The Postman Always Rings Nice

By DrKSSMDPhD, October 2, 2015

[Ed. Note: Dr. KSS writes about medicine and biotech stocks for the Irregulars. He has agreed to our trading restrictions, and his words and opinions are his own. You can read his past articles, latest comments, and bio here.]

We love when readers write in, and most of the questions, even though privately put, are worth answering for the group. We’ll try to bundle those up and answer them on a rolling basis with directed columns.

On the biotech thread after the recent article on Aurinia ($AUPH), a reader recently queried about Spectral Medical ($EDTXF), a $107M-dollar Canadian enterprise.

Spectral’s objective is to get to market a blood-purifying cartridge to treat Gram-negative bacterial sepsis. While many bacteria can kill in the right setting, remember that bacteria tend to be lumped into three major groups: Gram-positive cocci (often pus formers, such as Staphylococcus and Streptococcus), Gram-negative bacilli (abundant in the GI tract, like E. coli), and anaerobes (often Gram-positive bacilli, and common in the aerodigestive tract).

Of all of these, I think most of our medical readers would agree that the Gram-negative bacilli are the worst behaved. Gram-negative sepsis can quickly become life-threatening because of its ability to cause a crash in blood pressure and to affect other organs (particularly the kidneys). Recall that carbapenem-resistance Enterobacteriaceae (CRE, which Achaogen $AKAO is chasing with plazomicin) are mostly Gram-negative rods.

Why are Gram-negatives so lethal? It’s because of a structural molecule in their cell walls called endotoxin. Endotoxin is a dangling lipopolysaccharide molecule that overall bears significant net negative charge in physiological conditions. Once we believed that endotoxin came from Gram-negatives only as they died, but better studies conclude that live Gram-negatives secrete it as a kind of death ray that deeply perturbs the body. Women who have gotten pyelonephritis from urinary tract infections may remember the cardinal clinical feature of endotoxinemia: called rigors (“RYE-gors”), they are intense shaking chills, often so bad patients think they may be seizing. They are from endotoxin binding to Toll-like receptors and setting off inflammatory cascades.

Remember the spectacular failure of Regado (now Tobira $TBRA)? It had devised an RNA aptamer, a molecule designed to bind to coagulation factor IXa and perturb its ability to cause clotting. But RNA and other nucleic acids also bear negative charge on their surfaces. In phase 3, Regado’s study was abandoned on safety concerns, as patients were having ...

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