Wednesday I attended the ‘Where to Find the Drugs: The Ubiquitin Component Systems, Are They the Next Generation Kinases?’ Breakout Session (see Tuesday’s post for more details), and learned about the extraordinary opportunities and challenges for drug discovery in this area. Velcade is the first drug targeting the Ubiquitin Proteaseome System (UPS), introduced by Millennium in 2007 for multiple myeloma and generating $1B revenue in 2008. While success of a drug targeting a class of molecules is often ‘paves the way’ for future drugs, it was clear from the session that a lot research is still needed to explore the mechanisms that can be exploited for therapeutics.
The UPS is a complex network of enzymes and protein components designed to break down proteins, part of the the important ‘ecosystem’ necessary to maintain the proper functioning of the cell and prevent malignancy (2006 review). The borders between the UPS and kinase signaling systems are essentially non-existent, and there are many parallels. The E3 protein components represent the largest family, with 600 members, similar to kinases. There are a wide variety of enzyme functions found in the UPS, which makes it distinct from the kinases, which mostly catalyze one type of reaction. Dr. Mark Manfredi, Director of Cancer Pharmacology, Takeda/Millenium, talked about two other drugs targeting the UPS in their pipeline. MLN 9708 is in clinical trials and has a similar MOA to Velcade, which targets the proteasome, but has a much faster off-rate, meaning it will have greater bioavailability and greater efficacy towards solid tumors. Another Millenium compound in clinical trials is MLN 4924, targeting Nedd8 Activating Enzyme (NAE) of the UPS. NAE is a validated target distinct from the proteasome, and Manfredi commented that there are many unique MOAs to be exploited with the UPS, which is exciting, but this means that more time must be spent with pharmacokinetics and pharmacodynamics (PK/PD) studies in these discovery programs.
I had the good fortune to speak with Sir Philip Cohen personally after the session. Sir Cohen, as the ‘father’ of kinase biology, and currently spearheading UPS initiatives, has a unique perspective on the path forward for this area. Sir Cohen was the driving force behind the MRC Protein Phosphorylation Unit, which was founded in 1990 towards the goal of understanding the role of protein phosphorylation and cell regulation in disease. The Unit has always interacted closely with academia and industry, perhaps making it one of the original ‘translational research’ institutions, even before this term existed. Sir Cohen’s latest endeavor is the SCottish Institute for ceLL Signalling (SCILLS), where he is building the Protein Ubiquitination Unit first, cherry picking the best and brightest researchers from the UPS field. When I asked him the single most important lesson that he learned in his kinase work, which has helped with understanding the UPS, his answer was more in the organizational aspects than in the science. Sir Cohen said that “Having a critical mass of leading players is important. Often, in academia, investigators work in silos, which does not advance the field. With the MRC Unit, we pooled grant money and set up teams to do tasks such as DNA cloning and mass spectrometry, allowing the scientists to concentrate on their research.” Sir Cohen is clearly very passionate about SCILLS and it will undoubtedly have a big impact on UPS research and the resulting therapeutics.
The UPS story will surely have many parallels to that of kinases because the similarities in their science and its ability to provide a cohesive platform amenable to sharing reagents and ideas both within and between organizations. The UPS’ increased complexity gives researchers a choice of which component interactions or enzymes to target for drug discovery, which can be seen as both an advantage or disadvantage. When I asked Sir Cohen about the most promising targets for the UPS, he said that small molecule inhibitors of E2/E3 enzyme complexes are likely to be the best. He indicated that similar to the protein kinases, there are other therapeutic areas such as inflammation which will be an exciting area to watch. Development in the two areas will likely be synergistic and bode well for important new therapeutics in both.

Tuesday at the BIO convention, I attended a session titled ‘Spreading the Word: New Technologies Mean Everyone is a Journalist,’ which covered how new media such as blogs and twitter are being used and are shaping communication in the biotechnology industry. The panelists were Brian Reid, Media Director, Weisscomm Partners, Ed Silverman, Bureau Editor, Elsevier Business Intelligence, Jen S. McCabe, Chief Patient Advocate at Organized Wisdom, Shwen Gwee, Lead Business Analyst, Vertex Pharmaceuticals, and Jerry Johnson, Executive Vice President, Brodeur Partners. Ed Silverman was the only ‘classical’ journalist in the panel (by training) and commented early in the session that although the canons of traditional media have legitimate reservations about this new class of ‘reporters,’ that they can be seen as ‘insects’ that are quicker and will likely take over when the ‘dinosaurs’ of old media crumble. Ed has watched the dynamics and power of new media as Pharmalot, the blog-style Pharma news website that he pioneered, rose to meteoric fame. Jen McCabe, who gave her presentation in clear ‘web 2.0′ style, walking through the audience, clarified that she sees herself as a ‘recorder, not a reporter.’ She proved this by twittering from her pink Mac throughout the event.
This meeting of old vs. new media is a familiar one in biotechnology, and was even evident in what I think was a poor name for the session, which Brian Reid indicated was due to the fact that he had to choose it almost a year ago–new media moves much more quickly than this. Shwen Gwee gave an excellent presentation on the foundations and benefits of social media (video excerpt), emphasizing that social media is more of a ‘pull’ than a ‘push’ of information, when done correctly. Shwen is a ‘rock star’ in the so-called ‘Med 2.0′ movement, a driving force between the Social Pharmer ‘unconference’ in April of this year. Jerry Johnson did a great job explaining that a corporate SM strategy needs to be more than just a vague idea that ‘our company needs a blog,’ and emphasized the power of face to face interactions and ‘self-organization’ in the growth of social networks. Jerry is passionate about using social media to involve and inform the community and scientists about biotechnology through IamBiotech, which you can learn more about at the BIO exhibit (#2200). Jen McCabe gave a dynamic, fact-filled presentation about the success in building communities and tracking metrics at Organized Wisdom. Jen has done the seemingly impossible and has come up with formulas for calculating ROI and predicting growth for SM initiatives. Throughout the event, Brian Reid gave his insights from his unique experience both using Social Media professionally for his clients at Weisscomm Partners, and personally, being interviewed by the Wall Street Journal and Newsweek as the foremost stay-at-home dad. The panel members promised to upload their presentations to Slideshare tagged with ‘bio09′.
While most of the conversation centered around implementing social media at the corporate level, I was curious about the panel members’ thoughts on engaging scientists with social media, and how to encourage participation. This was definitely a topic they had considered, and indicated that as with corporate SM implementations, the value needs to be demonstrated up front. In other words, clearly answer the scientists’ innate questions ‘what’s in it for me’ and ‘how will my career suffer if I don’t participate.’ From my own experience with the San Diego Biotechnology Network and with social media, I agree with this generality, and plan to motivate scientists during a ‘Social Media for Scientists‘ presentation I am giving with colleague William Gunn on May 28th. I plan to encourage scientists to ‘Just Do It’ and get involved with SM sooner rather than later, because it is highly experiential and the benefits are highly specific to the user. William Gunn will talk about the extraordinary advances that will result when scientists start sharing and discussing data in real time. This panel at BIO 2009, and the efforts of BIO in engaging SM (including this blog post) are truly exciting initiatives that deserve attention and support from the biotechnology community.

