Pre-Conference Seminar Day

• Breaking down the exciting landscape of novel drug conjugate design and mechanisms of action
• Exploring emerging trends across conjugate design and targets
• Spotlighting novel conjugate innovation across multi payload ADCs, bispecific ADCs and degrader antibody conjugates

• Laying out innovation-led approach to novel ADC therapies leveraging dual payload and target design
• Assessing design rationale and differentiated advantages of proprietary DuetTx platform
• Introducing preclinical efficacy and safety profile of dual payload ADC assets as first-in-generation advancing to clinical development

• Exploring stabilized linker designs and optimized dual payload combinations to enhance ADC stability, efficacy, and overcome  drug resistance
• Assessing flexible conjugation methods through thiol maleimide and copper free click chemistries to allow precise drug bundle attachment and optimal DAR
• Explaining how site-specific conjugation of drug bundles enables high-DAR mono and dual payload ADCs with superior efficacy, stability and safety 

Experience a structured networking format designed to help access and broaden scientific insights and connections specific to your day-to-day ADC expertise

• Describing dual payload ADC conjugation strategy and physicochemical properties to demonstrate co-delivery therapeutic benefit versus single payload therapies
• Exploring biodistribution data and in-human dosimetry calculations to predict safe radiation exposure
• Evaluating immunological and imaging studies to achieve in situ vaccination response

• Discussing the growing need for novel ADC payloads in the face of ADC patient resistance mechanisms
• Weighing up the pros and cons of novel cytotoxic, catalytic, oligonucleotide, and immune stimulating payload safety and efficacy
• Assessing MoA characterization of ADC payloads beyond classical cytotoxic agents

• Exploring rationale and design of OBI-221, a dual payload bispecific ADC targeting cMET/HER3
• Outlining lessons learned from pursuing a two hit, two target approach to guide future ADC innovation opportunities
• Evaluating initial characterization of OBI-221, contextualized with early clinical performance of TROP2 ADC leveraging same design principles 

• Contextualizing Double Hit Lymphoma (DHL) as a rare and highly aggressive B-cell lymphoma with rapid disease progression, treatment resistance, and poor patient survival outcomes
• Evaluating studies indicating CDK9 as a key driver of the aggressive and therapy-resistant behavior of DHL
• Developing a bispecific ADC to target CDK9 to selectively target DHL cells and mitigate off-tumor, on-target toxicity associated with past clinical failures 

At the end of the seminar day, don’t miss this summary panel discussion to discuss, debate and challenge your speakers and ADC peers on the cutting-edge of ADC design, exploring the most promising areas of ADC innovation, benefits against traditional therapies, and hurdles to advance novel conjugates into and through the clinic.

• Breaking down design of XB404 leveraging Adagene and SMARTag platforms to develop a masked ADC targeting ROR1/2
• Emphasizing rationale of XB404 masked mechanism to minimize on target, off tumor safety in ROR1/2 expressing tumors
• Laying out preclinical characterization across in vitro cytotoxicity and bystander activity and in vivo efficacy in CDX and PDX models

• Highlighting the benefits and potential of conditionally activated ADCs against traditional conjugate design
• Exploring Conditionally Active Biologic mechanism leveraging tumor pH and physiological conditions for ADC activation
• Spotlighting PD profiles of conditionally active ADCs to demonstrate improved therapeutic index

• Demonstrating rationale to develop conditionally active ADCs to overcome challenges with target mediated toxicity and improve therapeutic index
• Laying out ADC masking mechanism leveraging steric masking nanobody peptide activated by a variety of proteases in the tumor
• Highlighting development of ADCs leveraging masking technology including preclinical efficacy and safety profiles

Experience a structured networking format designed to help access and broaden scientific insights and connections specific to your day-to-day ADC expertise

• Utilizing novel linker chemistry to circumvent the need for ADC internalization for payload release
• Applying novel linker payload technology to unlock development against previously inaccessible ADC targets
• Demonstrating novel target accessibility through preclinical efficacy and safety data of anti-VEGF avastin ADC YL242

