JDRF Reports New Progress in Translational Research

Last week, the Juvenile Diabetes Research Foundation (JDRF) reported that for the fourth time in 18 months, one of the non-profit organization's biotechnology partners had signed a collaboration agreement with a large pharmaceutical company to move research on type 1 diabetes into the final phases of clinical trials.

According to the JDRF, the newest development is the latest example of success in its Industry Discovery and Development Partnership (IDDP) program, through which JDRF provides early-stage research funding to drug and/or biotech companies working on technologies and therapeutic candidates.

The latest example was JDRF's industry partner Bayhill Therapeutics Inc., which just entered into a collaboration agreement with Genentech, Inc., a wholly-owned subsidiary of the Swiss pharmaceutical giant the Roche Group, to further develop and potentially commercialize a novel antigen-specific immunotherapeutic which aims to reverse the immune response that causes type 1 diabetes.

Other IDDP partners that have created similar commercialization agreements with big drug and biotechnology companies during the past 18 months include: Tolerx, which joined with GlaxoSmithKline to develop an anti-CD3 antibody to preserve beta cell function in newly-diagnosed patients; MacroGenics, which is developing a similar antibody with Eli Lilly and Company; and Toronto-based Transition Therapeutics, which has also signed a commercialization agreement for a beta cell regenerative therapy with Eli Lilly & Co. To date, JDRF has awarded more than $29 million in research funding to 25 companies through its IDDP program.

Collectively, these are just the latest examples of JDRF's program which first made public headlines in a front-page Wall Street Journal story on January 26, 2007 describing the organization's new push to help fund for-profit companies doing drug research.

These follow a number other deals that JDRF unveiled in preceding years, including a deal announced in October 2006, in which JDRF announced it would pay up to $3 million to Sangamo BioSciences Inc. for a phase-2 clinical trial of a protein drug that showed promise against diabetic neuropathy. Just a few weeks ago at the ADA Scientific Sessions in New Orleans, Sangamo BioSciences Inc. presented (abstract entitled "Reappearance of Nerve Potentials in Severe Diabetic Peripheral Neuropathy Patients with Unmeasurable Nerve Conduction Using Vascular Endothelial Growth Factor Zinc Finger Protein Activator") positive Phase 2 therapeutic data which resulted from this early JDRF-IDDP partnership.

In that presentation, they reported that the trials resulted in statistically significant and clinically relevant improvements in subjects with moderate and severe diabetic neuropathy as compared to placebo. The biotechnology medicine was referred to as "SB-509" and was reportedly well-tolerated in both multi-dose studies.

The logic behind these deals is simple: they're examples of what's known as "translational research", which is sometimes also referred to "bench-to-bedside" research which aims to assist in bringing promising therapies that might not otherwise ever see commercialization without JDRF's assistance to market.

In effect, JDRF is helping to, as the banking industry sometimes refer to it, "de-risk" the development of these products, and in doing so, make these therapies more attractive to companies which might bristle at the cost of bringing them to market.

Although JDRF aims to assist a variety of potential treatments with this IDDP program, fundamentally, the organization is pushing hard to to treat the root-cause of type 1 diabetes, rather than simply more palliative treatments, which is what virtually every type 1 diabetes treatment to date has been for nearly a century (88 years, to be precise). Palliative treatments simply treat the symptoms and manifestations of the disease, without ultimately eradicating the disease(s) which made the patients sick in the first place.

Increasingly, there is a growing consensus with Alexander "Zan" Fleming, MD's assessment (who formerly headed diabetes drug review at U.S. Food and Drug Administration) and now serves as Chief Medical Officer of Kinexum, which is the firm behind the newly-branded start-up known as Exsulin Corp. of the current situation:

The development of therapies for T1D has been neglected in favor of efforts in advancing therapies for the larger T2D population. Pharmaceutical companies have also been deterred by lack of clarity around the regulatory expectations for such therapies.

The U.S. Food and Drug Administration (FDA) and other regulatory authorities have long been in a quandary about how to approve therapies directed at the underlying autoimmune cause of type 1 diabetes (T1D). Therapeutic targeting of islet autoimmunity has been focused to date on persons with some remaining beta-cell function, essentially those just diagnosed with T1D. This target population requires reenrolling in a registered clinical trial, which are relatively long and difficult to conduct. These and other challenges have slowed the pharmaceutical industry's pursuit of T1D therapies, even though it afflicts more than 1 million North Americans.(Footnote #1) The larger type 2 diabetes (T2D) population has dominated the attention of regulators and pharmaceutical companies alike. For T2D drugs, the regulatory efficacy end point, hemoglobin A1c (HbA1c), was validated by landmark trials as predictive of microvascular benefit, (Footnotes #2 and #3) and the design of T2D registration trials has become standard. For some time, the FDA assumed that HbA1c should also be the primary end point for T1D therapies.

Footnotes:

#1. National Institute of Diabetes and Digestive and Kidney Diseases.
2003. National Diabetes Statistics Fact Sheet: General Information and National Estimates on Diabetes in the United States, 2003. U.S. Department of Health and Human Services, National Institutes of Health. Bethesda, MD.

#2. The DCCT Research Group. 1993. The effect of intensive diabetes treatment on the development and progression of long-term complications in insulin dependent diabetes mellitus. N. Engl. J. Med. 329: 978-986.

#3. The UKPDS Study Group. 1998. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications complications in patients with type 2 diabetes (UKPDS 33). Lancet 352: 837-853.



To be sure, there is some debate on whether all of the new type 2 therapies represent genuine progress. Some drugs, such as Merck's Januvia (sitagliptin), are extremely costly to the nation's healthcare "system" and this drug's benefits are somewhat questionable. Regardless, no one can deny that when it comes to new and improved diabetes treatments, the rule in the pharmaceutical and biotechnology industries is follow the easy money, with particular emphasis on the word EASY.

It took 43 years for the first fundamentally new insulin variety (Eli Lilly & Co's. Humalog, or insulin lispro rDNA injection) to hit the market. Prior to that, the last fundamentally new insulin product was the Lente series (insulin zinc suspension), which was considered by most doctors to be far superior to NPH (insulin isophane suspension) in terms of predictability of time-activity profiles yet is no longer marketed today. NPH only remains on the market today because it's easy to sell in pre-mixed varieties such as 70/30, 50/50, etc. (it can be pre-mixed without changing the activity profile of the 2 insulins, while Lente products cannot). The pharmaceutical industry sees a potential goldmine in the massive type 2 market if they can convert even a small percentage to using those products, and not having to mix insulin is a key feature used to sell to millions of primary care physicians worldwide. Of course, these products do not deliver superior glycemic control, but they help to convert these "insulin naïve" type 2 patients into insulin users, which is the business objective.

Market leader Novo Nordisk A/S reportedly has several insulin products in various stages of development right now, and these are designed to be "weight neutral" products, another pitch aimed more at converting the type 2 market into insulin users rather than a fundamental advance in treatment. But beyond almost non-existent insulin development, Novo only recently set up a biotech unit outside of Seattle (see here and here for details) to pursue "inflammation" drugs aimed at the root cause of insulin insufficiency (there are different forms of inflammation in type 1 and type 2 diabetes, but ultimately, no current drugs on the market can stop either of these destructive inflammation processes). Novo's move was more sizzle than steak, as the company really has nothing in it's inflammation drug pipeline, while rival Eli Lilly & Co. has 2 partnerships for potential autoimmunity treatments and beta cell regeneration therapy in various stages of development. At present, these target newly diagnosed patients, but there are a number of different efforts which ultimately hope to be effective in long-standing type 1 diabetes as well. However, in order to measure the effectiveness of these treatments, it's necessary to see if they work on newly-diagnosed patients first, then perhaps they can be expanded to include the majority of patients who are long-past the honeymoon phase.

Regardless, it is heartening to see solid progress being made by these efforts; the JDRF should be commended on helping to bring new therapeutics to market beyond palliative treatments like a closed-loop insulin delivery system, which has plenty of critics (not the least of whom are the healthcare providers who will be expected to foot the ongoing costs, which will be much higher than current treatments). Whether the JDRF/Bayhill Therapeutics Inc. drug effectively arrests autoimmunity remains to be seen, but so far, the initial results appear promising. That, combined with several other therapies in various stages of development (see here and here for more background on some of these), perhaps combined with Exsulin's INGAP product (see here for some additional background) could spell the first fundamentally new forms of treatment for type 1 diabetes since the discovery of insulin in 1921. So far, this looks like the folks at Boston Consulting Group who created the following diagram (with a few additions of my own, noted in red) looks to be pretty much on target!

