Model or Muddle?

When I read last week that Emory University was putting part of its royalty income into a new company to accelerate the development of drugs for global diseases, I was hopeful that it had launched a new model for university technology transfer (FierceBiotech article).  The new LLC (limited liability corporation), called Drug Innovation Ventures at Emory (DRIVE), is “expected to provide global solutions to address worldwide drug development and commercialization needs,” according the University press release (Emory PR).  DRIVE “will provide the financial, business, project management and regulatory expertise to effectively move drugs through lead optimization and pre-clinical testing — a stage of drug development often termed the “Valley of Death” — and into proof-of-concept clinical trials,” and it will be the “industrial partner” for the University’s in-house Institute for Drug Development (EIDD), headed by one of the better-known academic drug discovers, Dennis Liotta.  Among other activities, EIDD is also the custodian of the Global Health Primer, a catalog of drugs in development for global diseases (GHP) which was transferred last spring from the late advocacy group, BIOVentures for Global Health (see my post, “Downsize or Downhill?”).

 

I looked for more information on DRIVE and its plans, but what I found was not encouraging.  DRIVE has a website (DRIVE), but it is sparse.  I found a presentation Dr. Liotta gave at the Atlanta Clinical and Translational Science Institute in February 2013 (Liotta presentation) which provided some details but raised questions, too.  First, DRIVE’s will work only on antiviral drugs for diseases which are caused by RNA viruses, many of which are of global concern like measles, influenza, Chikungunya, hepatitis C, dengue, and yellow fever.  Second, it appears DRIVE will be operating as a virtual company working primary through contracts and those contracts appear to be primarily at EIDD.   Also it is noted on slide 5 that DRIVE will use Emory’s administrative system for HR, finance, and grants/contracts, although I’m not sure how Emory can negotiate a contract with itself.  Third, DRIVE will depend heavily on three principals; the organization chart on slide 6 lists four employees (and one to be hired) and the rest to be contractors.  Two of the principals have substantial biotech/pharma drug development experience- George Painter, CEO, and Abel de la Rosa, CSO (although his experience is more in business and not science)- and the third- David Perryman, COO- is an attorney with negotiation but not operational experience (slides 7-10).  Fourth, it is not clear where DRIVE will get its “therapeutic opportunities” (slide 13).   The Emory press release stated that DRIVE will be the “industrial partner” for EIDD, but although the EIDD has a list of eight project areas, but none seemed to be ready to move into the preclinical, let alone clinical, studies needed to generate sufficient data to attract licensees, either established companies or venture-backed start-ups (and none of the projects list current [later than 2010] publications) (EIDD Projects).  Planning and conducting clinical trials is challenging, and from the presentation it looked like DRIVE will be using the Emory’s Winship Phase I Clinical Unit, which was started in 2009 to conduct cancer trials.

 

Not clear at all was the funding of DRIVE. The press release stated the initial funding will be $10 million from the royalties received through Emory’s license for the HIV drug, emtricitabine.  Emtricitabine was discovered by Drs. Liotta, Schanazi, and Choi at Emory (although the discovery was disputed, see IP Advocate Case Study) and licensed to Triangle Pharmaceuticals in 1996.  Triangle Pharmaceuticals was acquired by Gilead Sciences in 2003.  Gilead completed its development and sells the drug as Emtriva (Wikipedia article), and it is included in Gilead’s combo HIV drug, Truvada (approved in 2004), and Bristol-Meyers Squibb’s drug, Atripla (2006).  Will the $10 million be upfront funding or over time?  Did Emory purchase equity or give it as a grant?  Ten million dollars is a good start but few drug development companies, even virtual ones, can make progress on multiple products for that amount.

 

Also not clear is who is in charge (and liable).  The press release said DRIVE will be wholly-owned by, but separate from, Emory; the presentation (slide 4) stated DRIVE’s agreement with Emory allows it “independence to run like a biotechnology business.”  I don’t know enough about LLCs to say if Emory is liable for injury that may occur during trials.  And the University and the principals may not have the same motivation for forming DRIVE.  In the release, the Emory president stated, “This financially self-sustaining public-private enterprise fits within Emory’s vision of working collaboratively for positive transformation in the world through discoveries that are of global benefit.”  One of the principals, David Perryman, may have a different view.  To quote a Medcity news article (Medcity article):

 

In an interview with David Perryman, one of the leaders of DRIVE, he said the reason for the company is to create a way to steer clear of the entangled bureaucracy that can threaten the advancement of technology at any university.  It’s also to ensure that leadership can tap their own real world experience to ensure the technology gets to the appropriate group to commercialize it.  “A lot of universities are getting into technology transfer and by and large, they don’t know how to do it,” Perryman told MedCity News in a phone interview.