• Linker Engineering: Introducing AQUALINK platform utilizing simple sugar groups as a spacer to engineer hydrophilic ADCs
• Antibody Engineering: Identifying unique conjugation sites that can shield around the hydrophobic payload to result in overall hydrophilicity to the ADC
• Breaking down novel hydrophobic ADCs In vitro and in vivo data to demonstrate differentiation from conventional ADCs 

• Exploring how Topo1 and Topo1 ADCs elicit immunogenic cell stress in vivo through the induction of cellular senescence
• Delineating the host immune cell requirements for Topo1-induced immunogenicity
• Identifying biomarkers of immunogenic cell stress mediated by Topo1 ADCs

Bring your burning questions to this closing panel with all the seminar day’s presenters. With all ADC pharmacology topics up for discussion, hear the speakers delve into mechanistic and PD investigation for traditional and novel ADCs to model and characterize the next wave of ADCs heading to the clinic.

Discussion Highlights Include:

• Exploring how pharmacology and mechanistic investigations can strengthen existing ADC knowledge and influence future ADC development
• Debating the therapeutic properties of conditionally active and masked ADCs to assess their ability to differentiate against traditional ADC profiles
• Discussing computational modelling and PK/PD approaches to tackle translational considerations for noncytotoxic payload and novel format ADCs

• Understanding the need for ADC novelty to overcome patient resistance and deliver differentiated tolerability to widen therapeutic index
• Evaluating the tolerability of ISACs and AOCs to assess the risk benefit profiles of alternate payload mechanisms
• Understanding how considerations across bystander activity and target selection are crucial to manager toxicity of bispecific and peptide drug conjugates

• Understanding strategies to accelerate development cycle for novel ADC linker-payloads
• Defining the importance of safety profiles of novel payloads, contextualized through assessment of free payload versus ADC tolerability comparison
• Evaluating in vitro assays to employ for early payload safety profiling leading up to in vivo studies 

• Leveraging PDOs as functional ADC patient avatars, preserving tumour heterogeneity and normal tissue biology to reflect clinical efficacy and toxicity
• Capturing ADC responses beyond antigen expression to assess target engagement, internalization, payload sensitivity, and tissue penetration
• Enabling development of next generation PDO therapeutic strategies to allow testing of combination therapies and comparison with SoC data 

Experience a structured networking format designed to help access and broaden scientific insights and connections specific to your day-to-day ADC expertise

• Breaking down rationale and mechanism for click-to-release chemistry to develop ADCs with reduced off-target toxicity
• Highlighting key toxicity and PK aspects from the TGW101 program to support the safety benefits of the Click-to-Release ADC approach
• Bringing learnings from TGW101 improved safety profile to ongoing ADC discovery across targets, protein formats and payloads to advance click-cleavable ADCs with mechanism-driven improved tolerability and therapeutic index

• Assessing the importance of safety-led ADC innovation to widen therapeutic index and maximize patient benefit
• Evaluating lessons learned from early development of ADCs: What can be done to improve tolerability and therapeutic index?
• Exploring the breadth of ADC innovation to widen therapeutic index across less potent payloads, conditionally active ADCs, and novel linker-payload chemistry

• Contextualizing ADC clinical class effect toxicities to understand barriers to progression to standard of care and early-stage therapies
• Explaining the physician’s perspective and patient attitudes to ADC treatments given anti-tumor efficacy and associated toxicity profiles
• Breaking down clinical toxicity mitigation strategies: What are the top learnings to pass back to ADC developers?

Re-join your expert speakers in a closing panel discussion as they explore the best approaches to characterize, predict and mitigate ADC’s largest barrier to widen therapeutic index. Bring your top questions as the speakers discuss best methods to predict ADC clinical safety profiles, optimize patient selection, and mitigate adverse events.

