Xceleron

By Mike Butler, President and Chief Executive of Xceleron

Mike Butler, President and Chief Executive of Xceleron, a specialized bioanalytical service provider explains how Xceleron is helping its clients to answer critical early clinical development questions

Pharmaceutical companies face enormous challenges.  It's difficult to imagine running a business that is more complex than an innovative pharmaceutical company.  Setting aside for a moment whether or not a company should be vertically integrated and the regulatory hurdles that must be overcome in our complex world, the basic challenge of generating chemical or biological entities to meet an unmet medical need is enormous.  Our customers must de-convolute the complex biochemical interactions that underpin the effectiveness and safety of a drug candidate, completely characterize its chemical and physical structure, ensure its safety, create a large-scale manufacturing process and distribute to the four corners of the world.  Can you imagine trying to build a laptop if we didn't even know for sure if the component parts would connect, let alone how the electrical circuit would perform when they were assembled?  No other business proposition is as complex as that faced by the modern pharmaceutical industry.

Andrew Witty, CEO of GlaxoSmithKline, recently wrote that the pharmaceutical industry had to do more with less and still be innovative.  He called for a more rigorous allocation of resources, a streamlined development phase (by, for example, ending earlier the progress of unpromising candidates), more innovative partnerships in R&D and more frequent partnering between larger pharmaceutical companies and smaller specialist firms.

Xceleron is a small innovative development service company playing a part in helping overcome the significant challenges outlined by GlaxoSmithKline's CEO.  We use a unique analytical platform called Accelerator Mass Spectrometry (AMS) to measure investigational drugs and their metabolites in drug development.  The innovative clinical investigations we support would not be possible without this unique approach.

Xceleron has conducted client studies in Phase 0, Phase 1 and Phase 2/3 clinical development.  The value that our clients are deriving from Phase 0 varies enormously according to their objectives.  To give you some insight, we've helped determine likely efficacy by confirming compound disposition in target and non-target tissues, quantified rate of conversion of pro-drug in isolated target cells and estimated the likely pharmacokinetics prior to full development.  Supporting later development, we see a couple of interesting uses.  Firstly, smaller companies are able to back-fill required information prior to an asset sale, once safety and human efficacy are confirmed.  Secondly, for portfolio management, Phase 0 microdosing has a place in establishing fast follow-on candidates.

In Phase 1, our customers gain insight to the downstream develop-ability and likely cost of goods of a candidate in early development.  This is information is especially important for so-called BCS2 compounds and it can be gained from a simple absolute bioavailability study design.  Often in phase 1, our customers also save time because they don't need to plan an entirely separate line of clinical investigation.  For example, we've included light ¹⁴C doses in food-effect studies, SAD and MAD studies and have shown that we can co-administer a PET ligand and ¹⁴C and generate absolute bioavailability from an imaging study.  Essentially, our customers can derive absolute bioavailability from a simple additional arm on a previously scheduled phase 1 study. 

In Phase 2/3, our customers talk about two distinct advantages of working with ¹⁴C LC AMS, irrespective of the need for sensitivity or to overcome radio-instability or safety issues.  For small molecule drugs, ¹⁴C LC AMS offers significant time and cost savings because using a light ¹⁴C label precludes the need for GMP material and animal dosimetry and distribution studies.  Also in Phase 2/3 we're seeing significant uptake in our innovative absolute bioavailability clinical design.  Time and money is saved because there is no need for IV-specific safety data, formulation effort, or large-scale GMP manufacture of an IV dose.  For instances where absolute bioavailability is required by the regulators, our approach provides an attractive option over the traditional crossover design.

Considering the challenges our customers face in the pharmaceutical industry, we expect to see even more growth in each of the areas I've described in the very near future.  We have demonstrated value in identifying strong lead contenders, expedited late-stage asset development and helped identify drugs that would likely fail later and more expensively.

If I was to gaze into the future and run the risk of being proven wrong by our customers, I'd expect to see us conducting more and more target studies that engage the platform's ability to enable investigations beyond systemic circulation.  I see great potential in following disposition and localized kinetics.  We've already conducted a number of such studies and I expect many more as we move toward more fit-for-purpose approaches to individual asset R&D.

About

Mike has 20 years experience in science-driven businesses in Europe, US and Asia.   He has been President, Scientific Operations and Chief Scientific Officer with Aptuit, Group Vice President at MDS-PS and Group Director, Business Development for Huntingdon Life Sciences.