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Forge Therapeutics Raises $15M Series A Financing to Develop First Novel Gram-Negative Antibiotic in Decades

Forge Therapeutics, Inc., a biotechnology company discovering first-in-class antibiotics using a breakthrough drug discovery platform, announced today the completion of a $15M Series A financing. The round is led by MagnaSci Ventures, with participation from Evotec AG, Alexandria Venture Investments, MP Healthcare Venture Management, Red Apple Group, and WS Investments. Forge has used its enabling technology to identify a novel LpxC inhibitor effective against multi-drug resistant bacteria ‘superbugs,’ and the funding will support the program into clinical studies.

“This financing is an important step forward to solving the ‘superbug’ epidemic, an urgent global health issue in desperate need of innovation. We’ve been impressed with the strength of the Forge team, their technologies and their commitment to innovating the antibiotic space,” said Brian T. Dorsey, Founding Partner at MagnaSci Ventures. “With our investment and resources, we look forward to working together on developing the first novel antibiotic against Gram-negative bacteria in decades.” In connection with the Series A financing, Mr. Dorsey will be joining Forge’s Board of Directors.

“We are pleased to have such quality investors join us in our pursuit to eradicate deadly ‘superbug’ infections with novel antibiotics stemming from our robust drug discovery engine,” said Zachary A. Zimmerman, Ph.D., CEO of Forge. “The proceeds from this financing, coupled with the non-dilutive monies received from government agencies CARB-X and NIH/NIAID, will advance our LpxC inhibitor into clinical studies.”

With its proprietary chemistry approach, Forge develops small molecule inhibitors targeting metalloenzymes.  Forge’s lead effort is focused on LpxC, a zinc metalloenzyme found only in Gram-negative bacteria and which is essential for bacteria to grow. Forge has discovered novel small molecule inhibitors of LpxC that are potent in vitro, efficacious in vivo, and effective against drug resistant Gram-negative bacteria ‘superbugs.’

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Nova Southeastern University Researchers Studying How to Disrupt Bacteria to Treat Infections

Bacteria are everywhere. And despite widespread belief, not all bacteria are “bad.” However, to combat those that can cause health issues for humans, there has been an over-reliance on the use of antibiotics – so much so, that many of them are now proving ineffective due to bacteria developing increased resistance to them.

“More and more antibiotics are essentially becoming useless,” says Robert Smith, Ph.D., assistant professor in the Department of Biological Sciences at NSU’s Halmos College of Natural Sciences and Oceanography. “Even the most routine infections, such as ear infections that are often seen in children, are becoming more challenging and expensive to treat.”

This notion isn’t new – just prior to winning his Nobel Prize in 1945, Alexander Fleming, the scientist who discovered antibiotics, warned that overusing them would lead to bacteria that were no longer killed by these drugs.  Since then, scientists and bacteria have been locked in a deadly arms race. While scientists rush to discover new antibiotics, bacteria fight back by developing new tools to resist antibiotics. In recent years, the bacteria have been winning.

So this paradigm led researchers at NSU to take another look at how bacteria do what they do to see if there was another way to approach this issue. Researchers are now focusing on developing new ways to treat infections that reduce the use of antibiotics. And what the NSU researchers found, working with colleagues from Duke University and the University of Minnesota, was interesting.

Their findings are detailed in the March 27th edition of Scientific Reports (http://www.nature.com/articles/s41598-017-00588-9).

One way that bacteria infect people is by working together. First, they build a home called a biofilm, and then use chemicals to “talk with each other.” This allows the bacteria to coordinate an attack on the infected person. Led by NSU graduate Cortney Wilson, Smith’s lab recently discovered that by shaking the house that the bacteria have built, the ability of the bacteria to talk to one another is affected. Wilson earned her Master’s from NSU and is now at the University of Colorado, Boulder.

