Antibiotic Croissants; How Matinas Could Revolutionize the War Against Superbugs
ACCESS Newswire
NEW YORK, NY / ACCESSWIRE / March 4, 2015 / In hospitals where a sterile environment is essential to preventing infection among the immuno compromised, it's a battle of ever stronger antibiotics against ever more resistant superbugs. The two sides are locked in a seemingly never-ending positive feedback loop where stronger antibiotics breed stronger resistance, which breeds still stronger antibiotics. All the meanwhile, the actual patients are caught in the crossfire with ever more devastating infections countered by equally scary and often lethal side effects from these trained, engineered microbial killers.
The antibiotic niche in biotech has really been heating up in recent years, both in terms of trial successes as well as outright acquisitions. Astellas Pharma (OTC:ALPMY) looks set to have its new antibiotic Cresemba for fungal infections FDA approved shortly. Roche (OTCQX:RHHBY) just acquired an early stage phase 1 antibiotic enhancing drug for $750M. Cempra (NASDAQ:CEMP) has been going nearly parabolic since announcing positive phase 3 results in January that met all endpoints for its oral solithromycin against bacterial pneumonia. Tetraphase Pharmaceuticals (NASDAQ:TTPH) is likewise trading near all time highs after reporting positive phase 3 data for its synthetic antibiotic Eravacycline for abdominal infections, and expects to submit a new drug application by the end of the year. All these are antibiotics that are tailored to attack drug-resistant microbes.
Another recent case highlighting this is that of Trius Therapeutics, which was acquired for $13.50 a share by Cubist Pharmaceuticals in July 2013 after trading in the $5 range a year earlier. Cubist was after Trius's antibiotic tedizolid phosphate which had reported positive results in a phase 3 trial in 2011, and a second phase 3 trial in March 2013. On top of that, Merck (NYSE:MRK) then acquired Cubist last month for $8.4B, or $102 a share. Cubist was trading at around $56 when it acquired Trius.
And it's not only Big Pharma that's investing more in anti-infectives. President Obama plans to pour another $1.2B into the War on Superbugs.
But no matter how many new antibiotics are engineered and how much Big Pharma pays to acquire them or the government pays to subsidize them, superbugs will inevitably keep adapting, and old molecules will eventually become obsolete. In order to really influence the superbug/superantibiotic battle long term, and hence be relevant to the market long term, an entirely different approach may be needed.
That approach may be coming from a small biotech firm called Matinas BioPharma (OTCQB:MTNB).
Matinas is a company that specializes in lipid-based drugs, and up until January, it had nothing to do with the antibiotic niche. Its lead candidate was (and still is) an omega 3 fatty acid molecule for the treatment of hypertrigliceridemia and dyslipidemia, two blood lipid disorders that lead to early heart disease.
But late last month, Matinas acquired a small private firm called Aquarius BioTechnologies that also happens to specialize in lipid molecules. These molecules are called cochleates, meaning they are cochlear, shaped like a snail shell, or a croissant. Below is an electron micrograph of these molecules.
Inside these naturally occurring lipid croissants, they place very powerful antibiotics - antibiotics that, if they float around freely in the body without cochleate croissant envelopes, usually cause serious and even lethal side effects for patients for whom these treatments are an absolute last resort. Usually these are immunosuppressed or immunocompromised patients in a hospital setting with a superbug infection who have no other choice but to risk their lives taking the one antibiotic that could save them.
But, if these potentially lethal antibiotics are packaged within a lipid cochleate envelope, they are much less toxic to the body. So how do the antibiotics fight infections then, if they're stuck inactive in a croissant? The answer is, the croissants are swallowed by immune cells that recognize them correctly as foreign molecules. They are then unfurled inside the immune cells by calcium diffusion. Think of it like loading the immune cells with specialized antibiotic ammunition. The newly armed immune cells from the patient's own body then attack the superbug infections armed with antibiotics already inside them.
The beauty of this approach, aside from its originality, is its longevity. The battle between superbugs and super antibiotics will keep raging. But to whatever level the battle is escalated, these cochleates can still maintain market relevance because they can house many different antibiotic molecules, theoretically all the molecules listed above, sheltering patients most side effects.
Do Antibiotics in Cochleates Work?
The short answer is we don't know yet. At least for humans. But antibiotics encapsulated in cochleates have been studied since 2000, and they do work in preclinical mouse models, seen in the data below. The graph below compares the survival rate of mice with a fungal infection being treated with an antibiotic called amphotericin B both inside cochleates (CAMB) and freely at different doses, with control and empty cochleates.
Both the cochleated amphotericin B (CAMB) and the free amphotericin B treatments scored 100% survival rates, whereas empty cochleates and control mice all died. It took nearly 15 years for Aquarius to take over the research from these initial data and proceed with human trials.
Phase 1 has been completed. 48 healthy patients were given CAMB at different doses and tested for adverse events. No serious side effects were reported, and all were mild. There were no reported effects on the kidneys at any dose. Compared with the side effects of intravenous free amphotericin B which include kidney damage, tremors, and high fever doctors refer to as "shake and bake" that can be fatal, and from the phase 1 data it seems that cochleates indeed protect against the potentially lethal side effects of this otherwise dangerous antibiotic.
Now the question is, can CAMB cure sick patients of fungal infections as well? (They can in mice, but mice medicine doesn't sell very well.) The answer to that question we will find out in phase 2, which will begin this year in collaboration with the National Institute of Health, results for which are due in Q4. The study will be open label, and it doesn't take long to see if a fungal infection is being treated successfully or not.
If phase 2 results are positive, Matinas would be in a position similar to the antibiotic-focused biotechs above, all now trading at the top of their ranges. Is a Big Pharma acqusition possible even at this point? Though it may not be very likely, let's not forget that Roche just acquired a phase 1 antibiotic enhancer for $750M on January 13. If cochleated amphotericin B works, Big Pharma may take notice once again.
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