 

In my experience, new ventures succeed when they have a well-thought out plan that is executed well by managers with the right skills and experience and are backed by patient investors with aligned interests.  I am not sure about DRIVE.

 

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The Good, the Bad, and the Ugly

Recently Bernard Munos, former pharma exec and now principal of his InnoThink Center for Research in Biomedical Innovation, published an analysis of output of the pharmaceutical industry’s research and development effort and found the industry’s claim to innovation to be modest at best.  As described by FierceBiotech (FierceBiotech review) (the article is available to those with a Nature subscription at Munos 2013), Dr. Munos looked at the NMEs (new molecular entities or drugs that are not rehashes of already-approved drugs) approved 2000-2012 (a total of 353) and found of those with known mechanisms of action (324, leading me to wonder how a drug can get approval without the FDA requiring that the applicant knows how it works) about half had novel actions and half did not.  From this finding, he concluded “there does not seem to be enough [known] mechanisms able to yield multiple drugs, to support an industry. The drug hunter’s freedom to roam, and find innovative translational opportunities wherever they may lie is an essential part of success in drug research,” and ”… if innovation cannot be ordained, pharmaceutical companies need an adaptive–not directive–business model.”  My interpretation of this conclusion is that big pharma may be more successful in finding truly new drugs if its R and D is driven by an understanding of the pathology of disease (any and all diseases) rather than a goal of adding drugs to a company’s existing franchises, that is, the diseases for which the company has drugs already.  Of course, one could say that big pharma does not want (or need) to be innovative; it just needs to find drugs that can offer some (maybe even marginal) improvement over current treatments and that society (us) agrees are worth a price that includes a high profit margin.  Or if it wants to be innovative, it could figure out how make affordable meds for the rest of the world.

But on to the good.  One company that seems to be trying an adaptive R and D model with the goal of pumping up its drug discovery effort is GlaxoSmithKline plc (GSK) (I apologize for writing another post on this company).  Several weeks ago, GSK announced that it was actively soliciting academic researchers for participation in its Discovery Partnerships with Academia program (DPAc) through a “competition” called Discovery Fast Track (GSK press release).  Specifically academics are invited to submit a “therapeutic hypothesis” with supporting data (cell-based assays are OK) which is judged by a panel of GSK scientists on several factors (lots more detail at Discovery Fast Track).  Awarded to a winner (up to 20 announced by August) will be a free trip to Philadelphia to present to the GSK reviewers and the opportunity to be evaluated for DPAc participation (about 10 to be selected).  As noted on the Fast Track website, “If your concept is chosen, GSK will collaborate with you to test the full diversity of our compound collection using our pharmacological screening platforms to discover active compounds. We will share key results from the screen to provide you with the best possible chemical probes to interrogate your translational biological assays.”  So, although the evaluation does not get the academic investigator funding, it does get her/him a 50/50 chance at a multi-year DPAc collaboration with funding and the aim of generating a clinical candidate (e.g., Vanderbilt DPAc announcement).  So the good is that academic researchers can test their concepts for drugs (not drugs themselves which academics rarely discover) in an industrial-strength drug discovery program with a small chance of contributing to finding a treatment for a disease.  Also good is that GSK is trying a new way to identify and support academics with novel concepts of disease pathology through which it can find clinical candidates with novel mechanisms of action, an approach that should be more effective than the prevalent franchise-driven, serendipitous process.  Also good is that GSK seems not to be putting any market-driven preconditions on participation in Fast Track or DPAc (What GSK Is Looking For).  Any potential therapy, including those for diseases of the rest of the world and that may lead to drugs with low profit margins, is welcome.

The bad is that participation requires commitment at an early stage in research, and there are lots of hoops to jump through and paper to read for the researcher and her/his institution to understand the commitment (e.g., Terms and Conditions).  But, from my experience on both sides of the table, having more information, even if it is written by lawyers, is better than less.  My read is that GSK, in keeping with its (relatively recent) corporate value to be transparent, has done a good job of protecting both sides’ interests in the potential results of the programs.

