A D V E R T I S E M E N T F E A T U R E

A D V E R T I S E R R E TA I N S S O L E R E S P O N S I B I L I T Y F O R C O N T E N T

Nosopharmwww.nosopharm.com

Advancing first-in-class anti-infectivetherapies to combat multidrug resistanceNosopharm is an innovative biotechnology company that is focused on exploring untappedmicrobial biodiversity to discover new drugs to fight antimicrobial resistance.

Infectious diseases are a major cause of global mor-tality, accounting for more than 9 million deaths eachyear. The increase in antimicrobial resistance makesthese infections much harder to treat. Antimicrobial-resistant organisms are a leading cause of health-care-associated infections and are considered oneof the top ten public health threats worldwide.

Nosopharm is on a mission to discover and developfirst-in-class anti-infective therapies to address thiscritical challenge. Founded in 2009 and headquar-tered inLyon,France, thebiotechnologycompanytar-gets antimicrobial-resistant bacteria and fungi thatare responsible for the most concerning hospital-acquired infections.

“We are one of the very few biotech companiesdeveloping high-potential first-in-class antibiotics,”said Philippe Villain-Guillot, Nosopharm’s CEO andco-founder. “Novel drugs that can overcome antimi-crobial resistance are urgently needed to safeguardpublic health.”

Medicinal mining of microbesNosopharm has developed an innovative drug dis-covery platform called ExploRhabdus, which inte-grates natural products, anti-infective screening,microbiology and medicinal chemistry. The platformharnesses the therapeutic potential of the bacterialgenera Photorhabdus and Xenorhabdus. The complexlife cycle of these bacteria, which have a symbioticrelationship with nematodes, requires the productionof a broad range of antimicrobial compounds (Fig. 1).

When the nematode infects an insect, the bacteriaproduce immuno-modulating and toxic compoundsthat kill the insect. The nematode and the bacteriause the dead insect as a source of nutrients to repro-duce. To this end, the bacteria produce antibioticmolecules that prevent microbial competitors fromdegrading the dead insect. Until recently, the antibi-otics made by Photorhabdus and Xenorhabdus werelargely understudied.

Yet these powerful molecules have three keyadvantages for anti-infective drug discovery. First,they have undescribed chemical scaffolds, suggest-ing novel mechanisms of action and making themeffective at treating infections that are unresponsiveto other antibiotics. Second, they are not toxic tothe nematode, increasing the likelihood that theyare safe for eukaryotic organisms such as humans.Third, they interact with the biological matrices ofthe dead insect, representing a natural primary filterfor drugability.

“Xenorhabdus and Photorhabdus are a high-valuebioresource for anti-infective drug discovery,” Villain-Guillot said. “With our unique and ever-expanding

expertise in the biomining of these bacteria, the drugdiscovery platform ExploRhabdus provides a higherprobability of obtaining drug candidates by avoidingthe main pitfalls of natural product drug discovery.”

Aiming for eradicationNosopharm’s drug discovery platform has enabledthe discovery of several new antimicrobial moleculessuch as odilorhabdins. Using a unique antibacte-rial mechanism, odilorhabdins bind to the bacte-rial ribosome and disrupt protein synthesis, killingbacteria rather than simply slowing their growth. Themost advanced program in Nosopharm’s pipeline isNOSO-502—a first-in-class odilorhabdin antibioticthat targets multidrug-resistant Enterobacterales,which are top-priority pathogens according to theWorld Health Organization.

The main hospital pathogens of the Entero-bacterales family are Escherichia coli and Klebsiellapneumoniae. They have been detected in 20–30%of hospital-acquired infections in Europe and theUnited States. These pathogens have reached highrates of resistance to multiple drugs, including last-resort antibiotics called carbapenems. In Italy, a G7member state, carbapenem-resistance rate was29% in 2019.

NOSO-502 has demonstrated antibacterial activ-ity against multidrug-resistant clinical isolates,including NDM carbapenemase producers. It hasalso proven to be effective in Enterobacteralesinfection models, such as peritonitis/sepsis, urinarytract infection and respiratory tract infection. “Uponsuccessful completion of clinical development,NOSO-502 will be the first novel antibiotic classfor Enterobacterales infections to be introduced intothe clinic in 40 years,” Villain-Guillot said.

Expanding the arsenalNosopharm’s product portfolio includes twoadditional programs intended for the treatment ofsystemic Pseudomonas aeruginosa infections andCandida infections.

The pathogen P. aeruginosa is involved in ~10%of hospital-acquired infections in Europe and theUnited States. Carbapenem-resistant P. aeruginosa isconsidered by the World Health Organization to bea critical priority for the research and developmentof new antibiotics.

The main fungal hospital pathogens belong to theCandida species, which has been detected in 6%of hospital-acquired infections in Europe and theUnited States. Very few antifungal drug classes areavailable to treat these infections. This is of par-ticular concern because some multidrug-resistantCandida species are rapidly emerging.

“The current therapeutic arsenal, ageing and inneed of renewal, no longer enables clinicians to copewith the dire situation posed by these life-threaten-ing multidrug-resistant pathogens,” Villain-Guillotsaid. “We remain firm in our commitment to workwith existing and future partners to further developour entirely new antibiotic classes, which are des-perately needed to tackle the growing and globalthreat of antibiotic resistance.”

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Fig. 1 | ExploRhabdus, Nosopharm’s drug discovery platform. The platform harnesses the therapeuticpotential of the bacterial genera Photorhabdus andXenorhabdus. 1.Xenorhabdus or Photorhabdus live in theintestine of the host nematode. 2. The host nematode infects an insect. 3.Xenorhabdus or Photorhabdus arereleased within the insect and kill it. 4.Xenorhabdus or Photorhabdus produce antibiotic molecules thatprevent the microbial competitors from degrading the insect’s body. 5.Xenorhabdusor Photorhabdus colonisethe nematode, which along with the bacteria use the insect’s biomass as a source of nutrients to reproduce.

Philippe Villain-Guillot, CEONosopharmLyon, FranceTel: +33 6 26 63 24 89Email: p.villainguillot@nosopharm.com

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www.nature.com/biopharmdeal | December 2021 | B11