Techniques to accelerate the drug discovery process

We at Prize4Life are primarily concerned with accelerating translational ALS research—indeed, our organization and programs are shaped around the mantra of acceleration. ALS patients, like patients of many other diseases, have no time to spare. I want to share some other recent innovative techniques that have caught our attention for helping to propel drug discovery, an infamously difficult, expensive, and lengthy process. We are always looking for new ideas and approaches that we can adapt for ALS, so if you see something that sounds promising and fits within our framework, please shoot us an e-mail. Here’s the latest:

A recent Nature article discusses the Wellcome Trust, the UK’s largest non-governmental funder of biomedical research, which has a 5-year Seeding Drug Discovery Initiative (SDDI). Launched in October 2005, the program is designed to facilitate the development of drug-like small molecules that address unmet medical needs. “We consider projects in all disease areas, from any originating environment,” says Richard Davis, the business development manager at the Trust in the Nature article. “A project could be from an academic institution, a spin-out company or even an established pharmaceutical company because we ultimately base the decision [to grant an award] on the excellence of the science.”

Since 2005, the Trust has given out £80.4 million in 30 different grants (to 19 academic institutions and 11 companies). The support covers a variety of therapeutic areas, and company beneficiaries have primarily been small biotechs who have been struggling in the current unfavorable funding climate. Like Prize4Life, SDDI is a results-based initiative that aims for sustainability so that “projects to progress to a stage whereby there is sufficient evidence to make the project results, intellectual property and outcomes attractive to follow-on developers or investors who may be from the commercial or not-for-profit sectors.”

The Wellcome Trust and SDDI generally encourage the use of Contract Research Organizations (CRO’s) because they are efficient and cost-effective, saving the Trust from having to expend resources on infrastructure for every project they fund. This emphasis on leveraging CRO’s and outsourcing is also an important trend we have blogged on recently: see it here.

Another recent innovative translational research effort we have been following is a joint venture between three large pharmaceutical corporations. Merck, Pfizer, and Eli Lilly have announced plans to create a charity to research cancers in Asia. The new charity will develop a database of data derived from lung and gastric cancer samples, and make it available to cancer patients and scientists worldwide. "Through its work and the subsequent sharing of information, the Asian Cancer Research Group hopes to empower researchers, foster innovation and improve the prognosis and treatment of patients with cancer,’’ said Gary Gilliand of Merck Research Laboratories in an NJ.com article.

Finally, the Chronicle of Philanthropy has recently reported on the increasing number of charities who have gone into the drug-development business, lowering the risk assumed by drug companies in the treatment of rare diseases. Like Prize4Life, the Cystic Fibrosis Foundation and a number of others are increasingly collaborating with pharma and biotech to assume some of the risk of drug development, and hoping that those collaborations propel advancements that may otherwise be a long time in coming.

Let us hope that these creative approaches have the desired effect of hastening drug discovery for ALS and other diseases.

Poetry by guest blogger Dr. Cathy Wolf

Prize4Life guest writer and PALS Catherine Gody Wolf shares two poems and the story of her diagnosis. Dr. Wolf recently appeared on CNN using a new brain-computer interfacing technology (see the piece here).

It was in my modern dance class in the summer of 1996 when I was 49 that I noticed my left foot refused to flex. Then whenever I ran, my left calf hurt. I decided to give my leg time to heal and enrolled in a masters swimming class. My legs did not work too well, but I swam with my arms. By the fall, my left calf had not healed, and, if anything, hurt more. I went to an orthopedic doctor who x-rayed my calf and pronounced the bone sound. He referred me to a local neurologist. I had always been on healthy, ate well and at 5’3” was a slim 115 pounds. I didn’t get sick. The neurologist mentioned amyotrophic lateral sclerosis as a distant possibility. I looked it up in the Merck Manual and was horrified. “This could not be happening to me,” I thought.

But it was. After trips to three high-powered ALS centers and treatment for neuropathy and Lyme disease, in the fall of 1998 I accepted my diagnosis of ALS.

My employer, the IBM Thomas J Watson Research Center, was accommodating. My family, husband Joel and daughters Erika and Laura, were supportive. After I had a tracheostomy and was on the ventilator full time, I hired an excellent lawyer to do battle with my insurance company and won round-the-clock nursing.

