Startup Lands $150M for Delicate Dance Between Cancer Cells & Immune Cells

Clasp Therapeutics’ novel T cell engagers could offer advantages over others in this class of cancer immunotherapies. The startup is based on the research of Johns Hopkins University scientist Bert Vogelstein.


Cancer immunotherapy comes in several forms, and one area of growing research interest is a type of drug called a T cell engager. These drugs bind to a cancer cell and a T cell simultaneously, bringing both of them together to spark a therapeutic effect. Robert Ross, CEO of Clasp Therapeutics, likens T cell engagers to the chaperone at a middle school dance who grabs a boy and a girl in each hand, getting them to dance together. But in cancer drugs, just as in school dances, sometimes the pairing just isn’t right.

The wrong pairing in cancer happens when a drug that’s targeted to a tumor also hits healthy cells, causing toxic effects. Clasp is developing a new kind of T cell engager designed to specifically target only cancer cells. The preclinical startup, which splits its operations between Cambridge, Massachusetts, and Rockville, Maryland, launched on Wednesday, revealing its science along with $150 million in financing.


The targeting ability of a T cell engager comes from its design: one antibody binds to a specific target on a cancer cell and another antibody binds to a target on a T cell. However, while the cancer targets addressed by these drugs are more abundant on cancer cells than healthy tissue, some amount is still found on healthy tissue. That limits how high a dose can be safely given to patients before the toxic effects become unacceptable. Ross said Clasp’s drugs won’t face that limitation.

.
“We are going after targets that are expressed on tumor tissue, but should not be expressed on normal tissue at all,” he said. “The beauty of that is you can dose up and up and up.”

Clasp isn’t disclosing it’s cancer targets just yet. But Ross said they are mutations that don’t exist in human bodies except in malignant tissue. Also, Clasp can go after targets that are inside of a cell. The targeting ability of the antibodies that comprise currently available T cell engagers can only address targets on a cell’s surface. Clasp’s approach leverages the human leukocyte antigen (HLA) system, which presents proteins on the surface of a cell to tell the immune system which cells belong to the body and which do not. Even when a tumor target is inside a cell, HLA still presents peptides from that target on the cellular surface. By going after that specific signature, Clasp’s drugs can hit intracellular tumor targets and avoid healthy tissue, Ross said.

One of the ongoing problems of cancer immunotherapy is patient selection. Clasp addresses that by designing a therapy to address a particular combination of a cancer-driving mutation and HLA type. It’s here where Clasp builds on existing clinical practice. HLA typing has been done for years as a way to match organs to transplant patients, Ross explained. There are tests for that. Those tests can also be used to understand if a patient has the right HLA type for a Clasp drug.


Clasp’s approach is not as personalized as a CAR T-therapy, which is made by engineering a patient’s own immune cells. But designing a drug for a particular HLA type offers what Ross calls a “spectrum of personalization,” a well-defined group of patients who have a particular cancer mutation and a specific allele. The scope of patients eligible for a Clasp drug will be smaller than that of say, a checkpoint inhibitor. But one problem with that type of immunotherapy is some patients don’t benefit and it’s not clear why. Going after a defined patient spectrum means there’s a much better sense of who will benefit and who will not, Ross said. He added that as someone who earlier in his career was a practicing oncologist, there’s also value in telling patients which treatments won’t work for them. But with Clasp’s technology, finding a therapy that will work is a matter of using the same scaffold to design a drug addressing a different cancer mutation and HLA type combination.

“I strongly believe in the power of immuno-oncology,” said Ross, whose experience includes senior roles at Bluebird Bio and Surface Oncology. “I also strongly believe we need to do a better job in selecting patients.”

Website: worldtopscientists.com

#cancercells #immunecells #fightagainstcancer #immunotherapy #cancerresearch #cancerimmunology #cancerawareness #immunesystem #beatcancer #cancerwarriors #immunedefense #cellularimmunity