A round table was convened by 24/7 Biopharma to answer questions about ADCs prior to CPHI Milan. Those taking part included Jin Seok Hur of Axplora, Denis Angioletti of the HAS Group, Jan Vertommen of Lonza, Brett Bobzien, Simone Manzini from PROCOS SpA, and James Rogers of Sterling Pharma Solutions.

 

 

 

Given Europe’s lead in ADC contract manufacturing, how is Axplora positioning its capabilities to capture increased US-market demand despite US tariffs?

Axplora. When our clients in the US think about Axplora, they are not buying geography – they are buying reliable supply and regulatory risk reduction on one of the most (if not, the most) complex molecule in their portfolio. Tariffs are definitely of concern and need to be monitored and dealt with accordingly, but our value-add is not a commodity item where a few percentage points have a dramatic impact on the sourcing decision. The real obstacle comes in the form of a failed inspection or a delayed IND submission, neither of which has occurred in the history of our Le Mans site.

From a cost perspective, where Axplora really competes is by removing the multi-site overhead that most of this industry still carries. Every ADC program involves several parties, since the antibody and the final drug product are rarely sourced from the same place, so the question is not how many contracts a client holds, but where the seams fall. Conventionally, linker-payload synthesis and bioconjugation sit with two different providers, which places a handoff at the most technically sensitive interface in the molecule, and every handoff carries its own quality checks, stability studies and comparability questions. At our Le Mans facility, we co-locate payload-linker synthesis and bioconjugation at one site under a single quality system, with cross-trained teams, who carry the project through the handoff rather than across it. That structural efficiency compounds over a program’s life in a way that tariff exposure on a single shipment does not.

Regulatory approvals and familiarity also play into that de-risking strategy that our clients are looking for. Because the site (as well as all our CDMO sites) holds both FDA and EU approvals, it serves as an additional point of security for when it comes time to submit the filing.

What specific strengths does Axplora offer in HPAPI synthesis, linker–payload chemistry and bioconjugation that differentiate Axplora from other European CDMOs?

Axplora. First, there is our depth and experience within high potency. Axplora has more than 35 years in HPAPI synthesis and purification – the site made its name on docetaxel in 1992 and paclitaxel in 1999, produced its first cGMP ADC payload batch in 2006 and validated its first ADC payload in 2011. We operate to OEB 6 containment with an occupational exposure limit below 30 ng/m³, which is the band the current generation of payloads requires. This history is what has allowed us to become a key supplier in six of the 15 FDA approved ADC drugs on the market today.

Second, we have a similar calibre when it comes to purification expertise. Axplora’s heritage includes world-class preparative chromatography and we apply it on both sides of the molecule – isolating linker-payloads to a purity that removes trace impurities before they ever reach the antibody and using FPLC on the conjugate to hold precise DAR control. Chromatography is a core technology for us as a company, and our depth of knowledge in it is what has allowed us to take on novel or difficult-to-isolate payloads.

Third, and most importantly, our ADC services are expertly structured to maximise throughput and delivery. Because of the single site model, our ability to learn, translate and execute allows us to be able to take on difficult project requirements when it comes to speed, reliability and efficiency. Everything is closely integrated both intra-site and intersite (where necessary or appropriate), and this is what has made taking on projects that other competitors question as feasible for us. This efficiency has also given us the ability to investigate next generation ADC technologies, including dual payloads, steroid payloads and degrader conjugates.

How does Axplora manage regulatory and quality challenges when producing ADCs destined for the US market and what experience does Axplora have with FDA expectations for HPAPI and conjugation processes?

Axplora. Our qualification for the US market is a matter of record rather than assertion: components in six of the 15 FDA-approved ADCs currently on the market, more than 320 cGMP clinical and commercial batches delivered, and no failed regulatory inspection in the site’s history.

That history is considerably longer than the modality itself. Le Mans was first inspected by the FDA in 1994, when the site’s high-potency work was in cytotoxics rather than conjugates and the expectations we absorbed then around containment, cleaning validation and cross-contamination control transferred directly into the payload business. Every CDMO site holds FDA and EU approval, with several also holding PMDA approval and we have supported IND filings in the United States, Europe and Japan. This means US clients inherit an inspection cadence they neither scheduled nor paid for.

Where reviewers press hardest on an ADC is at the interface between the two halves of the molecule. The questions that generate deficiency letters are rarely about payload synthesis or conjugation considered separately; they are about whether the client can demonstrate that linker-payload critical quality attributes have been linked to conjugation performance and, in turn, to final drug substance quality, with analytical evidence supporting the control strategy from end to end. Because our workflow is consolidated to one team, the same workflow and organisation that sets the payload specification is the same one that must meet it at conjugation

The same continuity extends beyond drug substance and into drug product. Our QC scope covers drug product testing and has been inspected in that capacity.

With most ADC contract manufacturing at commercial scale, how does Axplora balance clinical-stage flexibility versus large-scale commercial throughput and capacity planning?

Axplora. This is achieved through a forward-centric approach to our suites. The recent Le Mans expansion added a dedicated commercial-scale manufacturing suite for multi-kilogram production, which protects the development and clinical-scale assets from being crowded out by commercial campaigns. A Phase I client is not queuing behind a launch.