Key Challenges Ahead For JDRF's New CEO

On May 13, 2010, the Juvenile Diabetes Research Foundation (JDRF) issued a press release that it's CEO, the guy who formerly ran Novocell (a company that hopes to cash in on widespread islet transplantation for type 1 diabetes -- note that the company recently changed it's name to ViaCyte) had resigned, after just a little over 1 year on the job -- in fact, he didn't even stick around long enough to give the organization's annual "State of the Foundation" address! He claimed he was leaving for personal reasons, and would be returning to be with his family in Southern California (the JDRF is based in New York, although the CEO before him lived in St. Louis and split his time between his home and JDRF headquarters New York).

I could understand it better if this wasn't becoming a recurrent pattern for JDRF's CEOs in recent years. But for some reason, the JDRF has not been able to hold onto a CEO lately. What makes this even more puzzling is the fact that the job market has been tight for many top executives in many fields, including the nonprofit sector. According to The Wall Street Journal "No one knows how many out-of-work CEOs are looking for corner office suites, but recruiters say their numbers are growing. Fewer big businesses are switching bosses these days and mergers and bankruptcies have further reduced their job prospects. Only 48 companies in the S&P 500 index changed leaders last year, the lowest level since recruiters Spencer Stuart began tracking it in 2004."

Over the last few years, there has been a parade of new CEO's in the top slot at JDRF, each leaving sooner than the predecessor. In each case, the CEO stepped down rather unexpectedly after a short time on the job. JDRF Board Members should probably be asking WHY is this happening, and then what is the organization's leadership doing to prevent it from happening again so quickly?

I believe the JDRF needs solid leadership, but frankly, I think it's been a huge mistake to try recruiting leaders from the "diabetes industry" because of the very reasons we saw with Alan Lewis. Private industry can offer executives more money, and it's very tempting for them to take their leadership skills elsewhere and/or to cash out altogether. By looking to diabusiness for candidates, the organization likely hopes to have someone who has some understanding of the disease so their learning curve won't be so steep. That's fair enough, but isn't the lure of big bucks from a for-profit company a bit too tough for a nonprofit to compete with?

In fact, during 2009, we know that CEO Alan Lewis took no salary from the organization, although it's worth mentioning that he volunteered to do so. But going back to previous CEOs, the salary in 2008 for Arnold Donald was $531,040 plus another $82,138 for contributions to employee benefits plans and/or deferred compensation plans. Grand total: $613,178. When it comes to CEO and other top executives' pay, that's quite low on the scale. Most CEOs have unexercised options in the stock of the companies they lead that's worth more than 10 times that amount (or more). So we know that the pay as CEO of JDRF isn't extraordinary. As a matter of fact, the organization's Senior Vice President of Scientific Affairs, Robert Goldstein, and Richard Insel, JDRF's Chief Scientific Officer -- according to the organization's annual IRS filings -- are the highest paid employees, not the CEO. But the demands and hours required for the CEO of the JDRF are typically far less than they are for CEO of almost any for-profit company, so it's a pretty cushy job with a big-shot title. The top job is usually awarded to someone who has already lead a company or organization, but has no other responsibilities and is now quite financially comfortable and doesn't really need a salary. But that also means that they could easily be distracted or lured away, as was the case with Mr. Lewis.

JDRF's Latest CEO Search Ended More Quickly Than The Last

In June, the JDRF announced that it had hired yet another new CEO (this one to replace Alan Lewis). The organization filled this position much, much more quickly than it did when Peter van Etten stepped down (it took the organization well over a year to fill the vacancy at that time), but given the recent history of CEOs stepping down, I think the JDRF absolutely must have succession plans outlined and in place so the organization isn't left without clear leadership in the event that the top exec leaves again. I should remind my readers that the newest CEO is the third CEO the organization has had since Peter van Etten retired from the position at the end of 2005 after serving 6 years in the position. In other words, the last CEO was the organization's third new leader in less than four years. Mr. Lewis also had the decidedly unflattering description of having had the shortest tenure as JDRF's CEO since the CEO position was first created in the oranization.

JDRF's Board of Directors named fellow-JDRF Board Member Jeffrey Brewer as CEO, who is perhaps best known for a string of internet startups which he then sold and made a personal fortune from. Mr. Brewer also has a personal connection with type 1 diabetes, as his young son Sean was diagnosed the disease since 2002, but he's also a relative newcomer (although not as new as several of the recent lineup of JDRF CEO's have been), having quickly risen through the ranks of various leadership posts in the largely-volunteer run organization.

The naming of Mr. Brewer as CEO, as might be predicted, did set off an immediate question given his role in pushing so the organization so hard to fund the so-called "artificial pancreas" project, which many long-time fundraisers (including a few of the organization's founders) and supporters view as a significant deviation from the organization's core mission to find a CURE for type 1 diabetes and put itself out of business. Some have called it a costly boondoggle that will mainly enrich the drug and medical device companies, who will charge healthcare providers handsomely for the technology that the JDRF has largely shepherded through the costly development cycle. This is no small issue, some 47 million Americans lack any sort of healthcare coverage at all (including an estimated 3 million Americans with diabetes) and they will most likely not have any sort of coverage until major portions of the U.S. Healthcare legislation become effective in 2014. Even if it gains FDA approval, the costly devices will very likely to remain inaccessible to many patients (even in spite of JDRF's support) largely because of the cost, thanks to durable medical equipment caps that exist on many plans. I recently communicated with a parent who had 2 children with type 1 diabetes, and she had to stagger the timing when each child could get a new insulin pump over a period of 2 years thanks to this very issue. She also felt that JDRF should not really have to fund studies to justify insurance coverage for the devices when for-profit companies stood to make millions on the devices. Her feeling was that the organization's resources would be better spent on autoimmunity treatments that would help with a so-called "biological" cure given the issues we collectively face with uncontrollably rising healthcare costs.

Donor-Centric Organizations Require Complete Financial Transparency; The JDRF Isn't There -- Yet!

The JDRF has provided few concrete details on the actual budget for it's Industry Discovery & Development Partnership (IDDP) program, which unless I'm mistaken, is how the "Artificial Pancreas" project is being funded. While JDRF funds certain elements of these programs, private industry should ideally be picking up part of the cost, but without financial disclosure, many fundraisers/donors feel as if they're deliberately being left in the dark about an important program being sponsored by the organization.

Section 6104 of the U.S. Internal Revenue Service code requires that a nonprofit organization to make its Form 1023 (or 1024 if applicable), 990, and 990T [501(c)(3)s only] available for public inspection, and JDRF claims this information is posted on it's website, but I have always found it far easier to locate these tax documents via The Foundation Center. The Foundation Center is a national nonprofit service organization recognized as the nation's leading authority on organized philanthropy, which maintains one of the most comprehensive databases of U.S. tax returns for U.S. nonprofit organizations anywhere. Using this, one need not search countless pages looking for a needle in a haystack; just enter the name or tax ID code (which can be found on the tax filing itself) and voila, a listing comes up without any other stuff. You can access this extensive database here or by using this widget (Note: the widget requires JavaScript to be installed on your computer in order to function):



(Incidentally, you can look up any other nonprofit here, too, including the ADA, the DRI, the Diabetes Hands Foundation and many others on this site.) But donors are left with few details on just how much the organization has allocated to the IDDP project, and some long-time fundraisers feel entitled to know. Former JDRF CEO Arnold Donald pushed to make the organization much more "donor-centric" (see here for details) but that requires an ongoing organizational commitment to succeed.

Not too long ago, a nonprofit survey asked "What does 'nonprofit transparency' mean to you?" and the responses generally fell into two categories: (1) financial accountability and (2) openness about missions and programs. Given how broadly-defined the JDRF's IDDP program really is, many donors/fundraisers want to know more about exactly how much is actually being spent on the various programs here to determine if it's a real deviation from the organization's stated mission or not. Unfortunately, the public filings have answered few (if any) of their questions.

