CARB-X dishes out $48M in grants to antimicrobial startups

CARB-X is making it rain.

The international antimicrobial consortium today announced grants totaling $48 million, spread across 11 companies in the U.S. and U.K.

Launched in mid-2016, CARB-X stands for Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator. It comes in response to the growing threat of drug-resistant infections — and the concerning lack of late-stage antibacterial drugs. As of March 2016, just 37 antibiotics were in clinical development for the U.S. market.

According to Thursday’s media release, CARB-X will spend up to $450 million from 2017-2021 to support innovative diagnostics and drugs in this field. More specifically, the accelerator aims to boost many preclinical programs that have the potential to move into human trials. By then, they’ll have a good shot at securing traditional forms of investment.

According to the CDC, some 20 million Americans are hit with a drug-resistant strain each year and 23,000 of those patients die. And the worst may be yet to come.

Federal initiatives, including the 2012 Generating Antibiotics Incentives Now Act (GAIN Act), are also underway. The GAIN Act creates a path for important antimicrobials to receive priority review, fast track designation, and a five-year extension of patent exclusivity.

Guy Macdonald, CEO of grant-winner Tetraphase, said the incentives for startups in this space are vital.

“For a small biotech company like ours, funding from these types of organizations is very important and helpful in continuing to advance our pipeline of novel antibiotics towards our ultimate goal of helping physicians and patients who are in urgent need of new treatment options,” Macdonald said in an email forwarded by a company representative.

The eleven recipients encompass three investigational new classes of antibiotics, four outside-the-box product ideas, and seven new molecular targets. That includes:

Cidara Therapeutics
San Diego, California

Awarded $3.9 million over 13 months, and potentially up to $3 million in the following 11 months for its Cloudbreak immunotherapy platform and lead candidate CD201, designed to treat serious multi-drug resistant bacterial infections.

ContraFect Corporation
Yonkers, New York

Awarded $1.1 million over 15 months, and potentially up to $1 million in the following nine months to progress antimicrobial lysins, which could combat drug-resistant Pseudomonas aeruginosa infections.

Entasis Therapeutics
Waltham, Massachusetts

Awarded $2.1 million over nine months, and potentially up to $4.2 million in the following 12 months to develop an oral antibiotic for Gram-negative bacterial infections, including carbapenem-resistant Enterobacteriaceae (CRE).

Forge Therapeutics
San Diego, California

Awarded $4.8 million over 15 months, and potentially up to $4 million in the following 18 months for its pioneering chemistry platform, which could deliver the first novel class of ‘superbug’ antibiotics in decades.

Microbiotix Inc  
Worcester, Massachusetts

Awarded $1.6 million over 12 months, and potentially up to $1.6 million in the following 12 months for its Type III secretion inhibitors that aim to boost the body’s ability to fight bacteria and potentiate host defenses against P. aeruginosa-resistant pneumonia patients.

Oppilotech Ltd
London, United Kingdom

Awarded $120,000 over six months to perform computational modeling to develop potentiators, which weaken the bacterial membrane and break antibiotic resistance.

Proteus IRC
Edinburgh, Scotland

Awarded $640,000 over 21 months, and up to $480,000 more in the following 20 months for its new optical imaging technology that could increase the speed and accuracy of diagnoses in bacterial lung infections.

Redx Pharma
Alderley Park, United Kingdom

Awarded $1 million over 18 months to progress novel bacterial inhibitors that target multi-drug resistant bacteria and serious hospital-acquired infections.

Spero Therapeutics
Cambridge, Massachusetts

Awarded $1.6 million over 12 months, and potentially up to $5.4 million in the following 24 months for its combination drugs aimed at disrupting the Gram-negative bacterial membrane, allowing antibiotics to reach their targets.

Tetraphase Pharmaceuticals
Watertown, Massachusetts

Awarded $4 million over 18 months to further  TP-6076, an investigational synthetic fluorocycline antibiotic that targets the most urgent multi-drug resistant Gram-negative bacteria.

Visterra
Cambridge, Massachusetts

Awarded $3 million over 12 months, and potentially up to $4.2 million in the following 12 months to develop an antibody-drug conjugate (ADC) engineered to kill strains of the deadly Pseudomonas bacteria.

The CARB-X collaborators include:

The U.S. Biomedical Advanced Research and Development Authority (BARDA), Britain’s philanthropic Wellcome Trust, the R&D Centre for Antimicrobial Research (AMR Centre), Boston University, MassBio, the California Life Sciences Institute (CLSA), and the National Institutes of Health’s National Institute of Allergy and Infectious Disease (NIAID).

The Broad Institute of MIT and Harvard will host CARB-X and RTI International will provide technical and regulatory support services, through computing systems that can identify, track and monitor the research programs.

Photo: jarun011, Getty Images

A lot to GAIN: Zavante awaits pivotal data on retro-antibiotic

When the current drugs stop working and there’s a shortage of anything new, what options does the medical community have to combat antibiotic resistance?

Circa 2010, the answer was ‘not a lot.’

