Combating Superbugs with CARB-X

Heather Shane runs the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) at the California Life Sciences Institute (CLSI). This program provides funding and business support to startup companies who are developing innovative solutions to solve antibiotic resistance. I asked Heather about how the program works and why antibiotic resistance is such a big problem. CLSI is the non-profit partner of the California Life Sciences Association (CLSA), and supports the foundations of innovation – workforce development, STEM education and entrepreneurship – that have made California home to the world’s most prominent life sciences ecosystem.

What is CARB-X?
Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), which launched in August 2016, is the world’s largest public-private partnership focused on combating the threat posed by untreatable bacterial infections. We aim to help companies develop a suite of pre-clinical products that can then be taken forward by public or private investment. CARB-X addresses several goals laid out in President Obama’s National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) initiative: to accelerate research and development for new antimicrobial therapeutics and rapid and innovative diagnostic tests, and to promote international collaboration for antibiotic research and development.

The CARB-X consortium was awarded a five-year $250 million grant from the Biomedical Advanced Research and Development Authority and additional funding is provided by the two accelerators in the UK: the AMR Center and the Wellcome Trust. There are two U.S.-based CARB-X accelerators – one at MassBio in Cambridge and one at the CLSI in the Bay Area.

Why did CLSI get involved in CARB-X?
CLSI is dedicated to supporting life science entrepreneurship and to improving public health. Becoming part of CARB-X allows us to expand on the success of our FAST accelerator and help companies push forward innovations addressing antimicrobial resistance outside of the Bay Area.

How big a problem is antibiotic resistance?
It is a really serious problem. I am glad it is finally on the global radar. Over 700 000 people die each year from untreatable bacterial infections. Bacteria are rapidly developing resistance to antibiotics, and if we do not develop solutions now, it is estimated that by 2050, 10 million lives will be lost every year from bacterial infections that cannot be treated. Imagine a world where you can’t go to the dentist or have surgery. It will seem like the stone ages.

CARB-X is one step in solving this problem. We also need global health education to minimize inappropriate antibiotic use in both animal and human health and we need to address policy and economic incentives, such as removing the link between profit and sales volume. Antibiotics are a public good, like fire stations. Their value is not measured by how often they are used. We also need to develop point-of-care diagnostics to allow targeted prescribing of the right doses of antibiotics to each patient.

How many companies are involved in the CARB-X accelerator at CLSI?
We opened our first application round in August and had over 160 applications by the September 2. We are in dialogue with many companies at the moment. The CARB-X accelerator program as a whole aims to support 20 projects with our current funding, with the aim to advance at least two products into clinical trials. CLSI anticipates that approximately five companies will be enrolled in our CLSI CARB-X accelerator by the end of Q1 2017.

Are you currently seeking applications to the accelerator program?
Yes. Applications are open for round two which closes on October 31. It’s a centralized process through the CARB-X website. There are three steps to the application process. The first is a non-confidential expression of interest form. Selected companies then progress to a confidential short application form and finally to a longer grant-style confidential application. We have set it up like this to avoid people wasting time on a long application form up front. By the time they have progressed to the third form, they have a higher likelihood of getting a grant through the CARB-X program.

What sort of companies are you looking for?
They have to be making products that address antimicrobial resistance and advance human health. This could be diagnostics, antibiotics, adjunct therapies, peptides, microbiome modulators, small molecules, large molecules - any technology that could help treat, prevent or improve clinical practice surrounding resistant antibacterial infections. We are looking for game-changing technologies.

As far as the product development stage, companies should be beyond pure screening or library work and have not progressed further than Phase I clinical trials.

All potential applicants should know that we are focusing mainly on therapeutics for gram negative bacteria listed on the CDC’s Serious or Urgent threat list for the first year because this is the most pressing problem. That isn’t to say that companies working on solutions for other types of bacterial infection won’t be successful, but gram negative infections are our priority this year.

How does the program work? Do you offer funding to all companies? What other support do you offer them?
Companies who are part of the CARB-X accelerator will receive funding, business mentorship and access to a suite of technical services from CARB-X partners.

We have a pool of over $50 million that will be offered as non-dilutive grant funding to successful applicants in the first year. This means that companies get to keep their IP and equity. CARB-X funds projects, not whole companies, so the companies need to have enough resources to be able to maintain operations for at least 12 months independent of CARB-X funding, and have matching funding for the CARB-X project as well.

In addition to funding support, the CARB-X accelerator program also offers entrepreneurial support from a team of business mentors. As part of the application process, we ask companies to identify what kind of help they need e.g. competitive intelligence, fundraising, regulatory or preclinical development strategy. This helps us pair companies with the right mentors. We expect that the needs of each company will change over time, so it won’t be a static pool of mentors. The mentors will change as the company grows and evolves.

We hope that the CARB-X program will help participants to build their networks and will spur interactions and collaborations independent of CARB-X.

The consortium is led by Kevin Outterson of Boston University School of Law, and the executive team includes experts with decades of experience in antibiotic drug development, including John Rex, SVP at Astra Zeneca and, starting next year, Barry Eisenstein, formerly SVP of Scientific Affairs at Cubist and currently at Merck. In addition to BARDA and the four accelerators providing the business support, the CARB-X consortium includes many partner organizations offering technical and regulatory support to companies. These include the Broad Institute of MIT and Harvard, which offers chemistry services for antibiotic discovery as part of their Collaborative Hub for Early Antibiotic Discovery (CHEAD), the National Institute of Allergy and Infectious Disease (NIAID), which offers pre-clinical services to CARB-X projects, and RTI International, which offers project management, preclinical study design and support services to product developers.

Companies do not have to physically move to be part of a CARB-X accelerator program. All these services can be offered remotely.

Do you have any tips for companies who are interested in applying to be part of the program?
Look at our website, the expression of interest form on our funding page and the slide deck on the events page. The slide deck has helpful information including funding priorities. It also gives insight into anticipated challenges during product development based on product modality. Think about how you propose to overcome these problems when completing your application.

In the initial expression of interest form, you have 500 words to summarize your project, so be concise and don’t waste any space on the problem of antibiotic resistance – this is well understood by the review committees. Get straight into describing your product.

If you have any questions after reading the slide deck, the website, and the funding page, contact me.

We have had an outpouring of support from experts in the antimicrobial resistance field, but we need to build networks of experts everywhere, as we don’t know where our participating companies will be based. So if you are an expert and you would like to get involved, please email me. You may be located really close to one of our portfolio companies. I want to hear from people who have a passion to help with this. It is very rewarding helping early-stage companies to progress.

What other programs does CLSI offer for early-stage biotech companies who are not developing solutions to antimicrobial resistance?
Our FAST accelerator program focuses on life science innovation through supporting entrepreneurship and career development. It is a 12-week program that pairs companies with business mentors for intensive coaching. Together the entrepreneurs and mentors build a compelling product development story which is presented to a broad audience, including potential investors and partners at a final FAST showcase. This happens twice a year. Our current group of five companies starts this week.

To apply to be part of the FAST program, companies must be a fellow member of the CLSA, be based in California, be pre-commercial, have less than $5 million in funding and less than 12 employees. It costs $200 a year to become a fellow member of CLSA and this gives access to group purchasing discounts, and reduced or complimentary registration for executive education and networking events and partner events such as the BIO Investor Forum.