Warp Drive Bio LLC's back-to-nature drug discovery approach landed another deal, this time a potential $387 million pact with Roche Holding AG to discover new classes of antibiotics for drug-resistant gram-negative pathogens. Warp Drive CEO Laurence Reid called it a "huge opportunity to make a contribution to a global problem."

Under the terms, Warp Drive will get up to $87 million in up-front, option fees and milestone payments related to preclinical achievements. Up to an additional $300 million in payments are linked to clinical, regulatory and sales milestones for products licensed to Roche, in addition to tiered royalties – up to double digits – on any products that make it to market.

The initial payments will cover Warp Drive's work, in collaboration with Roche, to "canvass over 100 new classes of novel natural products that we predict – we don't know, we predict – have the potential to be antibiotics," Reid told BioWorld. "Then we'll sift through that set in our collaboration with Roche and pick a subset of those to go into drug discovery," to determine antibiotic activity and capability. Warp Drive will hand off to Roche an undisclosed number of those classes that are identified as development candidates – i.e. "ready to go into the last phase of preclinical testing."

The $87 million will more than cover the cost of that work, while also supporting product opportunities to which Warp Drive will retain the rights, he added.

Founded in 2012 with the aim of applying new drug discovery techniques to identify molecules in nature, Warp Drive boasts two platforms. Its Small Molecule Assisted Receptor Targeting, or SMART, technology aims to create small-molecules against previously undruggable targets. The lead project focused on drugs designed to antagonize RAS proteins, a long-studied target associated with one of the highest mutation rates in cancer but one that had stymied drug developers. In early 2016, Warp Drive disclosed a deal with Paris-based Sanofi to develop three oncology programs targeting oncogenes, including RAS. (See BioWorld Today, Jan. 12, 2016.)

Earlier this year, it inked a deal with London-based Glaxosmithkline plc for its SMART platform to discover drugs against "high-value intractable targets."

Warp Drive's other platform, Genome Mining, aims to ferret out natural drug products within a massive database of more than 135,000 strains encoding more than 3 million biosynthetic gene clusters using what amounts to a genomic search engine. By employing a synthetic biology approach, the company can then engineer and express products for isolating and testing. In essence, "we come at chemistry through genomics and use DNA analysis to really comprehensively catalogue sets of natural products," Reid said. The Genome Mining platform is designed to get around the limitations and time-consuming efforts that caused drug developers to move away from natural products, which offer chemical diversity and evolutionary optimization that makes them more advantageous compared to synthetic products.

The platform has four components: The database of genomic sequences of soil-living bacteria; the bioinformatics capabilities for searching that database to extract genes responsible for biosynthesis; the genomics technology for isolating and manipulating those genes; and the chemistry capabilities to manipulate the structure of the natural product with the desired characteristics of a pharmaceutical.

Warp Drive chose to tackle the drug-resistant infection space for its initial genome mining effort, looking for natural products related to certain classes of known or approved antibiotics such as beta-lactams and aminoglycosides. Its 2016 deal with Sanofi includes work on an aminoglycoside program.

The collaboration with Roche goes a step further – looking for brand new classes.

"Over the past year, we've really invested quite significantly in beginning to hunt for completely new chemical classes of antibiotics," Reid said, adding that the work has garnered "a lot of interest from the outside world," especially as the World Health Organization and other global groups raise increasing awareness for the need of innovative products in the area of antimicrobial resistance.

Last year, a U.K. report, titled "Review on Antimicrobial Resistance," predicted that if nothing is done, by 2050 10 million people per year will die from infections that previously responded to antibiotics, with the cost in terms of global lost production between now and 2050 estimated at $100 trillion. (See BioWorld Today, May 19, 2016.)

There are a few new antibiotics in late-stage development. Paratek Pharmaceuticals Inc., for example, has reported positive phase III data for omadacycline, its broad-spectrum antibiotic, in community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections and is preparing regulatory submissions. Omadacycline, described as a first-in-class aminomethylcycline, has qualified infectious disease product designation from the FDA. (See BioWorld Today, April 5, 2017.)

Nabriva Therapeutics plc, meanwhile, is in pivotal testing with pleuromutilin antibiotic candidate lefamulin in community-acquired bacterial pneumonia. (See BioWorld, Sept. 19, 2017.)

But the years during which pharma tended to shy away from antibiotic development amid regulatory changes, limited commercial upside and an overall decline in investments in the space has created a dire need for new efforts.

Committed to the space

Warp Drive entered discussions with Roche in the early part of this year. "It became clear that we both were committed as part of our strategy to hunting for truly novel antibiotics," he said. "That really brought us together." A deal was signed in about six months.

Specific details of the five-year collaboration remain confidential, but Warp Drive will identify and evaluate more than 100 novel classes of potential antibiotics that were previously undiscovered and never before analyzed for their treatment impact. To put that into perspective, there are currently 10 classes of natural antibiotics that have been approved, with the most recent, daptomycin, originally discovered more than three decades ago.

Warp Drive initially will work with Roche as an exclusive partner on its antibiotics discovery efforts. The company still may seek partners for other programs such as its beta-lactam development.

"It's very exciting to have them as a partner," Reid said of Roche. "They're one of the few large pharmas today that are really committed to the antibiotic space."

After more than a decade away from the field, Basel, Switzerland-based Roche, got back into antibiotics with 2013's deal with Polyphor Ltd. While that potentially $510 million licensing agreement for macrocycle antibiotic POL-7080 was terminated by Roche in 2015, the pharma firm has since inked further deals with Discuva Ltd., which it extended in February, to develop antibiotics against gram-negative bacteria using Discuva's SATIN technology platform, and with Japan's Meija Seika Pharma Co. Ltd. and Canada's Fedora Pharmaceuticals Inc. to develop beta-lactamase inhibitor OP-0595. The latter, inked in early 2015, was worth up to $750 million in combined up-front, development, regulatory and sales-based milestone payments. (See BioWorld Today, Nov. 5, 2013, and Jan. 14, 2015.)

Roche also partnered with Atlas Ventures-based startup Spero Therapeutics in 2014 to develop anti-infectives targeting drug-resistant bacterial infections. (See BioWorld Today, April 10, 2014.)

In 2016, the company received an award from the Biomedical Advanced Research and Development Authority (BARDA), which agreed to provide more than $35 million over two years – and potentially $151.6 million over five years – to support work on diagnostics for detecting viral and bacterial infections and an investigational antibiotic against drug-resistant bacteria.

The good news is that more players continue to enter the field. In addition to funding from BARDA, other organizations have stepped in, including the new Global Antibiotic Research and Development Partnership (GARDP), in which the German government led a commitment by G20 countries to reinvigorate R&D in antibiotic research, and CARB-X, or Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), a public-private partnership between the U.K.'s Wellcome Trust and BARDA, which awarded a second $17.6 million tranche of funding for research earlier this year. (See BioWorld Today, April 3, 2017, and July 11, 2017.)

And venture capital has invested, too. The last few months has seen a $42 million series B round for Venatorx Pharmaceuticals Inc. to support its combo approach comprising a broad-spectrum beta lactamase inhibitor and an approved beta-lactam antibiotic; a $65 million series B for Iterum Therapeutics Ltd. to support late-stage development of sulopenem in gram-negative multidrug-resistant infections; and a $5.5 million series A round for startup Peptilogics Inc. to advance its engineered cationic antibiotic peptide, or ECAP, platform to ply multidrug-resistant bacterial infections. (See BioWorld Today, May 22, 2017, July 26, 2017, and Oct. 2, 2017.)