Mr. Brewer has had the great fortune to be able to dedicate personal time that many parents of children with diabetes simply do not have the luxury of doing, which means he's out-of-touch with many donors'/fundraisers' needs. In fact, he's had no relevant personal experience in the kinds of day-to-day challenges many parents of kids with diabetes face. Today, many parents of kids with diabetes struggle with complicated insurance issues that grow ever more costly by the year, routine changing of drug formularies that virtually force the switching of preferred insulin brands, and routine denial-of-coverage for such things as insulin pumps not to mention long, drawn-out appeals processes. Many cannot even get such basics as test strips covered, and will likely never be able to get coverage for a costly, closed-loop "artificial pancreas" that Mr. Brewer has been such a big proponent of. We can only hope these not-so-small details are not lost on him. That's why I believe former CEO Arnold Donald's goal of making the JDRF more donor-centric was such a critical strategy, and why it will likely be even more critical moving forward.

Safety In The Organization's Highly Decentralized Structure

First and foremost, the JDRF is now, and always has been a highly decentralized organization. That's always been one of the organization's key strengths. While highly autocratic CEOs have found that challenging to adapt to, it also ensures the organization's creativity and resilience to setbacks like the loss of a leader. Have a look at this video presentation from the 2010 State of the Foundation address to JDRF board members:



Now the key speaker, Leo Mullin, sounds remarkably confident in JDRF's ability to recover from a fundraising perspective, as if the broader economy was a minor inconvenience. So far, JDRF's volunteers and fundraisers have done remarkable work to ensure the foundation has been able to keep funding its research commitments. In that regard, the organization has done better than many peers, but no one should delude themselves into thinking the organization is somehow immune to challenges in the nonprofit fundraising environment. Given that the prevailing economic consensus is generally that this will be a largely jobless economic recovery and even then, we shouldn't expect much of a turnaround until 2012. Clearly, the new CEO has his work cut out for him.

Can Changes At The Top Impact Continuity In JDRF's Strategy?

It's safe to say that during former CEO Alan Lewis' highly abridged tenure (you may catch an interview with Mr. Lewis here), he most likely was NOT able to make any meaningful changes in direction or influence the organization in any material way, shape or form. To his predecessor's credit, Arnold Donald, who stayed in the job only slightly longer, about 2-3 years if memory serves me correctly, did slightly better in his efforts to help reshape the culture of the organization to be more of a donor-centric organization. But that type of effort requires consistency and routine, not the annual CEO parade that has become such a regular occurence at the organization following Mr. van Etten's departure. Change in the corner office may actually have had the opposite effect -- alienating faithful fundraisers such as myself. Last year, although I attended the Manhattan walk with a group, I raised just $50 (a record low for me), which was at least $4,500 less than I had raised in each of the 6 previous walks. Although I have a very personal relationship with type 1 diabetes, having lived with this disease for 34 years (effective July 24, 2010), in recent years, the JDRF and in particular the New York City chapter, has done much to alienate me as an adult with type 1 diabetes.

That's a separate conversation about the clique-y and snobbish nature of the New York City chapter (which includes the money raised by outer-borough parents, even though those individuals are scarcely even represented in any boards or review panels) of wealthy parents of kids with type 1 (most send their kids to private schools, unlike the experience of many suburban parents), and the presumption that any adult affiliated with the chapter simply MUST be a parent of a child with type 1 diabetes was downright insulting. In the New York City chapter, my experience has been mostly negative, more closely resembling Bravo TV's "The Real Housewives of New York City" than it does an organization with a truly charitable mission. But I am optimistic that startup organizations like Act1Diabetes can wrestle some more meaningful representation within the JDRF New York City chapter than the current leadership does because I believe it's badly needed, at least in NYC. But my point is that donors must be central to the organization's ongoing success, and frankly, that varies considerably from one chapter to to the next. More uniformity in how donors are recognized and addressed would benefit the organization as a whole. Let's hope he keeps the "donor-centric" theme alive and well, because failure to do so could adversely impact fundraising for the organization!

The issue of who diabetes organizations represent is a hot topic nationwide these days, and it even came up in the recent Roche Social Media Summit I attended in Orlando a few weeks ago. The fact is that kids with diabetes eventually do grow up, and how well those connections established as children with diabetes survive is playing an increasingly important role in the ongoing sustainability of many charitable organizations. Other JDRF chapters are leading JDRF into this territory far better than the NYC chapter has, fortunately, and I think that's been a benefit to the organization. Let's hope he keeps the "donor-centric" theme started by former CEO Arnold Donald alive! Just how prepared Mr. Brewer is to address all of these issues is unclear, but I think it's apparent that he has his work cut out for him.

Is JDRF A Donor-Centric Organization?

Back in December 2006, JDRF published an interview that Kelly Close conducted with the organization's then-incoming Chief Executive Officer (CEO) Arnold W. Donald. (That interview can be downloaded here.)

I recently re-read that interview because I recalled Mr. Donald making some statements about how he felt that JDRF needed to become more a "donor-centric" organization, and I was looking for the quote. I was also comparing Mr. Donald's view and trying to understand how the new CEO, Alan Lewis will address this issue. I found the quote from former CEO Arnold Donald, and have provided an excerpt from that interview below:

Interview with JDRF CEO Arnold W. Donald, Publish Date: December 2006

KC: Where do you think there is the most potential for improvement in the [JDRF] organization?

AD: Wow. The most potential. I haven't [ranked] it that way ... I come from a continuous improvement orientation, and I see improvement opportunities everywhere. I don't care how good something ism you can always improve, but I would say first and foremost is our ability to live our intent of being donor-centric.

KC: How do you mean?

AD: Every donor or volunteer should feel that they are totally connected to JDRF. They should feel they are proactively communicated with. That their connection to type 1 is understood by JDRF. They should be treated with integrity and caring and know that their opinions count. It doesn't mean we are always going to do exactly what a given volunteer's opinion is, but if they understand why we've done something, even if they would do it differently, it creates the basis of alignment.

KC: Right. But how do you get everyone on the same page?

AD: It requires a lot of components. Number one, it requires orientation of behavior by all of the staff. It requires certain technology, databases, information systems, and what not, that we're working on and we've had some issues with and we're organizing around trying to address. If you don't feel like it's a donor-centric organization when you get the same letter three or four different times, or your name comes and is misspelled, or it comes and it's referencing a child that's not yours, then that's a problem. So having the right information in databases is important.

KC: That counts.

AD. These are little things, but they are symptoms of a more core issue of being truly best in class of being donor-centric. For example, we have tons of communication. I couldn't tell you all the different communications we have. Having said that, I can't tell you how many times I've been told by volunteers, donors, and staff that they don't feel communicated with. So therefore, in that mix somewhere we don't quite have it right, and communication is everything. So we're going to have a difficult time being truly donor-centric of people don't feel like we're communicating effectively with them.

A few months later, in the 2006 State of the Foundation Address, Mr. Donald again spoke about the efforts the organization was making to build it's donor pipeline, especially with it's high-net worth cultivation and stewardship strategy. In his address, Mr. Donald made the following statement:

"We've determined that our donors want information on research that is clear, concise, and targeted to their interests. Information that shows milestones and outcomes on their investment; regular research reports; site visits; and phone conferences with researchers. We're finding that we're engaging both current and prospective donors in an ongoing dialogue that involves them in JDRF's research program in deeper and more committed ways, and motivates them to make new and significant leadership gifts."

Of course, as JDRF's 2008 Annual Report notes that while 2008 was a banner year for JDRF in terms of fundraising and research dollars allocated, the organization expects an extremely tough year in 2009, and is expecting that to continue possibly into 2010.

Now, I certainly do not want to diminish the importance of major donors (who attend some of the organization "galas" to the tune of $500 or $1,000 a plate), and big donors are indeed valuable, but I was curious if everyone in the Diabetes O.C./online donor community feel like JDRF is truly donor-centric, by sharing the latest-and-greatest research news, and presentations with us?

Personally, I've never attended a JDRF gala (frankly, I'm not sure I'd even want to) nor would I spend such an amount to attend a back-tie party, but I have consistently raised a few thousand dollars each year in my walks, yet I get the sense that I'm not a big enough fundraiser to be entitled to get such information. Often, I feel like JDRF is more interested in stupid black-tie parties than in addressing my need to feel like JDRF keeps us as well-informed about different programs the organization funds with the money I help raise.

Case in point: I had to really search out information about Industry Discovery and Development Partnership (IDDP) program and translational research efforts, and most of the information I found came from sources other than JDRF. Is it really so hard to put a Powerpoint presentation on the organization's website? I don't think so.

