Mark S. Duxon, CEO
To reduce cost and improve the bottom line, the pharma industry has taken a more nuanced approach to drug discovery over the last decade, applying the R&D budget much more cautiously than before the financial crisis of 2007/2008. Previously, companies may have tested a novel molecule in as many as 10 to 15 preclinical animal models of a disease (prior to selecting a drug candidate for advancing into safety/tox screening and first time in man). Now, they focus on just a few judiciously chosen models that are thought more likely to predict clinical efficacy in later Phase II clinical trials. In such a scenario, having the right assays with the right experience is the key to success. Transpharmation is a global preclinical CRO that brings a robust and compelling business model to win the confidence of today’s pharma companies. Spun out of established healthcare company GlaxoSmithKline Pharmaceuticals (GSK) in 2010, Transpharmation delivers a best-in-class neuroscience/pain contract research offering in the preclinical space for global pharma and biotech companies. It deals with animal models, behavior, EEG, and biomarkers of disease areas such as sleep disorders, epilepsy, pain, depression, and schizophrenia, among others.
Driving Forward the Legacy of Poor Clinical Efficacy
The psychiatry drug discovery space, in the last two decades, has witnessed a significant reduction in its portfolio across the pharma industry. The reason: a high failure rate in Phase II clinical trials and a difficulty in showing superior clinical efficacy of novel drugs versus now established cheap, generic clinical gold standards. Indeed, this latter issue of differentiating drug, which produces the greatest effect, is also an issue in many preclinical models of disease too. Transpharmation has sought to tackle this head-on with several key business strategies and hence leads the market with its cross-therapeutic area in translational pharmacology; most notably across neuroscience and pain disease areas. “Since our inception, we have maintained a significant year on year growth because of our ability to focus on resolving clients’ pharmacology/drug discovery issues. We do this by listening to the scientific questions posed and bringing our own experience to the table to find solutions,” says Dr. Mark S. Duxon, CEO of Transpharmation. Backed by knowledgeable and expert resources in the form of senior PhDs (with a rich background in drug discovery), the company works closely with its clients to understand their needs in drug validation and achieve the best quality results.
Transpharmation differentiates from many of its competitors by offering extensive pharmacological validation of its assays and, most importantly, having these assays running all year round. “Coming from the pharmaceutical industry, we understand the need to offer pharmacological models that are consistent from one day to the next. Many of our competitors will claim to offer vast lists of assays, many of which to not get used from one year to the next. We simply believe it is of far more value to run one or two highly interrogated preclinical assays for each disease, which are used day to day and have been extensively validated with an array of clinically used molecules. Only then can a researcher truly put into context the data that they achieve with their experimental drug,” says Duxon. These assays are characterized by standard medicines that are used to treat patients in the clinic. “We employ preclinical models by conducting behavioral screening of small molecules and antibodies in rodents to understand the underlying potential translational efficacy of the tested drugs on humans,” adds Duxon. “Also, we can back translate clinical data to ensure our preclinical assays truly model what is seen in humans.”
We employ preclinical models by conducting behavioral screening of small molecules and antibodies in rodents to understand the underlying potential translational efficacy of the tested drugs on humans
Team Transpharmation has demonstrated this ‘back translation’ to animals in the major depressive disorder sphere to show that changes in brain electrical activity in depressed patients during sleep, could be replicated in a particular type of rat. Moreover, the Transpharmation group has demonstrated that the drug ketamine, which has been recently utilized for treating depression among human patients in the last two or three years, reverses these sleep changes. Accordingly, Transpharmation has been engaged in developing ketamine-sensitive assays in rodents to produce a drug screen that could identify novel antidepressants to treat patients resistant to first-in-line antidepressants.
By investing continuously in significant biomarker platforms, Transpharmation has further enhanced its experimental capabilities to analyze mRNA and proteins. These capabilities have helped to produce novel putative markers of disease progression of relevance to depression and schizophrenia. “Across a number of diseases,” Duxon continues, “It is common for there to be a 30-40 percent set of patients that do not respond to commonly prescribed clinical gold standards. This is true for neuropathic pain and major depressive disorder, to name just two. This represents a significant opportunity for pharma companies, both commercially and to meet unmet medical needs. Interestingly, it offers a significant opportunity in the CRO space as well; CROs that can offer preclinical models of treatment resistance have a compelling argument for clients to use their services over the many CROs that just offer the same old capabilities that have been on offer for 30-40 years. This is exactly what Transpharmation has sought to do and has been one of our pillars of success. To give an example of this success, we have worked with a client to identify blood biomarkers of animals that do not respond to a widely-used neuropathic pain medication, pregabalin. By doing this, we can identify such treatment-resistant animals and then screen them with new experimental medications to see if they might identify more efficacious medicines.”
Combining Technology and Biomarkers for Superior Results
Whilst Transpharmation has sought to use ‘best-in-class’ pharmacological validation of its models, married up with molecular biomarkers, it has sought to combine clinical neurophysiological endpoints into its battery of capabilities to add another layer of translational relevance to its preclinical animal studies. “Endpoints like EEG (electroencephalogram) reveal strong translation between animals and humans,” highlights Duxon. The use of EEG to quantify the changing electrical activity within the brain of a rodent exposed to a repeating pattern of sounds exemplifies the company’s commitment to providing cutting edge preclinical capabilities to its clients. This type of EEG, in particular, helps companies detect a phenomenon in the brain called mismatch negativity (MMN), the pattern of which may correlate to the same EEG patterns seen in psychosis. In humans, MMN is one of the most highly translatable endpoints to test novel molecules targeted to treat psychiatric disorders like Schizophrenia. By studying the effect of therapeutic drugs on the MMN of rodents, Transpharmation can help clients understand the potential impact of them on schizophrenic patients.
Moving forward, Transpharmation plans to expand its business base into the USA and strives to be the market leader in the CRO space. “We took a strategic decision to work with European and Japanese companies when we set up in 2010,” adds Duxon. “Following the financial crisis in 2008, I felt the last thing US companies (that were going through rapid portfolio and personnel changes) needed was another CRO knocking on their door. Things have now moved on considerably both for the pharma and biotech companies in the USA and for us a business. We will reach our 10th anniversary in several months’ time, and we have a very mature set of capabilities to go with that. So, the US market will be a focus for us in 2020,” mentions Duxon.