated to legal compliance, patent maintenance, and corporate governance. To be fair, you can't cut corners on regulatory legal spend in this industry.

Intellectual property (IP) disputes are common in the crowded TIL patent landscape.

The bispecific antibody market is a patent minefield. Instil Bio's lead asset, AXN-2510 (a PD-L1xVEGF bispecific antibody), is positioned against major competitors like Summit Therapeutics/Akeso's ivonescimab and BioNTech's BNT327. The company's IP strategy is critical, especially since their composition of matter coverage for this asset is projected to extend into 2040 in the U.S. Still, the closer you get to commercialization, the more aggressive the patent challenges become.

The legal risk isn't just about defending patents; it's about the freedom to operate (FTO). Given the complexity of bispecifics-which combine two different mechanisms of action-you defintely have to worry about infringing on a competitor's patents for either the PD-L1 or the VEGF component, or the structural linker technology itself. This is a perpetual, high-stakes legal battleground that requires constant monitoring and significant legal resources, even if no active litigation is public in 2025.

Strict FDA and EMA (European Medicines Agency) requirements for Good Manufacturing Practice (GMP) compliance.

Instil Bio has shifted its operational model, which dramatically changes its GMP risk profile. The company closed its UK manufacturing operations in early 2024, moving to a strategy of relying on collaborators and other third parties for manufacturing and clinical trial operations.

This reliance introduces a critical legal and regulatory risk: Instil Bio remains legally accountable to the FDA and EMA for the quality of the drug substance and drug product, even though they don't directly control the manufacturing facilities. This means their legal team must enforce rigorous Quality Agreements and audit protocols to ensure the contract manufacturer is compliant with current Good Manufacturing Practice (cGMP) standards. The EMA, for instance, has recently focused on tightening guidance on qualifying novel impurities in chemically synthesized medicines, which directly impacts the supply chain control required for complex biologics like AXN-2510.

• Risk: Reliance on third-party cGMP compliance.
• Action: Must conduct frequent, legally-vetted supplier audits.
• Financial Impact: The nine-month $16.6 million in restructuring and impairment charges likely included legal fees for terminating or modifying prior manufacturing contracts.

Data privacy regulations (HIPAA in the US) govern patient data in clinical trials.

Clinical-stage biopharma companies handle vast amounts of protected health information (PHI) from patients enrolled in trials. In the U.S., the Health Insurance Portability and Accountability Act (HIPAA) mandates strict technical and administrative safeguards. Since Instil Bio received FDA clearance for its Investigational New Drug (IND) application for AXN-2510 in July 2025, and is initiating a U.S. Phase 1 trial before the end of 2025, their data infrastructure must be fully compliant from day one.

Any data breach or failure to de-identify patient data properly could result in massive fines and, worse, jeopardize the integrity of the clinical trial data itself, leading to a regulatory hold. The cost of a single major breach can easily exceed the entire quarterly G&A budget. This is a non-negotiable compliance cost that is baked into the $21.2 million in G&A expenses reported for the first nine months of 2025.

Clinical trial design and reporting rules are constantly evolving, demanding high compliance.

The regulatory path for a global biopharma company is never straight. Instil Bio is navigating a dual-country strategy for AXN-2510, with a Phase 2 trial in China (enrollment completion expected in Q3 2025) and a U.S. Phase 1 trial expected to start by year-end. This requires meticulous adherence to both China's National Medical Products Administration (NMPA) and the FDA's rules, ensuring data collected in one jurisdiction is acceptable to the other.

The company made a strategic shift to a dose-optimization study in the U.S. to 'bridge the doses to the ongoing China trials.' This is a direct, tangible example of a regulatory-driven clinical design decision intended to accelerate the path to a potential global Phase 3 trial. The legal team is responsible for ensuring this 'bridging' strategy meets all reporting and ethical standards across both regulatory bodies. If the data reporting is inconsistent or incomplete, the entire program could be delayed, which is a massive financial risk.

Here's the quick math: The company is spending over $2.3 million per month on G&A, a significant portion of which is legal and compliance infrastructure to manage these complex global risks. You need to be sure that investment is buying you airtight compliance, especially with a new U.S. trial starting.

Next Step: Compliance Officer: Confirm all third-party manufacturing agreements meet the new EMA guidance on novel impurity qualification by the end of Q4 2025.