That matters because the two need genuinely different things. Early-stage programs need process development, rapid iteration and analytical method development, and our laboratory is resourced to build and validate methods alongside process work rather than after it. Commercial programs need repeatability and our Le Mans operation has completed over 320 batches at clinical and commercial stage GMP.

That being said, this is also possible due to the single site approach. Regardless of the scale, the quality system and team remain consistent, and this allows for a level of agility that can seamlessly move projects around the site where needed to maximise productivity while giving each project its due respect. Our versatility allows us to go from gram-scale development to multi-kilogram commercial supply on a continuum, which is why the same clients stay with us –  our average relationship length with large pharma is over 15 years and seven of the top ten global pharma companies work with us.

Supply-chain resilience is a priority – what steps has Axplora taken to mitigate risks given geopolitical tariffs and disruptions?

Axplora. Above the level of the individual site, we hold depth across a European network rather than concentration in a single plant. While Le Mans serves as the company’s ADC Center of Excellence and carries the highly potent linker-payload and bioconjugation work, other sites such as our facilities in Leverkusen, Germany, and Chasse-sur-Rhone, France, in the group handle non and less-highly-potent linker and drug-linker chemistry. In addition, our specialty business unit, Farmabios, covers steroids and highly potent drug-linker. That distribution gives us internal alternatives across chemistry classes and avoids the single-point-of-failure profile that a pure-play conjugation site necessarily carries.

We have also continued to commit capital through a period in which much of the sector deferred it. Our commercial suite came online in 2025 and commercial scale lyophilisation for linker-payloads follows in 2027, both underwritten by long-term client programs rather than by prevailing market conditions.

How does Axplora support clients on analytical characterisation, DAR control and batch-to-batch consistency throughout development and GMP manufacture?

Axplora. Analytics at Le Mans is a resourced function rather than a support service. The lab has developed, optimised or transferred approximately 140 analytical methods for ADC drug substance and validated more than 90 of them. Over 500 ADC samples are processed per year, resulting in more than 7,500 analyses per year at a 100% conformity rate – that volume across more than 15 ADC drug substance molecules is what builds genuine method judgment rather than method familiarity.

On DAR specifically, our advantage is that we control it with process rather than only measuring it. Preparative chromatography lets us isolate the target species and strip trace impurities and unwanted DAR species from the conjugate, so DAR distribution is a designed outcome. We hold this across conjugation chemistries – cysteine, lysine, affinity peptide and site-specific – each of which presents a different DAR control problem and we extend it to dual-payload constructs where the control problem is harder again.

Batch-to-batch consistency then comes from the same argument of integration that runs through everything else we do. When payload-linker quality drifts, its effect surfaces at conjugation. Because we own both steps, we can trace a conjugate excursion back into payload synthesis in days rather than through a supplier investigation. This has been shown time and time again through more than 320 cGMP batches spanning several complex ADC programs.

Which strategic partnerships, technology platforms or planned investments is Axplora pursuing to expand ADC offerings over the next 3-5 years?

Axplora. We are part-way through a multi-year investment program exceeding €100 million running to 2027. At Le Mans, a €30 million commitment has built out our bioconjugation capability and now brings commercial lyophilisation and sterile scale-up on site for early 2027. In Italy, our Farmabios operation is building a 4,500 sq m laboratory hub for February, 2027, co-locating development, quality control and microbiology alongside commercial HPAPI production at OEB 5 containment. Both projects express the same conviction: the way to take risk out of a highly toxic and complex molecule is to stop moving it between buildings. Together, they also give us a tiered containment network, OEB 5 up to 100 ng/m³ in Italy and OEB 6 below 30 ng/m³ at Le Mans, matching containment to the molecule rather than over-engineering everything.

The site and teams are also equipped to handle several different challenges and opportunities stemming from next generation therapeutics, whether that be dual payloads, steroid payloads and degrader conjugations.

______________________________________________________________________________

Given current ADC contract manufacturing landscape and the HAS-Cerbios merger in 2025 expanding Proveo’s development and manufacturing capacity and resources, how is Proveo positioning its capabilities to capture increased US-market demand despite US tariffs?

HAS Group. The 2025 integration of HAS and Cerbios has significantly strengthened our position in the ADC space by combining complementary expertise across APIs, HPAPIs, linker-payloads, conjugation and development services. Through Proveo, we can offer an integrated ADC solution that covers the entire value chain, from linker-payload development and manufacturing through conjugation and drug product support, with a single project management structure and co-ordinated supply chain.

From a US market perspective, we continue to see strong interest in outsourcing ADC development and manufacturing. ADCs remain one of the most highly outsourced modalities in the pharmaceutical industry and many biotech and pharma companies prioritise technical expertise, quality, speed and reliability over geography alone.

The HAS-Cerbios combination has increased our scale, investment capacity and technical depth. We are expanding both R&D and manufacturing resources, including additional ADC capacity and enhanced capabilities in linker-payload chemistry and conjugation, which are often the most critical bottlenecks in ADC development.

Importantly, we are already supporting and pursuing multiple ADC programs with US-based biotechnology and pharmaceutical companies. This demonstrates that innovative US developers continue to value specialised expertise and integrated solutions, particularly in complex modalities such as ADCs.

While tariffs may influence supply chain decisions in some cases, our strategy is to focus on what matters most to clients: speed, strong scientific know-how, operational flexibility, reliable execution and the ability to support programs from early development through commercial supply. As a Swiss-based organisation with global reach and a US presence, we believe we are well-positioned to continue serving US innovators and capturing growth in this rapidly expanding market.

