The road to any successful drug will have some wrong turns and detours, so scientists celebrate successes along the way. Nathan Trinklein, co-founder and chief scientific officer of Rondo Therapeutics, remembers one particular success at his previous company. One patient in the clinical trial had a tumor that, on imaging scans, looked the size of a baseball. But after treatment with the experimental therapy, Trinklein said it went away.
“It’s a profound thing to see a drug you’ve sketched out early on on paper and then see a patient’s tumor actually disappear in a phase 1 trial,” he said.
The company developing the therapy, Teneobio, specializes in a type of cancer drug called a bispecific antibody. Ango bought the biotech last summer for $900 million, which is also a success to celebrate. But Trinklein and Teneobio’s former colleague Shelley Force Aldred had unfinished business. Although bispecific antibodies are effective against blood cancers, they are insufficient against solid tumors. Rondo CEOs Trinklein and Force Aldred founded the company to advance bispecific antibody science and the treatment of solid tumors.The San Francisco-based startup, which launched Wednesday, has received $67 million in terms of financing.
Unlike monoclonal antibodies, which only bind to one target, bispecific antibodies have two arms, one that binds to proteins on the surface of T cells and the other that binds to antigens on cancer cells. Locking these two molecules simultaneously brings the T cell close to the tumor, so it can do its job of killing the cancer.
For most bispecific antibodies in development, including those developed by Teneobio, the arms that lock onto T cells bind to a protein called CD3. Trinklein said the scientific field has found that bispecific antibodies are more difficult to treat solid tumors if they target only CD3. Solid tumors are more challenging than liquid tumors because they have more components that suppress the immune response. Even if a drug can activate an immune response by binding to CD3, solid tumors quickly shut down that response, Trinklein said.
The immune system functions at different levels, Force Aldred said. Binding to T-cell receptors stimulates an immune response that is appropriate for liquid tumors. But in the more complex environment of solid tumors, drugs need to reach another layer. Rondo’s drug not only triggers an immune response, but also maintains it, Force Aldred said. Trinklein likens this approach to starting a car (as in a car, instead of this type of vehicle).
“How do you start a car, but leave it running long enough to do something? That’s what we’re trying to do,” he said. “Start the car and let it go, so those T cells can do their job and kill the tumor cells.”
Rondo is finding new targets and pairing them with previously unexplored antigens. Trinklein did not specify these targets, saying that some of them have biological properties that are well known in scientific research, but they have not yet been developed for bispecific antibodies. Antibody research over the past 30 years has focused on finding antibodies that bind to their targets with the highest affinity, Trinklein said. But with Rondo’s method, higher affinity is not necessarily required. If binding to the receptor over activates T cells, it can trigger toxic effects.
Rondo’s method uses antibodies that bind to and activate immune cells just the right amount — what Force Aldred calls the “Goldilocks zone.” Just as a car might need a little acceleration rather than a slam on the pedal causing a vehicle to crash, the Rondo drug taps the gas pedal by activating T cells to trigger activity, but doesn’t cause toxic effects.
“You have to do this very carefully,” Force Aldred said. “When you hit the gas, you have to find the Goldilocks zone.”
Rondo has a number of companies pursuing biologics that bind both T cells and solid tumors. Takeda acquired partner Maverick Therapeutics last year For control the program focused on a type of bispecific antibody called a T-cell engager. Janux Therapeutics, in partnership with Merck, is also developing T-cell engagers. last year end, Bristol Myers Squibb acquires rights to Immatics lead drug candidate, an antibody-like biologic There are two components, one that binds and activates T cells and the other that targets antigens on cancer cells. After a few weeks, Sanofi agrees to buy Amunix Pharmaceuticals, which develops T-cell engagers, for $1 billion upfront It employs a technique that masks them before they reach their destination, an approach designed to overcome the toxicity challenges of other types of cancer treatments.
Rondo was founded in 2020, according to California company records. Force Aldred said the biotech grew at full speed last year with seed investment from friends and family, setting the stage for the Series A funding announced this week. The round was led by Red Tree Venture Capital and Canaan Partners. Other participants include Johnson & Johnson Innovation – JJDC, Novo Holdings and SV Health Investors.
Rondo has two bispecific programs and two early preclinical leads, Force Aldred said. The two bispecific programs target two different types of cancer, but are undisclosed. With the Series A cash, Rondo plans to advance lead programs into the clinic to validate the biotech’s approach in solid tumors.
Photo by Rondo Therapeutics
