CARB-X announces funding for global scientists racing to discover new antibiotics

A year since launching, the international partnership CARB-X today announces its second round of antibiotic research and development funding – alongside a call for greater global support.

The seven projects supported include:

• five potential new class antibiotics for Gram-negative bacteria
• potential new treatment for drug-resistant gonorrhea
• new molecule targeting a superbug causing serious infections in cystic fibrosis patients
• phase 1 clinical trial of a new oral broad-spectrum antibiotic.

Today’s funding announcement is for one company in France, one in India, one in Switzerland, two in the USA, one in the UK and one in Ireland.

Drug-resistant infections currently cause around 700,000 deaths worldwide annually – if antibiotic resistance continues at its current rate that could rise significantly within a generation.

Kevin Outterson, Executive Director of CARB-X and Professor of Law at Boston University, said: "Drug-resistant infections are complex and developing new antibiotics challenging, timely and costly. But restoring the R&D pipeline is vital to address the seriously increasing threat of superbugs which have become resistant to existing drugs. This is a global problem and CARB-X is a critical part of the global solution. We are looking to support the best potential new treatments and diagnostics across the world. We are especially pleased that today’s awards mean we are now supporting scientists in six countries. The projects offer exciting potential. But we need greater global support from governments, industry and civil society to get the new treatments the world urgently needs."

CARB-X – which stands for Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator – is a partnership between:

• UK charity Wellcome
• the US Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response
• the National Institute of Allergy and Infectious Diseases(NIAID), part of the National Institutes of Health.

CARB-X was launched in July 2016 to address the gap in antibiotic research and development and innovations to improve diagnosis and treatment of drug-resistant infections. The G20 has called for global antibiotic R&D efforts like CARB-X to refill the pipeline with safe and effective drugs.

Antibiotic discovery is challenging due to the complexity of bacteria, which are easily able to genetically modify and become resistant to medicines, but also because of declining investment by larger companies.

The most recently approved new class of antibiotics was discovered in the early 1980s. However, CARB-X funding is focused on the most resistant, Gram-negative, bacteria, and the last new class of antibiotics approved for treatment against these was discovered in 1962.

Responsible use of existing antibiotics and equitable access, particularly in low-income countries where need is greatest, is also vital to address the global health problem. Both are a condition of CARB-X funding.

Tim Jinks, Head of Drug-Resistant Infections at Wellcome, said: "Antibiotics are fundamental to modern medicine but overuse and inappropriate use have led to dangerous bacteria developing deadly resistance. Wellcome is committed to helping ensure we get the urgently needed new treatments. Drug discovery must also go hand-in-hand with concerted action to ensure antibiotics of last resort are reserved for patients where first-line treatments will not work. And we must ensure these treatments can be made available in all countries for those who need them."

Many of the CARB-X projects are at an early stage and it will still take some time before it is known whether they can become safe, effective treatments for patients. CARB-X is also supporting a Phase 1 clinical trial of a new oral and intravenous broad-spectrum antibiotic. Ensuring appropriate use of this type of antibiotic is critical – and used appropriately it can save lives.

BARDA’s Director Rick Bright, PhD, said: "The support announced today will help speed development of new antibacterial products to treat patients with serious, life-threatening infections to enhance domestic health security and global preparedness. We are committed to revitalizing the antibacterial pipeline through a combination of incentives; today’s announcement is another example of our commitment to promote and accelerate medical countermeasure innovation through novel public-private partnerships like CARB-X."

"These awards build upon the scientific opportunities created by prior NIAID investments in drug development programs to assist with antibiotic development, and are consistent with our strategies for new approaches to address antibiotic resistance," said NIAID Director Anthony S Fauci, MD.

This latest funding is part of an overall commitment of up to US$455m by the US government and Wellcome over a five-year period and follows the announcement in March 2017 of the first 11 projects to receive funding – eight in the US and three in the UK.

The projects were selected from among 368 applications from around the world. CARB-X expects to make further funding announcements later this year. Product developers can visit CARB-X.org for additional information on funding opportunities.

Second round of projects funded by CARB-X

Achaogen Inc: Progressing a new class of antibiotics into Phase 1 trials - LpxC inhibitors to treat Pseudomonas aeruginosa

Initial investment of up to $3.2m with potential option payments up to $8.2m

Achaogen is developing a new class of antibiotics that inhibit LpxC, an essential enzyme unique to Gram-negative bacteria. Achaogen’s lead LpxC inhibitor has the potential to treat infections due to multidrug-resistant Pseudomonas aeruginosa, one of the drug-resistant bacteria on the World Health Organization’s top priority list, and positively impact the excess morbidity and mortality in affected patients. Funding under CARB-X will support Achaogen in advancing their lead LpxC inhibitor through initial Phase 1 clinical trials, with the potential to bring a new class of antibiotic with activity focused on Gram-negative infections to patients for the first time in decades. Achaogen (NASDAQ:AKAO) is a South San Francisco-based late-stage biopharmaceutical company passionately committed to the discovery, development, and commercialization of innovative antibacterial treatments for multi-drug-resistant Gram-negative infections.