What specific strengths does Proveo/HAS Group offer in HPAPI synthesis, linker–payload chemistry and bioconjugation that differentiate Proveo from other European CDMOs (eg, Germany/Switzerland competitors)? How does this fit with your expertise and capabilities in small molecules, highly potent APIs (HPAPIs) and oncology?

HAS Group. One of our key differentiators is that we come to ADCs from a position of strength and know-how in small molecules and large molecules, HPAPIs, oncology compounds and linker-payload chemistry. At HAS and Cerbios, we have decades of experience developing and manufacturing complex APIs and highly potent compounds, which are the foundation of many ADC programs.

In the ADC conjugation field specifically, we are also not newcomers. Cerbios has been active in ADC development and manufacturing for more than ten years, continuously investing in dedicated infrastructure, analytical capabilities and conjugation expertise.

What makes us unique is our ability to support customers across the entire chemical value chain, from small molecule synthesis and HPAPIs to linker-payload development, bioconjugation and ADC manufacturing, and for the entire product lifecycle, from early development up to Commercial supply. Many organisations offer conjugation services, but fewer combine that with deep expertise in highly potent chemistry and linker-payload manufacturing.

Following the HAS-Cerbios integration, we can offer an even broader platform that combines chemical and biological know-how, supported by additional investments in ADC development and manufacturing capacity. Our goal is to be a strategic partner for innovators from early development through commercialisation.

How does Proveo/HAS Group manage regulatory and quality challenges when producing ADCs destined for the US market and what experience does Proveo/HAS Group have with FDA expectations?

HAS Group. Quality and regulatory compliance are absolutely crucial in the ADC field and a full CMC and regulatory support is an essential part of our service. One of our strengths is that we combine decades of experience in GMP manufacturing of APIs, HPAPIs, oncology compounds and ADC-related products with a strong quality culture and a long history of serving regulated markets worldwide, including a vast presence in the US market. HAS has been supporting global pharmaceutical customers for many years, while Cerbios has extensive experience with highly potent compounds, linker-payloads and ADC manufacturing.

In the ADC space, we have more than ten years of experience supporting development and manufacturing programs, which has allowed us to build dedicated expertise in areas such as containment, analytical characterisation, process control, technology transfer and supply chain management for these highly complex products.

From a regulatory perspective, our approach is to engage our quality and regulatory experts from the earliest stages of development, ensuring that processes, analytical methods, documentation and manufacturing strategies are designed with eventual regulatory expectations in mind. This is particularly important for ADCs, where the integration of small molecule, HPAPI, biologic and conjugation components creates unique challenges.

We also have significant experience supporting programs for US and global customers, including molecules progressing through clinical development and commercial manufacturing. This experience has provided us with a strong understanding of FDA expectations regarding GMP compliance, data integrity, process robustness, quality oversight and lifecycle management.

Ultimately, our objective is to be more than a manufacturer. We aim to be a long-term development and commercialisation partner, helping customers navigate both the scientific and regulatory complexities of bringing innovative ADCs to patients worldwide.

With most ADC contract manufacturing at commercial scale, how does Proveo/HAS Group balance clinical-stage flexibility versus large-scale commercial throughput and capacity planning?

HAS Group. One of the realities of the ADC market is that you need to support both ends of the spectrum. On one side, biotech companies require flexibility, speed and strong technical support during early clinical development. On the other, successful programs need a clear path toward commercial supply.

At HAS Group and Proveo, our strategy is to build scalability into the platform from the beginning. We support customers from early development through clinical manufacturing, while continuously investing in the infrastructure and expertise required for late-stage and commercial production. The HAS-Cerbios integration has strengthened this approach by providing additional resources, manufacturing capabilities and investment capacity.

From a technical perspective, our experience in small molecules, HPAPIs, oncology compounds, linker-payloads and ADCs allows us to design robust and scalable processes by applying QbD principles early in development, reducing challenges when programs progress into later phases.

We have been active in the ADC field since the early days and have seen first-hand how rapidly portfolios can evolve. That’s why our capacity planning is driven not only by current projects, but also by the future needs of our customers. We continue to expand our ADC development, linker-payload and bioconjugation capabilities to ensure we can support programs all the way to commercialisation.

Ultimately, our goal is to offer the flexibility of a specialised development partner while providing a credible pathway to commercial manufacturing as programs mature.

Supply-chain resilience is a priority – what steps has Proveo/HAS Group taken to mitigate risks (raw material sourcing, alternate suppliers, inventory strategy) given geopolitical tariffs and disruption)?

HAS Group. Supply-chain resilience has become a critical topic for the pharmaceutical industry, particularly in light of geopolitical tensions, tariffs and global disruptions. At HAS Group and Proveo, our strategy is based on diversification and flexibility.

We have developed partnerships and collaborations with organisations across different geographic regions, allowing us to reduce dependency on any single country or supplier network and increase the resilience of our supply chain.

Moreover, a dedicated research program has established a standardised set of materials and single-use parts, which allows our supply chain to effectively manage stocks and ensure business continuity.

Another important aspect is our broad internal manufacturing footprint and expertise. Through HAS and Cerbios, we combine capabilities in small molecules, HPAPIs, oncology compounds, linker-payloads and ADCs, enabling us to maintain greater control over critical activities and reduce reliance on external partners for key development and manufacturing steps.