The ugly is that some people, even those who should know better or at least should take time to read the relevant information, may suspect GSK of trying to misappropriate university intellectual property.  For example, it was reported that shortly after the GSK press release, the UCLA vice chancellor for research and his associate vice chancellor sent an email to all faculty advising they not participate because the GSK terms and conditions are in conflict with their obligation to report all discoveries to UCLA for evaluation for patent protection (Pharmalive article).  The concern being that, by applying to the GSK program and making public her/his concept for treating a disease, the investigator, and her/his assignee, the university, may lose a chance to get a patent and future intellectual property rights.  I think there are several reasons why this concern is unfounded.  First, GSK states explicitly that the applicant should not submit any confidential information and should contact the university technology transfer office (TTO) before applying.  Also last week the company added a few more hoops (“enhancements”) to the process to involve the TTOs, like requiring explicit approval (GSK Enhancements).  Second, one should note that at this early stage of research, the best the university could do is file a patent application on a “method” of finding drugs to treat a disease, and the patent courts have raised the requirements for obtaining method of treatment patents over the past few years.  An applicant needs to provide an example compound that demonstrates the method in an animal model, so the university’s application will be lacking in the required “reduction to practice.”  Third, patents on methods of finding don’t have much commercial value since the methods can be used before a patent issued (likely several years) and there are allowances for use after it is issued (for a discussion of these two points, see a 2008 post by UCSF’s TTO director at MySDScience.com blog).

As I have noted in previous posts about university technology transfer and the obligation of universities to apply their research results to social good (like global health), universities should welcome anyone willing to put resources into getting something useful out of their research regardless if there is a risk that some time off in the future (for drug discovery maybe decades) the university is not in a position to tap a revenue stream.  Fortunately, it looks like other universities are not reacting like UCLA, and several are actively promoting participation the Fast Track/DPAc program (e.g., Princeton meeting notice).  I hope GSK gets lots of applicants especially those with ideas for treating global diseases and is successful in finding innovative drugs, especially for world markets, and other companies imitate its success.

Tech Transfer for the Rest of the World

Last week, I attended a discussion organized by the Harvard chapter of the student-oriented Universities Allied for Essential Medicines (UAEM) on “Global Access Licensing of Biomedically Relevant Technologies” (Harvard UAEM).  The panelists were representatives of local university and medical center technology transfer offices (TTOs) who spoke for about an hour on their efforts to promote access to essential medicines and improve global health in the rest of the world (ROW) specifically through application of a “Statement of Principles and Strategies for the Equitable Dissemination of Medical Technologies” (AUTM Statement), a document written by tech transfer officers and backed by the UAEM in 2009.  The Statement provides guidance on patenting and licensing (and calls for biannual self-assessment), but, in my opinion as expressed my post, “An Academic Approach to Global Health”, was unlikely to have much effect.  The organizers did a great job in selecting the speakers and attracting a small but informed audience of mostly academics (students and faculty), who participated during the hour and a half question and answer period.  My regret was that the time was too short to allow a full discussion of the issues and to ask the TTO reps what progress, if any, they have actually made.

First, a bit of background on university technology transfer.  US government funding of health-related research has been and continues to be in the tens of billions of dollars per year.  For example, our local complex of academic institutions and medical centers received $1.8 billion in 2012 (Boston Globe 4/25/13 article), and the funding results in a tsunami of information, the vast majority of which is made public and used mostly by other scientists to generate more information, but a small amount is diverted mixed with existing information, becomes knowledge, and is used to make products, mostly by companies looking to make a buck.  TTOs facilitate the process by creating a financial incentive to companies to use the information by turning it into a patent-protected “invention,” even though the relation of the invention to a useful product is hypothetical and the universities lack the wherewithal and inclination to find out.  The idea is that a company would be more likely to develop a product if it, or some aspect of it, is patented and therefore exclusively owned by the company and not available for copying by a competitor, at least until the patent expires (now 20 years).  So TTOs spend time and money on patents with the hope that a company will negotiate an exclusive, income-generating license.  This rarely happens because the university invention is typical many steps away from being a product and the majority of TTOs lose money, but it happens often enough that just about every research university has a TTO with an average of six employees.  To hedge their patent strategy, TTOs patent methods of finding or making products which are even more removed from products but are attractive to start-up companies and venture capital because they could generate multiple products and revenue (for more on VC funding strategies and view of academic inventions, see Bruce Booth’s recent post at Life Sci VC).

So has the UAEM been effective in getting TTOs to facilitate the diversion of the academic tsunami into yielding products for global health?  As far as I can tell, no.  In his introductory presentation, Anthony So, UAEM advisor and Duke University faculty member (So Bio), stated that the potential is there since academic patents underlie 153 pharma products sold over the past 40 years, citing a study of Stevens et al. 2010, but which I found in my review of the publication was closer to 40 (see my post, “Slicing the Baloney”).  He also cited an example of a method of making a standard malaria drug that originated at UCSF, was licensed to Amyris, a startup, in 2003 and as of last month will used in making drugs by a major pharma, Sanofi (Amyris press release).  Use of the process will lower the cost of the drug, which is good, but the invention is not resulting in new, essential, medicines.  As was pointed out by the TTO discussants, their technology (and patents) is very early on the path to products and their ability to induce their licensees (should they even have one) to develop ROW products diligently or at all is minimal.