More information: http://www.achaogen.com/. Media contact: Denise Powell at dpowell@achaogen.com

Antabio SAS: Developing a novel virulence-inhibitor that can boost the effect of antibiotics in the treatment of Cystic fibrosis

Initial investment of up to $2.8m with potential option payments up to $6.1m

Cystic fibrosis (CF) is a genetic condition leading to long-term infections and progressive lung damage. The most frequent infection in adult patients is caused by the bacterium Pseudomonas aeruginosa (PA), which grows as biofilm clusters that are resistant to immune clearance and conventional antibiotics. CARB-X funding will help support Antabio’s Pseudomonas Elastase Inhibitors (PEI) project. The PEI project seeks to develop inhibitors of the PA LasB elastase virulence factor, thereby targeting the bacterium’s ability to evade the immune system and cause disease, and when given alongside antibiotics, helping to clear PA infections. Antabio is a private biopharmaceutical company developing novel resistance-inhibitors that can be combined with antibiotics to treat drug-resistant infections caused by the most critical Gram-negative pathogens. Antabio is headquartered in Labège, France.

More information: www.antabio.com. Media contact: press@antabio.com

Bugworks Research India Pvt Ltd: Developing a new class of antibiotics to inhibit bacterial DNA topoisomerases

Initial investment of up to $2.6m with potential option payments up to $3.6m

In partnership with CARB-X, Bugworks is developing a novel first in class broad-spectrum antibiotic to kill multi-drug resistant Gram-negative bacteria that have been identified by the World Health Organization as critical and high priority infection threats. Our lead compound, a Gyrase-topoisomerase inhibitor, is being developed as an intravenous and oral treatment for multi-drug resistant infections, with a low risk of developing resistance because it inhibits two essential targets in the replication machinery and has been designed to by-pass efflux resistance mechanism of the bacteria. In pre-clinical testing, Bugworks’ novel broad-spectrum antibiotics have demonstrated efficacy against deadly Gram-negative superbugs. Bugworks is based in Delaware, US, and operates its R&D facilities in Bangalore, India.

More information: http://bugworksresearch.com/. Media contact: Anand AnandKumar at anand@bugworksresearch.com

Debiopharm International SA: Developing a new class of antibiotics to treat drug-resistant gonorrhea

Initial investment of up to $2.6m with potential option payments up to $1.4m

Debiopharm International SA, a Swiss-headquartered global biopharmaceutical company, has developed a novel class of antibiotics which inhibit bacterial fatty acid biosynthesis, an essential pathway in major pathogens including Neisseria gonorrhoeae, the causative bacterium in the sexually transmitted disease gonorrhea.  N. gonorrhoeae’s resistance to antibiotics is a major global medical problem having acquired resistance to practically all classes of antibiotics (CDC). Debiopharm, in collaboration with CARB-X, will utilize their state-of-the-art Fabiotics drug discovery platform to develop novel therapeutics to combat drug-resistant gonorrhea.

More information: www.debiopharm.com. Media contact: Christelle Tur at christelle.tur@debiopharm.com.

EligoChem Ltd: Antimicrobial peptides have the potential to be potent antibiotics to treat drug-resistant Gram-negative bacteria

Initial investment of up to $1.5m with potential option payments up to $3.3m

EligoChem Limited is progressing a project, powered by CARB-X, to select and develop antimicrobial peptides as Gram-negative antibiotics. The CARB-X funded project focuses on candidate selection from of a series of helical antimicrobial peptides with potent Gram-negative antibiotic action and low frequency of resistance potential.  These peptides have significantly reduced toxicity potential compared to other known antimicrobial peptides. EligoChem is based in Discovery Park, Kent, UK, and focused on the design of amphiphilic compounds that possess good absorption and low attrition risks, particularly suited to antibiotic research.

More information: www.eligochem.com. Media contact: Andy McElroy at andy@eligochem.com.

Iterum Therapeutics: Oral and intravenous formulations of sulopenem under investigation in Phase 1 clinical trials for the treatment of serious drug-resistant infections

Investment of up to $1.5m

Sulopenem, which is being supported by CARB-X funding, is an antibiotic under study for the treatment of infections caused by multi-drug resistant bacteria in hospital and community settings. These include the most urgent drug-resistant antimicrobial threats defined by the US Centers for Disease Control. Sulopenem is highly effective against the pathogens most commonly associated with uncomplicated urinary tract infections, complicated urinary tract infections and complicated intra-abdominal infections, including potent in-vitro activity against Enterobacteriaceae mutants of E. coli and K. pneumonia. If approved, sulopenem will be available as a tablet and an intravenous formulation. Future clinical studies will focus on urinary tract and complicated intra-abdominal infections. With careful stewardship from medical professionals and appropriate use by patients, sulopenem could be effective in the treatment of infections in patients in the community and could be useful in the early discharge of patients from hospital. Iterum Therapeutics is headquartered in Dublin, Ireland.

More information: www.iterumtx.com. Media contact: Stephen Lederer at stephen.lederer@ymail.com.

VenatoRx Pharmaceuticals:  Working to discover a new class of antibiotic that beats resistance caused by beta-lactamase enzymes

Initial investment of up to $3.4m with potential option payments up to $6m

VenatoRx Pharmaceuticals is aiming to develop a new antibiotic class that circumvents the most prevalent form of antibiotic resistance.  Since the discovery of penicillin, dozens of drugs, collectively known as beta-lactams, have been introduced that kill bacteria by targeting their cell wall.  Unfortunately, bacteria have developed hundreds of beta-lactamase enzymes that prevent these drugs from working. VenatoRx has found a new drug class that kills bacteria by hitting the same cell wall target, but is impervious to beta-lactamase enzymes. VenatoRx is a private pharmaceutical company dedicated to the discovery and development of novel anti-infective agents. It is headquartered in Malvern, PA, USA.

More information: http://www.venatorx.com. Media contact: IR@venatorx.com