Moving Ahead: More ADC Progressing Through the Clinic and Beyond Oncology and Hematology
Published on 19th September
This week from September 20-22, 2017, the 8th World ADC, the industry’s leading forum, discussing the latest developments and breakthroughs in antibody-drug conjugates, will be held in the Sheraton San Diego Marina, San Diego, CA.
Organized by Hanson Wade, the annual summit is expected to draw record attendance of over 650 from large and small pharmaceitical and biotechnology companies, academia as well as CROs, C(D)MOs and suppliers to the industry. Covering every element of ADC development, the summit curates the latest, cutting-edge, science and transformative industry insight.
Industry experts and key opinion leaders, as well as representatives from companies including Pfizer, ImmungGen, Seattle Genetics, Takeda,Genentech, AbbVie/Stemcentrx, Seattle Genetics, Immunomedics and many others from the more than 200 different organizations will present ground-breaking, scientifically novel ADC case studies, and openly talk about the experiences they gained.
Confirming the importance of ADCs
On August 17, the U.S. Food and Drug Administration (FDA) approved inotuzumab ozogamicin (Besponsa™, Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) and only weeks later, gemtuzumab ozogamicin (Mylotarg™, previously known as CMA-676; Wyeth Pharmaceuticals, a subsidiary of Pfizer) for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia or AML, and adults and children 2 years and older with relapsed or refractory CD33-positive AML was again approved, bringing the number of commercially available ADCs to four.
The approval of these new agents confirms the importance of antibody-drug conjugates as a class of therapeutic agents, something that is also confirmed by the increased number of proposed therapies in which antibody-drug conjugates are used as a single therapeutic agent as well as in combination with other complementary drug classes, including immune-checkpoint and DNA damage repair inhibitors is creating excitement among researchers and physicians.
The progress seen this year has created much excitement. We’ve seen progress in the development of novel antibody-drug conjugates, as well as a growing the number of ADCs entering and progressing through the clinic. We’ve also seen new targets and linker-drugs with different mechanisms of action being validated and evaluated in early preclinical and clinical trials. And we’ve seen progress in the development of, more precise, targets and improved linker-drug chemistry, site-specific conjugation and improvement in CMC.
This year, during the 8th World ADC summit, Femtogenix revealing a new class of sequence-selective DNA-interactive ADC payloads. Pyridinobenzodiazepines (PDDs) will be introduced for the first time and their design, novel DNA mono-alkylating mechanism of action, and potent in vitro cytotoxicity and in vivo antitumour activity when used in an ADC format will be described.
Eisai will be discussing Chlorotoxin in Peptide Drug Conjugates: Improved Understanding of Tumor Targeting. Chlorotoxin is a tumor targeting peptide that naturally occurs in scorpion venom and has shown activity in human glioma clinical trials. They will give insight into how Peptide Drug Conjugate (PDC) containing chlorotoxin was used to identify a novel mode of action of chlorotoxin, revealing its true target on cancer cells and the mechanism for tumor targeting which is separate and distinct from its neurotoxic properties in venom.
Heidelberg Pharma will be revealing how Antibody Targeted Amanitin Conjugates (ATACs) represent a new class of ADCs using the payload Amanitin. This payload introduces a novel mode of action into oncology therapy, the inhibition of RNA polymerase II. The presentation will include improvements of the technology and an update of the development of HDP-101, the first Amanitin loaded ADC directed against BCMA and scheduled to enter Phase I trials in Multiple Myeloma by the end of 2018.
Tarveda Therapeutics will address the discovery and development of potent and selective, miniaturized drug conjugates for the treatment of patients with solid tumors through presentation of its novel Pentarins™. Pentarins bind to either cell surface targets, as is the case with lead candidate PEN-221, or intracellular targets as with PEN-866. All Pentarins are uniquely designed to drive efficacy through deep and rapid penetration into solid tumors resulting in sustained payload accumulation and cancer cell death.
Seattle Genetics will be giving their latest insight into Design Principles for Maximizing the Drug Delivery Efficiency & Therapeutic Index of ADCs. Toxicology and xenograft studies indicate that the optimized design both decreases off-target toxicity and improves antitumor activity, and they are currently planning to evaluate this design clinically with an anti-CD48 antibody for patients with multiple myeloma.
But in addition to antibody-drug conjugates as a single agent, the combination of ADCs with other complementary drug classes, including immune-checkpoint and DNA damage repair inhibitors has created excitement among researchers and physicians.
It’s a start
But the excitement does not stop there.
As the executive editor of Onco’Zine, The Onco’Zine Brief and ADC Review | Journal of Antibody-drug Conjugates, I’m convinced that the approval of the latest ADC is just the first step of what will soon be a plethora, an abundance, of novel ADCs in more therapeutic areas beyond oncology and hematology. Scroll through our drug map (part of our ADC University) and discover not only the latest ADCs for the treatment of patients with cancer and hematological malignancies, ther are noa more antibody-drug conjugates for the treatment of diseases beyond these therapeutic areas.
While regulatory approvals are indeed important, the work done by researchers and clinicians, as well as the willing cooperation of the often forgotten patients willing to participate in clinical trials, is the key to success. But the progress made so far is just the beginning.
The increased efforts are important – contributing to the greater promise for patients awaiting more effective and less toxic treatment regimens. But success is not possible without building new (international) relationships and collaborations. The open discussion during this weeks 8th World ADC, as well as learning from colleagues, networking with potential collaborators and partners and sharing the latest approached in making ADCs more efficacious is key to future successful breakthroughs – especially with novel ADCs moving beyond oncology and hematology.
The development of novel therapies requires a lot of dedication and work as well as a sharp focus on the key challenges the field is encountering.
And much more work—from early discovery, preclinical, clinical and beyond–is indeed still ahead of us.
Last Editorial Review: September 19, 2017
Featured Image: Downtown San Diego at night. Courtesy: © 2017. Fotolia. Used with permission.
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