A personal view on antibody drug development

Oliver Schon, PhD, is VP Research & Development at BiVictriX Therapeutics, a UK-based emerging drug discovery and development company generating a pioneering first-in-class next-generation ADC anti-cancer therapeutics which exhibit superior selectivity towards cancer. Dr Schon is applying his broad expertise from lead discovery to manufacture in order to progress differentiated, safe and developable bi-specific therapeutic ADC candidates to clinical development. He says it is no secret that the costs of antibody drug development are steadily increasing to ‘eye-watering heights’ per approved drug1. He shared with DDW's Megan Thomas his opinion on these challenges in this dynamic environment. Whilst we celebrate the number of approved AB-, bispecific- and ADC drug candidates, the industry and payors alike have failed so far to develop meaningful mitigations to curtail this trend 2. At the end of the day, society as a whole and the national healthcare system specifically will have to reimburse these huge upfront costs. Technical advancements and AI Technical advancements in big pharma and small biotech as well as the undeniable emergence of AI could offer some of the answers. Huge data lakes have been generated for years now; it's time to put those to good use in order to shorten timelines, decrease costs or even make a particular activity redundant altogether and still enable solid decisions. Great strides of using existing data by interrogating those cleverly have been made in the large-scale manufacturing of biologics – an otherwise significant expense during drug development. Whilst we often talk about synergistic effects for a therapeutic drug candidate, the industry collectively should aim to put this concept into practice in the context of drug- and clinical development. Biological targets The choice of a biological target invariably determines the future success of a drug. Whilst antibody therapeutics are exquisitely selective, they - in most parts - aim to shift the cells’ fate into a particular direction. This is even more relevant for combination therapies or bispecific antibodies. Clinical trial results of those combinations and bispecifics were on numerous occasions underwhelming and didn’t stand up to their expected efficacy – not even in an additive way. We may have to explore disease complexity and signaling cascades more critically before entering costly and long clinical trial. Cellular signal redundancies and sub-optimal signal pathway manipulations have been reported as a reason for clinical failure3; pre-clinical models often do answer the questions we ask, but are they the appropriate models to use? Approaches are emerging to establish fully simulated cells that will enable drug developers to test their hypothesis for a desired outcome in silico before embarking on expensive experimentation4. Precision therapies The mantra of block-buster therapies to treat an entire disease is shifting – particularly in oncology. It now is widely accepted that cancer is a very heterogenous disease and not all patients benefit fully from the same therapy. Precision cancer therapy might cover a smaller patient pool, but potentially with a significantly higher efficacy and potential for cure with fewer relapses which otherwise add to the overall healthcare costs and negatively affect the patients’ quality of life. Looking forward Lastly, the constant expansion of complex biological modalities with a claim of differentiation from all other, already validated platform modalities5. Therapeutic platform development takes years until it reaches clinical validation, and those costs will have to be absorbed. Time will tell which of those many new modalities prove worthy of a marketing approval. Biography Oliver Schon, PhD, has been VP, R&D at BiVictriX Therapeutics since September 2021. Dr Schon obtained his PhD in Cancer Research from The University of Cambridge before joining Sir Greg Winter’s biotech venture Domantis in 2003 which was acquired by GSK three years later. Dr Schon continued to work at GSK for over ten years dedicated to developing biologics and cell therapy platforms for use in the clinic until he joined IO-focussed American biotech Agenus Inc in 2017; it was here that he amassed considerable CMC and biologics-based therapeutics manufacturing experience, developing numerous bispecific antibodies from discovery up until Investigational New Drug application (IND) and beyond. References https://www.evaluate.com/vantage/articles/data-insights/what-productivity-problem-biopharma-still-has-its-head-sand https://www.nature.com/articles/d41573-021-00079-7 https://pubmed.ncbi.nlm.nih.gov/31910414/ https://turbine.ai/ https://www.creative-biolabs.com/blog/bsab/reduction-and-fragmentation-of-bispecific-antibodies/