Summit seeks a much-needed superdrug

Company explores candidates against antimicrobial-resistant bacteria

Kristen Smith
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ABINGDON, U.K.—Since acquiring the Discuva Platform in 2017, Summit Therapeutics has used their new capacity to identify novel-mechanism antibiotics that may revolutionize the treatment of antibiotic-resistant infections. Recent news releases affirm their significant progress in detecting potential new treatment options with razor-sharp specificity to minimize the potential for resistance seen in many of today’s broad-spectrum options. Specifically, Summit has announced successful preclinical testing on drugs to treat Neisseria gonorrhea and the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.), all of which have been named as priority targets due to current rates of antimicrobial resistance (AMR).
“AMR is a worldwide problem. We need to see scientific innovation to prevent an era of untreatable infections,” said Dr. David Roblin, president of R&D at Summit. “Through the Discuva Platform, we are using novel science to create targeted, new mechanism antibiotics that are optimized against resistance development. Our goal is to develop the most appropriate drug for a specific patient, thereby improving patient outcomes and giving physicians options to address the spread of AMR.”
Researchers can use the Discuva system in three important ways. First, it allows them to identify novel targets, using rapid throughput of mutant pathogens from their in-house library. Secondly, they are able to elucidate the mechanisms of action, by examining the bacteria both upstream and downstream from the insertion point, which allows them to see specifically where the bacteria impacts the genes and how its functionality changes upstream. Lastly, they are able to avoid potential resistance by interrogating surviving bacteria to narrow the antibiotics’ attack.
According to Roblin, gonorrhea’s growing antibiotic resistance is an emerging public health crisis, making the need for a new treatment for gonorrhea imperative. An estimated 78 million people are currently infected, with infection rates nearing epidemic proportions in Southeast Asia. The current global treatment standard is the antibiotic Ceftriaxone, delivered intramuscularly, though there have been numerous reported cases of “super-gonorrhea” completely resistant to known treatments. Dosage once hovered at 250 mg to treat gonorrhea, but now it is routine to administer 1,000 mg because of decreased efficacy. Complicating the issue, Ceftriaxone is also the preferred course of treatment for many other acute conditions, including meningitis, sepsis and pelvic inflammatory disease, making drug resistance potentially lethal.
“We as an industry need to think about what we can do differently,” remarks Roblin. “We need to limit our approaches to only advance new mechanisms that work in a precision way, moving away from non-inferiority trials that approve different, but not better treatment options. We need to find alternatives that allow for more rational prescribing, and we need to share our strategies and successes to attract more research and deeper investments.”
With collaboration from Örebro University in Sweden, Summit has identified SMT-571 as its lead gonorrhea candidate, proving to be more potent against diverse, global gonorrhea strains from actual patient cases, including numerous multi- and extensively-drug resistant strains.
Neisseria gonorrhoeae continues to evolve and acquire resistance to every marketed antibiotic with which it has been challenged. The concern of practitioners is once 5 percent resistance to the current standard of care is reached, there will be no new treatments available for gonorrhoea,” commented senior author Prof. Magnus Unemo of Örebro University, a WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections. “Antibiotics with a new mechanism of action will be important in addressing the global health threat of gonorrhea. In the published data, we demonstrated that SMT-571, a new mechanism antibiotic, had consistently high potency across hundreds of relevant clinical strains of N. gonorrhoeae, including those that are multi- and extensively-drug resistant. I look forward to the continued development of SMT-571.”
Next up, they will continue to collect and test the most virulent strains, keeping a careful eye on any signal of drug resistance in the lab. They are also seeking a treatment that will be effective with just one or two doses, as compliance issues arise in the at-risk populations most affected by AMR. Once they have identified a precise and effective candidate, they intend to amplify their success to drive further investment in R&D and innovation.
Says Roblin: “We must be more successful than we’ve been in the last 10 years. We need to have success and share our strategy, to attract the attention of more researchers, and more investors. We need to clearly demonstrate the economic benefits of new treatments and grab the attention of the payers.”

Kristen Smith

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