A T-cell player with backing from Roche takes next big step for BiTE drugs with 'on-off' switch to avoid toxicity
The bispecific T cell engager field is absolutely packed with big-name players who have crowded in despite some high-profile failures in the class. Now, a Bay Area biotech thinks it may have the key to tackling BiTE toxicity, using an old “on-off switch” idea to give doctors more control of the drugs’ effect on patients.
San Francisco-based Soteria Biotherapeutics uncloaked Monday with a $42 million Series A co-led by Roche Venture Fund and 5AM Ventures with participation from the Novartis Venture Fund to advance its bispecific T cell engagers with an “on-off” switch the founders think can avoid some of the dire safety flags endemic to the class.
The biotech’s tech, dubbed T-LITE, works by using an oral small molecule drug to bind and activate the two components of the BiTE drug in vivo, giving physicians the ability to decide when and for how long to engage the drug in patients. It’s a process known as chemically induced dimerization, and Soteria thinks it can give their drugs that sought-after “switch” that other BiTE drugs don’t have, CEO Kristine Ball told Endpoints News.
So dimerization is the “on” function, but how about “off?” According to CSO and co-founder Zach Hill, whose research alongside cofounder Alex Martinko — now the senior director of protein science — and Jim Wells of UCSF undergirds Soteria’s tech, physicians can simply stop dosing the oral small molecule. Without the constant presence of that chemical ligand, the tumor cell antigen and T cell engaging components of the BiTE drug revert back to their dormant forms without lasting effect.
Using chemically induced dimerization in therapeutic applications isn’t a new concept, Hill says, but using that process to bind and direct antibodies in a cell therapy application is a big advance and could give Soteria a big leg up over its myriad competitors in the space.
“We really had this idea that Jim presented to us of saying look, is there a way to make a new generation of chemically induced dimerization domains that utilize better small molecules and have proteins that have better properties,” Hill said. “So he really tasked us with this grand challenge and eventually Alex and I were able to come up with the idea of making these around antibodies.”
With that breakthrough in hand, the Hill-fronted brain trust set up Soteria in 2018 with the help of a small seed fund has been “essentially incubating” ever since, Hill said. Ball, who came to the team with decades in the field, including for a stint on the board of directors at Forty Seven before its acquisition by Gilead in March 2020, joined the team late last year to help take the wraps off its launch plans.
“Our technology is unique because the T-LITEs can modulate the T cell activity by controlling the timing, duration and level of bispecific complex formation … which should allow us to widen that therapeutic window, push dose and have more efficacious treatments,” Ball said.
Bringing Roche’s venture arm onboard to the concept was a lucky one for Ball as she was pointed to a contact through a life sciences poker group, of all things, and cold-pitched the fund on Soteria’s tech. The excitement over the possibility of tamping down safety risks was enough to earn their interest, and the rest is history.
Soteria kicked off its lead program late last year and hopes to select a candidate for that program sometime this year. The company expects to use the proceeds from the round to narrow that search and move the program into IND enabling studies. Meanwhile, Soteria will look to flesh out its early pipeline, and that process will be made infinitely easier by Soteria’s plug-and-play design program. Creating a new drug is as simple as switching out the tumor antigen component of the T-LITE, Ball said, giving the company plenty of synergy in its development process.
“Once we get our first T-LITE where we like it, there’s plenty of efficiencies from program to program,” she said.