Well, the great news is that JDRF's New England Chapters (collectively, except for a few chapters in Western Massachusetts and Connecticut) have done an excellent job of addressing this deficit ... with a blog, and that blog has some good stuff you might want to check out. These include presentations, videos, and other information so that anyone can see these things, not a privileged few who managed to attend the original event. Among the items they share is presentation from Todd Zion about the SmartCells program (the bad news: human clinical trials are still quite a way off ... Phase 1a clinical trials are not scheduled to begin until Q2 2010). Also, catch my interview with SmartCells' CEO Todd Zion from back in 2007.

I basically lifted almost all of their content in their update from April 2009, but be sure to catch their archives, too -- they contain some good stuff that should make other JDRF chapters look to replicate! FYI, their blog can be found at http://jdrfne.blogspot.com/, and the specific post I'm referring to can be found here, but also be sure to browse through their archives, too -- there's some good stuff there!

JDRF New England Chapter's Tenth Annual Spring Research Briefing
Wednesday, April 22, 2009

The Tenth Annual Spring Research Briefing was held on Monday, April 6, 2009 at the Boston Marriott Newton. The information shared that night was an inspiration and surely proof that our quest for a cure is closer to reality than ever.

We heard from two excellent presenters: Dr. Alan Lewis, JDRF's new President & CEO, and Dr. Todd Zion, Co-founder, President & CEO of SmartCells, Inc. Dr. Lewis introduced himself to the JDRF family in the New England area and shared his perspective of diabetes research currently and his vision of where JDRF can help expedite progress toward a cure. Dr. Zion focused on research being done on a product being developed at his company, SmartInsulin, a once-a-day, glucose-regulated, injectable formulation for treating diabetes.

Following you'll find video and slides of the evening's presentations, as well as video of the question and answer session with our presenters. A special thank you to Victoria Bergantino, Greg Ford, Geoffrey McLaughlin, and April Watkins of Bentley University (Bentley is my alma mater!), and to their professor, Mark Frydenberg, for making this possible!


Tuesday, April 21, 2009
Dr. Alan Lewis, President & CEO, JDRF


Presentation from Dr. Alan Lewis

Presentation from Dr. Alan Lewis

View more presentations from BringingTheCureHome.

Dr. Todd Zion, Co-founder, President & CEO, SmartCells, Inc.
Tuesday, April 21, 2009


Presentation from Dr. Todd Zion

Presentation from Dr. Todd Zion

View more presentations from BringingTheCureHome.

Question and Answer Session


Clinical Trial Initiative

Finally, I should also just include the organization's Clinical Trial Public Service Announcement (PSA) which coincides with a new tool they've added to find type 1 clinical trials.

To find a cure, JDRF needs people with type 1 diabetes to consider participation in human clinical trials of experimental new therapies.

The JDRF Type 1 Diabetes Clinical Trials Connection is here to help people with type 1 diabetes better understand what is involved in participating in a clinical trial, and to simplify the process of finding trials that may be of interest to them or to their family members.

The goal of this service is to serve as a resource on the latest research advances, new research studies, and information about opportunities to participate in clinical trials.

Participating in a clinical trial is an important way for people to help to find a cure for type 1 diabetes and its complications. That's particularly true today, when JDRF's nearly 40 years of research leadership has brought us to the point where scientific advances made in the laboratory are being tested in people.

Clinical Trial PSA (YouTube video):



Conclusion? Some JDRF Chapters Are Donor-Centric, Others Have A Lot of Work to Do

I don't know about all of you, but personally, I'd like to see more of these online initiatives from the JDRF National Organization, not simply an innovative local chapter (I don't have great affinity for the New York City chapter anyway, they've been able to coast for years on their location which enables them to have a walk that raises lots of money on a per capita basis, even though the local chapter is dominated by rich "mommies and daddies" who frankly, don't care much beyond their own social circle, but that's a conversation for another day)!

The $100,000 Diabetes Cure

At a scheduled chat held on Twitter by the Diabetes Social Media Advocacy (DSMA) folks held on Weds., November 3, 2010 (see HERE), one of the topics was related to pharmaceutical companies and social media. There is a great deal of well-deserved skepticism about pharma's über-lusty interest in largely patient-controlled social media space, because right now, they do not engage in much two-way conversation which is at the very heart of what social media is all about (see HERE for more). Presently, pharma is trying to use social media as an advertising channel which does not accept comments, to talk AT patients, not WITH them. Needless to say, this type of communication really does not fly in social media, so most pharma social media efforts have bombed royally. Many claim they do not accept comments to protect adverse reporting which must be directed to the FDA, but many patients suspect that's a cop out because they want the FDA to issue formal guidance that will absolve the industry of any legal liability for what is really little more than common-sense behavior in the social media space. Anyway, in the chat, there were many comments on the theme of how pharma isn't interested in cures, just in selling more product. I commented that I felt the profits in a cure would blow away those earned on selling the next-best-treatment which has pretty much been the diabetes model since the discovery of insulin in 1921.

Conventional wisdom among people with diabetes (PWDs) is that because diabetes is such a huge cash cow for the drug, biotech and medical device companies that this industry (some call it "Dia-Business", the "Diabetes Industry" ... Diabetic Investor David Kliff once even referred to it as the "Diabetes Industrial Complex") that there's no chance of a cure coming from any of these companies who are the biggest financial beneficiaries of keeping patients chronically ill, but never cured. Many just lump all of it together under the collective umbrella of "Big Pharma"), but the idea is that because the industry makes so much money from keeping people with diabetes just well enough to survive, that they are knowingly not pursuing curative therapies. I don't believe this to be true. But before I delve into that, perhaps I should share some relevant historical (that's relative, I'll only go back earlier in the last decade) perspective.

Would You Cure A Profitable Disease?

Back in October 2003, a very popular article by author Dara Mayers entitled "Would You Cure A Profitable Disease?" was published in Diabetes Health magazine (the magazine was still known as "Diabetes Interview" back in those days) explored this topic. The author, Ms. Mayers, tried to be objective, but still suggested that profits were a big dis-incentive to the diabetes industry, thus discouraging at least this segment from actually seeking a cure. She wrote: "Nonetheless, cures for type 1 and type 2 do not seem to be coming from the pharmaceutical industry."

However, that logic is a tad hypocritical (a bit like the pot calling the kettle black), as neither federally-funded researchers, nor researchers funded by non-profits at universities and/or other research centers have managed to find a cure yet, so pharma is in exactly the same boat.

Prospects for drug and biotech companies look very rosy indeed because of demographic growth in the elderly population (which account for about 33% of all drug industry sales anyway, but is expected to grow rapidly as the Baby Boom heads into retirement and their senior years) as well as huge potential for new drugs stemming from discoveries in genomics and biotechnology. There is little doubt that manufacturers have aggressively raised prices to increase their margins, although there is little solid evidence of actual financial benefits to healthcare providers who are footing the bill for their "new and improved" products. That's exactly what has happened with former commody products like insulin. Whether its good or bad is irrelevant; businesses have logically chosen to increase their margins because they have a fiduciary responsibility to do so, and if they can get away with it, why not?

But increasing margins on old products can only work in a non-competitive environment. Pharmaceuticals is already one of the widest-margin U.S. industries, and as long as these companies enjoy monopolies, that can occur. Patent expiration has historically slashed the prices on widely-used medicines.

Now, thanks to The Patient Protection and Affordable Care Act (the so-called healthcare reform legislation sometimes derided by opposition as "Obamacare") which was signed into law by President Obama on March 23, 2010 contains a section called the "Biologics Price Competition and Innovation Act of 2009" (a.k.a. BPCI Act), that's pretty certain to change. That legislation amends the Public Health Service Act, and the Federal Food Drug and Cosmetics Act to create an abbreviated approval pathway for biologic products that are demonstrated to be "highly similar" (biosimilar) to, or "interchangeable" with an FDA-approved biological product. Whether any biologics can EVER be considered "interchangable" remains an unclear, although the FDA has in the past hinted that would not be the case (see HERE).

Regardless, since this is now law, it means the FDA is now obliged by U.S. law to provide guidance for follow-on biopharmaceuticals (generics) inclduing insulin, which has potential to reduce costs significantly, so the era of 10% annual price increases may soon come to an end, especially since the patents on most pricey insulin analogues are due to expire in the next few years (see HERE).