How does Proveo support clients on analytical characterisation, DAR control and batch-to-batch consistency for complex ADC products throughout development and GMP manufacture?

HAS Group. Analytical characterisation and product consistency are among the most critical aspects of ADC development. At Proveo, we leverage more than ten years of ADC experience, together with a strong foundation in small molecules, HPAPIs, linker-payloads and bioconjugation. This combination allows us to understand the entire molecule, from the payload and linker all the way to the final conjugated product.

We support our clients with our experience from early development through GMP manufacturing with integrated process development and analytical expertise. The goal is to build robust processes that deliver consistent product quality and facilitate scale-up from clinical to commercial manufacturing.

For ADCs, maintaining control of critical quality attributes, including DAR and batch-to-batch consistency, is essential. Our approach combines process understanding, analytical characterization and strong development-to-manufacturing alignment to ensure product quality is maintained throughout the lifecycle of the program.

Because we are active across the entire ADC value chain, including linker-payload manufacturing and bioconjugation, we can take a holistic view of product characterisation and process control, helping our customers de-risk development and prepare for later-stage and commercial manufacturing.

Which strategic partnerships, technology platforms or planned investments is Proveo /HAS Group pursuing to expand ADC offerings (eg, payload/linker innovation, site-specific conjugation, fill–finish) over the next 3-5 years?

HAS Group. As the ADC market continues to evolve, our strategy is to strengthen both our capabilities and our partnerships across the value chain. Through Proveo, we are continuing to reinforce collaborations with leading technology and supply chain partners to provide customers with an integrated ADC solution, from antibody production to drug product manufacturing including new modalities.

At the same time, the HAS Group is investing in expanding its ADC platform and manufacturing infrastructure. Our objective is not only to increase capacity, but also to broaden the range of services we can offer to customers as programs move from development into commercialisation.

Key areas of investment include advanced purification and manufacturing technologies such as chromatography, nanofiltration, and lyophilisation capabilities, which are increasingly important for supporting next-generation ADCs and complex bioconjugates. These investments are designed to enhance product quality, process robustness and supply chain efficiency across the entire development lifecycle.

We are also closely following innovations and investing resources in new areas such as novel linker-payloads, site-specific conjugation technologies and emerging ADC formats. Combined with our expertise in small molecules, HPAPIs, linker-payloads and more than ten years of ADC experience, this positions us to remain a long-term partner for innovators developing the next generation of targeted therapies.

______________________________________________________________________________

Given Europe’s lead in ADC contract manufacturing, how is Lonza positioning its capabilities to capture increased market demand in America despite US tariffs?

Lonza. Lonza is well-positioned to support growing US demand for ADCs through our integrated global network and end-to-end bioconjugation capabilities. Through our One Lonza approach, we support customers across the entire ADC lifecycle, from cell line development and ADC design to commercial ADC manufacturing. This approach covers development and manufacturing of the four key ADC modalities: mammalian, payload-linkers, bioconjugation and fill-finish.

At the same time, we are continuing to invest in regional manufacturing capabilities to meet customers’ needs for flexibility and supply chain resilience. By combining deep ADC expertise with a diversified global presence, we help our customers navigate evolving market dynamics and shifting trade policies, while maintaining speed, reliability and continuity of supply.

What specific strengths does Lonza offer in HPAPI synthesis, linker–payload chemistry and bioconjugation that differentiate the company from other European CDMOs (eg, German/Swiss competitors)?

Lonza. Lonza offers integrated expertise across HPAPI synthesis, linker-payload development and bioconjugation, enabling customers to advance increasingly complex ADCs from early development through manufacturing. Our capabilities span biologics, linkers and small molecules, allowing us to address the scientific and manufacturing challenges associated with novel ADC formats.

A key differentiator is our Synaffix technology platform, which includes GlycoConnect® for site-specific conjugation, and our HydraSpace® hydrophilic spacer technology. These offerings improve conjugation precision, maintain consistent drug attachment and support favourable pharmacokinetic and tolerability profiles. Augmented by our linker-payload expertise, these technologies help customers control drug-antibody ratios (DARs) and payload distribution while improving manufacturability and reducing development risk.

Multiple biotech companies are licensing Lonza’s ADC platform technologies. By integrating our ADC technology platforms into their product pipelines, our customers find they can de-risk and accelerate their development timelines and overcome potential developmental hurdles, shortening time to clinic.

How does Lonza manage regulatory and quality challenges when producing ADCs destined for the US market and what experience does Lonza have with FDA expectations for HPAPI and conjugation processes?

Lonza. ADCs are multi-modal in nature, combining biologics and small molecules. Each component requires a separate technology platform and sets of capabilities, creating unique chemistry, manufacturing and controls (CMC) challenges, as well as intricate procedures for cleaning and analytics.

Lonza addresses these challenges through specialised infrastructure, including closed systems, dedicated containment suites, advanced air handling, and stringent safety protocols, to facilitate safe handling of cytotoxic payloads. For example, our on-site incineration facility is designed to process cytotoxic liquid and solid waste, reducing dependence on external waste management partners while enhancing compliance and safety. We implement robust, risk-based cleaning and validation strategies to ensure residual cytotoxic payloads remain within established acceptance criteria, mitigating risk of cross-contamination in accordance with current Good Manufacturing Practice (cGMP) expectations. Our advanced analytical programs support product characterisation and release across a range of linker-payload combinations.