Sir Elton John gave an inspiring and eye-opening keynote speech yesterday about the success and shortcomings of HIV/AIDS research, and I know many of us are still thinking about how we can further the science and make the necessary improvements in education to make a difference. Today, BIO is featuring Sir Philip Cohen, another Knight of the British Empire, often seen as the ‘father’ of kinase biology/phosphorylation research, and one of the most cited scientists in Europe. Sir Cohen, Director of the MRC Protein Phosphorylation Unit, University of Dundee, and Director of the Scottish Institute for Cell Signaling, is speaking in a Breakout Session this morning titled ‘Where to Find the Drugs: The Ubiquitin Component Systems, Are They the Next Generation Kinases?’ He is cited as saying “I am very confident that the (Ubiquitin Proteasome System) market has the potential to become even bigger than Kinases.” The speaker lineup at this 10:00 a.m. session is impressive, including Dr. Frank Mercurio, CSO, BioTheryX, Dr. Mark Manfredi, Director of Cancer Pharmacology, Takeda/Millenium, Prof. Mike Tyers, CH Waddington Professor of Systems Biology at Univ. Edinburgh, Dr. Giovanni Ferrara, ITI Life Sciences Advisory Board, and Dr. Sheridan Snyder, Founder, BioCatalyst International.
This session was organized by the MRC Protein Phosphorylation Unit, the Scottish Institute for Cell Signalling (SCILLS) and ITI Life Sciences, and is supported by Scottish Development International. I sat down with Neil Wilkie, Programme Manager at ITI Life Sciences on Tuesday, to discuss their involvement in the session and UPS in general. Neil said that ITI is literally an “Intermediary Technology Initiative” in which the Scottish government has earmarked 150M £ over a period of 10 years to promote the growth of biotechnology in the region. He explained that ITI did an exhaustive and highly analytical search of the scientific and patent literature a few years ago to determine the ‘next big thing’ in drug discovery. They found a ‘sweet spot’ with the UPS system, with mentions of it in the literature rapidly rising, but with room in the intellectual property space for them to start carving out a niche in the area, towards the goal of stimulating growth in Scotland Biotech. Perhaps coincidentally, Sir Cohen lives and works in Scotland and obviously thinks there is something behind their assessment. I think this session is a ‘must see’ and I will be there! It begins at 10:00 a.m. today in Room B304, and if you can’t be there you can look for live updates from me on Twitter at @comprendia.

I spent part of Monday morning in the Ireland Pavilion (#3303) talking with them about the biotechnology they’re highlighting at the BIO convention, as well as the region as well. I spoke with Jonathan O’Connell, Chief Financial Officer of Ireland’s Merrion Pharmaceuticals, about the announcement they made last week (PDF) regarding preliminary results on Orazol™, a tablet formulation of the Novartis drug Zometa®. The company acquired a unique drug delivery technology from Elan in 2004 which boosts absorption in the intestine. As a result, therapeutics that are normally given only by injection can be formulated as tablets, leading to many benefits, including safer treatment, less pain, and improved pharmaeconomics. At BIO 2009, Merrion is focused on partnering their Phase 2 compounds, and continues to develop and seek out therapeutics which are amenable to their technology, including, notably, insulin, which they are working on with Novo Nordisk. Personally, I found the technology to be very promising and I suggest that you seek them out in the Ireland Pavilion.

I also spoke with Sean Davis from Enterprise Ireland (EI), which ‘fosters’ companies like Merrion in their early development phase. Davis says that EI has been around for 35 years and currently takes on 70-80 companies per year. The EI does 5-6 months of due diligence for each company and covers R&D aspects, commercialization, and technology transfer. EI benefits from the Irish government’s commitment to promote biotechnology in the region, stemming back 20 years ago when they began to focus on education. Their goal at BIO 2009? Presenting six of their ‘success stories’ from the region and partnering with US entities who realize the potential of companies who have been well-positioned for success by EI. I highly suggest visiting the Ireland Pavilion, #3303 in the exhibit hall.