Summary of the third NP2D meeting at Zermatt, Switzerland, April 14-17th 2008

The Natural Peptides to Drugs (NP2D) meeting is an international meeting held in Zermatt, Switzerland, near the magnificent Matterhorn mountain in the Alps. This wonderful venue offers unique lectures and opportunities to share knowledge between academic and industrial research leaders as well as industrial and business decision makers. The meeting concept came after discussions between academic and industrial specialists waiting for a venue focusing on peptide-based drugs, where everyone can experience progresses at the research, development and marketing levels.

NP2D aims to highlight novel peptide R&D strategies covering all possible fields from the discovery to the market, including aspects such as drug design, production, delivery, intellectual property and regulations. To ensure the congress world class quality and success, the meeting has:

The two first meetings, held in 2004 and 2006, were warmly welcomed by about 100 attendees each time. The high quality of the presentations, the flexible program schedule aiming to facilitate networking and discussions, and finally the natural beauty of the site brought a lot of enthusiasm. Hence, encouraging comments, advises and meeting output opportunities led the organizers Drs Reto Stöcklin and Dimitrios Noukakis to renew the experience and organize the third NP2D edition named “Exploiting biodiversity for health: antimicrobial peptides, toxins, hormones and more!”.

The meeting was sponsored by long standing as well as new partners playing important roles in the peptide arena, respectively Lonza, Almac Sciences, Peptide & Elephants and NeoMPS. The 2008 plateau of lecturers proposed outstanding and oriented keynotes either from the academia or industry that brought considerable value to the received information and stimulated numerous exciting debates. The 2008 edition proposed a new program formula with the so-called “Lift presentations”. These short presentations gave the unique chance to companies to present briefly their activities to the audience. The sessions were appreciated and the organizers are planning to pursue this experience in the next NP2D editions. In brief, we summarize below some of the high quality lectures that highlighted the 2008 NP2D meeting:

Prof. Dietrich Mebs (University of Frankfurt, Germany and Toxinomics Foundation, Geneva, Switzerland) launched the meeting explaining how diverse and valuable for drug discovery is the natural source of venom peptides. Venom peptides are naturally evolved by an exceptionally high mutation rate and thereby are of great interest for drug discovery. He mentioned that the peptide numbers range from 100-1000 for each cone snail, scorpion, snake or spider specimen, leading to an estimated total of millions of bioactive molecules.

Prof. Manjunatha Kini (University of Singapore) presented novel toxins from snake venoms. Venom is a source to discover potential and novel anti-coagulants, that could be administered either by oral, sublingual or intestinal routes. He gave the example of the synergic effect of Hemextin A and B. He followed by the discovery of the first potential natural beta-blocker, namely the beta-cardiotoxin. Finally, Prof Kini showed novel snake toxin families with drug potential.

Dr Michael Hanley (Amylin Pharmaceuticals’ Chief Scientific Officer, USA) presented the approach of Amylin to discover novel bioactive peptides. They have a polypeptide hormone library that is built by in silico and experimental approaches based on the human genome data. Dr Hanley also explained the high rate of failure for peptide drug candidates when they are poorly soluble or have disulfide bonds. He underpinned the high importance of well-chosen animal models to increase the success rate in clinical trials. Finally, Dr Hanley pursued the discussion by showing that the marketed drug peptide is often completely different from the early discovery candidates.

Prof. Baldomero Olivera (University of Utah, USA) brought an overview of the cone snail venom potential in drug discovery with peptides targeting either nerve sodium or potassium channels. He gave the example of the omega-conotoxin MVIIA (a calcium channel blocker) that was discovered in his laboratory, developed under the name of Ziconotide by Dr George Miljanich and was approved later as a drug under the name of Prialt (Elan Corporation, USA). He also presented other potential cone snail derived drugs with efficacy in protecting organ transplantation and against myocardial infarction. Prof. Olivera explained that cone snail venoms have probably the highest mutation and thereby evolution rates leading to a large structural diversity.

Dr Amanda Proudfoot (Merck Serono Research Center, Switzerland) presented the potential of tick saliva peptides as anti-inflammatories. She described three tick peptide candidates able to modulated chemokine effects either in vitro or in vivo, namely Evasins. The current given hypothesis is that Evasins bind directly to chemokines, hence preventing proper chemokine receptor interaction and normal inflammatory-linked responses. Dr Proudfoot presented their studies on the resolution two of three Evasin 3D structures. She concluded that these anti-inflammatory peptides have novel structures and therefore provide novel anti-inflammatory scaffolds.