Is Diabetes Too Profitable to Cure?

Aside from fatter profit margins, in the grand scheme of things, when one compares the margins on chronic medicines to those of specialty medicines (think of things like cancer treatments, which are given quite rarely to a relatively small number of patients), the margins are comparatively low on chronic medicines, but much higher on specialty medications like cancer treatments. Thus, if one could transform a disease like diabetes from being a chronic disease to a curable disease, it's safe to presume that a curative medicine(s) would be among the world's biggest blockbusters, making today's blockbusters like Pfizer's Lipitor look pretty miniscule by comparison.

In fact, a diabetes cure (or cures) might possibly be some of the biggest blockbusters the drug and/or biotech industry has ever witnessed. And there is a rapidly growing number of companies whose very business models do not exactly focus on keeping patients chronically ill, but on eradicating their diseases. They haven't succeeded ... yet, but these companies see enormous profits in bringing cures to market.

Finally, the drug industry doesn't hold secret, backroom meetings about how to keep would-be competitors out of their business; they are fiercely competitive with each other, and there are genuine risks that Federal antitrust regulators would step in if they acted in a truly anticompetitive manner, which does serve as a natural control mechanism. It also seems unlikely that any drug company would want to tip off their competitors what they plan or are researching unless it's pretty far along in development and already in the public domain.

To cure type 1 diabetes, the consensus among researchers is that two things need to happen: 1) first, the autoimmune response that caused the disease to occur in the first place must be fixed, creating a state of "self-tolerance" to islets/pancreatic beta cells and 2) second, the functionality of the destroyed islets/pancreatic beta cells must either be replaced with new islets, or restored via regeneration.

There are a variety of companies, many of which are startups, pursuing various parts of this equation. For example, on islet replacement, there are companies who are pursuing xenotransplantation by encapsulating islets from another species (such as pigs, whose insulin is more similar to regular human insulin than some insulin analogues like Novolog, Apidra, Lantus or Levemir based on amino acids and molecular weight). Listed below are a number of companies operating in various spaces in the cure-related therapies (by category).

Islet Replacement Therapies:

Living Cell Technologies (LCT), a publicly-held firm based in New Zealand but listed on the Sydney, Australia stock-exchange.

In addition, others are trying a slightly different route, developing what they are calling Islet Sheet Technologies. Several companies which are not publicly-held firms are pursuing this technology. While it does not appear they are quite as far along as LCT, fellow d-blogger Elizabeth Snouffer did a great piece back in April 2010 about Islet Sheet Technology. Visit her post HERE for more details. Among the firms she writes about are Scott King's (NOT the former editor of Diabetes Health magazine, the OTHER Scott King heading up a firm known as Cerco Medical).

Both involve masking islets to protect the transplanted cells from immune response. The long-term viability is still being researched, but could potentially be replaced without major surgery.

Autoimmunity Treatments:

MacroGenics, Inc. is a publicly-held company based in Rockville, Maryland whose partnership with Eli Lilly & Company, Inc.'s failed to meet it's Phase III trial objectives in October 2010 (see HERE)

Tolerx, Inc. is another firm based in Cambridge, Massachusetts that has a similar, but not identical approach to addressing the autoimmune response that causes type 1 diabetes. Tolerx claims to have a slightly different approach, and was paired with GlaxoSmithKline plc thanks to the JDRF. The company's Phase III human clinical trials are reportedly complete, although the trial results have not yet been released to the public. (Note: in March 2011, Tolerx and GSK ANNOUNCED that otelixizumab had failed to meet its primary efficacy endpoint, although full details will be announced at the American Diabetes Association's Scientific Sessions taking place in June 2011).

Another privately-held firm, DiaKine Therapeutics, Inc. has several products for diabetes in it's development pipeline. On the autoimmunity front is a product known as lisofylline (LSF), which the company describes as a synthetic small molecule with "novel" anti-inflammatory properties that may work in stopping the autoimmune response that causes type 1 diabetes. This is presently in Phase II human clinical trials according to the U.S. Government's ClinicalTrials.gov site, so it has a longer development timeframe than Tolerx's product.

In March 2009, the JDRF announced a partnership on another autoimmunity treatment from Bayhill Therapeutics, Inc. and what was then known as Genentech (now part of Roche). Known by the unglamorous name "BHT-3021" which differs slightly in that it works as an antigen-specific treatment for the insulin molecule itself. However, details on progress have been few and far between on this treatment.

July 2011 Update: Following disappointing results for both the Macrogenics and Tolerx treatments (though the Macrogenics treatment will go back to trials with funding from the National Institutes of Health, suggesting that there may be some evidence that this treatment was not a total failure), in June and July 2011, there were two new autoimmunity partnership deals announced, the first via the JDRF, the second via the Iacocca Foundation. The first one was with a Watertown, Massachusetts-based biotech company named Selecta Biosciences, Inc. for the development of an type 1 diabetes autoimmunity vaccine technology. The other was ANNOUNCED on July 19, 2011 where The Iacocca Family Foundation boosted investment in a Seattle-based biotech firm known as Kineta, Inc. which also has an autoimmunity treatment known by the acronym "ShK-186" in development which is being developed not only for type 1 diabetes, but several other autoimmune diseases as well. For more detail, see the press release HERE.

Islet Regeneration Therapies:

Finally, the companies now pursuing islet regenerative therapies (once dismissed as wishful thinking, but since proven to be not only realistic, but possibly a better alternative to transplantation) are the following different firms:

Transition Therapeutics, Inc., a Toronto (Ontario), Canada-based biotech startup, is a privately-held firm funded by venture capitalists.

Exsulin Corporation based in Burnsville, Minnestota is another privately-held firm that is majority owned by a limited liability corporation (LLC) known as Kinexum, LLC which is based in Harpers Ferry, West Virgina (in the Washington, DC exurbs).

CureDM, Inc., based in Wilmington, Delaware developing a product they call Pancreate™ (proisletide acetate). In April 2010, the firm signed a commercialization agreement with Franco-German global pharmaceutical giant Sanofi Aventis S.A. best known as the maker of Lantus and Apidra insulin analogues.

So Where Are the Cures?

All of this begs the question: where are the cures, then?

This year, one of my favorite medical writers, Sharon Begley, who writes for Newsweek magazine, but previously wrote for such well-known newspapers as The Washington Post and The Wall Street Journal, looked directly at this question.

In the May 15, 2010 issue of Newsweek, the cover story was hers and entitled, appropriately enough "Desperately Seeking Cures", probing into why the road from promising scientific breakthroughs to real-world remedies has become all but a dead-end (those are her words, not mine!).

In fact, she even cited stats from the FDA, stating that from 1996 to 1999, the U.S. Food and Drug Administration approved 157 new drugs. In the comparable period a decade later—that is, from 2006 to 2009—the agency approved 74. Not among them were any cures, or even meaningfully effective treatments, for Alzheimer's disease, lung or pancreatic cancer, Parkinson's disease, Huntington's disease, diabetes or a host of other afflictions that destroy lives.

Her story found several culprits, most notable was the fact that the nation's biomedical funding and training system are set up to do one thing, and she notes that they do that superlatively: make discoveries. Back in 2008, Ms. Begley wrote another story with a similar title, although less in-depth "Where Are the Cures?".

In that article, she wrote "Discoveries is what scientists dream of, that is what gets them published in leading journals (the coin of the realm in academia) and that is what gets them grants from the National Institutes of Health. She added that the less glamorous work of testing potential treatments in actual patients -- the grunt work, as she referred to it, that turns a breakthrough into something that can actually be tried in patients is seldom on their academic agenda. That responsibility falls elsewhere, and helps explain why so much money is spent yet few cures ever seem to emerge from the billions we spend.

Patent Problems

Another factor: the nation's patent system, which tends to reject applications that are already published in scientific and medical journals that helps researchers advance their own careers, and without patent protection, hardly any drug or biotech company would be interested.

Then there is a not-so-little matter of licensing discoveries from NIH-funded research; sometimes startup firms see potential in these discoveries, but cannot afford big upfront payments that a big drug company like Pfizer or Lilly could afford, and the NIH has been asking as if all companies had Pfizer's pockets.

"NIH has no skin in the game, so they have no inducement to work with a company" to get a discovery from the lab to patients, says Eric Gulve, president of BioGenerator, a nonprofit in St. Louis that advises and provides seed money for biotech startups. "There isn't a sense of urgency." A top lab chief at the NIH laments that when scientists like himself push the licensing office to move a discovery toward commercialization, "it's just another piece of paper to them." Without the license, the startup struggles to stay alive.

