Multiple Sclerosis: A Message to Ann Romney

Dear Ms. Romney,

Yesterday, I read Jennifer Rubin's "Right Turn" blog in The Washington Post, entitled "Ann Romney on her husband and the race, the second time around" (http://www.washingtonpost.com/blogs/right-turn/post/ann-romney-on-her-husband-and-the-race-the-second-time-around/2012/01/02/gIQA3l3gWP_blog.html), in which Ms. Rubin described her telephone interview with you. I was impressed by your wisdom and political maturity, as best exemplified by your declaration:

“We understand there are a lot of things that are out of our control. We are who we are.”

Ms. Rubin also alluded in her column to your observations regarding your ongoing struggle with multiple sclerosis:

"But of course her own health issues provide a constant connection to voters. She said that on the campaign trail, 'Everywhere I go people come up asking about MS.' As first lady, she would 'have a huge concern about bringing attention to and provide funding to find a cure for MS.'"

I would like to bring to your attention the efforts of an Israeli biotechnology company named Compugen, a world leader in the predictive computerized discovery of new therapeutics, which specializes in the fields of immunology and oncology. In October 2011, Compugen participated in the 2nd International Conference on Immune Tolerance in Amsterdam, during which Joseph Podojil, Ph.D. of the Feinberg School of Medicine Northwestern University, presented for the first time scientific data pertaining to CGEN-15001. CGEN-15001 is a novel protein drug candidate consisting of the extracellular region of CGEN-15001T, a previously unknown membrane protein predicted by Compugen to be a member of the B7/CD28-family, fused to a mouse antibody Fc domain. At that time, Compugen reported in a press release (http://www.cgen.com/Content.aspx?Page=press_releases&NewsId=571):

"Dr. Podojil presented data demonstrating that administration of CGEN-15001 in the experimental autoimmune encephalitis (EAE) animal model of multiple sclerosis (MS) resulted in a dramatic improvement of disease symptoms and abolishment of spontaneous relapses. In addition, the study results demonstrated that short-term treatment with CGEN-15001 led to long-term inhibition of disease symptoms as well as of the underlying spread of pathological immune responses."

In short, although there can be no certainty that CGEN-15001 or any of the other B7/CD28-like proteins discovered through use of Compugen’s Protein Family Members Discovery Platform will ultimately result in a cure for MS, the preclinical results for CGEN-15001 as well as for CGEN-15021 and CGEN-15091 (see: http://www.cgen.com/Content.aspx?Page=press_releases&NewsId=562) certainly provide hope.

Should you need additional information concerning Compugen's efforts, do not hesitate to contact me.

Meanwhile, please stay healthy as you and your husband navigate the trials and tribulations of the Republican primaries. I admire your courage.

Best,
Jeffrey

[As noted in prior blog entries, I am a Compugen shareholder, this blog entry is not a recommendation to buy or sell Compugen shares, and in September 2009 I began work as a part-time external consultant to Compugen. The opinions expressed herein are mine and are based on publicly available information. This blog entry has not been authorized, approved or reviewed prior to posting by Compugen.]

Maureen Dowd, "She Made Me Run!": Sorry, Maureen, But Mitt Is No Flip-Flopper in Bed

I am not enamored of the lackluster crop of Republican presidential candidates. I would have been happier if Mitch Daniels, Paul Ryan and Chris Christie had all thrown their hats in the ring. And in my humble opinion, there are those past and present candidates, including Donald Trump, Herman Cain and Newt Gingrich, who have embarrassed themselves by suggesting that they are fit to serve as chief executive of the United States. However, Maureen Dowd stepped over the line by casting aspersions on the commitment of Ann Romney, Mitt's wife, who suffers from MS, to her husband's candidacy.

In her latest New York Times op-ed entitled "She Made Me Run!" (http://www.nytimes.com/2012/01/01/opinion/sunday/dowd-she-made-me-run.html?_r=1), Maureen Dowd writes of Mrs. Romney:

"At Iowa campaign stops, the elegant Ann introduces her husband by describing how steadfast he has been as she fought her disease. In the post-Elizabeth Edwards age, candidates can’t risk looking as if they are placing their ambition ahead of a spouse’s health. So it’s a calculation for Romney’s image that Ann be seen as a driving force rather than a victim."

Dowd then pokes fun at Callista Gingrich, whose "stubbornness" is purportedly keeping Newt in the race, and mocks Donald Trump's current wife, Melania, who seems to be claiming that America hungers for Donald as president, before concluding:

"You don’t become president without clawing your way into the Oval Office, but voters prefer pols like J.F.K., Ronald Reagan and Barack Obama who wear their ambition lightly.

