Kite Pharma Inc. has moved to exclusively license two programs from an immunomodulatory technology developed by privately held Alpine Immune Sciences Inc. (AIS) as part of a new R&D agreement that includes $5 million up front and additional research funds. Together, the partners will leverage the technology to better engineer Kite's next-generation chimeric antigen receptor (CAR) and T-cell receptor (TCR) candidates.

Under the terms of the collaboration, in addition to the up-front and R&D funding, AIS is eligible to receive milestone payments based on successful achievement of pre-specified research, clinical and regulatory milestones totaling $530 million plus low single-digit royalty payments on potential product sales. Kite gains an exclusive, worldwide license to research, develop and commercialize engineered autologous T-cell therapies incorporating two programs coming from the AIS platform.

The deal brings the first outside money into Seattle-based AIS since a $1.3 million seed round and later $1.3 million top-up by Seattle's Alpine Bioventures, a venture capital firm created by former Dendreon Corp. CEO Mitchell Gold and biotech stock researcher David Miller in 2013.

Biotech investor and executive Jay Venkatesan joined Gold and Miller in July as a managing partner of Alpine Bioventures to lead the creation of new companies and now serves as AIS' CEO. Gold is AIS' executive chairman.

The science behind AIS, Gold told BioWorld Today, was developed by a group of scientists who once worked at Amgen Inc.'s now-shuttered Seattle campus. "The goal was to create a totally new approach to manipulating the immune system through the immune synapse — the point at which a T-cell and an antigen-presenting cell interact or a T cell and a tumor cell interact," he said.

The result is AIS' variant immunoglobulin domain platform, or vlgD, which is based on proteins native to the immune synapse, re-engineered to engage multiple targets simultaneously. The injectable, soluble proteins can be designed to treat cancer, autoimmune conditions or infectious diseases.

Kite is leveraging an outgrowth of the vlgD technology that AIS calls TIP, short for transmembrane immunomodulatory protein. The primary difference is vlgDs are standalone drugs while TIPs are engineered to become part of engineered cellular therapies to potentially increase specificity, persistence and efficacy. Early data from the TIP program suggest it might be particularly effective in hematologic cancers, AIS said.

By expressing one of the two TIPs that they licensed from AIS on the surface of its TCR or CAR-T cell therapies, Kite hopes to improve the therapies' efficacy by overcoming immunosuppression in the tumor microenvironment.

"We're still very much in the early days of understanding immunotherapy," said Gold. "The unique element of what we're doing at Alpine is the ability to hit multiple targets in the immune synapse simultaneously. So, as opposed to having to apply a multitude of different drugs that may not necessarily work well together, we can design those attributes into a single molecule, which would not only have potentially better biology, but also be much more cost effective for payers at the end of the day."

Kite, which was unable to provide a representative for comment, has been actively expanding its access to new technologies and R&D capacity this year. In April, the Santa Monica, Calif.-based company expanded development and manufacturing services with Neostem Inc. subsidiary PCT, which is providing it with services for Kite's lead engineered autologous T-cell therapy clinical program. In March, it went a step further, buying out privately held T-Cell Factory BV for €20 million (US$21 million) up front in order to further bolster its pipeline development and access to Europe. (See BioWorld Today, March 18, 2015.)

In September, the company broadened its agreement with the Netherlands Cancer Institute (NKI), securing an exclusive option to license a number of T-cell receptor gene sequences to develop and commercialize cancer immunotherapy candidates targeting solid tumors, while also building expanded access to additional resources and research facilities through a master services agreement with NKI, which will conduct preclinical research related to candidates under the agreement.

Earlier this month,Kite formed an exclusive, worldwide license with the NIH for intellectual property related to TCR-based product candidates directed against MAGE A3 and A3/A6 antigens for the treatment of tumors expressing MAGE, which include lung, pancreatic, gastric and breast cancers, among others.