The Role of Nonprofits

Of course, Ms. Begley did mention how an increasing numbers of nonprofit organizations are trying to fund the next steps in "translational research". Among them is a big one in type 1 diabetes research: the Juvenile Diabetes Research Foundation (JDRF). Increasingly, nonprofits like JDRF are stepping in to fund the research needed to take promising concepts from discovery to commercialization, filling a badly-needed void.

In fact, Ms. Begley wrote an entire article on that very subject back when she was still writing for The Wall Street Journal back in 2007 entitled "Why Nonprofits Fund For-Profit Companies Doing Drug Research" in which the JDRF along with others like the Michael J. Fox Foundation for Parkinson's Research, and the Myelin Repair Foundation (for multiple sclerosis) who have all veered away from the NIH model of "here's some money; go discover something."

Instead, these organizations are managing and directing scientists more closely, requiring them to share data before it is published, cooperate, and do the nonsexy development work required after a discovery is made. But it isn't always popular to do so. In the 2007 Wall Street Journal article very clearly acknowledged that:

"Charities realize that writing checks to for-profits might not be what their donors had in mind. 'We debated whether it was right for our money to go to a company that might make a profit,' says JDRF board member Michael White. 'We're not unconcerned about that. But we've invested so much in discovery, what we need now is to take these things to market. We're taking on the role of 'venture philanthropists.'"

And not all of these investments will even pay off; for a very relavant example, as already noted, on October 20, 2010, MacroGenics, Inc. and it's big pharma partner, Eli Lilly and Company announced that a potential autoimmunity treatment called teplizumab, whose Phase III human clinical trial called Protégé, did NOT meet the primary efficacy endpoint of the study, which was a composite of a patient's total daily insulin usage and HbA1c level at 12 months (see HERE for more detail). A similar treatment from a startup called Tolerx and it's big pharma partner (thanks to the JDRF's involvement) GlaxoSmithKline remains upbeat about their own treatment, called otelixizumab, is wrapping up analysis of it's own Phase III human clinical trial called DEFEND.

One key unresolved pitfall Sharon Begley wrote about: "blockbuster-itis" in the drug industry, but it appears that experience may have taught non-profits how to prevent pharma "blockbuster-itis" from killing the goose that lays the golden cure egg.

Egg on the JDRF's Face?

Occasionally, the big pharma company will do something that really p!$$es their nonprofit "partner" off in their relentless drive for fat profits. In one JDRF program for islet regeneration efforts, the Toronto-based biotech startup known as Transition Therapeutics, which JDRF partnered with Eli Lilly & Company, did see fairly solid evidence of efficacy of it's gastrin-based therapies in patients with both type 1 diabetes as well as type 2 diabetes.

But then big-pharma partner Eli Lilly & Company decided to push clinical trials towards type 2 diabetes and cancelling the type 1 trials, theorizing that it could potentially sell the product to far more type 2's than patients with type 1, thus increasing the company's bottom line faster. The company likely assumed if is eventually approved for that indication, then they could then move to "extend" the drug's label approval to type 1 patients, albeit that could take many years more, which was not quite what the JDRF had in mind when pairing these organizations together. In fact, JDRF had invested fundraiser dollars in the program only to see clinical trials in type 1 patients cancelled by a greedy pharma partner.

Social Media Pushes for Greater Transparency

Of course, things were easier before patient-bloggers hit the scene. For example, last autumn (2009), fellow diabetes blogger Joshua Levy and I speculated on what Lilly's move meant as trial results for Transition Therapeutics treatment known as TT-223 and the fact that they pulled the plug on the type 1 trial. I actually wrote about it in my mid-year progress report. Bill Ahearn is the Vice President, Strategic Communications for JDRF International went so far as to contact Joshua Levy in the comments on his blog about the Transition Therapeutics approach, while I received an e-mail from another JDRF staffer with very similar comments. Had this occurred a decade ago, the organization might have controlled the dialog either by ignoring it and allowing it to pass, or with carefully-scripted press releases. But it became a public relations disaster for the organization, and patient bloggers effectively forced the JDRF to confront it head-on, as these things had gone viral, hence the response.

To be sure, there is no prior, proven pathway for "venture philanthropists" as JDRF called themselves (in Ms. Begley's 2007 Wall Street Journal article), so one can call this a training exercise for JDRF's Industry Discovery and Development Partnerships (IDDP) program. No doubt, the JDRF was embarrassed by Lilly's move and had to do damage control as a result. But this move demonstrates the power that the social media space (including patient bloggers) has had on even nonprofit organizations. Although the investment was reportedly relatively small and Lilly's interest in the treatment (especially now that the company faces a "patent cliff") could bring it to market, where it could then be researched "off-label" in the type 1 universe, thereby saving Lilly millions. If it does not gain approval for type 2 diabetes, that does not necessarily mean the drug would be dead, either (although Lilly might loose interest by then) forcing the JDRF to find a new pharmaceutical partner.

One thing is certain: JDRF probably learned it's lesson from this experience. In recent IDDP announcements, virtually all require the partners to meet key milestones before the organization pays any more. This may prevent another of the TT-223 fiasco from occurring on the organization's dime in the future.

Be Prepared to Mortgage Your House for a Cure

In 2008, diabetes writer David Mendosa INTERVIEWED Zoe Heinenman Myers, the vice president of marketing for the company now known as Exsulin (it was known as Kinexum Metabolics at that time), and then at length with Lisa Jansa, the company's new CEO about where this interesting treatment stood. David asked numerous questions that would be of interest to patients with diabetes. But the element that really stood out in my mind was the following quote, which was taken from PAGE 3 of the story:

"Something as big as INGAP won't come cheap. 'We don't anticipate that it will exceed $20,000 for a single course of treatment,' Lisa [Jansa, CEO of Exsulin] told me. Later, however, she is confident that as they scale up production they will be able to bring the cost down."

Exsulin also told David Mendosa that the company was not certain if periodic re-treatments might be required, something that current clinical trials may answer. Perhaps with an effective autoimmunity treatment, that need would be eliminated. Right now, we simply do not know the answers to these questions. This is why the term "remission" has become favored by the medical profession over using the term "cure". As former New York Yankees player and manager Yogi Berra once famously said "It ain't over till it's over." But regenerating islets solves only half the type 1 diabetes puzzle; the autoimmunity issue must also be solved, so its possible that the cost of a cure could easily be in the $100,000 range, including any periodically necessary re-treatments for either (or both) components.

All of this makes me wonder: will we see an asset-backed securities market emerge for diabetes cures (maybe as "Cure-Backed Securities?"), and how much will for-profit insurance companies be willing to pay for? What if that market works anything like Fannie Mae and Freddie Mac?

It seems clear that the margins on any curative therapies are destined to become blockbusters, which means the drug industry's own desire for billion-dollar products may push even more of them into the high-margin cure therapies, rather simply more than new-and-improved versions of lower-margin century-old products, and follow-on biologics will undoubtedly help. We have already seen Lilly, Sanofi Aventis and others partner with startups in curative therapies. It appears that non-profits like the JDRF's experience with Lilly and Transition Therapeutics means the days of writing checks without milestones being met required of pharma partners are permanently over, and not a moment too soon!

2009 Mid-Year Progress Report: Part 1

At the end of 2008, I didn't do my annual review of the diabetes cure-advancement and treatment landscape (you can catch my 2007 summary, my 2006 summary and my 2005 summary), a tradition I began in early 2006 and continued for several years afterwords where I highlight some of the diabetes-related developments (from my perspective, naturally) during the preceding year and share my thoughts and insight into the coming year. Most of my readers know that my observations are far from casual, they are based on a thorough review of these trends for the past year (often more) and have a solid basis to substantiate them. Since we're now more than 3/4 into 2009, there's little point in trying to recap last year, as we'll be ready for a recap of 2009 in just a few months! But I can provide some perspective on where things stand right now, and perhaps frame where they're likely to be going in the foreseeable future.