Discussion Highlights Include:

• Understanding transferable learnings and new considerations to assess the safety profile of non-cytotoxic and novel format ADCs
• Breaking down how best to deploy in vivo and in vitro models to improve prediction of ADC clinical
• safety profiles
• Tackling opportunities and strategies to identify high risk patients and mitigate clinical ADC toxicities
• What are the toxicity-led barriers to overcome for ADCs progression to earlier-line patient therapies

• Giving a retrospective view to highlight the growth and make-up of ADC combinations over the past ten years
• Understanding the highs and lows of ADC combinations: What has been the most impactful to patients?
• Evaluating the current landscape and future directions of ADC combinations to combat payload resistance and push ADCs to earlier line therapies

• Combining Sofe-M with SoC agents across in vitro and in vivo ovarian cancer models to show superior, well tolerated anti-tumor activity, including enhanced cytotoxicity with olaparib in HRD models
• Sofe-M alone or with bevacizumab was highly effective in induction and subsequent treatment in tumor models with moderate SoC responses
• Contextualizing preclinical findings to support clinical development of Sofe-M in combination with other approved therapeutic agents for ovarian cancer

• Explaining rationale for combining a HER2 ADC with trastuzumab
• Describing preclinical and clinical results of combination trials, highlighting clinical benefit of ADC antibody combinations
• Investigating mechanism to understand how antibody combination helps ADC overcome binding site barrier to improve tumor penetration and improve efficacy 

Experience a structured networking format designed to help access and broaden scientific insights and connections specific to your day-to-day ADC expertise

• Contextualizing the need for novel payloads and payload combinations to circumvent resistance mechanisms to Topo1 and other classical payloads
• Breaking down a rationale-driven approach for novel payload combinations beyond dual cytotoxics
• Laying out preclinical approaches to identify and optimize dual payload combinations to set up translation for success

• Leveraging a cutting-edge cell free platform and novel payload classes to discover high-DAR dual payload ADCs aimed at overcoming resistance to single payload ADCs
• Demonstrating synergistic efficacy of Topo1-based combinations with diverse mechanisms, including DDR inhibitors, to enhance anti-tumor activity
• Validating improved preclinical efficacy of dual payload ADCs across in vitro and in vivo/PDX models to support their potential in resistant tumor settings

• Leveraging understanding of ADC immune system interactions to unlock clinically relevant checkpoint inhibitor combinations
• What are other rationale-driven ADC combination partners in the immune oncology field?
• Deep diving into preclinical Fc effect function to interpret role played in ADC combinations, contextualized with Fc silent versus wild type clinical readouts  

Rejoin your ADC combination speakers and attendees after lunch for a closing panel discussion to discuss, debate and evaluate the opportunities and challenges in combination clinical performance, optimizing partner selection, the power of ADC sequencing and dual payload conjugates, and more. Make sure to come with your thoughts and questions prepared!

Discussion Highlights Include:

• Contextualizing the growing importance of ADC combination therapies as more ADCs advance to earlier-line patient therapies
• Understanding the best rationale to smartly select appropriate ADC combination partners
• Undergoing preclinical investigation to support and justify clinical ADC
• combination trials
• Evaluating the ability of ADC sequencing and dual payload combinations to combat resistance to payloads

• Contextualizing CQA requirements from approved and marketed ADCs
• Breaking down CQA considerations across small molecule and biologic ADC components
• Supplementing CQA expectations with regulatory CMC guidance from available Health Authority published guidelines 

• Evaluating conjugatable impurities in ADC linker-payloads for potential toxicological
• Linker-payload conjugatable impurities present at ≤1.0% weight/ weight are unlikely to pose a risk to
• Contextualizing how data provides science-based justification to increase qualification limit from 0.15% to 1.0% weight/weight for linker-payload intermediates

• Surveying market trends across ADCs formats to examine key challenges across the development lifecycle from discovery to manufacturing
• Highlighting the benefits of state of-the-art analytics and process equipment and providing an overview of Sartorius’ ADC-optimized solutions
• Discussing the advantages of single-use equipment for ADC processing and introducing a new manufacturing-scale TFF system