“We found that shaking the bacteria forced them to face a decision; do they want to grow, or do they want to cooperate,” Smith said. “And if we shook them at just the right frequency, we created enough confusion that the bacteria could do neither effectively.”

Smith notes that this strategy to prevent bacteria from talking to one another has promise in reducing the need for antibiotics. The team of scientists hope to begin testing their theory in more species of bacteria, and eventually in mice.

“It is a very exciting time for our research team. We are looking forward to building upon our very promising results and to moving our strategy into the clinic.”

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New Arsenal Against MRSA: New Study Reports Cannabinoids Effective Against Antibiotic-Resistant MRSA

Researchers have found that cannabinoid-based therapies have unique anti-bacterial properties that fight MSRA and other infectious bacteria. In vitro studies demonstrated that bactericidal synergy was achieved against multiple species of methicillin-resistant Staphylococcus aureus (MRSA) utilizing a proprietary cannabinoid-based therapeutic platform. MRSA species tested included community acquired- (CA-MRSA), healthcare-acquired- (HA-MRSA), and mupirocin-resistant (MR-MRSA) strains of MRSA.

Researchers also found that using unique strategic cannabinoid-based cocktails, fractional-inhibitory concentration (FIC) levels demonstrating synergy between mixtures of individual cannabinoid-based components ranged from 0.06 to 0.28. FIC findings below 0.5 indicate significant killing potential of the mixture. The work was led by NEMUS BIoscience, Inc. and the company’s discovery and research partner, the University of Mississippi (UM).

Dr. Mahmoud ElSohly, professor at the National Center for Natural Products Research (NCNPR) at the University of Mississippi commented: “Historically, many types of anti-infective compounds are derived from plants so to have a series of cannabinoid-related compounds exhibit activity against this dangerous pathogen is in keeping with prior efforts of drug development. I believe that these compounds, in addition to the bacterial killing capability, could also offer benefits associated with anti-inflammatory and anti-fibrotic properties that could enhance healing, especially against an organism associated with skin and soft tissue infections. The University, in conjunction with Nemus, is looking to expand the anti-infective capabilities of this series of compounds.”

Recently, the World Health Organization (WHO) placed MRSA on their list as one of the top six organisms that pose a global public health threat. “This anti-infective platform will constitute the NB3000 series of Nemus molecules and formulations.  While there are a number of compounds in the development pipeline against MRSA, we believe that this family of drug candidates could possess an excellent safety profile in addition to efficacy in neutralizing this bacterium,” stated Brian Murphy, M.D., C.E.O. and Chief Medical Officer of Nemus. “These unique botanically derived components establish an anti-infective platform which could potentially be expanded into other types of bacteria, as well as viruses, and fungi.”

The University of Mississippi, the state’s flagship institution, is among the elite group of R-1: Doctoral Universities – Highest Research Activity in the Carnegie Classification. The university has a long history of producing leaders in public service, academics, research and business. Its 15 academic divisions include a major-medical school, nationally recognized schools of accountancy, law and pharmacy, and an Honors College acclaimed for a blend of academic rigor, experiential learning and opportunities for community action.

Nemus will work with Dr. Elsohly, the University lead researcher on this project, to have this data submitted to a future scientific meeting and anticipates performing further testing against a variety of other bacterial species. Commercially, the company looks to actively pursue partnering opportunities for these candidate molecules. “This work highlights the importance of Nemus’ relationship with the University which has significant experience and intellectual capital related to cannabinoid chemistry and physiology, dating back to 1968,” added Dr. Murphy.

Nemus Bioscience is a biopharmaceutical company, headquartered in Costa Mesa, California, focused on the discovery, development, and commercialization of cannabinoid-based therapeutics for significant unmet medical needs in global markets. Utilizing certain proprietary technology licensed from the University of Mississippi, NEMUS is working to develop novel ways to deliver cannabinoid-based drugs for specific indications, with the aim of optimizing the clinical effects of such drugs, while limiting potential adverse events. NEMUS’s strategy is to explore the use of natural and synthetic compounds, alone or in combination with partners. The Company is led by a highly-qualified team of executives with decades of biopharmaceutical experience and significant background in early-stage drug development.

