Antibacterial activity against MRSA

New class of antibiotics seems to have broad-spectrum antibacterial potential

July16th,2020
Ilene Schneider
SYDNEY—Recce Pharmaceuticals Ltd., which is developing a new class of broad-spectrum synthetic antibiotics, announced positive data showing significant in-vivo antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in rats with topical burns treated with its lead compound RECCE 327.
 
Conducted by an independent contract research organization to assess the dose-dependency of RECCE 327 and in-vivo antibacterial activity against MRSA in rats with topical burns, the study met its primary endpoints: a reduction in bacterial load in wound and percentage of wound contraction, evaluated on the fourth day following dosing.
 
According to James Graham, the company’s executive director, “RECCE 327 represents a new class of synthetic antibiotics with rapid, potent, and broad-spectrum activity against serious and potentially life-threatening multidrug-resistant pathogens. The antibiotics are bactericidal, which means they kill the bacteria rather than inhibit their growth. Designed to address the global health threat of antibiotic resistant superbugs, RECCE 327 shows efficacy, even with repeated use, making it better suited to combat superbugs.”
 
Rather than inhibiting a specific bacterial protein, RECCE 327 can overcome potential bacterial mutations through its universal mechanism of action that continuously kills pathogens. Once RECCE 327 enters the bloodstream, it binds to a pathogen’s outer membrane and interacts with the bacterial plasma membrane proteins, weakening the cell wall and building internal pressure, causing the bacteria to burst without affecting healthy cells. RECCE antibiotics can be formulated for intravenous, topical, nasal, oral and inhaled use and represent the first new classes of antibiotics in more than 30 years, Graham said.
 
Added Graham: “The positive data against MRSA further reinforces the broad-spectrum capability of RECCE 327. Results demonstrated RECCE 327 as effective in reducing bacterial load within a wound and showed enhanced wound contraction in comparison to the best in class antibiotic currently in use—Soframycin. Traditional antibiotics operate by a ‘lock and key’ mechanism of action. When a bacterium mutates/evolves, that mechanism of traditional antibiotics no longer functions, because the lock has changed. The new class of compounds synthesized by Recce are polymeric molecules designed to overcome these limitations.
 
“For example, Soframycin is only effective against most gram-negative bacteria but not against most gram-positive bacteria. Additionally, due to toxicity concerns, Soframycin is mainly used for local treatments. Rather than inhibiting a specific bacterial protein or process, in this case bacterial proteins involved in protein synthesis, RECCE 327 can overcome potential bacterial mutations through its universal mechanism of action.”
 
Furthermore, he explained that in previous in-vitro studies, treatment with RECCE 327 against S. aureus, E. coli and P. aeruginosa bacteria showed no resistance, even after over 25 repeated exposures. RECCE 327 continued to display the same clinically relevant kill-rates for standard bacteria and their superbugs forms, suggesting that RECCE 327 may be more effective against a wider range of bacteria and may come without the toxicity concerns associated with current antibiotics.
 
“Overall, RECCE 327 shows strong potential as an alternative treatment for resistant Staphylococcus aureus, one of the most common bacterial infections in humans, by demonstrating repeated efficacy at a range of dosing levels on topical skin conditions.” Graham said.
 
As to the next step, he explained, “While we continue to expand our pipeline, we plan on advancing RECCE 327 and new formulations of the drug for other serious infectious diseases with an initial focus on sepsis. As a new class of synthetic polymers, we are taking advantage of its versatility to further create broad-spectrum anti-infectives. Synthetic polymer drugs have the potential to be effective against deadly superbugs beyond those that are bacterial in origin, including viruses.”
 
A potential added benefit to using this class of antibiotics is that it would take the pressure off overusing existing antibiotics, which could result in reduced resistance to available antibiotics, he added. Therefore, Recce Pharmaceuticals is eager to see its synthetic antibiotics move through the required regulatory stages to combat the global health threat posed by antibiotic resistant superbugs.
 
“Parallel to the traditional regulatory pathway, the company has been given the green light to provide RECCE 327 to hospitals and medical practitioners under the Australian Therapeutic Goods Administration (TGA) Special Access Scheme Category A,” Graham noted.
 
At this time, Recce Pharmaceuticals is focused on conducting a first-in-human Phase 1 clinical trial study of RECCE 327 in 40 healthy subjects expected to be initiated in the latter half of 2020. The company also has been awarded accelerated regulatory pathways by the U.S. Food and Drug Administration, which will fast-track RECCE 327 through the regulatory review process, so it is available to treat patients with serious or life-threatening bacterial infections sooner.
 
“Our initial focus is on sepsis, which represents the costliest condition for hospitals to treat, and for which there are no approved treatment options,” Graham concluded. “Sepsis also represents a large global market opportunity expected to be worth $5.9 billion by 2026. However, our focus is on potentially improving patient outcomes and addressing the global issue of superbugs.”
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