Transpharmation
Revolutionizing the Preclinical Translational Research Arena

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 disease models (prior to selecting a drug candidate for advancing into safety/tox screening first time in man). Now, they focus on just a few judiciously chosen models that are 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 an 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, behaviour, EEG, and biomarkers of disease areas such as sleep disorders, epilepsy, pain, depression, and schizophrenia, among others.

Driving Forward the Legacy of 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 difficulty in highlighting the superior clinical efficacy of novel drugs versus the established cheap, generic clinical gold standards. Indeed, this latter issue of differentiating the drug, which produces the greatest effect, is also an issue in many preclinical models of disease. Transpharmation has sought to tackle this head-on with several key business strategies. The company leads the market with its focus on a 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 resolve clients’ pharmacology/drug discovery issues. We do this by listening to the scientific questions posed and bringing our 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 itself from 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 perform consistently every day. Many of our competitors claim to offer vast lists of assays, many of which to not get used from one year to the next. We believe it is of far more value to run one or two highly interrogated preclinical assays for each disease, which are used every 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 characterised by standard medicines that are used to treat patients in the clinic. “We employ preclinical models by conducting a behavioural screening of small molecules and antibodies in rodents to understand the underlying potential translational efficacy of the drugs on humans,” adds Duxon. “Also, we can back translate clinical data to ensure our preclinical assays truly model what is seen in humans.” Team Transpharmation has demonstrated this ‘back translation’ in 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, Transpharmation has demonstrated that the drug ketamine, which is, of late, being used to treat 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-line antidepressants.

"We employ preclinical models by conducting behavioural screening of small molecules and antibodies in rodents to understand the underlying potential translational efficacy of the drugs on humans"

By investing continuously in biomarker platforms, Transpharmation has further enhanced its experimental capabilities to analyse mRNA and proteins. These capabilities have helped produce novel putative markers of disease progression relevant 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, just to name a couple.

This represents a significant opportunity for pharma companies, both commercially and to meet the 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 many CROs which offer the same old capabilities since the past 40 years. This is exactly what Transpharmation has sought to do and has been one of our pillars of success. To illustrate this success with an example, we worked with a client to identify the 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 possibly 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 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 on schizophrenic patients.

Moving forward, Transpharmation plans to expand its business base into the U.S. 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 U.S. companies (which were going through rapid portfolio and personnel changes) needed was another CRO knocking on their door. Things have now improved considerably both for the pharma and biotech companies in the U.S. and for us as 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 U.S. market will be a focus for us in 2020.”