Disease and Market: Almost one in five of the European population currently suffers from moderate or severe pain persisting for more than 6 months and in Norway, Poland and Italy this number rises to over one in four (www.paineurope.com/articles/assessing-chronic-pain-in-europe). Patients commonly also suffer from associated anxiety and depression and these disease combinations constitute a huge economic and social burden. Clearly, new safe and effective medication is urgently needed to treat chronic pain.
Cluster: Pharmnovo has constructed an international cluster of industrial and academic collaborators with expert knowledge in the areas of pain and affective disorders and a track record of practical drug discovery and development. The central aim of this consortium is to ensure target pharmacological activity, adequate exposure profiles, safety and certainty by selecting and using validated and top-class prediction tools and lab services. The organization of the Pharmnovo cluster can be represented as a multidimensional chemical space with collaborators (R1-9) contributing to and modifying the overall efficacy of the company (Figure 1).
Figure 1. Drug discovery strength through collaboration
• Chemistry: Pharmnovo chemistry is based on collaboration between OT Pharmaceuticals (R1) and Pharmnovo chemistry design staff.
• Patents: We have extensive experience of patent prosecution and litigation and before filing a patent application we assess whether the application will become approved and whether the patent will stay valid. Our strategy is to file late to achieve a long patent life, which is evident in on-going projects.
• Marketing and Management: Sensa Corporate Advisors (www.sensa.se) (R2) is our partner management consulting firm, specializing in connecting business success to market development. By considering the market perspective at an early stage and developing it continuously throughout the project, a strong market focus is ensured.
• PKPD/DMPK: Combining academic and industrial expertise, Pharmnovo works with collaborators in the University of Nottingham (R3) and Prosilico (www.prosilico.com) (R4) to ensure human druggability at an early project stage. Prosilico’s unique and validated in silico prediction tools and referencing systems for ADME/PK in humans and animals have been applied to Pharmnovo’s compounds enabling improved ADME/PK and improvements of programme designs, knowledge, overview, safety assurance, druggability estimations and cost-effectiveness.
Phase I chronic pain project: Pharmnovo was formed in 2008, with several project ideas based on new delta opioid receptor agonists and our first CD has been chosen with plans to enter phase I clinical testing during late 2016/early 2017 (Figure 2). This project has identified completely novel, potent and very selective delta opioid receptor agonists possessing biased signaling compatible with a favorable efficacy and safety profile. These compounds are highly effective in in vivo animal models of chronic pain, investigated with PharmInVivo (R5) in Hungary (www.pharminvivo.webnode.hu) and are likely to show improved health benefits for chronic pain patients. Interestingly, our compounds possess efficacy mainly against chronic neuropathic pain, compared with acute inflammatory pain, giving us a unique therapeutic potential. These compounds will now be subjected to a phosphoproteomic analysis with the University of Bristol (R6) to investigate selective intracellular signaling pathways from a disease perspective with the potential to identify biomarkers that could facilitate compound selection and patient benefit.
Anxiety and Depression project: There is compelling evidence for the involvement of delta opioid receptors in affective disorders and, in collaboration with the National University of Ireland Galway (R7), Pharmnovo will now expand into psychiatric disease and explore the efficacy of our molecules in preclinical models of anxiety and depression. Pharmnovo is also working with the University of Reading (R8) to improve our understanding of intracellular mechanisms of drug internalization and recycling which will enhance our novel CGRP receptor antagonist project.
Pharmnovo has several ongoing projects, see Figure 2.
Figure 2. The Pharmnovo projects: With several projects in the preclinical phase (blue + light blue), combination targets (light blue) and our CD/Phase I project (green) Pharmnovo has a clear forward vision. Combinations include CGRP (calcitonin gene-related peptide) or NK1/2 (neurokinin 1/2) receptor antagonists in combination with our delta opioid receptor agonists.
Combination projects: Several projects/studies are in progress for combination treatments of chronic pain associated with anxiety and depression. Drug combinations include our high safety delta opioid receptor agonists with CGRP receptor antagonists for migraine and/or neurokinin receptor antagonists to give the patient a sustained pain/stress relief.
Offices: Pharmnovo AB is based in Gothenburg, Sweden and Pharmnovo UK Ltd in Liverpool, in collaboration with Liverpool John Moore’s University School of Pharmacy (R9).
Pharmnovo now wants to grow by working collectively with other Pharma companies, making use of our combined academic and industrial skills and experience to deliver new medicines to the market in a timely and financially efficient manner.
The Pharmnovo drug discovery cluster based on Academia and Pharma companies has taken its first product, a potent and very selective delta opioid receptor agonist to the late preclinical stage. The company will make contact with Pharma during September to November 2015. Our data for the CD/Phase I compound will be presented in our pain symposium at the European Neuropeptide Conference (ENC) in Aberdeen in September 2015 (www.abdn.ac.uk/events/summer-neuropeptides-2015/).
Bengt von Mentzer, CEO/David Kendall, CSO