Let me begin by saying that I had a very good reason for not writing a summary of 2008. I was in the process of moving into a new place. But United Moving didn't do the work for me, I did the move mostly by myself, and mostly when I had free time (meaning on the weekends and evenings). Of course, I still had a job to occupy my time during normal business hours. That resulted in blogging taking a back seat. Although I've since resumed, I haven't posted quite as often as I did, say, in 2005 or 2006 because the Diabetes OC community has grown so much since then that having thoughtful and unique content becomes more important today. Not all of my posts are the cheery, uplifting ones that some readers are necessarily seeking (that's never really been my focus or specialty ... there are plenty of others to fill that need, however), but from my perspective, I DO believe there is good news on cure-related progress to share. The challenge: where do I begin?

Some Good Sources for Research Progress Updates

First, let me share some places you might wish to be aware of related to progress reports. Ironically, I discovered these not from the JDRF website, but largely by accident. But this stuff is worthy enough of sharing with others -- the JDRF "shareholders"!!!

A while back, I have mentioned the Juvenile Diabetes Research Foundation (JDRF) New England project/blog, which had some very interesting presentations from their annual update near Boston this year. In fact, I lifted some of the New England chapter content and inserted it into my aforementioned blog posting. However, a few days ago, I received my college alma matter's alumni bulletin (the Bentley University Observer, page 12, although I found it took a long time to download). Anyway, that contained an interesting article I wanted to share with everyone (I scanned it, and you can download only that page/article here). Apparently, some faculty and students from Bentley were asked by the Bay State branch of the JDRF New England chapter to help create some online audio and video content for that particular blog. As might be expected, the article notes that the JDRF New England chapter's blog has since been recognized by other chapters throughout the U.S. and as an example of JDRF "best practices". We can certainly hope to see more of this type of stuff from JDRF's national organization in the future, and possibly other chapters following this lead, so that's good news indeed!

While some of my blogging peers (Kerri Morrone-Sparling of SixUntilMe.com, Manny Hernandez of TuDiabetes.com and a few others) have already joined, in 2006, JDRF's National organization evidently established a YouTube channel which anyone can join and follow at http://www.youtube.com/user/jdrfonline. That was done without much fanfare, but they've been better about putting some video content which is available to everyone (I don't find the TV commercials all that interesting, but some of the other stuff is).

Now, I could be mistaken, but the photo of the person on this YouTube channel appears to be Aaron Kowalski, who is perhaps best known for his work behind the "artificial pancreas" project, but has also been involved in the SmartCells/SmartInsulin deal signed last year. Anyway, the YouTube channel has some videos from JDRF's 2009 Annual Research Roundtable which took place in June 2009, including a short speech by international chairwoman Mary Tyler Moore, the new CEO Alan Lewis' 2009 State of the Foundation Address, and one from Dr. Richard Insel who is the Executive Vice President of Research for the organization. To the best of my knowledge, this is the first year that JDRF has featured videos of these speeches and presentations. I hope to see much more of this stuff in the future, but this is indicative of progress being made, although much of the work began under previous CEO Arnold W. Donald.

Finally, I would share a blogger who is relatively new to the diabetes blogging scene, Joshua Levy. He started a blog last June which can be found at http://cureresearch4type1diabetes.blogspot.com/. I knew of Josh, who has type 1 diabetes himself, from the Islet Foundation's Public Message Forum, and he is also a member of the Nathan-Faustman Yahoo! Group. Anyway, in the past, I followed his updates via an RSS feed of his Wiki updates/changes which alerted me of changes to his website related to diabetes. But his blog has some groundbreaking content, with the next item listed being a case-in-point.

JDRF-Backed Transition Therapeutics' Islet Regeneration Treatment Looks Dead for Type 1, Perhaps Not for Type 2

I generally share Josh's outlook and his definition of a cure, and although I don't always agree with everything he concludes, I'd say that 95% of the time, I do. Often, Josh has some observations which are well ahead of the public statements made by the JDRF or the researchers (not ALL research is funded by JDRF, even though much is). For example, he concluded (and I agree with him) that the JDRF's Transition Therapeutics islet regeneration treatment (based on gastrin, as Alan Lewis talks about) looks dead, at least for people with type 1 diabetes. See his posting here for more on that. Note that JDRF's 2009 Annual Update (which took place this summer) was still talking about this treatment, but as Josh writes:

"Transition Therapeutics is researching using a combination of two drugs to cause beta cell regrowth in an attempt to cure type-1 and type-2 diabetes. As of May 2009, they had officially marked their phase-I human trial for type-1 diabetes as closed. I haven't seen any published results for it, but I'm still looking. However, actions speak louder than words, and Eli Lilly (working with Transition Therapeutics) started a clinical trial in February 2009 using Transition Therapeutics's TT-223 product, but only for people with type-2 diabetes.

Also, in May 2009 they announced that JDRF and Transition Therapeutics had agreed that JDRF would stop funding clinical development of TT-223. Transition Therapeutics and JDRF terminated their agreement. Eli Lilly is taking over support for TT-223, but is applying the technology only to type-2 diabetes.

So the news from Transition Therapeutics for type-1 diabetics is not good. I will move Transition Therapeutics to my 'boneyard' of research that has not panned out if there is no good news in the next 6 months."

So far, JDRF has been pretty quiet about their decision to stop funding Transition Therapeutics, but unless something changes, we can probably conclude it is dead (at least for type 1 diabetes). For those interested in more background on this, and perhaps its applicability towards type 2, catch a video here for more details.

Exsulin Is Still Progressing

Not to worry on the regeneration front (at least not yet!), however, Exsulin Corp. (the name given to the treatment formerly known as INGAP) announced it's regeneration treatment is entering a second Phase 2 human clinical trial in people with type 1 diabetes (see here and here), so even if JDRF isn't behind this particular treatment, the progress will continue. The good news is that Dr. G. Alexander Fleming, Kinexum's CEO (and former Chair of professional education and training for FDA's Center for Drug Evaluation & Research [CDER] among other things), which is the company behind Exsulin Corp., is among the brightest people in diabetes research and knows this subject far better than most, as he also has intimate knowledge of the Food and Drug Administration, and can therefore help maneuver through this dysfunctional regulatory agency better than perhaps almost anyone else, so we can expect to hear more news from Exsulin in the coming year.

Before I get too far, though, let me take a step back and note that before we can get to regeneration (that's a separate topic I'll address in another blog posting I'll put in Part 2 or 3 of this subject), we need to acknowledge the not-so-little problem of autoimmunity, for which there are several possible treatments in various stages of clinical trials.

Consensus on What Will Be Required to Cure Type 1 Diabetes

Let me begin by acknowledging something that the consensus among most diabetes "experts" seems to be that a definitive therapeutic approach to a "cure" for diabetes will have to include a treatment(s) to control the autoimmune response that causes type 1 diabetes (T1DM) combined with another treatment(s) to replace and/or restore lost pancreatic beta cells, and in the case of type 2 diabetes, another treatment to also address the underlying metabolic defects as well. As a well-known diabetes (she's actually an immunologist) researcher, Dr. Denise Faustman, suggested in an interview with dLife (towards the end of the interview), that she expects it to be entirely possible for several autoimmunity "cures" to emerge although she declined to speculate on when such treatments might emerge. But we're closer today than we have been in decades!

First, I should begin by noting that the JDRF has a graphically-rich page on it's website dedicated to biotechnology and pharmaceutical "Industry Development and Industry Partnerships" that has updates on cure therapeutics which I highly recommend visiting: (click on the JDRF website and from there, select the "research" tab, and select "Industry Partnerships" or simply see click here. Because JDRF has an unfortunate habit of reorganizing it's website leaving some of its links dead, I felt it was useful to provide more detail than I have in the past).

First and foremost, on the autoimmunity front, inflammation is hot!

It's no secret that the drug industry is in the doldrums these days, with many blockbusters whose patents are due to expire soon and nothing much in the pipelines to replace these cash cow blockbusters. But one therapeutic area which seems to very hot these days is in drugs and biotech medicines to treat "inflammation".

Merriam-Webster defines the medical term "inflammation" as "a local response to cellular injury that is marked by capillary dilatation, leukocytic infiltration, redness, heat, pain, swelling, and often loss of function and that serves as a mechanism initiating the elimination of noxious agents and of damaged tissue."

