The genesis of San Diego’s RQx Pharmaceuticals began in 2010, with a chance encounter by two strangers at Zumbar Coffee & Tea in Sorrento Valley.
Floyd Romesberg says he likes to start his day at Zumbar because it’s a good place to get some paperwork done before he heads into The Scripps Research Institute, where his lab is focused on biological and biophysical chemistry, particularly on the processes affected by the forces of evolution. Court Turner, who is a life sciences venture partner at San Diego’s Avalon Ventures, also hangs out at Zumbar before work.
They had noticed each other before, but never spoke—until one day when Romesberg says their eyes met after he overheard Turner in an extended, biotech-themed conversation. Romesberg says he asked the young stranger, “So you’re a VC?”
In their ensuing conversation, Romesberg outlined his interest in antibiotics, a field of growing concern among healthcare providers due to the increasing number of drug-resistant pathogens. MRSA, also known as multidrug-resistant Staphylococcus aureus, may be the best known example of these infectious killers because of its prevalence in hospitals. But it is just one in a group of troubling, drug-resistant microbes known as the “ESKAPE” pathogens, for E. faecium, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa and E. coli.
Romesberg said his lab had made a breakthrough with arylomycin, a compound found in nature that was known to work as an antibiotic on just a few types of bacteria. Eli Lilly, Bristol-Myers Squibb, GlaxoSmithKline, and other pharma giants had tried for decades to enhance the antibiotic’s potency, without much success.
Romesberg’s team showed that the pathogens that are resistant to arylomycin shared a key feature—a mutation in the binding site of an essential enzyme (Signal Peptidase) that sits on the surface (or just within it) of both Gram-positive and Gram-negative bacteria. Romesberg has suggested that the mutation, which added a floppy proline amino acid in the pocket of the binding site, was an adaptation that bacteria evolved millions of years ago as a defense against arylomycin.
Arylomycin binds to the enzyme and blocks its enzymatic activity, which is crucial for the microbes to survive. Romesberg’s team found that bacteria without the mutation are potently killed by arylomycin. More importantly, though, Romesberg said their research showed that arylomycin could be “optimized” to overcome and kill bacteria carrying the mutation that usually protects against arylomycin.
In other words, with a few tweaks to improve the molecule’s affinity for binding with a particular enzyme, arylomycin could represents a new class of broad-spectrum antibiotics that would be effective against a variety of infections, including those caused by MRSA and other drug-resistant pathogens.
Turner says the significance of Romesberg’s breakthrough was obvious. No fundamentally new class of broad-spectrum antibiotics has been developed since the quinolones were introduced to the clinic in 1962. And drug-resistant bacteria have never seen an antibiotic like this, he says.
Turner describes Romesberg’s discovery as exactly the sort of fundamental breakthrough that Avalon founder Kevin Kinsella seeks to invest in. Another key factor in deciding to start RQx, he says, was that Romesberg had done it before. He was a founder in Achaogen, an eight-year-old biopharmaceutical in South San Francisco focused on developing new antibiotics for treating multi-drug resistant Gram-negative bacterial infection.
And so RQx Therapeutics was born. In a regulatory filing at this time last year, Avalon disclosed that it was providing the first $1 million of what could be as much as $7 million in funding for the company. Since then, San Diego’s Correlation Ventures has joined as a venture investor.
Today, the company consists of five regular employees (including two former grad students from Romesberg’s lab). Over the past year, the scientific team has validated the target initially identified in Romesberg’s lab, and added hundreds of arylomycin analogs to the RQx library.
“The RQx story is early but very encouraging and impressive, especially considering that Big Pharma has been focused on this target for many years,” Turner says. At this point, he added, the team is focused on “getting the data to an inflection point that would be interesting to Big Pharma.
“If you can kill bacteria in a mouse, it’s very translatable [to human beings], so it would be easier to make early calls” to prospective industry partners, Turner says. “We are in a very good position now to partner the program.”
As for their initial meeting, which led directly to the founding of RQx, Romesberg says, “It really was pretty serendipitous.”