This talk will highlight how preclinical experiments can be used in conjunction with PK/PD modeling and simulation to support the discovery, development and preclinical-to-clinical translation of novel ADCs. The talk will also focus on novel P/PD-based strategies to improve the therapeutic index of ADCs.

Patient outcomes can be greatly improved by a bone marrow transplant in multiple disease settings, including autoimmune diseases and hematologic disorders. Prior to transplant, patients are conditioned by removing their own bone marrow stem cells using poorly tolerated toxic, non-selective chemotherapy and radiation. This presentation will highlight preclinical proof of concept data demonstrating that antibody-drug conjugates may be safer, targeted agents for patient preparation with the aim of extending the use of curative bone marrow transplant and improving outcomes for patients.

C’Dot Drug Conjugates (CDCs) are ultra-small (sub-10nm) targeted organic-silica hybrid bio-material nanodrug conjugates that have a payload capacity 10 times higher than antibodies. The ultra-small size of CDCs facilitates both effective tumor penetration, including the ability to mediate drug delivery across a disrupted blood brain barrier, and efficient systemic elimination which can reduce toxicities associated with prolonged residence in the circulation. Elucida Oncology developmental platform will be presented.

Strategies harnessing the potential of the innate immune system in cancer therapy are yielding promising clinical results. To improve on the current approaches, the targeted delivery of immunomodulatory payloads, such agonists of the Stimulator of Interferon Genes (STING) pathway, could yield a tunable platform for achieving increased efficacy and safety. ImmunoBiochem is utilizing its cancer secretome-targeted biologics platform to deliver high-potency immunomodulatory payloads selectively to the immune cells and stroma within the tumor microenvironment.

SMARTag™ technology uses a simple, robust manufacturing process to generate stable, site-specific ADCs. Our RED-106 noncleavable maytansine linker-payload is resistant to P-glycoprotein efflux, offering wider therapeutic windows as compared to other technologies. This advantage is illustrated by our anti-HER2 RED-106 ADC in comparison to the related drug, T-DM1.

Antikor is developing smaller-format ADCs that penetrate tissues more rapidly, clear faster from normal organs and are better-tailored for solid tumours. Our HER2 FDC (ANT-043) is in advanced development but our toolbox of antibody libraries and linker-payloads have yielded our second new FDC candidate (ANT-045). We will present compelling new discovery data that helps us understand the strengths of our novel platform and tumour cure efficacy data for ANT-045 for gastro-intestinal cancers, with uptake and imaging data to support our technological approach..

Avibodies™ comprise unique surface disulphides for precise loading of drug payloads (auristatins, maytansinoids) with superior tumor xenograft regression compared to conventional IgGs (targeting CD30). PK has been demonstrated in a Phase 1 clinical trial. With TagWorks NV2, Avibodies pre-target and upload tumors with the ADC-drug subsequently released by a systemic activator. In summary, Avipep’s novel Avibody designs enable precise site-specific loading of drug and isotope payloads for cancer imaging and ADC therapy.

Antibody-drug conjugates (ADCs) and small-molecule drug conjugates (SMDCs) represent two conceptually related strategies for the targeted delivery of potent cytotoxic agents to various types of cancer. In this lecture, I will present a comparative analysis of therapy and biodistribution results in mouse models of cancer, as well as clinical data and information on how ADCs and SMDCs can be potentiated using targeted cytokine therapeutics.

We will introduce a new linker antibody-conjugation technology that enables site-specific payload attachment to native antibodies ‘off-the-shelf’ in one or two steps without prior engineering. We will show that our linkers enable the incorporation of various functional chemistries and a loading of 2, 4 drugs or even 2 different drugs in one ADC. We found that the resulting ADCs have favorable physicochemical properties and showed very efficient anti-tumor responses in efficacy studies compared to conventional ADCs used at the same dosing, payload and drug load.

Antibody modification is often necessary to endow antibodies with non-native capabilities from antibody-drug conjugates (ADCs) for targeted therapeutics to fluorescent reporter molecules for use in diagnostic or imaging applications. This session will explore site-specific antibody modification through conjugation to the conserved antibody nucleotide binding site (NBS) and will demonstrate how various linkers and conjugation strategies can be utilized to leverage the UV-NBS technology for use in next-gen antibody pharmaceuticals.