We've got a new niche!

The SCN Blog has a new name and a new home: http://www.signalsblog.ca

After nearly four years and 207 blog posts, we finally outgrew our dish, so to speak. Late last year, we began planning with the newly-formed Centre for Commercialization of Regenerative Medicine, who indicated an interest to begin blogging in the sphere. (Perhaps you'll recall our name contest?) Why have two blogs competing when one can do the job? The result is Signals Blog (the new name came from an SCN staff member who sadly was not eligible for a prize), which will continue to bring the same level of insight, commentary and research news you've found on the SCN Blog, but will add new perspectives and news on biomaterials, regenerative medicine and commercialization.

We think it's a great partnership that will provide a more comprehensive view of the world of stem cells and regenerative medicine. 

To ease the transition for readers, all archived posts from the SCN Blog have been moved to their new home and RSS feeds will be updated to the new address. Comments will be closed on this site, but we'll keep a copy of the archives here for the short term. 

This is our final post on this site: please update your links and check out our new niche at www.signalsblog.ca!

View from the floor 4: Risk aversion in cell therapy development

by Paul Krzyzanowski

On day two (May 1) of the Till and McCulloch Meetings, Dr. Emily Culme-Seymour from the London Regenerative Medicine Network introduced work that leverages previous clinical trial information to support future cell therapy efforts. In an analysis of almost 3000 clinical trials extracted from clinicaltrials.gov, Culme-Seymour focused on cell therapy related trials. She found that half of the trials were in Phase 1 (40% were Phase 2 and only 10% were Phase 3), and almost three quarters of all cell therapy trials being conducted in the United States. 

With an overwhelming majority of cell therapy trials being found at
 relatively early stages, it suggests that that
 risk-aversion is partly involved in keeping cell therapy trials from
 launching Phase 3 trials. The idea of risk aversion was rearticulated with the finding that a significantly larger proportion of trials were of transient cell therapies such as Osiris’ Prochymal as opposed to permanent cell replacement. Culme-Seymour found that only 5% of trials were testing permanent therapies.

The numbers between autologous and allogeneic trials are approximately balanced.

The most basic conclusion is that future recipients of approved cell therapies will likely need repeated treatments to maintain efficacy. Permanent cell based treatments that will act as a one time “repair” will probably remain uncommon, at least for the near future.

Temporary cell based treatments may not be a bad thing overall. 

I believe the bias towards transient therapies to be a symptom of two factors: relative ease of their development and caution on the part of the community. 

Culme-Seymour explained that it’s less complicated to develop a technology that safely produces a temporary benefit. I would extend that to say that modifying, reversing, or even upgrading transient therapies for indications will be relatively easy while changing permanent modifications presents a whole new set of problems, namely how to undo the modification before the subsequent treatment.

I definitely don’t buy the argument that a commercial desire to sell (and re-sell, and re-sell) treatments to individuals drives the development of transient therapies versus permanent ones; it’s just a matter of what technology is currently available. Dr. Culme-Seymour’s work provides an excellent roadmap for those interested in following the prevailing trends in regenerative medicine product development.  

See also:
Clinical translation summary at Stem Cell Assays
Meeting Summary 3: Anticipatory ethics and the problem of expectations
Meeting Summary 2: Commercialization plenary
Meeting Summary 1: Commercialization plenary

 

View from the floor 2: Till & McCulloch Meetings

Commercialization plenary summary, part 2 of 4

by Paul Krzyzanowski

One of the most dynamic speakers of the conference thus far was Greg Bonfiglio of Proteus Venture Partners. A well-known VC speaker in this area, Bonfiglio shared his perspectives of how the commercialization of regenerative medicine technologies, and of biotechnology in general, has evolved.

Proteus Venture Partners supports or invests in companies developing diverse products for the regenerative medicine market, ranging from ambitious cell based therapies or compounds that trigger endogenous regeneration, to tools such as cell and cell-based assays that are needed to advance discoveries in this field. 

Bonfiglio illustrated that the early days of regenerative medicine companies were tissue engineering companies, but that they came out under extremely different conditions in the 1990’s where the funding was relatively easy. Inflated expectations crashed along with the market around 1999, with the IT sector leading the drop. 

Investment in regenerative medicine seemed to have been triggered with the announcement of $3 billion to be deployed through the California Institute of Regenerative Medicine (CIRM). This also had the effect of stimulating other governments to contribute money to the field.

Today the situation is very different. “We’re seeing a significant volume of clinical trials” says Bonfiglio, “It’s indicative of a mature market.” He continued to show that dramatic revenue growth in cell therapies has been seen over the last few years. 

That’s especially impressive considering the economic crisis of the last few years, which Bonfiglio described as “the worst economic environment of the last 75 years.”