I feared the day I would stop working. But I found other interests to take the place of work. I started writing poetry, first political, then about my feelings about ALS. I joined my local MDA fund raiser committee. I wrote occasional articles for Neurology Now. I became involved in the Wadsworth Center brain-computer interface research, and I was the main force in revising the ALS functional rating scale to measure the abilities of people with advanced ALS. Most importantly, I was there for my older daughter’s wedding and experienced the joys of being a grandmother.

After thirteen years of ALS, I have had my ups and downs. My poetry reflects this reality. First, I’ll give you a poem, Resolved, that reflects my attitude on a good day. Then I will give you a poem for a bad day, Routine Routine. The second poetic form is a pantoum, which has a specific pattern of repeating lines, reflecting the tedium of life with ALS.



Resolved
© 2005 Catherine Wolf

I refuse to die
I choose to defy
Prognosis (poor)

I will see
Daughters
Graduate
Marry
Grandchildren

I refuse to die
I choose to defy
Prognosis (guarded)

I must
Love
Help
Work
Dream
Eat chocolate every day

I refuse to die
I choose to survive
Prognosis (good)



Routine Routine
© 2008 Catherine Wolf

Every day I wake at ten-thirty
The nurse puts betadine around my trach, washes it off with saline
The aide pours a half can of liquid food in my feeding tube
They hoist me in the lift

The nurse puts betadine around my trach, washes it off with saline
They put me in my wheelchair
They hoist me in the lift
The nurse brushes my teeth with an electric toothbrush, no toothpaste

They put me in my wheelchair
They dress me
The nurse brushes my teeth with an electric toothbrush, no toothpaste
I am wheeled to my computer

They dress me
I delete spam, read personal email
I am wheeled to my computer
Every three or four hours they pour something in my feeding tube

I delete spam, read personal email
At around nine o’clock I go to the tv
Every three or four hours they pour something in my feeding tube
I watch the tivoed PBS News Hour

At around nine o’clock I go to the tv
Maybe Keith O
I watch the tivoed PBS News Hour
I am taken to bed at midnight

Maybe Keith O
Whether I’m tired or not
I am taken to bed at midnight
There are no holidays, no vacations

Whether I’m tired or not
The aide pours a half can of liquid food in my feeding tube
There are no holidays, no vacations
Every day I wake at ten-thirty

Innovating Innovation

Open innovation is inarguably a buzzword. At the very end of December, the Boston Globe ran an article about companies looking outside their walls for innovation. The article highlighted Prize4Life partner InnoCentive, among other examples of the for-profit world utilizing open innovation strategies.

A recent piece in Nature Reviews Drug Discovery discussed open innovation in the context of big pharma (another Prize4Life blog touched on this as well). Examples of incentive prizes pepper the headlines of business journals and popular press alike. Below are some more exceptionally good examples that I’ve found recently:

Several years ago Goldcorp, a gold mining company based in Toronto, Canada, was in dire economic straights. Faced with the possibility of closing, CEO Robert McEwen published Goldcorp’s geological data online and opened a contest—the “Goldcorp Challenge”—to find the best methods and estimates for prospecting. The competition offered approximately half a million dollars in prizes. Prize competitors identified 110 places on Goldcorp’s property, of which 80% yielded gold. Since the challenge launched, the company has found approximately 8 million ounces of gold, valued at over $3 billion. "We had applied math, advanced physics, intelligent systems, computer graphics, and organic solutions to inorganic problems. There were capabilities I had never seen before in the industry," says McEwen of the submissions in a Business Week article. "When I saw the computer graphics, I almost fell out of my chair."

In another particularly telling example, the Harvard Catalyst has followed Prize4Life’s lead. This week, and using federal stimulus money made available through the NIH, Harvard Catalyst launched a challenge with InnoCentive related to curing and treating Type 1 diabetes. Dr. Karim R. Lakhani, an assistant professor at Harvard Business School and one of the collaboration leaders, noted in a Harvard Catalyst release that, “Open innovation is an effective way to solve scientific problems in the business world.” Those who submit the best questions or ideas for the diabetes challenge (as determined by a review panel) will win between $2,500 and $10,000.