Lonza applies Quality by Design (QbD) principles to build scalable, robust and reliable manufacturing processes for complex molecules across clinical and commercial stages of development. By systematically defining critical quality attributes and linking them to process parameters, we can effectively control key product characteristics such as DAR and process-related impurities. For clinical-stage programs, this science and risk-based approach supports efficient process development and phase-appropriate control strategies, helping sponsors assemble the CMC packages required for Investigational New Drug submissions and early clinical development. On the commercial side, where Lonza has supported more than 50% of approved ADCs, we leverage our experience to establish validated manufacturing processes that meet the quality, CMC and regulatory expectations associated with marketed products, while supporting lifecycle management, inspections, post-approval changes and global regulatory submissions.

With most ADC contract manufacturing at commercial scale, how does Lonza balance clinical-stage flexibility versus large-scale commercial throughput and capacity planning?

Lonza. Balancing flexibility and throughput start with designing for scale early in development. That is why we encourage our customers to engage with us in the early stages and to plan for scalability as early as possible. For developers of novel bioconjugates, early engagement enables front-loading of key components of the development program, such as defining the conjugation strategy, delineating scalable manufacturing processes and conducting developability studies to facilitate lead selection.

From a product lifecycle perspective, early process design can reduce downstream manufacturing risks and early integration of chemistry, biology, and manufacturability can help avoid the pitfalls of siloed design and development, such as when the antibody and payload are optimised separately and conjugation occurs later. When integrated development and manufacturing teams adhere to QdB principles from the early stages, transitions from preclinical development to GMP manufacturing are smoother. Our provision of end-to-end support thus facilitates lifecycle planning and minimises technology transfer risk.

Supply-chain resilience is a priority – what steps has Lonza taken to mitigate risks (raw material sourcing, alternate suppliers, inventory strategy) given geopolitical tariffs and disruptions?

Lonza. For CDMOs, the volatility of the current geopolitical and economic landscape underscores the importance of maintaining a diversified global presence and a global manufacturing footprint. As noted, supply chain regionalisation is a key aspect of Lonza’s globalisation strategy. We aim to provide our customers with local and regional sourcing solutions – with facilities across Europe and Asia-Pacific, as well as in the US – to help them manage geopolitical and economic uncertainties. This approach helps us meet customer demand for resilient supply chains while facilitating long-term planning and collaboration. Regionalisation also allows us to maintain a flexible manufacturing network and to facilitate operational risk management, supported by real-time analysis and digital tools to improve planning and enhance efficiency.

How does Lonza support clients on analytical characterisation, DAR control and batch-to-batch consistency for complex ADC products throughout development and GMP manufacture?

Lonza. The advent of high-DAR ADCs and bispecific formats underscores the importance of tight DAR control, which can increase development costs and lengthen timelines. Heterogeneity has emerged as a key issue in DAR management, as higher DARs and multiple payloads compound the challenges of controlling species distribution, directly affecting safety and efficacy. By implementing strategies such as site-specific conjugation and well-defined payload ratios, Lonza is helping our clients achieve greater consistency and manufacturability for high-DAR and dual-payload ADCs.

We are also implementing advanced analytical methods that yield deeper insights into subpopulations, payload distributions and stability over time, thereby supporting ADC characterisation throughout development. Applying the principles of QdB can enable scalable, reliable manufacturing processes by linking process parameters to critical, clearly defined quality attributes.

A key aspect of Lonza’s approach is the use of plate-based screening platforms to accelerate insight generation, drug candidate developability and process optimization. These platforms enable creation of data-rich development workflows that help to generate large bioconjugate candidate libraries that can be screened and evaluated in millilitre and litre-scale studies to inform construction of a manufacturable process. Such data-driven process development, informed by QdB principles, helps to optimise processes and improve consistency.

Which strategic partnerships, technology platforms or planned investments is Lonza pursuing to expand ADC offerings (eg, payload/linker innovation, site-specific conjugation, fill–finish) over the next 3-5 years?

Lonza. As ADC pipelines mature and the category becomes more competitive, we are expanding our capabilities to help our clients manufacture complex, highly potent payload-linker constructs at clinical and commercial scale. These expansion initiatives encompass a combination of platform innovation, strategic licensing partnerships and manufacturing investments.

In addition to the GlycoConnect® and HydraSpace® technologies, our ADC platform technologies include SYNtecan™, a proprietary ADC linker-payload platform focused on topoisomerase-1 (Topo-1) inhibitors, with SYNtecan E™ (camptothecin derivative exatecan-based) positioned as the lead payload. We are also leveraging our dual-payload ADC technology to advance next-generation ADC programs. These technologies have been the centerpieces of recent strategic licensing partnerships where we are working alongside companies to develop innovative treatments for cancer and other diseases.

Notable recent manufacturing investments include expansion of our HPAPI payload-linker Center of Excellence in Visp, Switzerland, to enhance our HPAPI production capacity. This follows the expansion of our Stein, Switzerland, site, where we are constructing a dedicated cGMP filling line in collaboration with a major biopharma partner for commercial-scale filling of ADCs. We also seek to add bioconjugation capabilities in the U.S. and continue to invest in our capabilities at our Oss site in The Netherlands, with the aim of expanding support for early-phase ADC development and manufacturing.

