Harvard startup developing a novel category of antibiotics

When penicillin, the inaugural antibiotic sanctioned for general use, was introduced in the 1940s, The New York Times declared it as “the most powerful germ-fighting agent ever discovered.” In 1945, many of the researchers who were pivotal in its development received a Nobel Prize for its profound influence on medicine. Humanity had entered the antibiotic epoch, during which survival against various infections and ailments that were previously lethal became attainable.  

However, the current scenario has become considerably more intricate.  

Antibiotics function by attaching to or damaging various components of a germ’s structure. Penicillin, for instance, attaches to a segment of the bacterial cell wall and degrades it. Nonetheless, germs are intelligent; over time, they can develop resistance strategies — such as altering the target of an antibiotic so that it can no longer connect effectively or expelling the antibiotic from the germ’s cell walls. These resistance strategies get transmitted to other germs, indicating that antibiotics which were initially effective against an infection may no longer work.

This situation has triggered one of the most severe health crises of our era. Antibiotic resistance, according to the World Health Organization, led to over a million fatalities globally in 2019 and contributed to nearly 5 million deaths. Simultaneously, new antibiotic classes are being approved at alarmingly low rates. Between 2017 and 2022, merely a dozen antibiotics were sanctioned worldwide, and only two of those belonged to new classes that function differently from existing medications.

Introducing Kinvard Bio, a biotechnology firm that on Monday announced its inception from the Myers Lab within the Department of Chemistry and Chemical Biology at Harvard University. The startup is pioneering a new category of antibiotics with the aspiration of combating drug-resistant infections and diseases.

Andrew Myers, the Amory Houghton Professor of Chemistry and Chemical Biology at Harvard, had already established himself as a leading synthetic chemist globally when he resolved to direct much of his lab’s focus towards tackling the global health emergency caused by antimicrobial resistance. Chemists have long traveled to Harvard to learn from Myers. For over a decade, those scholars have contributed to innovations that can address this critical unmet health necessity.

The research conducted in the lab not only generates new compounds that may provide solutions to a stubborn problem but also fosters the next generation of scientists who can persist in confronting the challenge. Kelvin Wu, a co-founder of Kinvard Bio who co-helmed the research team as a graduate student in the Myers Lab, hopes that the company’s platform will aid in addressing the “resistance crisis.” He expresses, “Antibiotic discovery is a global issue that deeply concerns me.”

Kinvard Bio’s CEO Lloyd Payne reinforced Wu’s apprehensions regarding the narrowing treatment options. “There is an urgent requirement for ongoing innovation to introduce new antibacterials into the pipeline to ensure that we can successfully address challenging drug-resistant infections for generations to come.”

The new pharmaceuticals under development at Kinvard Bio concentrate on the bacterial ribosome, an antibiotic target that is highly validated in clinical settings, as per Payne. Although a number of antibiotics that target the ribosome already exist, the antibiotics from Kinvard Bio — termed oxepanoprolinamides — are structurally preorganized for optimal binding to the target.

“The bacterial ribosome is an immensely crucial target, as it is clinically proven and vital among a wide array of clinically significant pathogens, but what’s paramount — and this is truly essential — is that the oxepanoprolinamides bind to the ribosome in a remarkably distinct manner,” Payne elaborated. “There remains work to be done to advance the program into human clinical trials, but this binding approach offers promising potential for evading pre-existing resistance to currently utilized antibiotics.”

The Myers Lab has been focused on developing this category of compounds for over a decade. However, their origins go even further back — tracing to the 1960s, not long after penicillin heralded the world into the antibiotic era. In 1964, the Federal Drug Administration sanctioned lincomycin — an antibiotic derived from a soil microbe — representing a significant advancement, according to Payne, because, at that time, it served as an alternative for individuals allergic to penicillin.

“This was a previously underutilized class of antibiotics that was primed for revitalization,” noted Wu.

Myers’ group secured funding and additional assistance from Harvard’s Blavatnik Biomedical Accelerator to bolster their efforts, which include the synthesis and examination of new compounds, leading to a 2021 publication in Nature.

For certain design aspects, the team had to innovate entirely new chemistry. “One of the reasons this initiative has thrived is our capacity to assemble the molecules very efficiently. Through chemical synthesis, we can begin with simple building blocks and then interconnect them into a highly complex molecule,” explained Ben Tresco, co-founder of Kinvard Bio, who co-led the research group with Wu as a graduate student in the Myers Lab. “The reason these molecules differ so significantly from their predecessors — the other molecules that connect to this site — is because they are exceptionally optimized for binding to the bacterial ribosome.”

In 2024, the team received a $1.2 million grant from the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) along with additional support from the Blavatnik Biomedical Accelerator to further enhance the development of the antibiotics. Kineticos Life Sciences, an investment firm devoted to companies

In the fields of oncology, uncommon disorders, and resistance to antimicrobials, thanks to its association with CARB-X, was acquainted with the technology through Harvard’s Office of Technology Development (OTD). Kineticos nurtured and financed the enterprise via the Kineticos AMR Accelerator Fund I.

“OTD played a pivotal role in ensuring that investors were informed about the endeavors of the research team and that there was significant promise for the establishment of a new company,” stated Curtis Keith, the chief scientific officer at the Blavatnik Biomedical Accelerator.

Initial preliminary investigations have indicated that the antibiotics are effective against a diverse array of pathogens linked to various infections, even those resistant to alternative antibiotics.

The startup is initially constructing a pipeline that targets acute and chronic infections with substantial unmet patient needs, such as bacterial pneumonia, complicated urinary tract infections, and chronic respiratory infections, intending to develop both intravenous and oral preparations. Both methods of drug administration hold significance as oral antibiotics can successfully decrease hospital admissions and lengths of stay. Prolonged hospital stays elevate the risk of acquiring additional infections. Eventually, opportunities may extend to encompass notoriously difficult chronic infections like nontuberculous mycobacteria lung disease.

As per Keith, the research aligns with the core mission of the Myers Lab — leveraging synthetic chemistry to address some of the globe’s most urgent issues. “They’re not simply performing chemistry that will stay confined to the laboratory; the research team is dedicated to creating tangible solutions that could lead to effective and accessible antibiotics.”

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The investigation discussed in this article is supported by the National Institutes of Health and by CARB-X, whose funding for this initiative is partly sourced from federal funds allocated by the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority; Wellcome; Germany’s Federal Ministry of Education and Research; and the UK Department of Health and Social Care as part of the Global Antimicrobial Resistance Innovation Fund.