Experience a structured networking format designed to help access and broaden scientific insights and connections specific to your day-to-day ADC expertise

• Contextualizing existing resources and standards supporting mAbs and small molecule aspects of ADCs
• Exploring development of an ADC mimic reference material to support CQA assessment of ADC therapeutics
• Understanding the need for additional, future ADC guidance to support quality control and standards from development to commercialization

• Assessing the Mobius ADC Reactor as a single-use system developed specifically for ADC conjugation workflows
• Characterizing mixing time and temperature control across 10L to 500L reactor scales, contextualized with a GMP case study preserving ADC CQAs
• Evaluating wetted materials for tensile strength retention and extractables following exposure to 100% DMSO and DMAc via RP-HPLC and DI-GC/MS to establish a leachables dataset relevant to ADC impurity control strategies

• Understanding the sources and impacts of ADC charge variant profiles given impact from linker payload properties
• Undergoing CQA assessments to determine ADC clinical relevance
• Defining compound-specific, phase appropriate and value-focused control strategies

• Navigating the challenges of ICE charge variance characterization for high DAR ADCs
• Exploring case study assessment to understand how environmental temperature impacts ADC charge profiles determined by ICE
• Leveraging learnings to accurately characterize increasingly complex ADC charge variance profiles 

Reuniting the day’s presenters, don’t miss the final speaker panel discussion to ask any unanswered questions from the scientific presentations. With your fellow process, analytical, and CMC experts, break down the challenges and learnings across impurity qualification, charge variance characterization and comparability studies to best approach ADC regulatory submissions and understand the unique considerations in ADC CQAs from a small and large molecule perspective.

• Overviewing a late stage ADC case study with a pragmatic workaround of Gross Content Testing to ensure reliable assessment without traditional testing
• Understanding regulatory strategy for defining and justifying RSMs for ADC linker-payloads
• Explaining an alternative to the conventional QC approach for charge-variant profiling of ADC drug substance and drug product for release and stability

• Breaking down sponsor learnings and best practices from preparing for ADC regulatory submissions and Health Authority interactions
• Discussing what data and evidence is needed to support science based justifications for altering ADC specifications to avoid redundancies
• Debating the sponsor perspective: What are the top areas to prioritize for future industry-regulator interactions?

• Navigating a holistic and risk-based approach for both linker-payload and ADC drug substance process
• Exploring a case study of environmental monitoring of drug linker and ADC drug substance facilities
• Using case study examples to assess linker-payload and ADC microbial methods

Experience a structured networking format designed to help access and broaden scientific insights and connections specific to your day-to-day ADC expertise

• Highlighting the importance of optimizing container selection and process levers to optimize ADC DP lyophilization
• Optimizing ADC DP manufacturing process to reduce challenges with vial fogging through hydrophobic vial technology
• Showcasing learnings within ADC manufacturing control strategy

• Optimizing bioconjugation for dual payload ADCs, including cysteine conjugation and amino acid incorporation for controlled payload attachment
• Understanding manufacturing considerations to enable site-specific conjugation with scalability and consistency
• Developing robust analytical methods and CMC strategies to support global regulatory submissions for complex ADCs

• Investigating ADC molecular photosensitivity during manufacturing, focusing on payload specific observations at specific wavelengths
• Laying out opportunities to control manufacturing and minimize ADC DS photodegradation
• Utilizing learnings to set expectations and minimize ADC photodegradation across manufacturing sites 

• Exploring a state-of-the art facility for ADC development and GMP manufacturing with completed conjugation process optimization and scale up studies across conjugation chemistries
• Developing a proprietary hydrophilic linker technology SoluFlex Link designed to enable favorable physicochemical and pharmacological ADC properties
• Establishing a flexible and scalable system to accelerate ADC translation into GMP compliant materials, supporting rapid clinical progression and ultimately commercial supply