Without a doubt, antibody-drug conjugates are coming of age.

With favorable results from large randomized clinical trials with multiple ADCs reported during medical society meetings, including ESMO 2023 Congress (European Society for Medical Oncology), AACR (American Association for Clinical Research), ASCO (American Society of Clinical Oncology) and others, as well as increased collaboration between early, preclinical, drug developers and (large) pharmaceutical companies and a remarkable surge in mergers and acquisitions (including the US $ 43 billion acquisition of Seagen by Pfizer and AbbVie’s 10 billion acquisition of ImmunoGen,as well as the US $ 110 million acquisition of Synaffix by Roche) and growing investments, ADCs are indeed coming of age.

Over the last 18 months we’ve seen major turning points for the development of ADCs, including the ‘ground-shaking’ and ‘practice changing’ results from studies with trastuzumab deruxtecan (Enhertu®; Daiichi Sankyo and AstraZeneca) the accelerated US Food and Drug Administration approval of of mirvetuximab soravtansine (Elahere®; ImmunoGen) for adult patients with folate receptor alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens.

Looking with an eye for (more) detail, investors generally focused on  platform technologies. And while many investors did not disclosed specific ADC targets, nor the technology they invested in, available data shows that more than 25% of investments focused on linkers chemistries. In addition, the most frequent therapeutic targets in the development of novel ADC included HER2, HER3, TROP2, Nevtin-4 and Claudin 18.2.

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What to expect at World ADC: 2024 Highlights
During the upcoming 14th World ADC in London, held March 12the – 15th, expect to hear more about increased investments in the developments of ADC, as well the growing interest in combination trials with ADCs in Clinical Trials and how a growing number of preclinical ADCs are moving to early Phase 1 and 2 clinical trials.

During World ADC 2024 listen to speakers reflecting on the milestones reached and the challenges ahead, and explore the outcomes of intensified collaboration on strategy as well as on key elements of ADC development, including linker-payload optimization, target discovery and selection, (payload) toxicity management and advanced in manufacturing.

Don’t miss the presentations by Jia He, Beacon’s antibodies and biologics manager who will be joining the pre-conference speaker faculty discussing ‘Explore the Rise in ADC Combination Clinical Trials,’ and Jake Morris, Beacon’s ADC Insights Lead for the Clinical Lessons track on Day 2 to assess the current state of the ADC landscape.

Also among the key presentations from corporate partners are a series of presentations from lead partner WuXi XDC addressing the challenges along bioconjugate development journey from discovery to commercial manufacturing.

WuXi XDC Chief Executive Officer Jimmy Li, PhD. will present his talk “Accelerating Bioconjugate Development from Discovery to Commercialization with WuXi XDC’ s Fully Integrated Capabilities and Expanding Capacities” in the plenary session on Wednesday March 13th at 9:00 am.

Key highlights:

  1. One-stop discovery services platform to accelerate candidate selection, including mAb/protein generation, payload linker synthesis, conjugate generation and in vitro, in vivo characterization
  2. Fully integrated ADC CMC development with industry leading DNA to IND timeline of 13-15 months; mab/payload-linker/conjugation DS & DP development and manufacturing all by in-house team and facilities
  3. Rapidly expanding capacities for all ADC component manufacturing: to have five conjugation, four ADC DP facilities by mid-2026 in Wuxi city and Singapore, as well as global network of mAb facilities and multiple linker-payload facilities

The WuXi XDC team will also shares new developments during the scientific poster session on Linker-Payload Synthesis, Scalable Development Platforms, and New Conjugation Technology.

  • Scientific Poster 1: WuXi XDC’s Development Platforms Deliver Consistent & Scalable Conjugation Processes

As ADCs advance from the preclinical candidate selection stage into CMC development stage, scientists face more and more process development challenges. In early R&D stage, microgram scale of ADCs is generated with discovery stage conjugation protocols, which may not deliver batch to batch consistency in physical chemical properties. Once the project moves to CMC stage, the challenge of developing a robust conjugation process that can manufacture GLP tox and clinical materials with the consistent PQAs evolves. At WuXi XDC, toolboxes have been established to develop robust conjugation and purification processes for various types of conjugation technologies. PD studies were designed using QbD principles, focusing on specific conjugation chemistry using DoE approaches. This poster presents the solutions established for such challenging PD projects.

  • Scientific Poster2: Application of Flow Chemistry Process in Linker-Payload Synthesis

Many linker-payloads used for ADCs are highly potent and cytotoxic. The linker payloads are often produced at multiple hundreds of gram(s) to kilogram(s) scale. Deprotection and reduction of compounds by hydrogenation is common in linker-payload synthesis. However, hydrogenation is a challenging process due to safety requirements, and batch mode production limit’s reaction scale and can result in incomplete conversion due to the difficulty of applying high pressure. The equipment also requires costly cleanup. This poster reviews the use of an easy, small-scale, flow-mode operation that mitigates safety risks and offers high conversion.

  • Scientific Poster 3: Novel Conjugation Technology for Native Antibodies that Generates ADCs with Narrowly Distributed DAR

Interchain cysteines are the most clinically validated conjugation sites on mAbs for the generation of ADCs.  The conventional conjugation methods used for cysteine conjugation can result in heterogeneous products of wide DAR distribution. Increasing the DAR homogeneity of ADCs can improve the PK profile which may lead to an enhanced therapeutic window and patient safety. Using our WuXiDARxTM technologies as a basis, we produce homogeneous ADCs with flexible target DAR (e.g., 2, 4, 6). This technology platform is compatible with native human IgG1 antibodies and thiol-reactive linker-payloads and can achieve >70% target DAR species before column purification.

