with what it thinks is a better way to discover and produce antibody drug candidates—San Francisco-based Ablexis, Bothell, WA-based Alder Biopharmaceuticals, and Lebanon, NH-based Adimab are just a few companies we’ve covered at Xconomy that are taking creative approaches that seek to solve some of the traditional limitations of antibodies.
So Pritchard spent most of his time talking about product candidates, not the gee-whiz anything-is-possible-now nature of the technology platform. The lead drug candidate is KB001. This drug made the news last January during the JP Morgan Healthcare Conference, when KaloBios said it secured $35 million in upfront cash from Paris-based drug giant Sanofi-Aventis to co-develop the treatment.
The co-development agreement was structured as as a classic Big Pharma deal, where the bigger company takes responsibility for the broadest application of the drug, while the biotech keeps the rights to the orphan disease use. In this case, Sanofi gets the right to develop KB001 for infections people get in the hospital while they are on ventilators, and KaloBios will focus on developing the treatment for patients with cystic fibrosis and bronchiectasis. Something like 500,000 people a year are thought to get dangerous pseudomonas infections in hospitals each year, meaning that a big company like Sanofi is best suited to take on that market, while about 30,000 patients in the U.S. have cystic fibrosis, making that a niche indication suitable for a little biotech like KaloBios, Pritchard says.
The idea of using an antibody against pseudomonas infections is where things get really interesting. Cystic fibrosis is caused by a single missing or faulty gene that causes buildup of thick, sticky mucus in the lungs. That mucus becomes a haven for pseudomonas bacteria. Pseudomonas then causes havoc partly by puncturing and killing critical immune defense cells known as neutrophils. The body’s immune system tries to fight off the pseudomonas, but it’s a tug of war that over time leads to excess inflammation, scarring of the lungs, and ultimately suffocation.
“It’s the war between the immune system and pseudomonas that kills you,” Pritchard says.
There are conventional antibiotic small-molecules on the market today which are made into inhalable formulations to knock down the pseudomonas, like Novartis’ tobramycin (TOBI) and Gilead Sciences’ aztreonam lysine (Cayston). These drugs are effective at getting inside the bacterial cells and disrupting their machinery for a while, but eventually, as with most antibiotics, the bugs develop resistance.
Based on some novel research at UCSF, KaloBios is tackling this problem in a totally different way. The KB001 antibody is designed to hit a target called PcrV that is found on pseudomonas bacteria, but isn’t found on any cells in the human body, Pritchard says. Essentially, the antibody binds with pseudomonas and renders it unable to puncture white blood cells. So while the antibody doesn’t actually appear to kill the bug itself, it basically makes it a sitting duck for the body’s immune system to swarm and kill the invader like it wants to, Pritchard says. This is a different mechanism than classic antibiotics, and might mean that the pseudomonas won’t be able to develop resistance to the antibody, he says. “People can’t figure out a way in which pseudomonas gets resistance to it,” Pritchard says.
This drug still has a very long way to go
