New partnership for a new antibiotic class

Nosopharm and Evotec unite to develop antimicrobial candidates

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LYON, France & HAMBURG, Germany—July began with the news that Nosopharm and Evotec SE have initiated a partnership to advance NOSO-502, the former’s lead candidate, to the clinical stage, in addition to developing a second-generation odilorhabdin drug candidate. The initial focus of the agreement will be on chemistry, manufacturing and control, as well as clinical trial application-enabling and filing activities for NOSO-502, ahead of the planning of Phase 1 clinical trials in complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI). No financial terms for this agreement were released.
“We are delighted to see that such a renowned industrial biotech partner has decided to support the development of our new class of antibiotics,” said Philippe Villain-Guillot, co-founder and chief executive officer of Nosopharm. “We are very much looking forward to advancing our first drug candidate into the clinic and to expanding our drug development to a second candidate.”
NOSO-502 is the first of a novel antibiotic class known as odilhorhabdins (ODLs). The compound inhibits bacteria’s ribosome with a new mechanism of action, and is targeted against nosocomial infections caused by Enterobacteriaceae bacteria, including polymyxin- and carbapenem-resistant Enterobacteriaceae (CRE). Testing to date has shown NOSO-502 to be effective in vivo in models of Enterobacteriaceae infection, and in vitro it has shown antibacterial activity against multi-drug resistant clinical isolates—including Klebsiella pneumoniae, New Delhi metallo-beta-lactamase and OXA, among others. If approved, this candidate could be the first novel antibiotic class addressing Enterobacteriace infections to reach the clinic in 40 years.
The second program under this partnership will be a second-generation odilorhabdin clinical drug candidate for the treatment of hospital-acquired pneumonia and ventilation-associated pneumonia (HAP/VAP), known as NOSO-2G. This partnership will focus on lead optimization, profiling for candidate selection and further development of the candidate.
When asked what made Evotec an ideal partner for this work, Villain-Guillot points to Evotec’s acquisition of Sanofi’s infectious disease portfolio, noting that “This way, we get access to resources and expertise to be able to develop our compound to the end of Phase 1 clinical trials.”
“We have a very strong expertise in biology and chemistry, and we aim to explore further the clinical space of odilhorhabdins,” he says of the partnership. “We want to rely on the complementary experience of Evotec to explore this new clinical space. This will be a 50/50 collaboration.”
Nosopharm expects to file a clinical trial application for NOSO-502 in 2021, and to initiate first-in-human studies the same year. The clinical candidate selection process for NOSO-2G is expected to take place in the following year.
“It’s exciting to see the development of an entirely new antibiotic class, which is crucial in these times of rising antibiotic resistance,” noted Dr. Cord Dohrmann, chief scientific officer at Evotec. “We are thrilled to play a key role in this partnership and we believe that with the unique combination of our infectious disease expertise and drug discovery and early development platforms, the lead candidates will soon enter the clinic and bring hope to physicians and their patients living with nosocomial infections caused by multidrug-resistant bacteria.”
Villain-Guillot tells DDNews that NOSO-502 is the result of screening natural products.
As explained on Nosopharm’s website, “Nosopharm has designed and developed an innovative anti-infective drug discovery platform based on the medicinal mining of an original microbial bioresource: the bacterial genera Xenorhabdus and PhotorhabdusXenorhabdus and Photorhabdus are Gamma-proteobacteria from the Enterobacteriaceae family. Xenorhabdus and Photorhabdus are symbiotic bacteria of the entomopathogenic nematodes from the genera Steinernema and Heterorhabditis. These bacteria have a fascinating life cycle that requires the production of a great diversity of antimicrobial compounds.”
These two genera provide three major advantages, according to the company:
  • “They produce novel and undescribed antimicrobial molecules with original chemical scaffolds;
  • They produce novel antimicrobials that are not toxic to the nematode. This feature represents a natural primary filter for safety in eukaryotic organisms such as humans;
  • They produce novel antimicrobials that are designed to interact with the biological matrices of the dead insect. This feature represents a natural primary filter for drugability.”
Villain-Guillot notes that when testing its compounds, “We have shown that efficacy in several resistant infections, like urinary tract infections in mice. We did not observe any resistance so far, but we have to be cautious because bacteria can evolve resistance very quickly. Some bacteria may have some resistance somewhere in the world, so we have to watch this, but so far, no real issue of resistance to our compound. And now we have to carry on the development of the compound to enter trials by 2021.”
Antibiotic-resistant bacteria are a leading cause of hospital deaths worldwide, and as bacteria continue to evolve resistance to existing antibiotics, the problem is set to continue. In February 2017, the World Health Organization published a list of priority pathogens for the development of new antibiotics, which included Carbapenem-resistant gram-negative bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii) as critical priority targets. That year in the European Union and the European Economic Area, carbapenem-resistance rates for Klebsiella pneumoniae (Enterobacteriaceae), Pseudomonas aeruginosa and Acinetobacter baumannii were 7.2 percent, 17.4 percent and 33.4 percent, respectively.

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