Existing Challenges in Translational Research
Despite massive investments in drug discovery and preclinical research, >90% of therapeutics fail in clinical trials (Phase I through Phase III), with the majority (>70%) failing in Phase II (efficacy).1 A major root cause for these excessive failure rates are suboptimum laboratory animal models (LAMs) which have low phenotypic diversity, require disease induction and are studied under artificial conditions. Understandably, these suboptimal attributes have produced a long standing reproducibility crisis in translational research which is well acknowledged by the scientific community2, the National Institutes of Health 3,4 and the Food and Drug Administration.5 Based on these LAM failures, in 2022 the FDA Modernization Act 2.0 (Act) was passed, permitting in vitro models to replace the requirements for preclinical LAM studies. The FDA and NIH are advocating for development of in vitro models despite no evidence they will yield any greater benefit than LAMs. In reality, in vitro models are a further departure from living system and disease complexity so only time will tell if these in vitro models are predictive.
Comparative Medicine and Veterinary Clinical Studies
Comparative Medicine: A far more rational approach would be to bridge the translational gap by evaluating animals which naturally develop comparative diseases to humans. Notably, companion animal dogs naturally develop >100 diseases with molecular, cellular, and physiological homology to humans;6-18 co-exist in the same environment; and receive near equivalent level of care to humans. In turn, companion animal dogs largely mirror a human Phase II patient.
There is an increasing demand to leverage veterinary studies within the pharmaceutical industry to de-risk biomedical development. For example, Calviri is pioneering a novel neoantigen cancer vaccine in dogs which proposes to have applications in humans. Another example is a Valley Fever vaccine being developed for veterinary patients (dogs) that may pave the way for a human vaccine.