Theraclone Sciences Inc. and the University of Texas MD Anderson Cancer Center broadened an informal immuno-oncology (IO) relationship in a big way, jointly launching Oncoresponse Inc. to discover and advance therapeutic antibodies against targets identified during the treatment of cancer patients receiving the IO regimens.

To propel the start-up, the partners lined up a $9.5 million series A co-led by Arch Venture Partners, Canaan Partners and MD Anderson, with participation from Rice University and Alexandria Real Estate Equities. In addition to its therapeutic initiatives, Oncoresponse is envisioned as another spoke in the biotech hub that MD Anderson is seeking to build in Houston.

Founded in 2007 as Spaltudaq Corp., Seattle-based Theraclone has focused primarily on infectious disease, where it has programs in influenza, Ebola virus and HIV. The company leveraged its infectious disease initiatives to validate its I-Star technology platform, which enables rapid testing of tens of thousands of fully human antibodies to identify those with singular biological function and activity. The technology extracts and then replicates memory B cells from a blood sample of a human donor who has natural resistance to a disease of interest. With each memory B cell possessing the potential to differentiate into a unique antibody clone, the cells are activated to propagate and differentiate into antibody-producing cells.

Antibodies secreted into the culture medium then are harvested in sufficient quantity to enable screening for biological activity. Once the company identifies an antibody with the desired therapeutic activity, its gene sequence is obtained from the corresponding antibody-producing cells and the antibody genes are inserted into immortalized mammalian cells to enable production of unlimited quantities of the antibody clone for additional study.

Last year, Theraclone inked an agreement giving Gilead Sciences Inc., of Foster City, Calif., an exclusive license to develop and commercialize products incorporating broadly neutralizing HIV-antibodies for therapeutic applications in HIV. The antibodies were discovered by Theraclone researchers working in collaboration with the International AIDS Vaccine Initiative and the Scripps Research Institute using the I-Star technology. Although terms for that deal were not disclosed, the Gilead partnership represented "a lot of validation for the platform for finding rare antibodies from unique responders" – individuals who had "interesting" immune responses to an infection or disease, explained Theraclone CEO Clifford Stocks.

As IO exploded onto the cancer therapeutics scene, "we saw the opportunity to have an impact in cancer patients," Stocks added, citing options in checkpoint inhibitors, cancer vaccines, immunomodulators, cytokines, chemokines "and combinations thereof."

'THIS IS A PERFECT COMPLEMENT IN THIS POPULATION'

Specifically, Theraclone was intrigued by the prospect of interrogating the memory B cell repertoire of human immune systems that had achieved a durable response following immune priming with IO therapeutics. Last year, the company "made a pivot" into the IO arena to start screening those types of patients. MD Anderson was a principal referral source.

What was initially envisioned as a simple collaboration with a single MD Anderson investigator quickly gained traction at the institution, finally reaching the office of MD Anderson president, Ronald DePinho. At that point, "we came to them with an idea about how we could do something very broad and very big," Stocks told BioWorld Today.

Theraclone's cancer assets – including antibodies at the hit stage in lung, gastric and breast cancer as well as melanoma – were exclusively licensed to Oncoresponse, which also gained exclusive use of the I-Star platform in oncology. In return, Theraclone took an equity position in the newco.

In the short term, Oncoresponse will be managed by Theraclone under a research services agreement while maintaining its internal focus on infectious disease. Stocks, who serves as interim CEO of Oncoresponse, said more than a dozen Theraclone employees are already working full-time to continue discovery research on behalf of the start-up.

MD Anderson, through a strategic alliance, will provide access to samples and to physiologic, prognostic and genotypic data from patients who had exceptional responses to cancer immunotherapies, along with oncology and translational medicine expertise.

The partners expect to begin the actual tech transfer process in Houston in approximately 18 months and to have five to 10 Oncoresponse employees on the ground there by the end of 2016.

"In the interim, we can be building translational medicine in Houston," Stocks pointed out. To that end, antibodies that emerge from discovery efforts will be placed in the hands of investigators in Houston for preclinical validation as well as investigational new drug (IND) work-up and preclinical IND-enabling studies. MD Anderson will be involved in the design and management of human trials.

The financing is designed to propel Oncoresponse far enough down the road to validate the platform and develop preclinical candidates that could attract partners or additional investment, though Stocks declined to define that exact timetable.

Oncoresponse is MD Anderson's third major push into IO this year. In January, the institution partnered with Intrexon Corp., of Germantown, Md., and Ziopharm Oncology Inc., of Boston, in a broad exclusive licensing agreement to develop nonviral adoptive cellular cancer immunotherapies. In that effort, each company kicked in $50 million in common shares to MD Anderson and committed to provide $15 million to $20 million annually over three years for additional research and technology development. (See BioWorld Today, Jan. 15, 2015.)

In August, Immatics Biotechnologies GmbH, of Tuebingen, Germany, teamed up with MD Anderson to form a $60 million U.S. subsidiary designed to cross-pollinate the institution's cell therapy expertise and Immatics' Xpresident cancer peptide discovery technology to develop autologous and allogeneic treatments. Formation of the subsidiary was funded by $40 million from the parent company and a $19.7 million grant from the Cancer Prevention and Research Institute of Texas. (See BioWorld Today, Aug. 27, 2015.)

The opportunity to work in partnership with Theraclone represented yet another model for attacking the IO thesis that was too promising to ignore, according to Ferran Prat, MD Anderson's vice president of strategic industry ventures.

"Because of the nature of the technology that Theraclone has to offer, this is a perfect complement in this population of rare responders," Prat said. "In this case, there was a recognized asset that could be fully leveraged."

MD Anderson was sufficiently intrigued by the Theraclone platform to contact colleagues at Rice, leading to equity investment by both institutions in the start-up.

The partners hope that, by examining the immune systems of so-called super-responders to cancer immunotherapies, they may increase the success rates of these treatments.

"When you've got an antibody from one patient who did respond – if it's the right target and effector function – that antibody in another patient could make the difference between the person being a non-responder and a responder," Stocks said.

The partners expect to have multiple shots on goal, including the development of adjunctive therapies for existing cancer drugs and the design of new cancer-killing antibodies. Even if those objectives don't play out, there's the potential to apply a wealth of engineering technologies to the antibodies to develop antibody-drug conjugates, bispecific antibodies or chimeric antigen receptor T-cell candidates.

"There are a number of different ways you can go with the technology for getting to products that, ultimately, produce a clinical response in cancer patients," Stocks said.

Long term, the founders expect Oncoresponse to grow into a standalone cancer therapeutics company and a magnet for additional drug development investment in Houston.

"We will control our destiny," Stocks maintained.

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