______________________________________________________________________________

What specific strengths does PROCOS offer in HPAPI synthesis, linker-payload chemistry, and bioconjugation that differentiate PROCOS from other European CDMOs?

PROCOS. PROCOS’ key differentiator is its strong chemical and HPAPI heritage combined with an increasingly focused offering for the ADC value chain.

The company has been active in HPAPI manufacturing since 2018 and has progressively invested in dedicated containment, manufacturing and analytical infrastructure. Its expanded HPAPI platform includes dedicated cGMP manufacturing units, R&D and QC capabilities, with containment down to an occupational exposure limit of 1 ng/m³. This provides a strong foundation for the safe handling and manufacture of highly potent oncology compounds.

For ADCs, PROCOS has developed expertise around drug-linker and payload-linker chemistry, leveraging its core competence in complex small-molecule synthesis, process development, purification and scale-up. The company has publicly stated its objective of increasing payload-linker manufacturing capacity to multiple tens of kg per year, supported by additional investment and the recruitment of specialist expertise.

A further differentiator is the combination of process chemistry, HPAPI containment and scale-up capabilities within the same organisation. Rather than introducing capabilities on the bioconjugations, PROCOS can support customers upstream, from complex payload and linker synthesis through process development and GMP manufacture.

This chemistry-driven positioning is particularly relevant for biotech and pharmaceutical customers looking for a flexible partner able to manage highly potent small molecules and complex drug-linker programs while maintaining a clear path towards GMP scale-up.

How does PROCOS manage regulatory and quality challenges when producing ADCs destined for the U.S. market and what experience does PROCOS have with FDA expectations for HPAPI and conjugation processes?

PROCOS. The company brings decades of regulatory and quality expertise. Our campus in Cameri is approved by FDA, PMDA and AIFA, and has a long track record of successful inspections by these authorities, allowing it to manage US-bound projects within a global GMP framework – further supported by the Mutual Recognition Agreement between AIFA and FDA. This regulatory environment is supported by dedicated HPAPI production and QC infrastructure and by an integrated organisation covering R&D, quality, regulatory, manufacturing and supply chain.

PROCOS therefore applies a risk-based, phase-appropriate approach to process and analytical development, with particular attention to containment, impurity control, process robustness, traceability and reproducibility. Its experience with US-regulated pharmaceutical manufacturing provides an established quality framework for supporting customers whose products are ultimately destined for the US market.

Importantly, PROCOS does not position regulatory compliance as a final-stage activity: regulatory expectations are considered from process development and scale-up onwards, helping customers establish a manufacturing process that can transition efficiently into later clinical and commercial phases.

With most ADC contract manufacturing on a commercial scale, how does PROCOS balance clinical-stage flexibility versus large-scale commercial throughput and capacity planning?

PROCOS. It deliberately maintains a manufacturing model that combines flexibility at clinical stage with a clear scalability pathway towards commercial production.

Clinical ADC programs often require relatively small quantities, rapid development cycles and the ability to accommodate process changes as the molecule and manufacturing strategy mature. PROCOS’ chemistry-driven R&D organization and multi-purpose manufacturing infrastructure allow the company to work with high-value, relatively low-volume molecules without requiring immediate commitment to very large commercial batches.

For ADC customers, this creates a potential development-to-commercial continuum: projects can begin with process and analytical development, progress through clinical supply and scale-up.

At the same time, PROCOS has continued to invest in additional manufacturing capacity not only related to ADC. The new R11 facility, commissioned as part of the company’s expansion strategy, adds 20 reactors across four multi-purpose production lines, with capacities ranging from 1,000-6,000 litres. The facility was specifically designed to address demand for complex, high-value molecules, particularly those in clinical development, while increasing overall manufacturing capacity by approximately 25%.

Supply-chain resilience is a priority. What steps has PROCOS taken to mitigate risks given geopolitical tariffs and disruptions?

PROCOS. It considers supply-chain resilience an integral part of its CDMO proposition, particularly for complex and highly potent molecules where delays affecting a single critical raw material can have a disproportionate impact on a development program.

The company’s approach is based on supplier qualification, sourcing flexibility, inventory planning and early identification of critical materials, combined with close co-ordination between procurement, R&D, quality and manufacturing.

The scale and diversification of the Cameri site also provide an important operational advantage. PROCOS operates multiple production buildings and manufacturing lines and has continued to invest in additional capacity, reducing dependence on a single production asset and providing greater flexibility in production planning.

For US customers, the objective is not simply to absorb tariff-related cost increases, but to reduce the overall exposure of the supply chain to disruption. This means evaluating sourcing strategies early in the development cycle, identifying critical starting materials and intermediates, qualifying alternative sources where technically and regulatorily appropriate, and maintaining inventory strategies proportionate to the criticality and lead time of individual materials.

The current US trade environment reinforces the value of this approach. The 2026 US pharmaceutical tariff framework specifically addresses imported pharmaceuticals and pharmaceutical ingredients, while also creating differentiated treatment for certain products, including ADCs.

PROCOS therefore sees supply-chain resilience, rather than tariff mitigation alone, as the broader strategic objective.

How does PROCOS support clients on analytical characterisation, DAR control and batch-to-batch consistency for complex ADC products throughout development and GMP manufacture?

PROCOS. ADC development requires a significantly broader analytical strategy than conventional small-molecule API manufacturing because the final molecule combines multiple components and can exhibit structural heterogeneity.