In the pharma world, GlaxoSmithKline recently announced an open innovation strategy to deliver medicines for those living in developing countries, partnering with BioVentures for Global Health.

Crowdsourcing has been ever-present in philanthropy lately as well. Initiatives range from the JP Morgan Chase Community Giving Campaign, which enlisted Facebook users to vote on a non-profit nominee to receive a $1 million grant, to Pepsi’s ongoing Refresh Project, which makes monthly grants based on members’ voted preferences.

However, along with this preponderance of open-innovation projects comes new criticism for the model. Scott Belsky writes in Business Week that those involved in crowdsourcing need to rejigger their model so that it empowers participants. "Those involved need to innovate and start harnessing the crowd in more mutually beneficial (and thus sustainable) ways”, he says. Belsky criticizes one of the central tenets of crowdsourcing, the "forces that enable crowdsourcing are being used to get thousands of people to do work for free". Check out some ideas for improvement in his article “Crowdsourcing is broken: how to fix it.”

As open innovation becomes a bigger part of both business and philanthropy, thinkers and entrepreneurs will have the opportunity to innovate on innovation—-to develop and perfect nuanced techniques that harness the power of the crowd in a way that enables, and ultimately helps, all parties involved. Stay tuned.

--By Meghan Kallman

Notes from the International ALS/MND Symposium in Berlin

In December 2009, Prize4Life’s Scientific Program Officer, Dr. A. Sheila Menzies, was among the 900 ALS researchers, neurologists, clinicians, and caretakers who convened in Berlin for the 20th Annual Symposium on MND/ALS. The Symposium spanned three days and featured simultaneous sessions on ALS biomedical and clinical research.

The Symposium’s abstract book is available here. In addition to being a symposium guide, the booklet is a map of current ALS research, detailing the research landscape at the end of 2009.

Sessions covered a wide variety of relevant topics, ranging from discussions of proteinopathies to biomarkers to axonal transport. The proteinopathies session emphasized how the aggregation of mutated proteins in ALS patients is characteristic of other neurodegenerative diseases as (such as Alzheimer’s), suggesting a common disease mechanism (this topic was also recently covered in depth in a webinar organized by the Alzheimer Research Forum; find it here). A session on functional genomics explored the range of symptoms that may occur in ALS patients due to mistakes in the genetic code. A session on trial design showcased results of recent clinical trials, in the context of methodology, and encouraging trends in Knopp Neurosciences’ KNS-760704 Phase 2 clinical trial for ALS (read more on Knopp here and on ALS clinical trials here). The Biomarkers session predominantly featured discussions of protein-based ALS biomarkers.

A poster session saw several hundred people informally discussing their work with colleagues. Posters covered therapeutic strategies, human cell biology, epidemiology, and diagnostics, among other topics.

The clinical end of the spectrum hosted sessions on spiritual care, translating research discoveries into relevant care practices, information and conversations on exercise, metabolism, and nutrition, and a session on disease progression worked to increase audience understanding of current research focused on how to accurately portray expectations in terms of disease progression and life expectancy. A session on cognitive change explored the relationship between frontotemporal dementia and ALS, as well as covering cognitive assessments. A session on emerging disease models discussed options for identifying causes and developing therapies (see a related piece on the growing number of TDP43-based animal models here). The session on motor neuron biology provided in-depth conversation about the growth, development, and functioning of motor neurons themselves.

For more information on the sessions, see notes from the MND Alliance and ALS-TDI’s brief overview. Tune in to www.researchals.org for more in-depth scientific coverage of this and other meetings in the future

Professor Michael Strong, from the University of Western Ontario, is quoted on the MND Alliance’s site saying “The science has been very good this year. We are starting to see a real coming together of research work. No longer as research teams are we working in isolation but instead we are looking at ‘families’ of research ideas.”

Prize4Life was pleased to be present for these sessions, and for the opportunities to network and converse. We were also inducted into the International Alliance of MND/ALS Associations, at the annual Alliance meeting hosted by the Deutsche Gesellschaft fur Muskelkranke, held the week before the Symposium. Prize4Life joined the Alliance as an associate member, and is excited to be able to connect with such a respected body of organizations, exchanging information and participating in support fora with other ALS organizations worldwide.

