Flying high with Kite and Alpine?

SANTA MONICA, Calif. & SEATTLE—Kite Pharma Inc. has entered into a worldwide research and license agreement with Alpine Immune Sciences Inc. (AIS), a privately held biotechnology company, to discover and develop protein-based immunotherapies targeting the immune synapse to treat cancer. AIS will grant Kite an exclusive license to two programs from its transmembrane immunomodulatory protein (TIP) technology, which Kite plans to further engineer into chimeric antigen receptor (CAR) and T cell receptor (TCR) product candidates. This collaboration will accelerate Kite’s efforts to establish the next generation of engineered T cell therapies specifically designed to overcome the inhibitory mechanisms present in the tumor microenvironment, and to enhance immune response.

According to their website, Alpine’s powerful variant immunoglobulin domain (vIgD) platform is based upon proteins native to the immune synapse, which are re-engineered to engage multiple targets simultaneously. They can be designed to treat cancer, autoimmune conditions or infectious diseases. The vIgD technology activates the immune system by antagonizing inhibitory receptors on T cells and myeloid cells, agonizing activating receptors on the same cell populations or both.

Alpine’s TIPs are based upon the same naturally occurring proteins as the vIgD technology. vIgDs are standalone drugs. TIPs are engineered to become part of engineered cellular therapies (ECTs) to potentially increase specificity, persistence and/or efficacy.

“Our target within the company is to provide injectable therapies for cancer, additive to and/or synergistic with other types of immunotherapies,” says Dr. Jay Venkatesan, CEO and director of AIS. “Kite is interested in ways to increase the potency of T cells, or to make them last longer and function better. In solid tumors, the area around the tumor is immunosuppressed, and sometimes T cells can’t activate in the tumor microenvironment.”

As Venkatesan explains to DDNews, the TIP is a separate molecule expressed on a CAR or TCR. The TIP platform blocks inhibitory signals—a CAR T cell will have greater efficacy when the TIP platform is combined with it, because a T cell is more effective when it gets a costimulatory signal to amplify the immune response. The active part of the TIP molecule is on the surface of the T cell, and is anchored into the cell through the membrane.

“We’re doing interesting things,” Venkatesan says. “It’s very exciting, because it’s a different approach than using antibodies. We are providing an additional parallel path to augment other treatments.”

Dr. Mitchell H. Gold, executive chairman of AIS, says, “One of the advantages of the TIP approach is that you already have targeting, which exists thru TCRs or CARs. TIP rides along with the engineered cells and only acts where the T cells are acting. When treatments are more broad, medicines can create toxicity in other parts of the body, or off-target effects—even if the effects are more expressed on the tumor, you’ll still adversely affect some normal cells.” To minimize adverse effects, having a TIP on the cell will ensure that the boost of the T cell is only happening where it’s finding a target. This will hopefully result in better efficacy and/or safety.

“AIS was established with a team of experienced scientists to capitalize on our keen understanding of immunology and protein engineering,” says Gold. “At AIS, we have a robust discovery platform to identify molecules capable of directly modulating the immune synapse. We look forward to working with Kite, a company that uniquely understands the complexities surrounding cancer biology.”

Under the terms of the collaboration, Kite will make an upfront payment to AIS of $5 million and additional payments to support AIS’ research. AIS will be eligible to receive milestone payments totaling $530 million based upon the successful achievement of pre-specified research, clinical and regulatory milestones, plus low single-digit royalty payments on product sales. Kite will receive an exclusive, worldwide license to research, develop and commercialize engineered autologous T cell therapies incorporating two programs coming from the AIS platform.

“The field of immuno-oncology has the potential to significantly improve the outcome of patients with cancer,” said Dr. Arie Belldegrun, chairman, president and CEO of Kite, in an official statement. “We believe the ability of AIS’ TIP technology to modulate the immune synapse can be incorporated into engineered T cell therapies to advance CAR and TCR product candidates into multiple tumor types. This collaboration is another example of Kite’s continuing commitment to advancing our pipeline through transformative technologies grounded in innovative science.”