Any indications of success were tempered by warnings of significant challenges in the field, namely: standardization of cell lines, technologies for safe and reliable expansion of cells, methods to track cell migration & engraftment, and mechanisms for modulating immune function. Regulatory environments need to be updated and clarified as well.

Perhaps the most pressing technological need (reiterated later in the day by Stephen Minger) is to set rodent toxicology models aside. Bonfiglio emphatically stated that too many technologies fail today because successful results in rodent models don’t extend to humans.  

Some significant changes to biotech business models need to take place as well.

Bonfiglio painted the old, antiquated model of a pre-IPO company; one that would spend $90 million of precious start up funds to build a company that resembles a “miniature Johnson & Johnson”. The consequence is that most of investor funds would be spent on a façade (my word, not his!) that didn’t add any value to the underlying technology. 

“We’re in an industry that builds products that need to work”, said Bonfiglio. The new regenerative medicine model that’s taking hold is one of companies that are collaborative and capital efficient.  I presume the same applies to any biotech spinoff today.

“You definitely need to use [commercialization] centres to advance a virtual business -- [knowledge] translation centers that offer support like state-of-the-art facilities, GMP compliance, and access to deep knowledge of regenerative medicine at associated academic centers.”

On a more pragmatic note, Bonfiglio also warned everyone that the availability of funds has shrunk as venture capital risk tolerance has dropped.

The old model that investors went by assumed that the risks in new companies could be mitigated by bringing in experienced management, forging cross-company collaborations (i.e. to scale up industrial production of a biologic), or improving patent positions (i.e. by licensing some key technology that was lacking). Today, companies need to look nearly perfect. An abundance of preclinical data and successful Phase 1, if not Phase 2, clinical trials need to be completed before you can deal with most institutional investors.

This puts for-profit companies in the odd situation where the largest source of funding for commercialization comes from government and government-sponsored bodies, like CIRM. 

As industrial research seems to be moving back to quasi-academic settings, Bonfiglio ended on an upbeat note where collaboration is key and the idea of companies built within walls of patents and trade secrets is passé. “Don’t think of competitors as competitors.”  

“There is a false notion that the way to create and capture value in any industry is based on a [patenting] land-grab. There is little sense in fighting [with each other].  Our industry needs to settle disagreements without litigation.”

 

 

View from the floor 1: Till & McCulloch Meetings

Commercialization plenary summary, part 1 of 4

by Paul Krzyzanowski

Till and McCulloch Meeting (#TMM2012) attendees in Montreal had the opportunity to hear from four speakers involved in commercializing discoveries in regenerative medicine, from the perspectives of not-for-profit, financial and industrial organizations. I’ll separate these out into a few posts.

From Toronto’s Centre for the Commercialization of Regenerative Medicine, Dr. Michael May began today’s plenary by sharing a sincere assessment of the challenges faced by entrepreneurs and fledgling regenerative medicine companies in Canada. (I spoke with May late last year on the needs of Canadian startups in the biotech and regenerative medicine sectors.)

“Commercialization is very, very difficult … there are plenty of great ideas being developed, but [across Canada] there’s a lack of capital, universities have underused technology transfer offices, and we’ve seen premature company formation and licensing of technology to regions outside of the country.”

To counter these problems, May outlined plans at the CCRM to enable local start ups through the support of product development, the integration of scientific research and business, as well as industry engagement. A hallmark of the plan is product development core facilities, through which companies can eliminate the need to replicate common resources and instead focus their efforts on what’s valuable to startups: proving and developing their technologies. This is especially true for firms developing new methods of cell manufacturing, commercializing bioreactors, biosensors, biocompatible materials, and transplantable cells.

But perhaps the two hottest market needs identified by May, along with other presenters today, are well characterized human stem cell lines and the continued development of tissue mimetics for drug screening. 

“In just the last 10 months, we’ve evaluated 31 potential technologies and have formed 10 industry collaborations” says May, “We’ve also managed to generate revenues from iPS cell production”.  An industry consortium of 20 companies has also been formed, acting a proxy for the regenerative medicine industry. 

One of the highlights of May’s presentation was the report of an imminent spinoff in the next few months.  Contrary to common assumptions of startup, the company won’t be featuring a single lone researcher with a single concept: “[This company] involved technology from across Canada along with some international intellectual property.” 

It seems CCRM is developing a reputation as a successful technology broker.  May explained that CCRM also wants to play the role of a mentor or coach for researchers, and I think it’s fair to generalize that academic researchers seldom have the time to perform in-depth market research for commercializable products.

“We want to be internationally recognized as the leading global developer of regenerative medicine technology and patents,” said May. 

 

The payoff of patenting your research: Aldagen as a case study

by Paul Krzyzanowski

Without a doubt, scientific research has the potential to discover new knowledge that can be used to improve human life. New tools and new ways of doing things are constantly being developed or invented, but arguably need to be commercialized before their benefits become widespread. With commercialization can come profit, and from the perspective of a researcher seeing through rose coloured glasses, the path to profit may appear guaranteed once the patent is filed.

