September 24, 2018 – Kevin Outterson, the Executive Director of CARB-X, is calling on antibacterial researchers around the world to “help others learn from their setbacks” by sharing data from unsuccessful research in an effort to accelerate the development of life-saving antibiotics and other products to treat drug-resistant infections. Outterson applauded Achaogen of South San Francisco for already agreeing to share compounds and data from its discontinued LpxC inhibitor discovery program with Forge Therapeutics of San Diego.
In a ground-breaking agreement facilitated by CARB-X, Achaogen has agreed to the non-exclusive transfer of compounds, scientific data and assays to Forge from its innovative LpxC program. Achaogen announced last year that it had stopped the early development program due to unexpected toxicity findings. Forge plans to review Achaogen’s body of LpxC knowledge to potentially gain insight and apply the findings to its on-going LpxC research program. Using a different chemistry approach than Achaogen, Forge is developing a novel class of antibiotics to treat Gram-negative bacteria such as Pseudomonas aeruginosa and Enterobacteriaceae superbugs.
“Science is hard; most projects end for any number of reasons. Typically, this knowledge and even the compounds themselves would be shuttered and locked away after a project is stopped,” Outterson said. “Given the economic realities of antibacterial research and the urgent need for new antibiotics, we need to adopt a more collaborative approach where it makes sense to do so.”
CARB-X is encouraged by public data-sharing initiatives like the SPARK initiative announced by PEW Charitable Trusts last year and Wellcome Trust’s Open Research initiative launched in 2016 and would like to see more sharing of antibacterial research data. Improved access to the results of funded science research is also a priority for governments including the US and UK, and for the Bill & Melinda Gates Foundation.
“We need to find ways to unleash the power of collaboration to develop new approaches to combat drug resistance,” said Outterson. “We are proud today that Achaogen and Forge are pioneering a new way of working. Achaogen’s expertise and valuable work will not go to waste. With a different chemistry approach, Forge is optimistic that their LpxC inhibitor projects may advance.”
“We are supportive of this open science initiative to advance the science and potential solutions to the antimicrobial resistance crisis,” said Blake Wise, CEO of Achaogen. “Our LpxC program yielded a potent lead compound and we are very hopeful that our research will contribute to the development of novel antibiotics to treat gram-negative infections.”
Zachary A. Zimmerman, Ph.D., CEO of Forge, said: “We are confident that Forge’s novel chemistry platform called BLACKSMITH can advance our LpxC program toward the clinic. CARB-X’s open science initiative enables data from other programs, like Achaogen’s, to be shared across the broader scientific research communities, increasing our collective knowledge, as we fight against antibiotic resistant superbug bacteria.”
Wellcome Trust, a global charity based in the UK working to improve health globally and one of CARB-X’s major funders, provided the inspiration for CARB-X Open Science. A strong proponent of open innovation, Wellcome Trust’s Open Research initiative encourages Wellcome-funded researchers to share articles and data on a public database. Tim Jinks, head of Wellcome’s Drug-Resistant Infections Priority Programme, said: “We need new approaches and new ideas if we are to effectively tackle the rise and spread of superbugs. If companies share scientific data and expertise, and work more together overcoming scientific challenges, we can speed up the advances and innovation in product development needed to get the new treatments urgently needed for patients.”
New antibiotics, diagnostics and other products are needed urgently to treat bacteria that are increasingly resistant to existing antibiotics. According to the WHO, an estimated 700,000 people die each year worldwide from bacterial infections. In the United States, an estimated 23,000 people die each year from drug-resistant bacterial infections, according to the Centers for Disease Control and Prevention (CDC).
LpxC is an enzyme that plays a critical role in Lipid A biosynthesis, an essential process for the formation of the Gram-negative outer membrane. The outer membrane is key to drug resistance, shielding the bacteria from the killing effects of antibiotics. By inhibiting LpxC function, the growth and strength of the outer membrane is stunted, resulting in bacterial cidality, which means killing the bacteria. LpxC would represent an entirely new class of antibiotic against Gram-negative bacteria, the most dangerous type of superbugs. If approved by the FDA, this would be the first new class against Gram-negatives in more than half a century.
CARB-X currently supports 32 R&D projects, including projects under development at Achaogen and Forge. CARB-X, which stands for Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, funds projects in six countries and is working to expand its pipeline with great science from around the world.