Well, what can the UAEM do to hold the universities’ and the TTOs’ feet to the fire for getting research that is generously funded by the US public to yield products to improve ROW health?  The UAEM can first, redefine their mission as improving ROW health rather than improving access to medicines which is only part of the larger problem.  It can then encourage university administrations to:

  • recognize the reality of tech transfer and, rather than regarding the TTOs as profit centers, view them a facilitators of early-stage product development regardless of whether they think those products will be “profitable” or not; and
  • lower the barrier for using university inventions in ROW product  development by promoting the use of internal technology development funds on projects that may lead to ROW/affordable products (Harvard received a $50 million gift to fund their accelerator program this week [Harvard Gazette article]).

For the TTOs, the UAEM can push them to:

  • not patent methods of discovery or manufacture (patent products only);
  • avoid worldwide exclusive licensing (which constrains opportunity to license for the ROW) and actively seek licensees that are developing ROW/affordable products;
  • apply the “Statement of Principles” to all future licenses for health-related technologies not only those relevant to the neglected diseases (i.e., include the non-communicable diseases like cancer and diabetes) and for all middle- and low-income countries not only those defined by the World Bank as “undeveloped;”
  • apply the above to existing licenses and try to renegotiate them; and
  • promote the start-up of global health-relevant or affordable healthcare-relevant companies by helping aspiring entrepreneurs, whether enthusiastic students or someone in off the street, in business planning, advising, fund-raising, and no/low cost licensing.

And if the UAEM or the TTOs choose to take up my suggestions, I’m available to help.

Building with BRICS

One of my topics of interest is the role that companies in the low- and middle-income countries (rest-of-world or ROW countries) may have in developing new technology and products to address global health problems (e.g., my posts, “Healthy, Wealthy, and Wise Reprise” and “Missing the Boat from the Other Direction”).  I think these ROW companies, in addition to being more effective and efficient in the long run than the traditional aid programs in bringing widespread improvements in health, may also present partnering opportunities for the many biotech and medtech companies that have powerful technologies but will not be among the lucky few to attract multiple rounds of VC funding or lucrative corporate buy-outs.  They may also be potential licensees of the many global-health-oriented proto-products being cooked up by the many proto-ventures started up by recently-graduated, socially-minded entrepreneurs.  Finally, I also think that, given the pressing need to control health care costs in the US and Europe, these ROW companies have a good shot at exporting their affordable products to the “first” world markets and thus helping me in my dotage.

While trolling the web for recent information on the topic, I found a relevant report, “Shifting Paradigm:  How the BRICS Are Reshaping Global Health and Development” (GSHi report), that was published in April 2012 by  a new-to-me group, Global Health Strategies initiatives (sic).  This organization is described as an affiliate of Global Health Strategies, an international communications and advocacy consultancy based in New York with offices in India, Brazil, and China (GHS).  The report was sponsored by the Bill & Melinda Gates Foundation, but seems to be a one-off, since I found no news about GHS initiatives or its work since the report’s publication.  Here are some of the major points made in the BRICS (Brazil, Russia, India, China, South Africa) report.

  • While the dollar amount of foreign development assistance given by the BRICS is less than 10% of the seven top donor countries’ assistance ($6 billion vs. $100 billion in 2010), the growth rate in the assistance over the past five years has been about five times greater (10 to 30% vs. 4%).
  • The BRICS prefer bilateral health aid programs as opposed to multilateral such as the Global Fund, mostly likely because the former is more cost-efficient in building international prestige and trade relationships.
  • Support of health R and D and innovation by the BRICS governments is small relative to that of wealthier countries, but is growing and exceeds that of the private sector.
  • In the BRICS, a few companies have created some new technology and products while the governments are trying a range of innovative health care delivery programs.
  • Not surprising, the BRICS have huge domestic health care challenges; for example, in South Africa, 42% of the annual mortality is caused by HIV/TB with one-fifth of the population being infected by HIV and China has one-third of the world’s hepatitis B carriers.
  • Also noted in the report are the “beyond BRICS” countries of Indonesia, the Gulf States, Turkey, Mexico, and South Korea that have growing economies, a more active foreign assistance programs, and a growing health care export aims.