Instil Bio, Inc. (TIL) - PESTLE Analysis: Environmental factors

You're looking at Instil Bio, Inc.'s operational footprint, and the environmental factors for a clinical-stage biotech are a real concern, especially in the high-energy, high-waste world of cell and gene therapy manufacturing. The key takeaway is that the company's strategic shift away from its complex Tumor-Infiltrating Lymphocyte (TIL) platform and the closure of multiple manufacturing sites in 2024-2025 significantly reduced its immediate environmental liability, but the core challenges of cold-chain logistics remain.

Here's the quick math: Instil Bio's cash, equivalents, and investments totaled $83.4 million as of September 30, 2025. With nine-month operating expenses (R&D and G&A) of $42.4 million for the same period, the cash burn is still substantial, meaning capital efficiency-including energy and waste costs-is defintely a priority. Finance: draft 13-week cash view by Friday.

Management of biohazardous waste from large-scale cell processing facilities.

Cell therapy manufacturing, which was Instil Bio's original focus, generates significant volumes of regulated medical waste, or biohazardous waste. This includes single-use plastics, patient-derived materials, and contaminated lab consumables, all requiring specialized handling and disposal like autoclaving or incineration. The company's decision to discontinue its unmodified TIL program, ITIL-168, and close facilities like the one in Thousand Oaks, California, and the former Manchester, UK site, means a massive reduction in the volume of this high-risk waste stream compared to prior years.

The remaining clinical-stage operations for the bispecific antibody, AXN-2510, still produce biohazardous waste, but at a much lower intensity than the prior autologous (patient-specific) TIL process. The challenge now is ensuring compliance across a leaner, distributed clinical trial network, which still requires strict adherence to U.S. Environmental Protection Agency (EPA) and Occupational Safety and Health Administration (OSHA) standards for waste disposal.

Energy consumption of specialized cryogenic storage and cleanroom operations is significant.

The energy demand for cell and gene therapy is immense, driven by two factors: cryogenic storage and cleanroom operations. Cryogenic preservation of cell products requires maintaining ultra-low temperatures, typically in the vapor phase of liquid nitrogen ($\text{LN}_2$) at around $-190^{\circ} \text{C}$.

Even with the manufacturing scale-down, Instil Bio must maintain a robust cold chain for its clinical trial materials and cell banks. The energy required to run the specialized Heating, Ventilation, and Air Conditioning (HVAC) systems in Good Manufacturing Practice (GMP) cleanrooms-which must constantly filter and exchange air-is a major cost and environmental burden. A standard cleanroom can consume up to 100 times more energy than a typical office building. This is a non-negotiable cost of doing business in biotech.

The reliance on constant, high-power cooling creates a direct environmental footprint.

Need for a sustainable, traceable supply chain for critical, single-use manufacturing components.

The cell therapy industry relies heavily on single-use systems (SUS) to prevent cross-contamination between patient batches. This includes bags, tubing, filters, and bioreactors, all made primarily of plastic polymers. While SUS improves patient safety, it creates a sustainability problem: a high volume of plastic waste that is often biohazardous and cannot be recycled through conventional municipal streams.

For Instil Bio, the supply chain for these components must be traceable (a regulatory and quality requirement) and, increasingly, sustainable (an environmental and investor requirement). The industry is slowly moving toward more bio-based or recyclable SUS materials, but for 2025, the vast majority of these critical components are still single-use plastics that end up incinerated or landfilled.

• Minimize single-use plastic consumption in clinical trial logistics.
• Pressure suppliers for bio-based or chemically recyclable component options.
• Ensure full traceability of all critical components to meet regulatory standards.

Environmental impact of building and operating new, large-scale manufacturing sites.

Instil Bio has been actively reducing its physical footprint, which has a mixed environmental impact. The initial construction and build-out of a large-scale facility, such as the one in Thousand Oaks, required significant resources and energy. However, the subsequent termination of the Thousand Oaks lease and the listing for sale of the Tarzana facility in 2025 means the company is no longer responsible for the high operational energy and waste costs of those sites.

The environmental impact has shifted from high operational burn to decommissioning and asset disposition. This involves the complex, regulated process of decontaminating and disposing of specialized lab equipment and materials from a former bio-manufacturing site. This is a one-time environmental liability, but it must be managed meticulously to avoid regulatory fines, especially in California, a state with some of the strictest environmental regulations in the US.