Networks & collaborations: the great R&D facelift

As 2009, an economically brutal year, drew to a close, there was a new buzz about the future of pharmaceutical R&D. The Wall St. Journal, the New York Times, and the Boston Globe have all been commenting on it. Several weeks ago, Prize4Life attended the Partnering for Cures conference in New York City, which also emphasized this trend: increasingly, drug development is experiencing a move towards a more networked, collaborative approach to R&D.

Jonathan Rockoff reports in his piece for the Wall St. Journal that Eli Lilly & Co, like most other pharmaceutical companies, is trying to make its drug-development processes more productive while coping with both a recession and leaner pipelines. Lilly’s new approach mirrors that of other companies right now: they are hiring outside contractors to test drug candidates.

Pharma and biotech outfits have traditionally kept drugs under development close to their chests and conducted most R&D in-house, fearing intellectual infringement or losing a blockbuster to competitors. However, a large batch of patents on blockbuster drugs are expiring or will soon expire. With no obvious successors lined up, the biggest drug makers are "externalizing" much of their R&D, said Peter Tollman of Boston Consulting Group, a frequent adviser to drug companies.

By way of an example, Lilly is considering moving a molecule into Phase 3 testing that was developed by scientists outside its own research team. The potential market for the molecule under development is $16 billion annually. In the past, a major pharmaceutical company like Eli Lilly would have been far less likely to entrust any aspect of the development of such a potentially valuable compound to an outside team, and relying entirely upon outside scientists for the development of such a compound represents a significant change in strategy.

“By outsourcing human tests of such a potentially important drug, Lilly is among a crowd of pharmaceutical giants adopting out-of-the-box strategies to revive fallow research-and-development organizations,” Rockoff writes.

Sanofi, in another R&D ‘makeover’, announced that it intends to strengthen 'exploratory structures' that work in close collaboration with outside entities, reports a piece in FierceBiotech. It will pursue partnerships with public and private research entities, academic institutions and biotechnology companies.

"We are living through radical times of change for Research," said Dr. Marc Cluzel, Senior Vice President of R&D at Sanofi in the FierceBiotech release. “Tomorrow's research will be carried out through networks. We will be open to knowledge from outside sources, becoming a key partner. We need to reinvent R&D."

"Trying to do everything yourself won't work. The odds of owning everything and being at the right place at the right time are not high," echoed Peter Johnson, Lilly's vice president of corporate strategic planning.

A major driver of this shift is, presumably, cost. Lilly wants its contract research organizations (CROs) to reduce development costs and risks by quickly identifying things that won't work. Other companies such as Sanofi are leaving early-stage R&D almost entirely to its biotech partners, reports the WSJ piece. This approach enables companies to manage a much larger portfolio than they would if they were doing R&D in-house.

The Association of Clinical Research Organizations (ACRO) estimates that there are more than 1,000 CROs with greater than $20 billion in yearly revenue, staffed primarily by former drug-industry researchers. At its best, such a partnership enables both the contracted party and the contractor to work within their areas of strength.

In extreme cases, we’ll see rival companies such as Pfizer and GlaxoSmithKline combining HIV-drug businesses into a single company, figuring, figuratively, that two heads may be better than one.

Even the NIH is on board with the new emphasis on collaboration—it recently put up $27 million to see if social networking technology can virally link a generation of biomedical researchers, reports another article. The University of Florida and Harvard University Medical School received the grant money to establish sites to share ideas and data. The NIH-funded efforts will come in addition to the growing scientific social network site ResearchGate, which is rapidly becoming a well-established professional exchange platform for researchers around the world.

"National networking provides opportunities for scientists to collaborate in new, exciting ways to improve abilities to uncover underlying pathways and mechanisms of biology and to develop new diagnostics, treatments and prevention strategies," said NCRR Director Barbara Alving, M.D. "The infrastructure created and implemented through these awards has the potential to greatly facilitate the pace of biomedical research nationwide."

Prize4Life encountered the same trends—networking, outsourcing, collaborating—at the Partnering for Cures conference, a meeting of philanthropic organizations, medical research foundations, and the biotechnology and pharmaceutical industries intended to foster collaborations, held in the first week of December, 2009.

Speakers at the conference emphasized that non-profit organizations and disease foundations are well-positioned to assume risk. Indeed, these collaborations will be critical for reducing drug development costs, and finding a cure for orphan and infectious diseases. Panelists argued that companies will be more likely to invest in newer technologies if not-for-profit counterparts ‘de-risked’ them.