The GSHi report is also a good source for the various BRICS government programs that encourage health care technology development by companies and may be a source of funding for north-south (developed-developing world) company collaborations.  With few details, they are:

  • The Brazilian Development Bank’s (BNDES) Profarma program provides favorable financing to public and private companies that invest in health R&D.  Also the Brazilian government’s Fiocruz, primarily a vaccine R and D institute, has a nascent Center for Technological Development in Health which aims to mix public sector research and the private sector’s product development expertise.
  • In 2009, the Russian government committed $4.4 billion to Pharma 2020, a plan to significantly increase domestic capacity for health care technology production and innovation in partnership (and, unfortunately, with co-funding) with non-Russian companies.  Not mentioned in the report, but of interest to US nano/healthcare technology startups, is Rusnano, a government venture capital fund that has been active in the US (Rusnano USA).
  • The government of India’s Department of Biotechnology has a Small Business Innovation Research Initiative to fund proof-of-concept research and late-stage product development in small and medium biotechnology companies and a Biotechnology Industry Partnership Programme to fund companies on a cost-sharing basis in developing technologies to address the country’s health care problems.
  • While China’s Ministry of Science and Technology (MOST) is spending about $150 billion on domestic R and D across sectors, including about $1.3 billion on health R and D, the report identified only one unnamed program aimed a public-private partnerships in global health.  In September 2011, the Gates Foundation and MOST signed a memorandum of understanding that committed a total of $400 million to four areas, one of which was the development of new products for global health (Gates press release, Gates press release).  As far as I can tell, this program is still in the rollout phase with two efforts funded.  One was a conference in September 2011 to encourage Chinese companies to invent new diagnostics for global health (Gates blog) and the other was research grant program at Tsinghua University (TU grant program).  Achieving success in the former will be difficult in my opinion since the Chinese diagnostics industry is under-resourced for R and D since it is composed of 300-400 companies with the largest having only a 4% market share (Market Publishers report).

The model industry for successful public-private cooperation in global health product development is the vaccine industry of India.  Recently FierceVaccine reported there are a dozen major vaccine manufacturers in India, exporting to 150 countries, and their domestic and export revenues are forecast to increase by 150% by 2016, reaching $870 million from about $350 million today (FV article).  And China is emerging as competitor for public health vaccines, recently gaining WHO approval for its companies to apply for prequalification to supply UN agencies.  The first vaccine to be approved is likely to be a Japanese encephalitis vaccine invented and developed by the Chengdu Institute, part of the China National Biotec Group, the largest (state-owned) biotech company in China (Reuters article).  It remains to be seen how many of the other 36 vaccine companies will be able to meet international standards but high interest exists (Interview with PATH’s Zhang and partial company list at List of manufacturers).

Not exactly Lego-scale variety, but for companies with the global health ambitions, there are pieces to play with.

Tech Talk

Last year I wrote a post about the Harvard Global Health Institute’s Global Infectious Disease Symposium on new diagnostics and noted that it was fun to hear from Aydogan Ozcan, a professor of electrical engineering at UCLA (Ozcan faculty page).  He is an enthusiastic speaker and spoke on his work on cellphone-based diagnostic devices, aka “photonics-based telemedicine.”  One of his devices now under development with a UC Davis lab is a CD4+ white blood cell counter in which a phone is converted to an ultra-wide field microscope to image the shadows of cells which, with further processing, can be used to count cells and calculate volumes (TechMagDaily article).  While clearly there is a need for cheaper CD4+ cell counters for monitoring HIV treatment (e.g., Daktari Diagnostics’ first product), I think the shadow-imaging technology’s use may be limited to diagnosing conditions where cells change physically (cancer and some infections) and may be overly sensitive to sample preparation, so may not be the basis for other global health diagnostic products.

An Ozcan device that may have better utility and really make a difference in health care in developing countries was reported recently.  It is an attachment for phones that can read the output of rapid diagnostic test (RDT) strips, yielding a “digital universal reader for all RDTs, without manual decision-making” as Prof. Ozcan was quoted (R&D magazine article).  RDTs are widely available for many diseases (more than 7000 are listed on Alibaba RDT) and, being inexpensive and low-tech, are appropriate for under-resourced settings (see USAID’s and PATH’s RDT Info).  I was not able to figure out how universal the Ozcan device is (e.g., does it read outputs of the four main RDT types, lateral-flow, flow-through, solid-phase, and agglutination) since access to the related publication requires a subscription (Mundnyall et al. 2012).  However, the authors note in the abstract that they tested the device with RDTs for malaria, tuberculosis, and HIV so it may be multi-platform.  Possibly the attachment will be useful in point-of-care diagnosis by enabling more accurate and reliable reading which is influenced by lighting conditions, rate of color/image development, and reader/interpreter experience.  Depending on the sophistication of the phone, the device may also enable storage of images and related data and their transmission.  As the authors state:  “Providing real-time spatio-temporal statistics for the prevalence of various infectious diseases, this smart RDT reader platform running on cellphones might assist health-care professionals and policy makers to track emerging epidemics worldwide and help epidemic preparedness.”

