Antibody-drug conjugates (ADCs) are effective are multicomponent molecules constituted by a monoclonal antibody covalently linked to a potent cytotoxic agent. These biological agents combine high target specificity provided by the antibody together with strong antitumoral properties provided by the attached cytotoxic agent.

These drugs are complex molecules which uses the targeting ability of monoclonal antibodies with potent anti-cancer agent such as a payload or drug. This enables the cancer cells to be targeted effectively without damage to other, healthy cells. Antibody-drug conjugates are at the forefront of oncology therapeutics.

Current approved ADCs
Today there are 4 approved and commercially available  antibody-drug conjugates including brentuximab vedotin (Adcetris®; Seattle Genetics/Takeda) for the treatment of Hodgkin’s lymphoma and anaplastic large-cell lymphoma; ado-trastuzumab entansine (Kadcyla®; Genetech/Roche) for the treatment of Her2+ metastatic breast cancer inotuzumab ozogamicin (Besponsa™, Wyeth Pharmaceuticals, a subsidiary of Pfizer) for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia and gemtuzumab ozogamicin (Mylotarg™, Wyeth Pharmaceuticals, a subsidiary of Pfizer) for the treatment of adults with newly diagnosed acute myeloid leukemia whose tumors express the CD33 antigen.

However, with more than 80 investigational agents in development and a number ADCs in late phase clinical trials, the expectation is that this number will grow exponentially.  Some of these investigational agents have shown promising clinical results.  Among these are novel agents including sacituzumab govitecan (IMMU-132; Immunomedics) which demonstrated significant clinical activity in relapsed or refractory triple-negative breast cancer (TNBC), and [fam-] trastuzumab deruxtecan (DS-8201; Daiichi Sankyo) which, in patients with heavily pretreated HER2-low-expressing metastatic breast cancer has demonstrated a confirmed overall response rate of 50% and a disease control rate of 85.30%. [1][2]

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World ADC San Diego is the definitive opportunity for researchers and developers to gain and utilize key learnings in an open environment of knowledge sharing and exchange…

Beyond oncology
For oncological indications, Antibody-drug Conjugates carry highly cytotoxic agents to selectively kill the target cells. These payloads typically display picomolar to sub-nanomolar IC50 values in a free drug form, which may includes agents like auristatin, maytansine, calicheamicin, duocarmycins, pyrrololoenzodiazepines and α-amanitin. [2]

But outside the area of oncology and hematology interest in how ADC technologies may improve therapeutic options is growing. But the requirements, and as a result the complexity of the technologies for these novel Antibody-drug Conjugates are different. For example, the non-toxin-based payloads to be delivered to the target cells in non-oncological indications and modulate biological functions are designed in such a way that they do not affect cell viability. These payloads are  largely less potent compared to the toxins.  Hence, in the development of non-oncological ADCs this means that there is a higher standard in terms of selection of targets, antibody carriers, linker chemistry, as well as conjugation approaches to achieve sufficient binding, efficient internalization, and payload release for efficacy.[2]

9th World ADC
This November Antibody-Drug Conjugate community will meet again. During the 9th World ADC San Diego on November 12-15 at the Marriott Marquis San Diego, California, key influential researchers from around the world, will discuss clinical research experiences to help further the development of novel therapeutics.

The conference is expected to draw more than 600 industry stakeholders, and will feature over 60 scientific posters on the top innovations in ADC science within the past year, and over 76 data driven presentations from key speakers.

Research presented at this year’s 9th World ADC San Diego will shows how the scientific community continues to harness new technologies and insights to improve upon and develop more effective cancer treatments, including the use of ADCs outside of oncology, payloads with novel mechanisms of action such as non-cytotoxic payloads and ADC/Immuno-oncology combinations.

“As the industry’s longest standing and most comprehensive antibody-drug conjugate conference, World ADC San Diego is the definitive opportunity for researchers and developers to gain and utilize key learnings in an open environment of knowledge sharing and exchange,” said Fiona Mistri, Program Director of World ADC.

“World ADC San Diego will once again to be the environment in which scientists can communicate problems and solutions; share novel data and forge networks to develop more clinically impactful ADCs,” she added.

Posters and oral presentations
The program includes oral presentations and poster presentations. This year, expect some interesting updates.

Key Scientific Poster Presentations Include:

  • Generation of a THIOMABTM Antibody XTEN Conjugate (TXC) – Neelie Zacharias, Scientific Manager | 4:30pm Tuesday, November 13 (Genentech)
  • Evaluation of an Imaged Capillary Isoelectric Focusing (icIEF) Method for a Lysine Linked Antibody- Drug Conjugate (ADC) using Maurice – Morgan Rudick, Associate Scientist II | 4:30pm Tuesday, November 13 (Immunogen)
  •  Identification of a Novel PBD Dimer with Increased Conjugation Efficiency & Decreased P-gp Susceptibility – Shenlan Mao, Scientist | 4:30pm Tuesday, November 13 (MedImmune)
  •  MI180021: A Novel ADC with a New Marine DNA Binder Payload – Carman Cuevas, Director, Research & Development | 4:30pm Tuesday, November 13 (Pharmamar)

Key Speakers Presentations Include:

  • Unveiling Complex & Novel Biotransformations of Antibody Drug Conjugates Bearing CBI Dimer Payloads” Dian Su, Scientist | 10:30am, Tuesday November 13, Location: Discovery Stream (Genentech);
  • From Bench to Bedside & Back Again: The Development of a c-KIT ADC, Tinya Abrams, Senior Investigator | 2.30pm Tuesday November 13, Location: Clinical Stream. (Novartis);
  • Lessons Learned from Developing Processes for Late Stage Clinical Development”, Richard Silva, Senior Director, Process Development, CMC | 11:00am Tuesday November 13, Location: CMC Stream (ImmunoGen);
  • Disulfide Re-Bridging with Pyrrolobenzodiazepine Dimers Enable the Formation of Homogeneous, Potent & Differentiated Antibody & Fab Drug Conjugates, Nazzareno Dimasi, Associate Director, Research & Development | 2:00pm Wednesday November 14, Location: Discovery Stream. (MedImmune)
  • Harnessing Multiscale Modelling to Optimize Design of Antibody Drug Conjugates for Clinical Success”, Renu Singh Dhanikula, Senior Investigator | 2:00pm November 14, Location: Translational Stream. (Bristol Myers Squibb)
  • Development & Execution of a Diagnostics Strategy for Patient Analyses & Stratification for a Probody Drug Conjugate (PDC)”, Luc Desnoyers, Senior Director, CytomX | 11:00am, November 14, Location: Clinical Stream. (Translational Sciences)

In addition to scientific posters and oral presentations one of the features also includes the 5th Annual World ADC Awards (Tuesday, November 13) which is designed to recognize the extraordinary endeavors, teamwork and commercial acumen that has propelled the field to the forefront of cancer research today.

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