Abzena, a life sciences company providing a series of specific serviced for the development of antibody-drug conjugates, earlier this week announced the launch of ADC Cascade and Biologics Cascade.
The new services were launched ahead of 10th annual World ADC, a ‘must attend’ industry meeting for anyone involved in the development and manufacturing of ADCs, held October 8 – 11, 2019 in San Diego, CA.
ADC Cascade and Biologics Cascade adds to the company’s existing antibody-drug conjugation (ADC) and biologics development services (including mono and bispecific antibodies). These ex-vivo platform approaches allow efficacy and safety studies against clinically characterized on and off-target tissues.
Translational Risk
Clinical failure of ADCs and biologics remain high, and candidate lead selection is associated with significant risk for translation into clinical development. Preclinical testing evaluates target expression and toxicity in animal models but does not necessarily optimally link human tissue with clinical history and potential binding to healthy tissue, which may predict safety issues.
And while a better understanding of cancer biology has resulted in the development of a number of transformative anticancer therapies, bringing meaningful declines of mortality and morbidity to patients, successful translation of novel oncology drugs – from preclincal development to the clinic – remains among the lowest of all therapeutic areas [1]
A recent analysis of 7,455 clinical development programs between 2006 and 2015, published in Nature Reviews Drug Discovery, shows that the likelihood of regulatory approval for an investigatonal drug in phase I development is the lowest in oncology.
The analyses showed that only 5–7% of all phase I clinical drug development programs in oncology and <50% of investigational agents in phase III programs were ultimately approved by the U.S. Food and Drug Administration (FDA).[2]
And while some experts point to outdated impractical clinical-trial as one reason why some promising investigational agents may fail, there may also be safety concerns and simple corporate decision making why some of these drugs are never available to patients. However, some of fundamental reasons of failure go back to early development and preclinical trial design.
Safety issues
When preclinical evaluation of target expression and toxicity may points to a potential safety issue, a (human) patient population expressing the target of interest can, prior to candidate nomination, be defined and safety liabilities assessed.
Abzena’s ADC Cascade and Biologics Cascade, are clinically oriented services focusing on the early design and developability of lead candidates. Combining the company’s developability and conjugation chemistry services, with access to 175,000 high-quality, clinically characterized human tissue samples helps identify relevant patient subgroups, enhances lead selection through rational design and evaluate linker and payload (or other conjugated moiety such as RNA) combinations. These can be bound to clinically characterized on and off-target tissues. In addition, candidate selection can include ex-vivo safety and efficacy profiles.
“Patients and prescribers want assurance that new medicines are being developed that will improve their health and work safely,” noted Jonathan Goldman MD, Abzena’s Chief Executive Officer.
“ADC and Biologics Cascade is a new approach in translational medicine. We are delighted to offer our clients a new approach that integrates a large biobank of very well characterized tissues with our conjugation chemistry (ADC) and developability (biologics) services,” Goldman added.
Reference
[1] Mullard A. Parsing clinical success rates. Nat. Rev. Drug Discov. 15(7), 447 (2016)
[2] Ledford H. Translational research: 4 ways to fix the clinical trial. Nature 28; 477 (7366), 526–528