The truth is, the supposedly clear path from academic invention to return on investments is more like an overgrown trail through a jungle. 

The “Viagra effect”: how known drugs can be repurposed to target cancer stem cells

by Paul Krzyzanowski

Repurposing known drugs for new applications is a strategy with fascinating potential, with two of the most notable examples being Thalidomide and Viagra. Thalidomide was commonly used in the late 1950s as a sedative in pregnant women, later being associated with serious birth defects. Today, it is used to treat multiple myeloma. Viagra was being developed by Pfizer to treat high blood pressure when its ability to ‘treat’ erectile dysfunction was identified as a side-effect, resulting in a complete shift in marketing strategy.

The major allure of finding novel uses for existing drugs is that the long process of early Phase I clinical trials can be sidestepped, as the drugs are already known to be safely delivered. This approach decreases the overall cost of developing drug candidates and brings the development of treatments for rare and neglected diseases closer to reality.

The principle of identifying a drug candidate is straightforward: take a large number of different chemical compounds and test each one for some desired activity. Small molecule screening has long been used by pharmaceutical companies to identify potential drug candidates for probably as many disease conditions as there’s a market for.

Not all doom and gloom: Major investment in UK stem cell therapy initiative

While many researchers will feel disheartened by last month’s ruling in the Court of Justice of the European Union that prohibits scientific research patents on human embryonic stem cell products (see Ubaka Ogbogu’s article), it seems some positive news is emerging from Europe as well. Specifically, the United Kingdom has recently promised a huge investment in the development of a major cell therapy centre.

In an effort to emerge from the recession, the UK government has launched a program through its Technology Strategy Board that will create a series of Technology and Innovation Centres. Building off David Cameron’s 2010 announcement, the investment is not trivial (£220 million or ~$350 million) and the idea is to take advantage of the UK’s strengths in various research sectors to build an environment of business development mixed with research advances and opportunities.

The cell therapy centre will build on the UK’s expertise in stem cells and regenerative medicine and is described as “a unique centre where academics, businesses and clinicians (i.e. medical professionals with a special interest in cell therapies) will work together to focus on the commercial development of cutting edge technologies in cell therapy.” According to a recent article in the Guardian the centre has already gained the support of major multinational pharmaceutical companies such as Pfizer, GSK, and Astra-Zeneca, which should provide a good base of investment for such a lofty project.

Jumping the innovation gap: Breathing life into life science startups

by Paul Krzyzanowski

Canada was built upon the inventiveness and resourcefulness of people who lived here. Why then, have Canadians long heard and read about being second best, sellouts, and in general not that great? Thinking we aren’t competitive has almost become a national mantra. But it’s more than a state of mind: the innovation gap has a $9,500 per year impact (as compared to the United States) on our standard of living.

In the last two weeks, two reports on Canadian innovation were released. Both were critical of Canadian capacity for research and inventiveness, and both suggested ways Canada could come out on top when it comes to competing with the best worldwide. The reports warrant some scrutiny, particularly with respect to a fledgling industry such as biotech.

Entrepreneurial scientists: Moving from being outliers to everyday researchers

by Paul Krzyzanowski

Success in a research career is solely defined by ones ability to churn out great academic papers, right?

Don’t be so sure.

It’s true that successful research careers can be launched with a Science or Nature paper, but many skills other than purely academic ones are increasingly being recognized as important.

On this blog, David Kent recently discussed the requirement for scientists to be aware of governmental policies, clinical trials, and therapies outside of their own research, while Ben Paylor explained how important mastering science communications and the web are, particularly to engage the public.

In a world where a glut of university graduates exists, the standard package of courses and experience in many programs no longer places people on a fixed career path. Even alumni of law and medical schools are not immune to the challenging job market, reports Nature, and there are no longer any guarantees of employment upon graduation:

Is great science sitting on a shelf?

Patenting report shows disconnect in Canada

by Paul Krzyzanowski

Got a patentable idea? You might want to move to Switzerland. A recent article in the Globe and Mail compared Canada's patenting activity to other major countries, and the small European nation came out a clear winner.

2010 was a record year for US patents issuances to countries around the world. The Globe reported that US patents granted to Canadian applicants increased by 20 per cent – a commendable increase, until one notices that this was still behind those granted to applicants from other countries like Japan (up 26 per cent), Germany (up 25 per cent), South Korea (up 26 per cent) or the U.S. itself (up 24 per cent).  It’s possible that these across-the board increases simply represent a backlog of patents created by the 2008 credit crisis, but since total U.S. patent grabs have increased annually each year since 2007 it suggests that the recent poor economic conditions didn’t affect patenting activity drastically.