Further, non-profit foundations are in a unique position to facilitate relationships among stakeholders. Non-profits and disease foundations have the time and the mandate to identify relevant actors across sectors and to facilitate meetings and collaborations that are technically outside the purview of company operations.

In a conversation with Michael Milken, Jeff Kindler (CEO, Pfizer) spoke extensively about how partnerships between pharmaceutical companies and smaller biotechs, foundations, and disease organizations will be necessary in order to both survive and thrive in a changing global economy.

Competitive medical research has been internationalized in the last ten years, with important developments coming out of Asia and other regions. Emerging foreign research institutions are enticing skilled researchers to leave the U.S., and U.S. pharmaceutical companies are faced with new competition. Milken emphasized just how much ground the U.S. has lost in the global economy of late, noting that the U.S. approach to drug discovery and innovation needs to reflect the changes that are occurring worldwide.

Kindler also noted that the primary barrier to getting new treatments on the market is lack of clinical trials participants, and suggested that this is where disease organizations can be especially helpful. This is certainly the case in ALS, where a paper published in 2008 reported that the percent enrollment in ALS clinical trials is 25%, highly variable, and has not been improving over time; Gina Kolata, in a piece in the New York Times, wrote extensively about this issue in the context of the fight against cancer. Organizations such as the ALS Association have sites that offer information on clinical trials, as does the government site, clinicaltrials.gov.

Due to a combination of economic and political factors, it seems that all aspects of the research establishment are indeed beginning to look differently upon collaborations. Let us hope that this exciting trend bears fruit.

by Meghan Kallman

Boston Blazers and Prize4Life are teaming up to fight ALS!

Prize4Life is pleased to announce a new partnership—with the Boston Blazers, Boston's professional lacrosse team!

Still looking for a holiday gift for that special someone? How about taking them to see a professional lacrosse game?

The Boston Blazers will be highlighting the fight against ALS during their "Heroes Awareness Night" home game on February 6, 2010 at the legendary Boston Garden. The Blazers are partnering with P4L to bring attention to our cause and also help raise money to further our mission. They have generously agreed to donate half of the tickets purchased through this promotion to Prize4Life.

We'd love to have all of our supporters in attendance at the event. Come out and support Prize4Life, and enjoy the evening! Tickets are $30 and can be purchased directly from us, or through a special website: click here. You have to enter the code: P4L in order to be part of the group (ticket purchasers also have an opportunity to meet the team afterwords).

Alternatively, if you’d prefer to buy your tickets through us directly, just call (617) 914-4956. We’re looking forward to seeing you there!

NIH Approves Additional Stem Cell Lines For Funding

On December 2, the National Institutes of Health (NIH) declared that 13 human stem cell lines met new NIH ethics criteria, reports USA Today.

This approval re-opens of a source of funding closed to researchers using human embryonic stem cells since the Bush Administration’s 2001 executive order. Since 2001, researchers otherwise supported by the NIH have had to raise private monies to derive stem cells from the fertilized embryos left over from fertility clinics, reports the New York Times. In March 2009, President Obama signed an executive order which lifted that ban.

The first thirteen lines is merely the beginning of several hundred lines to be reviewed by the NIH in the next several months. NIH Director Francis S. Collins, MD, PhD, says that the NIH is reviewing new applications with extreme caution to ensure they meet ethics guidelines.

Eleven of the first 13 newly-approved lines were derived by Children’s Hospital Boston. They will be used to study rare congenital diseases. The other two stem cell lines were derived by Dr. Ali H. Brivanlou at Rockefeller University in New York.

This week (on Monday, December 14), the NIH approved another 27 human embryonic stem cell lines from Harvard University for federal research funding. The decision, however, limited funding to diabetes-related pancreatic cell experiments.

The second batch of cells, from Harvard University, have been used in studies of ALS, Alzheimer's disease, Huntington's disease, Parkinson's disease, and spinal injury, supported by other funding sources. A report in the Proceedings of the National Academies of Science last year called them the 'gold standard', says USA Today. Let us hope that these 'gold standards' lead rapidly to treatments and a cure for ALS.