The key to ambition is the ability to cloak it. Better yet, attribute it to your wife."

Personally, I find the juxtaposition of Mitt Romney's mariage with the turbulent matrimonial relationships of Newt Gingrich, Donald Trump and John Edwards to be inapt to say the least. Although Mitt has been accused of being a flip-flopper, no one has questioned his commitment to his wife.

Moreover, given the debilitating effects of MS, there is no doubt in my mind that Ann Romney is indeed devoted to her husband's candidacy. Should she become First Lady, her physical suffering will be placed front and center before the nation, and her fortitude and dedication are only to be commended.

In her prior op-ed, Dowd highlighted the courage of her brother, Kevin, a cancer survivor. Today, however, she would make light of the hardship of those suffering from MS. Sorry, Maureen, but this is an instance where Ann and Mitt Romney deserve our admiration.

CGEN-15001, Predictive Discovery and the Choice Facing Big Pharma

In recent months, Israeli drug discovery company Compugen has issued two press releases concerning a new therapeutic drug candidate, CGEN-15001, targeting multiple sclerosis ("MS") and other autoimmune diseases. As stated by Compugen in its July press release:

"[A]dministration of CGEN-15001 in an animal model of multiple sclerosis (MS) has been shown to completely abolish spontaneous relapses. In addition, administration of this novel molecule prior to disease onset demonstrated a pronounced delay of disease onset and a significant decrease in disease symptoms. These results, together with complementary results from earlier studies, strongly support a significant potential therapeutic utility for CGEN-15001 in the treatment of multiple sclerosis and other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes."

http://www.cgen.com/Content.aspx?Page=press_releases&NewsId=498

Although there can be no assurances whether these very early stage, preclinical results will ultimately translate into a new drug destined to alleviate the symptoms and suffering associated with MS and other autoimmune diseases, Compugen, in my opinion, has nevertheless achieved something quite remarkable:

• Compugen predicted and verified the existence of CGEN-15001T, a heretofore unknown member of the B7/CD28 protein family, which has been intensively picked over in the search for immune regulation candidates.
• CGEN-15001T in and of itself constitutes a promising antibody therapeutics target for cancer.
• The discovery of CGEN-15001T promptly led to the identification by Compugen of CGEN-15001, a soluble recombinant fusion protein comprised of the extracellular region of CGEN-15001T, which, as reported in the above Compugen press release, underwent testing in an animal model of MS.

As commonly known, autoimmune diseases entail the body attacking its own cells, and treatment usually consists of drugs intended to weaken the body's immune response with all the attendant dangers. Compugen, however, has stated that CGEN-15001 is expected to be devoid of general immunosuppressive effects and therefore have a decreased risk of opportunistic infections. How is this possible?

CGEN-15001 is thought to act as a "negative costimulator", and like other negative costimulators, it is thought to target tolerance breakdown, i.e. eliminate activated autoreactive cells and directly block the deleterious effects of self-reactive immune cell function in autoimmune diseases. This anticipated specificity, which does not target the B7/CD28 pathway, is expected to eliminate general immunosuppressive effects.

Equally remarkable, as reported in Compugen's July press release, Professor Stephen Miller of Northwestern University has stated with respect to CGEN-15001:

"These studies have also demonstrated that CGEN-15001 has the unique ability to inhibit proliferation, differentiation, and cytokine production of pro-inflammatory Th1 and Th17 responses while at the same time sparing or actually promoting regulatory Th2-derived cytokines. As far as I am aware, this potentially very beneficial pattern of inhibiting Th1/Th17 while promoting Th2 responses is unique among the reagents targeting the B7 family of co-stimulatory molecules that have been published to date.”

Shifting from a Th1 to a Th2 immune response would clearly prove beneficial in MS and other autoimmune diseases, since Th2 cells limit the proliferation of Th1/Th17 autoreactive pro-inflammatory cells and thereby protect the central nervous system.

But what about the bigger picture? Quite apart from their modes of action, the discoveries of CGEN-15001T and CGEN-15001 amount to powerful validation of the coming of age of predictive discovery. How is Big Pharma to react?

Obviously, there will be those R&D departments that feel threatened by this new science, capable of rendering their methodology, built over the course of decades at a cost of hundreds of millions of dollars, anachronistic. These departments will rejoice at any perceived failure or shortcoming involving the new science.

Other R&D departments, however, will embrace predictive discovery and seek out new modes of collaboration, particularly involving their cutting-edge testing capabilities.

In my opinion it's ultimately going to come down to a matter of accepting the inevitable, and those organizations willing to adapt to the rigors of predictive discovery are most likely destined to succeed.