PROCOS’ strength is the integration of process chemistry, HPAPI expertise and analytical development within the same CDMO environment. Its HPAPI platform includes dedicated QC capabilities while the company’s broader site infrastructure supports process and analytical development alongside GMP manufacture.

For ADC, especially on drug-linker related projects, the analytical strategy should evolve with the development stage. Early development focuses on understanding the molecule and establishing fit-for-purpose methods; later stages require a more comprehensive control strategy addressing critical quality attributes and process consistency.

PROCOS’ approach is therefore to connect analytical characterisation with process understanding to comprehend and control the process parameters that influence drug loading and product consistency.

This becomes particularly important during scale-up, where maintaining comparable reaction conditions, purification performance and impurity profiles is essential for achieving reproducible GMP batches.

Which strategic partnerships, technology platforms, or planned investments is PROCOS pursuing to expand ADC offerings over the next 3-5 years?

PROCOS. The company’s ADC strategy is centered on progressively strengthening the small-molecule side of the ADC value chain, particularly payloads, linkers and drug-linkers, while expanding the technologies and capacity required to support these products through development through commercialisation.

A significant milestone has been the expansion of the HPAPI platform and the stated investment to increase payload-linker manufacturing capacity with two additional cGMP units. The company has also highlighted the recruitment of specialised expertise in this chemistry area.

Technology development, not only in ADC, is another important pillar. PROCOS has invested in tools such as flow chemistry, automation and CHEMSPEED®, supporting faster process understanding, route development and process optimisation.

The company’s involvement in ADC-focused scientific forums, including World ADC, and its scientific contributions to GMP payload/linker development also reflect its intention to deepen its position within the ADC ecosystem.

Over the next 3-5 years, the strategic direction is therefore expected to focus on expanding our overall capacity including small molecules, payload/linker chemistry, HPAPI and drug-linker capacity, strengthening analytical and process-development capabilities and developing partnerships that can complement PROCOS’ chemistry expertise.

______________________________________________________________________________

Given Europe’s lead in ADC contract manufacturing, how is Sterling positioning its capabilities to capture increased US-market demand despite US tariffs?

Sterling. We’ve built a transatlantic network that gives customers flexibility in how they develop and manufacture ADCs for the US market. Our Germantown facility in Wisconsin, USA, provides high-containment HPAPI and linker-payload capabilities, while the Deeside facility in the UK provides specialist ADC bioconjugation and clinical GMP manufacturing.

Having these capabilities within one network means customers can balance supply-chain resilience and technical requirements without managing multiple CDMO partners.

With our conjugation facility based in the UK and our partnerships with UK-based mAb and fill-finish providers, customers can also benefit from the UK’s currently lower trading tariffs with the US.

What specific strengths does Sterling offer in HPAPI synthesis, linker-payload chemistry and bioconjugation that differentiate Sterling from other European CDMOs?

Sterling. Our main strength is our extensive bioconjugation experience, which brings with it technical expertise to tackle the most complex projects. Alongside our specialist HPAPI and linker-payload capabilities we can offer customers scientific excellence, as well as the equipment and technologies they require.

At the Deeside facility, we have more than 15 years of ADC experience and have supported over 100 customers across more than 700 ADC projects. Our bioconjugation technical services team has helped commercialise four of the currently approved ADCs, bringing a wealth of knowledge and experience to clients who are embarking on this journey. Our Germantown facility has dedicated cGMP HPAPI suites with containment validated to OELs below 0.001 μg/m³.

Having a truly integrated network of facilities with aligned systems and processes, also ensures that technology transfer across sites is seamless.

Our bioconjugation services include cysteine and lysine conjugation, as well as enzymatic and site-specific technologies.

Sterling’s approach is to be technology agnostic, so we can help customers select the strategy that makes most sense for their molecule rather than being tied to a particular platform.

How does Sterling manage regulatory and quality challenges for ADCs destined for the US market?

Sterling. We’ve supported ADC programmes from clinical development through to commercial manufacture, including launched products, so regulatory and quality requirements are considered from the start. This experience ensures that we are applying phase appropriate validation of analytical methods throughout customer projects.

Our Deeside facility holds an MHRA MIA (IMP) licence for clinical ADC manufacture, with support spanning process development, analytical qualification, GMP release testing, stability studies and CMC documentation.

Our experience across HPAPIs, linker-payloads and bioconjugation also help us build appropriate containment, process and analytical controls into programmes early, supporting regulatory submissions to agencies, including the FDA.

What steps has Sterling taken to strengthen supply-chain resilience?

Sterling. Supply-chain resilience is particularly important in ADC and HPAPI manufacturing where supplier networks are inherently narrower and qualification requirements are often more complex than those seen in traditional API supply chains.

At Sterling, we have strengthened resilience through a combination of our global manufacturing network, aligned systems and strategic inventory policies for critical materials. Beyond this, we place significant emphasis on building long-term supplier partnerships, maintaining strong customer collaboration and embedding robust planning processes through our S&OP framework.

These disciplines allow us to align demand, capacity and material availability across sites, ensuring the right materials are available at the right location and time to support customer programmes. For specialist ADC and HPAPI materials, where alternative sources can be limited and qualification timelines can be lengthy, we focus on proactive supplier management, early forecasting and risk assessment to protect quality, supply continuity and cost performance throughout the product lifecycle. Ultimately, resilient supply chains in the ADC space are built not only through inventory and dual sourcing strategies, but through close collaboration, disciplined planning and effective manufacturer partnerships.