Dr Jesper Lau (NovoNordisk A/S, Denmark) presented approaches to engineer proteins to improve their function and pharmacokinetics. He discussed the hurdles of biopharmaceutical delivery approaches such as nasal, oral, transdermal and pulmonary versus the common sub-cutaneous or intra-venous routes. Dr Lau exposed several current approaches to enhance drug formulation, half-life and efficacy. To insure a better and longer efficacy of the glucagon-like peptide-1 and insulin (treatment of diabetes), Dr Lau showed the advantages of chemical modifications such as pegylation and acylation, but also protein fusion to serum albumin and fatty acids.

Prof. David Craik (University of Queensland, Australia) presented promising and very stable plant circular peptides called cyclotides. Even though cyclotides have a structurally conserved framework and core, Prof. Craig mentioned that there are about 700 known cyclotide sequences with high structural diversity and possibly more than 50’000 predicted. Prof. Craig showed in vivo potential of cyclotides to treat disease such as multiple sclerosis. He explained that cyclic peptides are also present in cone snail venom and cyclotides should be used as a template in peptide based drug design, because of their superior stability and resistance to clearance enzymes. Finally, Prof. Craig showed several approaches to decrease the potential toxicity of cyclotides and resolve synthesis and manufacturing issues. He presented as well the promising cyclotide potential in generating pest resistant plants.

Prof. Kunwar Shailubhai (Senior VP Research at Callisto Pharmaceuticals Inc., USA) presented the ongoing clinical research with their orally delivered guanylin peptides. Prof. Shailubhai discovered uroguanyilin, a peptide hormone that modulates cellular guanylate cyclase-C and cyclic GMP, which has great promises against chronic constipation and inflammatory bowel disease. He explained that the synthesis and stability of the natural peptide is extremely poor. Therefore, they engineered modified versions up to a lead candidate that was successful in animal models. The drug will enter soon clinical trials under the name of Guanilib.

Prof. Richard Lewis (Xenome Ltd, Australia) exposed their research on anti-pain drugs. For this purpose, he showed several peptide candidates found in cone snail venom. One of them, a chi-conopeptide called Xen2174, holds great promises in vivo with animal models and started recently to be investigated in human as an analgesic for cancer, operative and chronic pain.

Dr Greg Stewart (MedTronic, USA) gave an overview of their drug delivery systems. Because of drug stability and patient convenience, he explained that delivery systems are gaining in interest and that the future of pharmaceuticals will probably be combinations of drugs and delivery systems. Dr Stewart showed the mode of action of their two current devices; pumps that are currently on the market and are inserted in patients under the skin. These patient-controlled systems are sharp and deliver monitored drug doses in targeted body fluids, depending on the medicine. Today, they are used to deliver analgesics such as morphine or Prialt (see above), brain medications and insulin.

The last part of the meeting was projected on “How to raise funds in peptide R&D”. Dr Kenneth Sorensen (Array Capital Management LLC, USA) gave a lecture and advice on routes to obtain funds and bring a potential drug to the market. He did a challenging comparison including the pros and cons of dealing with large or small pharmaceutical companies. In both cases, Dr Sorensen explained what are the most common hurdles faced during relationships with the pharmaceutical industry, in the case of small biotech companies or academic institutions aiming to push a drug to the market. Dr Sorensen’s presentation raised numerous important questions that launched the final part of the meeting on the topic of how to raise funding in peptide R&D. For this purpose, an unprecedented round table was organized with industrial experts in venture capital, mergers & acquisitions, who gave presentations followed by debates, namely Peter Hoffmann (Genzyme Pharmaceuticals), George Miljanich (Airmid LLC), Michel Mollard (Seventure Partners), Robin Offord (Mintaka Foundation) and Kenneth Sorensen (Array Capital Management).

As the two previous NP2D meetings, the 2008 edition was a very successful vintage that was greatly appreciated by the majority of the participants. Moreover, the unique location of Zermatt and the possibilities to have both side activities in the natural environment and personal meetings, raised considerable enthusiasm among the attendees and the sponsors.

The vision of the NP2D meeting certainly addresses the current needs of entrepreneurs in both academic and industrial areas. In this direction, probably one of the important comments came from Michael Hanley, Amylin Pharmaceuticals, who saw the NP2D meeting growing in size and international recognition during the next few years. The organizers are already very pleased to announce that the 4th NP2D meeting is programmed in Zermatt on April 11-14th 2010. The meeting registration offers a full accommodation package including the registration fee, hotel room, meals and recreational activities. Please book already your agendas!