All that being said, what is being or has been done to turn this invention into a product?  Not much as far a I can tell.  The likely assignee, the Regents of the University of California, has not filed a patent application (Ozcan Patents), and, if the plan is to license the know-how because the technology is not patent-eligible due to prior disclosure or art, UCLA has not listed it as available for licensing (UCLA Commercialization Opportunities).  It is possible that UCLA and Prof. Ozcan (and maybe Partners Healthcare since he was a researcher at Man’s Greatest Hospital, MGH, here in Boston) are negotiating with investors for a start-up company.  After all, a key to attracting cash these days is to have a founder with lots of media power (Ozcan Lab in the News).  Were I responsible for helping with the commercialization, I would not look for an exclusive licensee among the big diagnostics companies, most of which are not interested in RDTs, or the many RDT companies, for which the features added to their products would not likely increase sales (RDT is a commodity business).  I think the best route would be to start a virtual company that would license to companies developing RDTs or other point-of-care diagnostics based on propriety technology and therefore adding value to their products and justifying adoption by their most likely customers, the public heath agencies.  Two companies that come to mind are Diagnostics for All (DFA) which is (still) working on paper-based, ultra-cheap RDTs and the Institute of Bioengineering Technologies, Inc. (IBET) which is working on a field test for iodine deficiency.

Of course, the rub is funding such a start-up.  In my post, “Thinking Out of the Box” 6/23/11, I recommended three ways that the government- and/or donor-backed organizations could help global health diagnostics companies:

  • an advanced market commitment by public health procurement agencies like the USAID in which the agency would set the product specifications and front some portion of the contract to fund development;
  • similarly the diagnostic product development programs (the public- and private-funded non-profits, e.g., Foundation for Innovative New Diagnostics, FIND and PATH, PATH Dx) could award contracts through a competitive process for product development, rather than funding academic groups for research; and
  • more SBIR money could be made available to diagnostics companies through agencies like the NIAID.

Anyone want to go in with me on a start-up?

A Better World?

Last November, the Association of University Technology Managers (AUTM) released its 2011 Better World Report (2011 Report); the most recent of a series started in 2006.  AUTM is a membership organization composed of anyone in the technology transfer business, that is, employed by the many grant-funded research institutions (like universities, academic medical centers, government labs) which, thanks to the 1980 Bayh-Dole Act (AUTM Bayh-Dole), own the intellectual property created in the course of US Government-funded research, and who are responsible for the first step in turning lab results into something practical and useful.  Back in the 1990s, I was a tech transfer professional, an AUTM member, and editor of newsletter, and think highly of many of my former colleagues.  But, as I have written and said previously (e.g., “An Academic Approach to Global Health,” 11/12/09), I am disappointed at the failure of technology transfer offices (TTOs), especially institutions with large inputs of federal biomedical funding, to think and act creatively and responsibly to transfer technology to organizations (non-, not-for, low-, or for-profit) that are developing products for rest-of-world (ROW), global health problems.

So it was with interest that I read the latest Better World Report with its stated aim of showing “how academic research and technology transfer have changed people’s way of life and made the world a better place” and specifically the section on “Technologies to Improve Health” (there are also sections on technologies to restore the earth, enhance food sources, further the green movement, and replenish water supplies).  Given the Report’s emphasis on The World and the section’s lead photo of a mother and child not likely taken at the local mall, I expected to learn about products that were making the lives of the people, especially those not lucky to be US citizens, better.  Nine technologies were profiled:

  • Device for knee-pain sufferers from the École de technologie supérieure (Montreal)- not relevant to ROW health;
  • Insect catcher for researchers from Emory University- not relevant to ROW health (intended for use in research not public health);
  • DNA microarray from the Lawrence Berkeley National Laboratory- products made by licensee, Second Genome (Second Genome), are used primarily in academic research, so not relevant to ROW health;
  • Device for a chronic bladder condition from Massachusetts Institute of Technology- not relevant to ROW health;
  • Diagnostic for brain injuries from University of Florida- not relevant to ROW health;
  • Topical wound cleaning solutions from University of Georgia- products are made by licensee, Molecular Therapeutics LLC (Molec Pharma), and may be relevant to ROW health, if low-priced and distributed outside of US (current distribution is apparently through nine independent agents);
  • New drugs for malaria from University of Nebraska Medical Center-  a lead drug candidate is in late stage human trials by the licensee, Ranbaxy, the Indian generic drug maker (and since 2008 a division of the Japanese pharma company, Daiichi Sankyo Co. Ltd.), and may have a significant impact on ROW health (a great story that I wrote about in my post, A Long Strange Trip, 11/18/11);
  • Diagnostic test for Cryptococcus Neo-formans infection (an opportunistic fungal infection of immuno-compromised individuals) from University of Nevada- a prototype test developed by the licensee, Immuno-Mycologics Inc. (IMMY), is used or under evaluation in the US, South Africa, Thailand, Vietnam, India, Kenya, Uganda, Rwanda, Zimbabwe, Tanzania, Guatemala, Argentina, Brazil, and Mozambique and is likely to have a significant impact on ROW health;
  • Microchip diagnostic for HIV monitoring from University of Toronto-  a portable cytometer is under development by the licensee, ChipCare Corp. (U of T News) so while relevant to ROW, it will have competition especially if priced at $5-10,000 per reader as indicated (e.g., Daktari Diagnostics has said its reader will be $500, Daktari).

My grade:  C-.  Of the nine profiled technologies, only one (the Cryptococcus diagnostic) is in use to improve ROW health and three others may result in products which will improve ROW health.  With a good portion of the NIH’s 2012 $30 billion budget going to these institutions (note two of the profiled institutions are Canadian), there is room, and money, for improvement.  TTOs should be more active, first, in identifying, designing development plans for, and subsidizing the technologies that may result in ROW health products, and, second, in finding and motivating entrepreneurs, start-up and established companies, and non-profits like the product development organizations to license the technologies and develop products.  To lower barriers and costs, I recommend that the TTOs:

  • rather than granting exclusive world-wide licenses, license non- or semi-exclusively by indication, geography, price, or national origin of the proposed licensee;
  • grant multiple time-limited, no-cost options to interested parties to generate competition and proof-of-concept data;
  • seek out entrepreneurs interested in creating no/low-profit ventures (tap alums if needed) as opposed to chasing venture capital firms (who aren’t interested in global health markets anyway);
  • pool patents with other institutions to create patent packages needed for product development and make them easily accessed through standardized licenses;
  • stop patenting methods for drug and vaccine discovery or at least stop licensing them exclusively;
  • provide internal funding for proof-of-concept research on global health-relevant technology (some universities already have technology development funds to add value to early-stage research);
  • review all existing licenses for global-health-relevant applications and try to force renegotiation that requires licensees to develop ROW products;
  • know that, in addition to the “neglected diseases,” chronic conditions like cardiovascular disease, diabetes, and cancer are major contributors to mortality in low-income countries and therefore negotiate licenses for technologies for these indications that favor ROW products; and
  • dissuade their administrations from measuring TTO performance solely on revenue and persuade them that licensing for social good is a duty of a publicly-funded university.

Some of the members of AUTM are aware that more needs to done and the organization has a Global Health Initiative (AUTM GHI).  Unfortunately, the momentum of the initiative’s launch in 2009 seems to have faded.  The number of institutions endorsing the Initiative’s Statement of Principles and Strategies for the Equitable Dissemination of Medical Technologies has dropped from 13 per year to zero (Principles Endorsement), and at the upcoming annual meeting only one of 70 sessions is related to global health (Meeting Program).  I note though the plenary presenter will be Christie Hefner (“the chief steward of the iconic Playboy brand”) who will talk about “how to expand and extend a brand in the virtual world including providing tips for defending against global counterfeiters, choosing trustworthy licensing partners and more.”  While the Better World report is a good way for AUTM to document the pubic benefits of federally-funded research, AUTM should also be honest in assessing those benefits, how they were achieved, and figure out how to technology transfer successfully.  A better world?  How about a better way?

Slicing the Baloney

The shoving over Federal FY 2012 spending ratcheted up a notch this week with  publication of the President’s budget proposal and the many counter proposals being pushed by the several legislative factions and lobbies.  Of interest to the academic biomedical research lobby is the NIH budget which the administration’s plan will increase $1 billion to $32.3 billion (a 3.3% increase), or essentially flat since the increase in biomedical research costs is estimated to be about 3% (Fierce Biotech article), and which the House Republican plan will cut by $1.6 billion (AHS News).  Of course, to groups like the Federation of American Societies for Experimental Biology, the latter will mean lay-offs, research grinding to a halt, death, and destruction (FASEB News).  Moreover, according the FASEB president, his group is not seeking the additional funding “for itself but for the untold number of people whose lives could be saved or improved by medical advances” (Chronicle of Higher Education article).  I wondered what may be the evidence for federal research creating medical advances that save the lives of untold numbers of people if any of them are among the untold billions not lucky enough live in the US.