CARB-X is investing more than $500 million in antibacterial R&D from 2016-2021. The goal is to support projects through the early phases of development through Phase 1, so that they will attract additional private or public support for further clinical development and approval for use in patients. The scope of CARB-X funding is restricted to projects that target drug-resistant bacteria highlighted on the CDC’s Antibiotic Resistant Threats list, or the Priority Bacterial Pathogens list published by the WHO in 2017 – with a priority on those pathogens deemed Serious or Urgent on the CDC list or Critical or High on the WHO list.
CARB-X is a non-profit partnership launched by 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 (ASPR), the Wellcome Trust, and the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH). In May 2018, CARB-X added two new funding sources, the UK Department of Health and Social Care and the Bill & Melinda Gates Foundation.
CARB-X support for the Achaogen and Forge projects is possible thanks to funding from the Wellcome Trust and BARDA.
This news release is supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by an award from Wellcome Trust. The contents are solely the responsibility of the authors and do not necessarily represent the official views of CARB-X funders.
CARB-X is a non-profit public-private partnership dedicated to accelerating early development antibacterial R&D to address the rising global threat of drug-resistant bacteria. CARB-X is investing more than $500 million from 2016-2021 to support innovative antibiotics and other therapeutics, vaccines, rapid diagnostics and devices. In its first two years, CARB-X has built the world’s largest and most innovative pipeline of preclinical products against drug-resistant infections. CARB-X focuses exclusively on high priority drug-resistant bacteria, especially Gram-negatives. CARB-X is funded by 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 (ASPR), the Wellcome Trust, a global charity based in the UK working to improve health globally, the UK Government’s Global Antimicrobial Resistance Innovation Fund (UK GAMRIF), the Bill & Melinda Gates Foundation, with in-kind support from National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH). CARB-X is based at Boston University in the School of Law. https://carb-x.org/. Follow us on Twitter @CARB_X.
Achaogen is a biopharmaceutical company passionately committed to the discovery, development, and commercialization of innovative antibacterial treatments for MDR gram-negative infections. Achaogen’s first commercial product is ZEMDRI, for the treatment of adults with complicated urinary tract infections (cUTI), including pyelonephritis. The Achaogen ZEMDRI program was funded in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA). The Company is currently developing C-Scape, an orally-administered beta-lactam/beta-lactamase inhibitor combination, which is also supported by BARDA. Achaogen is also developing a new aminoglycoside program, which is supported by CARB-X. All product candidates are investigational, have not been determined to be safe or efficacious, and have not been approved for commercialization. For more information, visit the Achaogen website at www.achaogen.com.
At Forge Therapeutics, we are developing medicines targeting metal-dependent enzymes found in nature. Over 30% of known enzymes are metalloenzymes, covering all major enzyme classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Metal ions, including magnesium, zinc, iron, manganese, calcium, cobalt, and copper are the essential ingredient in these metalloenzymes. At Forge, we are the BLACKSMITHS of modern medicine, providing the tools to address any metalloenzyme challenge.
Forge’s lead effort is focused on LpxC, a zinc metalloenzyme found only in Gram-negative bacteria, which is essential for bacteria to grow. Forge has a strategic drug discovery alliance with Evotec AG and has been awarded multiple awards including CARB-X. In addition, Forge has amassed a rich intellectual property estate on metalloenzyme-targeted inhibitors to protect its BLACKSMITH platform and pipeline including technology licensed from UCSD. For further information, please visit the company’s website www.ForgeTherapeutics.com and follow us on Twitter @ForgeThera.
About BARDA and NIAID
The US Department of Health and Human Services works to enhance and protect the health and well-being of all Americans, providing for effective health and human services and fostering advances in medicine, public health, and social services. Within HHS, ASPR’s mission is to save lives and protect Americans from 21st century health security threats. ASPR leads the nation’s medical and public health preparedness for, response to, and recovery from disasters and public health emergencies. BARDA provides a comprehensive, integrated, portfolio approach to the advanced research and development, innovation, acquisition, and manufacturing of medical countermeasures – vaccines, drugs, therapeutics, diagnostic tools, and non-pharmaceutical products for public health emergency threats. These threats include chemical, biological, radiological, and nuclear agents, pandemic influenza, and emerging infectious diseases. NIH is the primary US federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses.
About Wellcome Trust
Wellcome exists to improve health for everyone by helping great ideas to thrive. We’re a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. The Wellcome Trust is a charity registered in England and Wales, no. 210183. Its sole trustee is The Wellcome Trust Limited, a company registered in England and Wales, no. 2711000 (whose registered office is at 215 Euston Road, London NW1 2BE, UK)