2018 ADC Symposium

Antibody Drug Conjugates (ADCs) are consist of an antibody linked to a payload drug, which is a new type of precision medicine. Currently, four ADC drugs have been approved, and the other ADCs undergoing clinical trials have been synthesized by conjugation technologies developed in the past two decades. The most significant disadvantage of these traditional conjugation technologies includes the lack of specificity at the connecting positions of the antibodies and the variable number of connections. In order to overcome these challenges, we provide a disulfide re-bridging conjugation method to improve the homogeneity of ADC. Based on this approach, our results show the benefits of better ADC drugs conjugation homogeneity, stability and efficacy.

BCMA is a promising therapeutic target for treating multiple myeloma. To exploit its therapeutic values, we have developed ABL201. ABL201 is an anti-BCMA antibody-drug conjugate that is made by conjugation of MMAF on N-terminal of a BCMA specific antibody by aldehyde linker. The N-terminal specific conjugation was more stable in vivo than thiol conjugation. ABL201 killed multiple myeloma cell lines effectively in vitro by inducing apoptosis. ABL201 also induced complete regression of tumors in H929 xenograft model after the administration of a single dose of ADC at 5mpk. ABL201 was well-tolerable to rats up to 62.5 mpk at a single dose. These results support further development of ABL201 to the IND-enabling studies.

LegoChem Biosiences is a clinical stage biotech with expertise in medicinal chemistry. It has several antibiotic programs for infectious disease with urgent needs and drugs in oncology and anticoagulant. It has extended its expertise to ADC and developed next-generation site-specific ADC platform with novel linker that improves stability of ADCs in blood circulation, effectively prevents premature drug release, efficiently facilitates liberation of the drug at targeted tumor cells and ultimately shows significant improved therapeutic index.

Highlights of presentation:

• LCB’s novel next-generation site-specific ADC platform technology
• Proprietary plasma-stable cleavable liniker enabling cancer-specific release of payload
• Proprietary PBD prodrug payload technology for ADC
• Review preclinical POC data and other key data
• LCB’s ADC pipelines and future development

Immunwork is developing a “T-E” drug-design technology platform, which can be employed for creating a large variety of T-E drug molecules with both targeting and effector functions. The targeting and effector moieties of a T-E drug, which each carry one or more targeting and effector elements, respectively, are prepared separately and joined by click reaction. The T-E new drugs cover ADCs, bispecific antibodies, and other multi-functional molecules for potential applications in oncology, autoimmune diseases, infectious diseases, diabetes, etc. The ADCs have the following features:

• The molecular constructs are based on novel, patented multi-arm linker units.
• Cytotoxic drugs are prepared in “drug bundles” of multiple drug molecules and conjugated site-specifically to the targeting moiety.
• Targeting moiety can be IgG, IgG-like variants, or other constructs with 3 or 4 binding elements.
• Modular feature is suitable for precision medicine.

Tangential flow filtration (TFF) is a mainstay of biopharmaceutical processing, allowing gentle and fast concentration / diafiltration of therapeutic proteins. The conventional TFF device is a cassette run in a stainless steel holder so far.

There is a growing demand for single-use disposable products within the biopharmaceutical industry device by the trend toward smaller batches, multi-use facilities, and faster development etc. The single-use TFF device is ideally self-contained, pre-sterilized, and holder-less giving easier installation, faster operation, and safer removal which is increasing need of closed device for purification of product which has high potent API like ADC, biological hazard products as well.

This presentation introduces the novel single-use TFF capsule type device, the concept, and the performance with some studies.

With an expected high annual growth rate of the global antibody-drug conjugate (ADC) market, it is essential that CMO’s have robust manufacturing platforms to ensure successful transfer to GMP production. Single Use Technologies provide many advantages, including improved safety, lower costs and greater flexibility. This poster will outline the advantages of a Single Use Platform and give a case study of how it can be used to manufacture ADC projects.

MilliporeSigma offers a complete single-use portfolio for bioprocessing through its Mobius® product line. This presentation focuses on three of these technologies well suited for use in antibody drug conjugate production: mixers, chromatography, and TFF. Mobius® Mix provides low shear, gentle mixing, while Power Mix is a high performance mixer for rapid dissolution. The Mobius® FlexReady Solutions with SMART FlexwareTM assemblies for Chromatography and TFF are predesigned and optimized, using innovative SMART flow paths. Here we will show examples of performance data which helps explain the features and benefits of these single-use technologies.

Antibody drug conjugates (ADCs) are a class of biomolecules that has seen rapid growth as an oncology therapeutic. ADCs are comprised of three parts: monoclonal antibody (mAb), linker, and cytotoxic payload, where each component plays a role in therapeutic efficacy. The small molecule linker/payload is a highly potent, toxic agent that requires special consideration for safe handling and containment during conjugation and downstream processing. To address these concerns, many ADC manufacturing in stainless steel or glass to single-use poses concern, as the conjugation step commonly utilizes aqueous organic solvents. A better understanding of the compatibility with and extractables from materials of construction is needed to enable widespread adoption of single-use technologies in ADC processing. This poster provides an overview of study design and associated results for evaluation of compatibility and extractables using Mobius single-use assemblies in the presence of 20% DMSO or 20% DMAc.

Activated Polyethylenglycols, aPEGs, are being coupled to many active pharmaceutical compounds to increase circulation times in human, to increase drug solubility and stability, and to overall increase patient compliance by reduced administration frequency. Pegylated linker payload constructs have been recently seen increased use in ADC development, as pegylation increases solubility and reduce potency. First patient dosages with pegylated MMAE has been recently reported. Challenges have been seen in the market by providing fast and reliable high quality aPEGs enabling consisting drug development from early phases through clinical phases and commercialization. Those challenges arise often from not well characterized product characteristics and definition of analytical methods and parameters. Examples of aPEG synthesis from small to full scale considering analytical and regulatory challenges will be addressed.

The complexity of the ADC supply chain can present challenges for originators looking to outsource the manufacture of their compound. There can be as many as 10 CMO’s involved in the process. This could present challenges in the transfer of information and add additional management responsibility to the originator. A well-functioning and integrated Program Management model within your ADC CMO business partners can lead to more efficient technology transfer within a CMO and between CMO’s and enhanced execution. This presentation will review best practices in successfully outsourcing ADC manufacture and testing and highlight how an integrated program management model can support that.