Coincidently, a recent publication in the New England Journal of Medicine by several notables of the academic technology transfer field, including my colleague, Ashley Stevens of Boston University, sheds light on this question.  In “The Role of Public-Sector Research in the Discovery of Drugs and Vaccines” (Stevens et al. 2011), they try to connect the dots between publicly-funded research in the biomedical sciences and specific products, which, of course, are really what are used to save or improve lives.  They found that “during the past 40 years, 153 new FDA-approved drugs, vaccines, or new indications for existing drugs were discovered through research carried out in PSRIs [public-sector research institutions]” and conclude “Public-sector research has had a more immediate effect on improving public health than was previously realized.”  This sounds impressive, and the study was cited by one news source in the context of the budget battles (Businessweek article), but I think some clarification is due.

First, the authors use the phrase, “discovered through,” rather than  “discovered by,” and don’t clearly say what they mean by the former.   I agree with Karl Popper, the philosopher, that all science is applied (eventually) so that the FASEB president is right (as is supported by the studies cited in Stevens et al.) in that publicly-funded science is good for society by generating knowledge that others can apply to creating (generally) useful products.  And for drug products, the application may take decades, according to Stevens et al. who cite Toole 2008 as finding the lag time between research funding and a product is around 17 years.  Although the authors imply that PSRI research is the proximate cause, or origin, the products they list, a quantification of the time frame is needed.

Second, the authors include a wide range of products in their total of 153 which I think should not have been included or at least counted differently.  I reviewed their list, nicely provided as an appendix, and found:

  • 8 diagnostics which are not drugs or vaccines;
  • 13 drugs which are variations of naturally-occurring substances like vitamins (e.g., calcitrol), hormones (e.g., estradiol, Factor IX, protein C), or bioactive molecules (e.g., nicotine, potassium, gallium) that were known before being used as drugs; and
  • at least 2 discontinued drugs (Calederol and Supprelin).

Moreover, the authors included products that are connected to the PSRI research by patents that claim:

  • a method of finding a drug (“screening”) which is not, in my mind, particularly relevant since the patent does not “enable” a specific drug;
  • methods of making or formulating a drug, also not particularly relevant since there can be many ways to make or formulation a drug; and
  • a method of treating, which may not be relevant since new uses often result from clinicians trying approved drugs for new uses.

I found the number of listed products connected to PSRI research by these kinds of patents and not a composition patent is 53.

Finally, I had a hard time confirming the connections supporting the authors’ discovery claim.  They used the FDA Orange Book as a primary source.  The FDA publishes the Orange Book, which I guess at one time was printed on orange paper but now is made of electrons, to identify therapeutically equivalent drugs to increase competition and lower prices (FDA Orange Book Preface) but it also lists the patents submitted by companies as part of their New Drug Applications (NDA).  These are the patents that confer “exclusivity” to the drug, that is, patents owned or licensed solely to the applicant which claim the product’s formulation/composition or approved use (more below).  I took a look at the specific patents listed in the Orange Book for a few of the listed products, picked the earliest issued (assuming it to be the primary patent), and checked the ownership.  I found only one in five was owned by a PSRI:

Product* Patent No. Owner
Abacavir sulfate 5034394 Burroughs Wellcome
Desloratadine 6100274 Schering
Triptorelin pamoate 5134122 Debiopharm S.A
Cetrorelix 5198533 Zentaris GmbH (DE)
Enfuvirtide 5464933 Duke University

*Generic name

Perhaps I am mis-using the source (the Orange Book), or perhaps my samples were instances in which a PSRI and a company discovered the product through cooperative research or independently as the authors acknowledge occurs (p. 537).

Granted my review of Stevens et al. is quick and superficial (the authors used additional sources that I did not have access to), but I think I have a case that the number of drugs and vaccines “discovered through” research conducted by PSRI may be substantially fewer than the 153 claimed.  I’d ballpark the number at 40 novel products (not new formulations or uses), primarily biologic drugs and vaccines which require less effort to find a bioactive, bio-available, and nontoxic product.   So what do we, the public, get for the billions invested in PSRIs each year?  Lots of publications to be sure (around 85000, NSF Scientific Publishing), lots of jobs for life scientists and research administrators, and lots of useful information that companies have turned to products.  And, since I accept the “discovered though” claim, at least a handful of antivirals and vaccines that are saving lives around the world.  Maybe we need an National Institute of Global Health to speed discovery.