[As noted in prior blog entries, I am a Compugen shareholder, this blog entry is not a recommendation to buy or sell Compugen shares, and in mid-September 2009 I began work as a part-time external consultant to Compugen. The opinions expressed herein are mine and are based on publicly available information. This blog entry has not been authorized or approved by Compugen.]

No Genomics Revolution? Compugen's Answer

Recently we have witnessed a profusion of reports that despite billions of dollars spent on genomics research, it has failed to yield the bountiful harvest of medicines and diagnostics that had been anticipated following completion of the first draft of the Human Genome Project (see, for example: http://www.nytimes.com/2010/06/13/health/research/13genome.html?hp; http://www.nytimes.com/2010/06/15/business/15genome.html; http://www.nytimes.com/2010/06/21/opinion/21mon2.html?ref=editorials).

In an earlier blog entry, I took issue with this conclusion (see: http://jgcaesarea.blogspot.com/2010/06/decade-later-genetic-map-yields-few-new.html). The science underlying human disease may be far more complicated than originally thought, and the "mere" mapping of the human genome is plainly insufficient to provide the next generation of drugs, but as evidenced by the lonely pioneering efforts of a tiny company named Compugen, I believe that genomics is essential to the future of medicine.

Compugen has spent the past decade engaged in computerized modeling of biological phenomena at the molecular level, giving rise, inter alia, to proprietary maps of the human proteome (all of the proteins in the human body) and peptidome (all of the peptides in the human body). Compugen's 12 predictive discovery platforms, with more on the way, have already yielded multiple new drug and diagnostic candidates predicted in silico, i.e. by Compugen's computers, to validate these platforms, without the need for inefficient trial and error methodology.

How many of you have a friend or family member suffering from multiple sclerosis? Almost all of us know someone who has fallen victim to this devastating disease. I think Compugen's announcement of today's date, describing the in vivo testing of a heretofore unknown protein predicted and discovered by Compugen, speaks for itself:

"Compugen . . . announced today that administration of CGEN-15001 in an animal model of multiple sclerosis (MS) has been shown to completely abolish spontaneous relapses. In addition, administration of this novel molecule prior to disease onset demonstrated a pronounced delay of disease onset and a significant decrease in disease symptoms. These results, together with complementary results from earlier studies, strongly support a significant potential therapeutic utility for CGEN-15001 in the treatment of multiple sclerosis and other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes.

* * * *

Professor Stephen Miller from Northwestern University, a leading scientist in this field who supervised the studies, stated, 'The capacity of CGEN-15001 to prevent the development of disease in this well-recognized animal model for multiple sclerosis, and more significantly to ameliorate its progression when administered in the presence of pre-existing disease is quite dramatic. Furthermore, these beneficial effects were shown to be long lasting and persisted through the study, indicating that CGEN-15001 may prevent disease progression as efficiently as immune tolerance induction, a process whereby the immune system no longer attacks the self antigens that cause the disease. These findings, together with those demonstrated in our earlier studies, are unique among the molecules targeting the B7 family of co-stimulatory molecules that have been published to date.'”

http://finance.yahoo.com/news/Compugen-Discovered-Protein-bw-3902315198.html?x=0&.v=1

As further observed by Compugen in an earlier press release with respect to the science leading up to the discovery of this protein:

"CGEN-15001 is a novel soluble recombinant fusion protein corresponding to the extracellular region of the Compugen discovered parent protein. The discovery of the parent protein, which is a membrane protein, was accomplished through the incorporation in Compugen’s LEADS Platform of additional algorithms specifically designed to predict novel members of the B7/CD28 family of co-stimulatory proteins. This approach relied on Compugen’s proprietary understandings and modeling of genomic structure, gene expression, protein structural domains, and cellular localization."

http://www.cgen.com/Content.aspx?Page=press_releases&NewsId=470

CGEN-15001 has yet to enter human clinical testing, and there can be no assurances that this particular candidate will ultimately become a therapeutic product. What we can be sure of, however, is that Compugen's predictive "discovery on demand" capabilities are constantly improving and continuing to yield an ever-growing number of significant therapeutic and diagnostic candidates, which are not confined to any one family of diseases, at a time when the pipelines of Big Pharma are growing drier by the day.

Unbeknownst to the world, we are witnessing, in my opinion, a scientific revolution in the making, which can no longer be ignored by Big Pharma and the scientific community at large.

[As noted in prior blog entries, I am a Compugen shareholder, this blog entry is not a recommendation to buy or sell Compugen shares, and in mid-September 2009 I began work as a part-time external consultant to Compugen. The opinions expressed herein are mine and are based on publicly available information. This blog entry has not been authorized or approved by Compugen.]