Forgetting about Idera Pharmaceuticals (IDRA) seems to make its value sink, but failed to make it disappear. With a stock that sells at less than a three quarter of a dollar and a market of $20 million, lower than a new comer biotech having drugs still in preclinical lab testing, the firm was capable of drawing investors’ attention, riding new data about an attractive possibility of beating all existing approaches to treating psoriasis. The surprising data, which bring hopes in treating other autoimmune diseases, in addition to psoriasis were presented by James G. Krueger, M.D., PhD, of The Rockefeller University, at the Late-Breaking Research Symposium on March 2nd, 2013, during the American Academy of Dermatology Annual Meeting.
Miracles happen, we know, especially with hard technologies in spite of histories of past failures. We have examples; the latest was AVI, which offered a miracle HI-TECH drug for Duchenne muscular dystrophy after changing its name into Sarepta (SRPT). Its dead stock resurrected and ran a marathon rally from the low price of one digit to the high twenties in record time.
Idera’s history is complicated. We happen to live it, follow up on each move its made and every mistake it used to commit. We knew its previous chairman, its original founders, their ambitions, disputes, rejections to their own baby and about the firm’s metamorphoses during which time many investors big and small, foreign and Americans lost tons of money that melted with the continued melting of the firm’s assets, together with its dreams.
Now we are witnessing news, probably good news, investors, including us, cannot ignore, while keeping our skepticism alive. Let’s see what the news says.
In the prestigious American Academy of Dermatology Annual Meeting, James G. Krueger, M.D PhD, of The Rockefeller University presented data suggesting that Idera’s selective Toll-like receptor antagonists, IMO-3100 and IMO-8400, normalized the gene expression of important cytokines in a preclinical study of skin inflammation that is commonly used as a model of psoriasis. The genes in question are related to the production of key mediators of psoriasis including Interleukin (IL) -17, IL-6, IL-12/23, IL-1, IL-21 receptor, and INF-gamma. These genes, Dr. Krueger announced, were restored toward normal levels. “Treatment with IMO-3100 and IMO-8400 reduces disease-associated expression of the IL-17 and IL-23 inflammatory cascade in the mouse IL-23-induced skin inflammation model,” Dr. Krueger said. “Genes that play a mediating role in psoriasis were returned toward normal levels with both compounds. The inclusion of Toll-like receptor (8 (TLR8) activity with IMO-8400 was additive to the effect on gene expression that we observed with the TLR7 and TLR9 antagonist compound. We are now extending this work, with the analysis of gene expression patterns in skin biopsies from patients treated with a TLR antagonist in a Phase 2 clinical trial.”
Commenting on the study, or the presentation, Robert Arbeit, M.D VP of Clinical Development at Idera said that the data presented by Dr. Krueger provide scientific support for the top-line results from the proof of concept Phase 2 trial of IMO-3100 in patients with psoriasis that Idera announced late last year. He is looking forward to presenting detailed results from the clinical trial at the International Investigative Dermatology Annual Meeting in May 2013. Dr. Arbeit informed that the firm has completed the single dose portion of a Phase 1 clinical trial of IMO-8400 in healthy subjects. IMO-8400 was well-tolerated and demonstrated target engagement of Toll-like receptors 7, 8, and 9 (TLRs 7, 8 and 9). Data from the multiple-dose portion of the IMO-8400 Phase 1 trial is anticipated during the second quarter of 2013.
Rationale behind TLRs and Idera's Autoimmune and Inflammatory Diseases Program: Knowing that Toll-like receptors (TLRs) might play a key role in inflammation and immunity, Idera is developing compounds targeting TLRs 3, 7, 8 and 9, which are expressed in different cells and serve unique functions. Idera’s drug candidates aim at modulating immune responses through either activation or inhibition of specific TLRs. Inhibition of specific TLRs may be useful in treating autoimmune disorders such as systemic lupus erythematosus (SLE), psoriasis and rheumatoid arthritis, by blocking the induction of multiple cytokines and signaling pathways. Idera's clinical candidates for application in autoimmune diseases are IMO-3100, an antagonist of TLR7 and TLR9, and IMO-8400, an antagonist of TLRs 7, 8 and 9.
Prohost observations: The firm’s programs are based on the notion that the causes of autoimmune diseases, for example, systemic lupus erythematosus (SLE) and psoriasis reside in the production of autoantibodies, damage-associated molecular patterns, or DAMPs, and pathogen associated molecular patterns, or PAMPs, that may contain host nucleic acids. Indeed, these stimuli activate TLRs 7, 8 and 9 and induce multiple cytokines and signaling cascades that intensify the damage to the body's own tissues and organs, thereby releasing more self-nucleic acids that promote disease maintenance and progression.
It is true also that in preclinical models of several autoimmune diseases, Idera’s drugs IMO-3100 and IMO-8400 inhibited TLR-mediated induction of Th1, Th17 and inflammasome1 pathways, leading to the suppression of multiple cytokines including tumor necrosis factor-alpha, or TNF-α, and interleukins IL-12, IL-6, IL-17 and IL-1β and improvements in multiple measures of disease.
True also is that the current monoclonal antibody treatments for autoimmune and inflammatory diseases block the activity of only one specific cytokine out of many, while Idera’s TLR antagonists are approach is designed to inhibit induction of immune responses to autoimmune disease stimuli rather than block one specific cytokine. This is all true and, probably feasible as therapeutics. The problem is what’s in the origin of our still unshaken skepticism. Of course we hope the firm would succeed in putting these products on the market. But will Idera be able to complete the task until fruition? Can it do it alone? We wish what is going on at Idera now is not a horrible déjà vu phenomenon. Same early and mid-stage successes that all have gone with the wind of inability to close any deal with partners that can take the products to the markets’ shores.
We are not pessimistic. We are just skeptical. We are ready to get rid of our skepticism. At this stage, we decided to wait and see, during which time, we would love to see a partner, or hear about one we hadn’t heard about during the time we were disinterested in Idera’s activities.
1. The inflammasome is a multiprotein oligomer consisting of caspase 1, PYCARD, NALP and sometimes caspase 5 (also known as caspase 11 or ICH-3).
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