In short, it's an immune response by the body used to heal infections or other ailments. Under normal circumstances, inflammation serves a protective purpose, so it should not necessarily be viewed as a bad thing. Inflammation helps to rid the body of infections and to heal itself, but too much of anything can have the opposite effect, having a destructive rather than protective effect. Both type 1 and type 2 diabetes have inflammation issues which lead to beta cell destruction, although the origins for inflammation in each disease is apparently quite different, as more recent research seems to suggest. At present, approved treatments for inflammation in each disease are mostly non-existent except for a few ailments such as cancer, although others for different autoimmune diseases have also started to emerge. Several aimed at addressing type 1 diabetes are in various stages in development.

Historically, the medical profession has treated most forms of inflammation the same way. The term "anti-inflammatory" usually refers to the property of a substance or treatment that reduces inflammation. In fact, anti-inflammatory drugs make up about half of all analgesics sold (including many over-the-counter products), remedying pain by reducing inflammation as opposed to opioids which affect the brain. Among the more common, over-the-counter ones are ibuprofin (brand names include Advil and Motrin) and naproxen sodium (brand name Aleve).

But this approach, to use a metaphor, is akin to sending out an entire army (using immunosuppresant drugs that largely shut the entire immune system down) to do the job that a single soldier with highly specialized skills could have done alone, and it also leaves patients prone to infections and other illnesses because the effectiveness of their own immune system has been reduced.

During the late 1980's and 1990's, newer research revealed that we could selectively target certain leukocytes (white blood cells) that caused specific types of cancer. The result was a gold mine for the drug and biotech industries, with extremely costly (and lucrative) medicines which seemed to work wonders for a handful of patients as well the bottom line of drug/biotech companies alike! But that business model has run into limits of governments and healthcare providers worldwide and their willingness to pay outrageous sums of money to save a mere handful of ill patients with specialized cancers. Like it or not, one might call this a form of performance-based medicine.

Certainly, an immunologic intervention resulting in an effective modification of the underlying immune process could potentially interfere with the etiology of an autoimmune disease and thereby preserve beta cell function, and/or set the stage for successful beta cell regeneration and/or replacement, or both. Ideally, immunotherapy offered to type 1 diabetes patients could be aimed selectively at salvaging the remaining beta cell mass (if any exists), while also creating a state of "immune tolerance" for the insulin-producing beta cells as immunologists refer to it. (The term "immune tolerance" collectively refers to the safeguards that the immune system naturally possesses to protect from harming self.)

A Newer Approach to Immune Tolerance

In contrast to immunosuppressant therapies which essentially shut the immune system down, immune tolerance therapies are designed to work in a different way. Rather than suppressing the immune system as a whole, these newer treatments aim to suppress only those parts of the immune system responsible for the autoimmune attack (or perhaps prevent it in the first place). The goal is to stop the autoimmune disease while leaving the body's infection and disease-fighting abilities intact.

Although a variety of approaches to immune tolerance have been successful in rodent (or even in some larger animal) models of autoimmune diseases, or in pilot clinical studies, to date, the achievements in larger human clinical trials have been rather modest. Researchers have learned that the similarities between mouse and human immune systems are pretty limited.

But according to the NIH Autoimmune Diseases Coordinating Committee, the range of potential therapeutic approaches available to treat autoimmune disease is expected to expand rapidly during the next decade as a consequence of progress in genetic and immunologic research conducted in the public and private sectors. These therapies are likely to include drugs, biologic agents, gene-based delivery systems, immunomodulation, cell-based treatments, tissue and organ engineering procedures, as well as therapies based on complementary and alternative medicine.

I've shown the following chart many times, but I use it for a reason: 2010 is the estimated time that some of the newer autoimmune treatments are expected to emerge, with more likely in the following years.



The question is if this is more of a retrospective look with a short window into the coming years, where is the future headed?

Here's where my references to some past efforts comes in. For example, in June 2009, I reported on some progress the JDRF had made with it's Industry Discovery and Development Partnership (IDDP) program (see here), whereby JDRF provides early-stage research funding to drug and/or biotech companies working on technologies and therapeutic candidates in an effort to provide incentives to more risk-averse drug and biotech companies to help commercialize products that would help facilitate JDRF's cure-related goals.

As a result of the trends noted above, a more mass-market approach to treatment seems to be taking place now. The basic idea is that these treatments will be delivered to a larger audience, but in order to do this, the costs must come down significantly. As a result, some are testing meds that were tried and approved for one condition to test their applicability in others. More recently, drug companies have engaged in trials to try and expand the market on certain existing drugs (for example, Gleevec, a drug that treats leukemia and other cancers) is reportedly being tested to treat the autoimmune response that causes type 1 diabetes in recently-diagnosed patients, and more recently, trials were announced to examine the use of several Rheumatoid Arthritis drugs such as Embrel, Remicaid, and Humira to see if they might also work in type 1 diabetes, not to mention other autoimmune diseases. It is very tempting to believe that one drug might treat another autoimmune disease, but as researchers have learned the hard way in the case of Lupus, that some drugs actually made the disease worse, not better. But the basic idea is that by ramping up production by leaving production up to drug and biotechnology companies, the cost can be brought down enough to make these drugs cheaper while also enriching biotech and drug companies by making their drugs applicable towards other types of autoimmune diseases. I could talk about each of these, but the reality is that right now, they're all in various stages of clinical trials. None is ready to address type 1 diabetes autoimmunity, but these could emerge in the coming years.

Autoimmunity "Cures" are Closer, But Not Likely Around the Corner

One of Josh Levy's postings summarizes some possible autoimmunity treatments in late-stage clinical trials. However, he includes some which aren't being tested with JDRF's help. To give you some idea of just how far along these are, consider that the following 4 programs are all now in Phase III Human Clinical Trials (note that there are a number of others in Phase I or Phase II Human Clinical Trials which I haven't even addressed here):

* Diamyd's GAD65 (several different studies; note: Josh considers this which is being trialed as a vaccine to be an autoimmunity treatment, I am not convinced yet, but let's see where it goes!)
* TolerRx/GlaxoSmithKline's CD3 (several different studies)
* MacroGenics/Eli Lilly's CD3 (several different studies)
* Teva/Andromeda Biotech's DiaPep227

He states "Now, make no mistake, these trials do not (emphasis mine) mean a cure is right around the corner." I'll borrow Josh's comment because he said it as well as I could:

"It is important to remember, however, that although there are four treatments in Phase-III trials, we are not close to a cure or established type 1 diabetes. All of the clinical trials in Phase-III and Phase-II are targeted at honeymoon type 1 diabetes; none at established cases. Even with that restriction. None of the treatments in Phase-III trials resulted in cures during their Phase-II trials. They all extended or increased the honeymoon phase in some way."

However, while his caveats are important to keep in mind, they DO demonstrate the type of quantifiable progress that has been lacking for a very long time on the autoimmunity front, and do suggest that quantifiable progress is being made (the same could NOT be said as recently as a decade ago).

A case-in-point: MacroGenics/Eli Lilly's teplizumab treatment is not without adverse events, no matter how glowing some reports may be. For example, a friend of mine who attended the Children With Diabetes Friends For Life Conference in Orlando this year said "Dr. Harlan from NIH wisely pointed out at CWD FFL that the anti-cd3 drugs can cause recurrent mononucleosis which can increase one's propensity to develop lymphoma. Why would someone put their child at risk for that simply for a year and a half of extended honeymoon?"

As I responded, "The issue is that they first seek approval on newly-diagnosed patients for anti CD-3 treatments, and then, will ultimately extend it to others, possibly long-standing T1DM patients if past drug approval history is any guide. This remains an area of discovery, and I suspect, we'll find that some treatments work for certain patients, while others will not. Of course, no one seems to question using Lantus (insulin glargine rDNA origin), a completely man-made creation for an entire lifetime which also has proven mitogenic effects, which I also find questionable for a relatively small improvement in HbA1c ... that logic also escapes me, but I am one of the few who seems to question this." At least there has finally been some attention paid to this, although most Lantus supporters cannot seem to be convinced otherwise, and most seem to make excuses for the technology rather than acknowledging the legitimacy of the question. That's a separate conversation, however.

Ultimately, what is likely to come out of the different autoimmunity-related trials is more refinement and perhaps better definitions on just which patients each treatment is likely to work, and perhaps improvements to these, with more similar types of treatments to follow. Also, hopefully, the adverse events from the early autoimmunity treatments can hopefully be reduced and/or eliminated.

I will follow-up on this Progress Report with a Part 2 in the coming months which will address another part of the cure equation (perhaps regeneration or replacement of insulin-producing beta cells), so be sure to check back!