It was that dire lack of options that led to a bipartisan initiative dubbed the Generating Antibiotics Incentives Now Act (GAIN Act), signed into effect in 2012. That year, the CDC estimates some 23,000 Americans died from antibiotic-resistant infections.

While the situation remains critical, the GAIN Act is working, said Ted Schroeder, founder and CEO of Zavante Therapeutics.

“The overall intent was to broaden the number of products that were available to U.S. patients,” Schroeder said in a phone interview.

That means new drugs and old drugs that could hold untapped potential.

San Diego, California-based Zavante is chasing the latter. With the passing of the GAIN Act, Cofounder and CSO Evelyn Ellis-Grosse picked up U.S. rights to an old antibiotic known as fosfomycin.

The discovery of fosfomycin dates back to 1969 and it has been used at low doses in regions outside the U.S. for several decades since. It is also sold locally as an oral formulation called Monurol, though Schroeder noted that its bioavailability is low.

In an era of antibiotic resistance, where’s the logic in going back to an older generation of drugs?

Schroeder cites two reasons. The first is the unusually benign safety profile of fosfomycin. It allows Zavante to take a “modernized approach to dosing,” upping the dose and administering it intravenously, he said. It was part of the reason Ellis-Grosse sought out the U.S. rights.

A second distinguishing feature is the drug’s one-of-a-kind “primitive” mechanism of action, which could help extend the life of the drug.

“It doesn’t need a specific binding protein, so the opportunity for cells to evolve around the antibiotic and create a new pathway for resistance is dramatically lower for this antibiotic than it is for the other classes,” he explained.

At a basic level, the drug is also effective against a broad spectrum of Gram-negative and Gram-positive activity, including activity against multi-drug resistant (MDR) pathogens associated with life-threatening infections.

For it to make economic sense, a variety of incentives had to come together for Zavante to launch and raise a $45 million Series A the following year.

Its formulation of fosfomycin, called ZTI-01, was designated a Qualified Infectious Disease Product (QIDP), part of the GAIN Act program. QIDP creates a path for important antimicrobials to receive priority review, fast track designation, and a five-year extension of patent exclusivity.

The latter benefit was critical. Prior to the GAIN Act, the antibiotic would have received just three years of patent exclusivity through the Hatch-Waxman Act of 1984.

“This antibiotic would not even be a discussion if it weren’t for the GAIN Act,” Schroeder said. “With three years of Hatch-Waxman as your only regulatory exclusivity, you couldn’t afford to invest $45 plus million to bring the product to the market here. You just don’t have enough time to make a return on that investment.”

Given a version of this drug is already approved in the United States, ZTI-01 qualifies for a 505(b)(2) regulatory pathway. Existing data and studies can be used as supporting evidence. It allowed Zavante to move directly from Phase 1 through to a pivotal Phase 3 trial in hard-to-treat urinary tract infections. The data readout is expected soon.

All going well, the drug could reach the market by the end of 2018. Once approved, there are many, many possible areas to expand into, Schroeder said.

“This isn’t the answer to the problem, but it’s a significant step forward,” he noted, of the push to get ZTI-01 to the United States to help fight antibiotic resistance here.

Photo: Andrew Brookes, Getty Images

Allergan and Paratek nail pivotal acne trial, while Foamix makes a late-stage stumble

Two drugs, four trials, three companies.

Data from two investigational acne therapies were released Monday, dispatching biopharma shares in opposing directions.

Allergan and Parateks’s sarecycline met both primary endpoints in its two pivotal Phase 3 trials, setting the stage for a new drug application (NDA) filing in the second half of the year.

Paratek, which holds all non-U.S. commercialization rights, saw its shares climb 11 percent in premarket trading. With a market cap of close to $80 billion, Allergan nudged up just under two percent on the promise of its U.S. rights.

The sun was not shining on Foamix in the same way. It’s investigational minocycline foam FMX101 looked iffy, demonstrating statistically significant benefits in one trial, while falling short of its endpoints in a second. Investors weren’t impressed, beating the company’s shares down 47 percent in premarket trading.

In a statement, Foamix CEO Dov Tamarkin, said a full analysis was underway.

“Whereas Trial 05 showed significance in both primary endpoints, Trial 04 did not meet significance for the IGA score endpoint. Our team has not yet received the full data set and we intend to provide an update on the program as soon as we complete our analysis.

Just last week, Foamix was looking pretty to many analysts who were encouraged by its solid Phase 2 results. If today’s news had been positive, the company could have moved forward to an NDA filing in the first half of 2018. A subsequent approval would have marked the Israeli company’s first foray into the market.

Instead, it’s back to the drawing board. Foamix ended 2016 with cash and investments of $131 million, enough to fund operations into mid-2019, the statement said.

Acne is the most common skin condition in the United States, which makes for a complex risk-reward equation. While it can cause scarring and severe emotional strain, significant side effects may not be worth it for patients with milder, transient forms.

Topical and oral antibiotics are the most commonly used treatments for moderate-to-severe cases. Taken systemically, they can cause headaches, dizziness, fatigue, nausea, photosensitivity and severe itchiness. It is also possible to develop a resistance to the therapies over time.

