With more than 500,000 people dying each year due to their bodies rejecting currently available antibiotics, profits are drying up and the world’s largest drugmakers are backing off. This is leaving the field to a group of ambitious startups, according to a study.

Four companies — GlaxoSmithKline Pharmaceuticals, Novartis International, Teva Pharmaceuticals and Mylan Pharmaceuticals — account for half of global antibiotic production, according to Access to Medicine Foundation’s Antimicrobial Resistance Benchmark. Of 138 research projects in the pipeline, nine in the clinical stage of development are considered novel, meaning they offer a much lower risk of rejection.

“We have reached a tipping point where large and prominent drugmakers have retreated from the antibiotics field and smaller innovative biotech companies have gone bankrupt due to the poor financial rewards on offer,” wrote Jayasree K. Iyer, the foundation’s executive director.

Impact investors see an opening to make a difference in combating antimicrobial-resistant infections. Last year, 37 antibiotics-related healthcare companies raised a record $250 million, more than three-folds the amount raised five years ago, according to PitchBook data.

HiFiBiO Therapeutics raised $67 million series C led by IDG Capital last August, the largest amount raised in the field. The Paris and Cambridge, Massachusetts-based company is developing single-cell profiling technologies to advance the antibody pipeline for cancer and autoimmune disorders.

Managing the waste from drug manufacturing is vital to the fight against antimicrobial-resistant infections. Manufacturing residue dumped into the environment gives bacteria opportunities to develop resistance, which leads to more infections. The foundation assessed 17 drugmakers for environmental risks, and found that 13 out have made some effort to limit their impact on the environment.

The AMR Industry Alliance, consisting of more than 100 companies in the field, is urging all firms involved in the making of drugs to set discharge limits.

  • Danish drug maker Novo Holdings launched a Repair Impact Fund in 2018 to accelerate early-stage development against resistant microorganisms. The fund has $165 million in its budget and has invested $48 million in eight companies, two of which are developing drugs that are in Phase l. 
  • CARB-X, an antibacterial therapy accelerator sponsored by the U.S. Department of Health and Human Services and led by Boston University, has invested $182.5 million in 55 projects around the world since it was established in July 2016.