How does Sterling support analytical characterisation, DAR control and batch-to-batch consistency?

Sterling. Our analytical teams work alongside process development and manufacturing, with capabilities covering method development and qualification, release testing and stability studies. Sterling continues to invest in analytical capabilities, offering a wide range of analytical techniques and equipment to support bioconjugation projects.

For ADCs, we assess critical quality attributes, including DAR and DAR distribution, aggregation, conjugation efficiency, free payload, impurities and product purity. Our experience across different conjugation chemistries helps us understand how process parameters affect these attributes and put the right controls in place to maintain batch-to-batch consistency.

DAR optimisation is considered early in every project, using analytics like mass spectrometry to determine DAR distribution and conjugate site occupancy. The aim isn’t simply to maximise payload loading, but to find the right balance between potency, stability, safety and pharmacokinetic performance for the molecule.

Which strategic partnerships, technology platforms or investments is Sterling pursuing over the next 3-5 years?

Sterling. We’re continuing to invest in both capacity and capabilities as ADC and wider bioconjugate programmes become more complex.

At the Deeside facility, a multimillion-pound expansion will add a new GMP manufacturing suite, doubling capacity and increasing batch sizes up to 5 kg of active drug substance. The investment also includes a new analytical services laboratory, with both due for completion later this year.

At the same time, we’re continuing to build experience across emerging conjugation technologies while remaining technology agnostic. New technologies are introduced to the site through customers, partners and our technical team. The Sterling technical team continuously expands the site’s conjugation capabilities by evaluating emerging and patented technologies to identify the most attractive technologies to bring onboard.

This includes cysteine and lysine conjugation, as well as enzymatic and site-specific technologies, allowing us to select the right technology for customer’s projects.

We’re also expanding our capabilities through established partners, including supply of targeting modalities (mAbs, diabodies, fragments, etc) and clinical fill-finish. As bioconjugation moves beyond established oncology ADCs into new modalities and therapeutic areas, we want to give customers the flexibility and opportunity to develop and scale increasingly complex products within an integrated supply chain where possible.

____________________________________________________________________________

Bibliography/sources provided by PROCOS SpA

1. US Food & Drug Administration (FDA) – Clinical Pharmacology Considerations for Antibody-Drug Conjugates – Guidance for Industry, March, 2024. FDA Guidance – ADC Clinical Pharmacology.
2. US Food & Drug Administration (FDA) – Guidance Recap Podcast: Clinical Pharmacology Considerations for Antibody-Drug Conjugates. FDA ADC Guidance Recap.
3. AAPS Journal / Springer Nature – Updated Recommendations for the Bioanalysis of Antibody–Drug Conjugates (ADC), 2026. AAPS Journal – Updated ADC Bioanalysis Recommendations.
4. AAPS PharmSciTech / Springer Nature – The Role of Contract Manufacturing in Antibody–Drug Conjugate (ADC) Drug Substance Development – Strategies for Successful Engagement, July, 2026. AAPS PharmSciTech – ADC Contract Manufacturing.
5. Organic Process Research & Development / ACS – Process Development for the First GMP Synthesis of SGD-9501-TFA, Part 2: Synthesis of the Payload, Linker, and Drug Linker, 2024. Authors include PROCOS scientists Lorenzo Pontini, Gabriele Cerai and Jacopo Roletto, together with Pfizer. ACS Publications – SGD-9501-TFA Payload, Linker & Drug Linker.
6. DCAT Value Chain Insights – The CDMO/CMO Report: High-Potency API Manufacturing, covering PROCOS’ €17 million HPAPI expansion, 10 ng/m³ containment and additional technologies. DCAT – High-Potency API Manufacturing.
7. DCAT Value Chain Insights – The CDMO/CMO and Suppliers’ Report: Small-Molecule APIs, PROCOS HPAPI expansion and manufacturing capabilities. DCAT – Small-Molecule APIs Report.
8. CPHI Online – PROCOS SpA – Company profile, site capabilities, regulatory approvals and global markets. CPHI Online – PROCOS SpA.
9. GB Reports – United States Life Sciences 2024 – Interview with PROCOS SpA covering HPAPI, ADC drug-linker manufacturing, US market exposure and expansion strategy. PROCOS – United States Life Sciences 2024 Interview.
10. 24/7 Biopharma – Redefining possibilities: PROCOS’ commitment to High Potency APIs, including payload-linker capacity expansion and ADC strategy. 24/7 Biopharma – PROCOS HPAPI & ADC Strategy.
11. World ADC London – 2026 partners and ADC industry ecosystem. World ADC London – Partners.
12. White House / Federal Register – Adjusting Imports of Pharmaceuticals and Pharmaceutical Ingredients into the United States, April 2, 2026, including the current Section 232 framework and ADC treatment. White House – US Pharmaceutical Tariff Proclamation.
13. European Commission – EU-US Trade Deal, including the 15% ceiling and treatment of pharmaceutical products and generic APIs. European Commission – EU-US Trade Deal.
14. Scientific literature – Challenges and new frontiers in analytical characterization of antibody-drug conjugates, with particular focus on DAR, CQAs and analytical control. Analytical Characterization of ADCs – PMC.