For more information, visit http://www.nemusbioscience.com.

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Antibiotics Weaken Alzheimer’s Disease Progression Through Changes in the Gut Microbiome

Long-term treatment with broad spectrum antibiotics decreased levels of amyloid plaques, a hallmark of Alzheimer’s disease, and activated inflammatory microglial cells in the brains of mice in a new study by neuroscientists from the University of Chicago.

The study, published July 21, 2016, in Scientific Reports, also showed significant changes in the gut microbiome after antibiotic treatment, suggesting the composition and diversity of bacteria in the gut play an important role in regulating immune system activity that impacts progression of Alzheimer’s disease.

“We’re exploring very new territory in how the gut influences brain health,” said Sangram Sisodia, PhD, Thomas Reynolds Sr. Family Professor of Neurosciences at the University of Chicago and senior author of the study. “This is an area that people who work with neurodegenerative diseases are going to be increasingly interested in, because it could have an influence down the road on treatments.”

Two of the key features of Alzheimer’s disease are the development of amyloidosis, accumulation of amyloid-ß (Aß) peptides in the brain, and inflammation of the microglia, brain cells that perform immune system functions in the central nervous system. Buildup of Aß into plaques plays a central role in the onset of Alzheimer’s, while the severity of neuro-inflammation is believed to influence the rate of cognitive decline from the disease.

For this study, Sisodia and his team administered high doses of broad-spectrum antibiotics to mice over five to six months. At the end of this period, genetic analysis of gut bacteria from the antibiotic-treated mice showed that while the total mass of microbes present was roughly the same as in controls, the diversity of the community changed dramatically. The antibiotic-treated mice also showed more than a two-fold decrease in Aß plaques compared to controls, and a significant elevation in the inflammatory state of microglia in the brain. Levels of important signaling chemicals circulating in the blood were also elevated in the treated mice.

While the mechanisms linking these changes is unclear, the study points to the potential in further research on the gut microbiome’s influence on the brain and nervous system.

“We don’t propose that a long-term course of antibiotics is going to be a treatment—that’s just absurd for a whole number of reasons,” said Myles Minter, PhD, a postdoctoral scholar in the Department of Neurobiology at UChicago and lead author of the study. “But what this study does is allow us to explore further, now that we’re clearly changing the gut microbial population and have new bugs that are more prevalent in mice with altered amyloid deposition after antibiotics.”

The study is the result of one the first collaborations from the Microbiome Center, a joint effort by the University of Chicago, the Marine Biological Laboratory and Argonne National Laboratory to support scientists at all three institutions who are developing new applications and tools to understand and harness the capabilities of microbial systems across different fields. Sisodia, Minter and their team worked with Eugene B. Chang, Martin Boyer Professor of Medicine at UChicago, and Vanessa Leone, PhD, a postdoctoral scholar in Chang’s lab, to analyze the gut microbes of the mice in this study.

Minter said the collaboration was enabling, and highlighted the cross-disciplinary thinking necessary to tackle a seemingly intractable disease like Alzheimer’s. “Once you put ideas together from different fields that have largely long been believed to be segregated from one another, the possibilities are really amazing,” he said.

Sisodia cautioned that while the current study opens new possibilities for understanding the role of the gut microbiome in Alzheimer’s disease, it’s just a beginning step.

“There’s probably not going to be a cure for Alzheimer’s disease for several generations, because we know there are changes occurring in the brain and central nervous system 15 to 20 years before clinical onset,” he said. “We have to find ways to intervene when a patient starts showing clinical signs, and if we learn how changes in gut bacteria affect onset or progression, or how the molecules they produce interact with the nervous system, we could use that to create a new kind of personalized medicine.”