Topical treatments typically have fewer side effects, which is where Foamix wants to carve out its space. The company has established a wide patent estate covering foam technologies for existing antibiotics. These can be applied to acne, rosacea and other skin conditions. FMX101, a 4 percent minocycline foam, was its most advanced candidate.

Was there a flaw in the study design or was the topical approach not enough to treat moderate-to-severe acne? The American Academy of Dermatology notes that oral drugs may be required when red, swollen acne is present. Based on the stellar Phase 2 results, FMX101 seems to have the potential.

Allergan and Paratek’s sarecycline is a tetracycline-derived antibiotic taken orally. While it is related to the mainstay acne antibiotics minocycline and doxycycline, it is considered “narrow spectrum,” which should reduce many of the side-effects associated with systemic antibiotic use.

According to the joint statement, the most common adverse events (greater than 2 percent) in the treated arm of the Phase 3 trials were nausea (3.2 percent), nasopharyngitis (2.8 percent), and headache (2.8 percent). Combined, the rate of discontinuation due to adverse events among sarecycline-treated patients in the two studies was 1.4 percent.

Photo: nicoolay, Getty Images

BIO CEO Company Snapshot: Tetraphase Pharmaceuticals

The BIO CEO & Investor Conference is now just a week away, and buzz for the event has never been greater. Tomorrow, Inside BIO is hosting its first ever twitter chat to discuss the annual buyside survey, which has been getting great responses from the investor community. Presentation spots are still sold out as well, and we’re continuing to highlight those companies slated to present. One such company is Tetraphase Pharmaceuticals, who went public this year. Read on to hear about their antibiotic drugs, and what they see in store for them in 2014 and beyond.

tetraphase

 

What is your company’s lead product or technology?

Our lead candidate is eravacycline, a novel, fully synthetic tetracycline antibiotic that has demonstrated potent activity against a broad spectrum of bacteria, including many of the multidrug-resistant (MDR) Gram-negative bacteria highlighted as urgent public health threats by the CDC. We are currently studying the safety and efficacy of eravacycline in two Phase 3 clinical trials in the indications of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). We expect data from both trials in the first half of 2015 and to file an NDA for eravacycline in the U.S. by the end of 2015.

How does your company go about differentiating itself from the competition?

As a company, Tetraphase is unique amongst its peers, as we have built a product pipeline of novel antibiotics using our internal proprietary antibiotic discovery engine. Our chemistry technology allows for the modification of the tetracycline scaffold in ways never before possible, overcoming resistance and revitalizing the tetracycline class of antibiotics, long considered one of the safest of classes. We believe Tetraphase represents a compelling investment opportunity in the Gram-negative space, given that we are the only public company where successful market entrance offers significant upside potential in valuation. In addition, eravacycline, which was discovered using our technology platform, is the only Gram-negative candidate in late-stage development that has the potential to be used as a monotherapy with convenient once- or twice-daily dosing, and that is expected to be available in both IV and oral formulations.

Your company went public last year. What are your company’s goals and priorities for 2014?

In addition to our IPO last March, we also completed a follow-on offering in November, raising total gross proceeds of approximately $130 million during 2013. With these proceeds, we are currently executing on our Phase 3 clinical program of eravacycline. In mid-2014, we expect to have data from the lead-in portion of the Phase 3 cUTI clinical trial that will identify an oral dose of eravacycline to take into the pivotal portion of the study. We also own worldwide rights to eravacycline – announcements of single or multiple partnerships for development and commercialization rights to eravacycline outside the U.S. are possible during 2014. We continue to make progress on our pipeline as well, and expect to file an IND on our second clinical candidate TP-271, an antibiotic being developed with funding from NIAID to combat serious biothreat pathogens.

Tell us something about your company that investors might not know. 

Those not familiar with the antibiotic space may not know that Tetraphase is benefiting directly from new regulatory guidelines and legislative action. In response to the rise in MDR infections and increased mortality rates and also to encourage the development of new antibiotics, the FDA no longer requires two pivotal studies per indication, permitting companies to file for regulatory approval with two Phase 3 studies in distinct indications. For eravacycline, we will be seeking approval from one Phase 3 study each in cIAI and cUTI. In addition, Tetraphase is benefitting from the GAIN (Generating Antibiotics Incentives Now) Act of 2012. Through the Act, eravacycline has received QIDP (Qualified Infectious Disease Product) designation for both the cIAI and cUTI indications, making it eligible for Fast-Track status, priority review, and an additional five years of U.S. market exclusivity should it ultimately receive FDA approval.

Investors also may not know that eravacycline actually has very broad-spectrum activity – covering not only Gram-negative bacteria, but also Gram-positive and anaerobic bacteria. Although we are pursuing Gram-negative indications currently, eravacycline has some of the most potent activity amongst currently marketed antibiotics against Gram-positive bacteria, including MRSA and VRE.

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Tetraphase’s President and CEO, Guy MacDonald, will be presenting on the second day of the conference, Tuesday, February 11th at 3:00pm in Basildon. You can see the full list of presenting companies here.

Company snapshots are meant to be previews of presentations given at BIO events by way of answering set questions. BIO does not substantiate or validate any claims mentioned in company snapshots or presentations.