Oxford BioTherapeutics
Clinical stage oncology company Oxford BioTherapeutics is expected to presents significant technological advances to its drug discovery platform OGAP®.  The company will launch OGAP®-Verify, a new version of the discovery platform at the 14th Annual World ADC Conference in London.

The company will also present two posters focusing on OGAP-Verify’s capacity to identify novel cancer-specific targets for the development of first-in-class therapies, particularly ADCs and other therapeutic antibodies, addressing unmet clinical needs in oncology.

Oxford BioTerapeutics will also present a number of posters.

  • Poster: Oxford Biotherapeutics’ OGAP Target Discovery Platform: Use of Quantitative Membrane Tissue Proteomics to Identify new ADC Drug Target (presented by Benjamin Thomas, Senior VP External Innovation during rack 1 Discovery Chemistry – Next-Generation Approaches to Target Selection: Advancing ADC Precision for Improved Delivery & Reduced Toxicity | March 13th, 2024, from 18:35 GMT

Despite recent progress in ADC development, only 10% of cancer patients are eligible for treatment with existing ADCs with ADC-target expression on patient tumors a major factor in patient eligibility. However, the majority of ADCs in development target the same nine proteins as those already approved. Leveraging OGAP®-Verify, OBT can identify first-in-class targets to treat patients who are currently ineligible for existing treatments. With its enhanced sensitivity, OGAP-Verify can detect protein expression levels as low as 50 copies-per-cell (which is more sensitive than IHC), uncovering targets missed by mRNA analysis. Moreover, it provides insights into normal tissue expression improving target selection and accelerating the drug target discovery process. By evaluating factors such as therapeutic index, protein abundance and benchmarking against known clinical ADC targets during target selection, OGAP®-Verify enhances the likelihood of success in ADC development.

  • Scientific Poster 30: Addressing Unmet Clinical Oncology Needs Through A Novel Therapeutic ADC Target Space in Cancer Patient Tissue Biopsies Using OGAP-Verify.(Presented by Abigail Houghton et al.  on March 13th, 2024, from 18:00 GMT

In this poster, Houghton et al describes the innovative use of the OGAP-Verify Membrane Protein Expression Database and its ability to identify novel therapeutic targets for ADCs by analyzing membrane protein expression in patient tissues. OGAP-Verify is the world’s largest quantitative membrane protein expression library generated using proteomics. Among other applications, it is used to identify targets overexpressed in cancers that are otherwise overlooked when using mRNA-based discovery techniques.

  • Scientific Poster 31: Identification of Novel Cancer-Specific Splice Variants Using Oxford Biotherapeutics’ Ultra-High Sensitivity Tissue Membrane Proteomics Database, OGAP-Verify, for First-in-class ADCs and Other Therapeutic Antibodies. Presented by Somdatta Basu et al. March 13th, 2024, from 18:00 GMT

In this poster, Basu et al describes Oxford BioTerapeutics’ use of its proprietary proteomic discovery platform, OGAP-Verify, to identify novel cancer-specific splice variants for the development of first-in-class therapies, including ADCs and Immuno-Oncology (IO) agents. OBT is conducting complex analyses to identify clean, novel cancer-specific protein targets bypassing the limitations of mRNA-based approaches.

On  Tuesday March 12th at 11:00am GMT José M. Mejía Oneto, MD, Ph.D, Founder and Chief Executive Officer of Shasqi (a biotech company whose mission is to make cancer drugs more effective with click chemistry) presents a session titled “CAPAC: A Modular Platform for Tumor-Targeted Drug Activation Using Click Chemistry In Vivo.” The session is part of the “Supercharging ADC Efficacy & Conquering Toxicity Through Transformative Emerging Conjugation Technologies” track as part of the 2nd Generation Conjugates Day.

As part of the session, Mejía Oneto is expected to share the background on the company’s novel Click Activated Protodrugs Against Cancer (CAPAC®) platform, which leverages click chemistry for tumor-targeted drug activation. The company will also share clinical proof-of-concept data and unveil preclinical data from the pipeline, showcasing the ability to use antibody fragments to activate high potency payloads at the tumor.

Other key presentations
A short overview of some of the expected highlights is never complete.  Other ‘must join’ sessions include:

  • Delving into SGN-CEACAM5C, an ADC With Novel TOP1 Drug Linker With Outstanding Preclinical Activity, presented by Ryan Lyski Senior Scientist, Pfizer (discussing SGN-CEACAM5C is an ADC with a potent topoisomerase I payload with distinct properties and outstanding preclinical activity).
  • Moving target: The Interplay Between ADC Design & Target Selection, presented by Krista Kinneer Director, Translational Medicine, AstraZeneca (Assessing FDA-approved ADCs and what they teach us about ADC target selection and examining the importance of matching the right technology and target to enable clinical success, using HER2 and TROP2 as examples and discussing how payload selection and biomarkers of sensitivity or resistance can influence criteria for ADC target selection)
  • ABBV-400 – A c-Met Targeting ADC With Activity in CRC & MET Amplified Tumors, presented by Martha Neagu Aristide Senior Medical Director, Abbvie.  In this presentation Aristide explores the background of ABBV-400, analyses the safety profile of ABBV-400 and forward planning for tox-related concerns, highlights the efficacy of this promising ADC and how it can provide hope for the treatment of MET amplified tumors, and discussing future directions and considerations for optimization.

This year, the organizers of 14th World ADC 2024 in London have shown that they have not left any stone unturned in preparing a superb program with all key players in the ADC Universe and beyond.

The 14th World ADC London 2024 will be held March 12th – 15th, at:

ExCel London
Royal Victoria Dock, 1 Western Gateway
E16 1XL

Featured image: World ADC 2018 Highlights

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