In what Henry Ji, president and CEO of Sorrento Therapeutics Inc., called a "validating deal" for its immuno-oncology (I-O) platform, the company inked an exclusive global license and collaboration agreement with Les Laboratoires Servier SAS for its fully human anti-PD-1 monoclonal antibody (MAb), STI-A1110, that could add a multiplier to the disclosed potential of €886 million (US$979.8 million).

"This is one of the biggest preclinical-stage antibody license deals, and we have a few dozen of these [assets], so that shows you the potential of what we have," Ji told BioWorld Today.

The agreement, which includes a nonrefundable up-front payment to Sorrento of €25 million, gives Servier exclusive access to develop, manufacture and commercialize multiple products derived from the preclinical candidate, which has moved into investigational new drug-enabling studies.

In an 8-K filing, Sorrento said it is set to receive nonrefundable payments of up to €78 million upon the achievement of undisclosed development and regulatory milestones related to STI-A1110 and up to another €73 million for a pharmaceutical product containing the STI-A1110 antibody and other products controlled either by Sorrento or Servier. The broad agreement also entitles Sorrento to nonrefundable sales milestone payments of up to €710 million per product, including a potentially unlimited number of combination therapies. Sorrento also is eligible to receive royalties ranging from high single- to double-digit percentages of product sales.

Sorrento agreed to forego, during a five-year period, the development, manufacturing or commercialization of PD-1-directed antibodies without Servier's consent. Servier, based in Neuilly-sur-Seine, France, also gained a right of first negotiation on any sale or transfer of rights to third parties for undisclosed clones from Sorrento's pipeline of immune checkpoint inhibitors.

I-O MAbs represent the most advanced of five platform technologies at San Diego-based Sorrento. The STI-A1110 deal allows Servier access to all hematological and solid tumor targets in which PD-1 is implicated, both as a monotherapy and in combination therapies. Sorrento agreed to provide sample materials, documents and know-how, including details on the manufacturing process. Servier will fully fund the development, registration and commercialization of any products emerging from the agreement.

In recent years, Servier has expanded its oncology business as part of its long-term growth strategy. The company has nine new molecular entities in development targeting breast and lung cancers and other solid tumors as well as various types of leukemia and lymphoma. The Sorrento asset gives Servier its first PD-1 inhibitor, with the potential for multiple combo shots on goal.

Sorrento and Servier had been talking "for many years," and the French firm had shown interest in the antibody-centric biopharma "for some time," Ji said.

"This agreement came about because they really wanted the PD-1 antibody," he added. "At the current stage they have nine oncology compounds for which they need combos. The asset that's ideal for these combos is the PD-1 antibody."

The companies did not disclose a timetable for moving into the clinic, but Kevin Herde, Sorrento's executive vice president and chief financial officer, said both companies are eager to begin human studies as quickly as possible.

'UNLOCKING THE VALUE' IN SORRENTO'S PLATFORMS

Ji said the Servier deal also differs significantly from Sorrento's PD-L1- and ROR1-targeting I-O collaboration with Nantkwest Inc. (formerly Conkwest Inc.), which is wider but not as deep. That effort is designed to integrate Nantkwest's natural killer cell-lines with fully human antibody libraries from Sorrento, and take advantage of the proteomics platform at Nantomics – a unit of the Nantworks conglomerate founded by biotech entrepreneur Patrick Soon-Shiong – as well as a cell production method and technology allowing for gene transfer without the need for lentivirus insertion. (See BioWorld Today, Dec. 26, 2014.)

Last year, Sorrento also extended its collaboration with Nantworks to discover and develop cancer I-O agents derived from Sorrento's G-MAB library – the same used to discover STI-A1110 – against Nantworks-identified neoepitopes of tumor-specific antigens drawn from its body of genomic and proteomic data. That deal called for Nantworks subsidiary Nantcell LLC to pay Sorrento $10 million in cash, provide a $100 million share of Nantcell equity and an unspecified share of profits from the partnership in exchange for an exclusive license to any antibodies or immunotherapies produced by the pair. (See BioWorld Today, March 17, 2015.)

Still, as a global license covering all facets of STI-A1110's development and commercialization, the Servier deal "is much bigger," Ji maintained.

Although Sorrento is precluded from working on PD-1-targeting antibodies for the time being, the company has plenty on its plate. A potential $1.3 billion-plus deal between Sorrento and Nantworks inked last year also aims to move Cynviloq (paclitaxel nanoparticle polymeric micelle) to a new drug application in the U.S. on the basis of a single experiment via the 505(b)(2) pathway, allowing for use of Abraxane (nab-paclitaxel) data in the submission package. The drug is already on the market in several Asian countries. (See BioWorld Today, May 18, 2015.)

Sorrento has been active in Asia this year, as well. In April, the company inked an antibody joint venture with South Korea's Yuhan Co. Ltd. Last month – through its subsidiary, TNK Therapeutics Inc. – Sorrento forged a chimeric antigen receptor T (CAR T) cell program alliance with Shenyang Sunshine Pharmaceutical Co. Ltd., or 3SBio. (See BioWorld Today, April 8, 2016, and June 10, 2016.)

Sorrento's CAR T programs targeting solid tumors expressing carcinoembryonic antigen, or CEA, and prostate-specific membrane antigen, or PSMA, have moved into phase I programs. The company also has preclinical CAR T assets targeting ganglioside GD3, the interleukin-13 receptor and the receptor tyrosine kinase, c-Kit.

Sorrento took note of the three patient deaths reported last week by Juno Therapeutics Inc. in its phase II CAR T program testing JCAR015 in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia, Ji acknowledged. (See BioWorld Today, July 11, 2016.)

However, "we have not encountered similar issues here," he said. Additional efforts using Nantkwest's natural killer cell-line based therapy and CARs derived from Sorrento's G-MAB library, though still preclinical, will not necessarily require preconditioning, Ji pointed out, "so we may not encounter the same issues as Juno."

Sorrento also is advancing its biosimilar program, reporting in May that STI-004, a biosimilar antibody for Xolair (omalizumab, Roche AG), was shown safe and effective compared to placebo in a combined phase II/III study in China that enrolled adult and adolescent patients with allergic asthma. Last year, Sorrento licensed rights to four biosimilar or biobetter antibodies, including STI-004, from Mabtech Ltd., a holding company for antibody development and manufacturing companies in China. (See BioWorld Today, May 23, 2016.)

The latest deal did not help Sorrento's shares (NASDAQ:SRNE), which lost 27 cents, or about 4 percent, Monday to close at $6.44.

In fact, Rodman & Renshaw analyst Raghuram Selvaraju seemed less concerned with the Servier agreement than with a quiet disclosure that Sorrento sold back 5.6 million shares of Nantkwest stock gained from their partnership agreement and purchased roughly 7.8 million Sorrento common shares originally owned by the Chan Soon-Shiong Family Foundation. Sorrento agreed to pay $15.64 million in cash to the Foundation to account for the difference in the valuation of the Nantkwest and Sorrento shares as of the date of the agreement, according to an SEC filing.

"In our view, this transaction effectively ends Sorrento's exposure to Nantkwest's stock performance, and eliminates Patrick Soon-Shiong's ownership stake in Sorrento," Selvaraju wrote. "While Dr. Soon-Shiong still has some exposure to Sorrento via warrants, in our view this transaction indicates that he is unlikely to launch a takeover bid for Sorrento in the near-term."

The future implications are important, he added, as "we continue to expect Sorrento to pursue initiatives aimed at unlocking the value inherent in its various technology platforms."