Ziopharm cuts Precigen ties, narrowing its R&D focus

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Ziopharm has scaled back an alliance with Intrexon unit Precigen in oncology and will now focus solely on a pair of immuno-oncology platforms.

Shares in the company dipped almost 5% on news of the business revamp, suggesting investors aren’t wholly convinced by the new plan, which sees the earlier wide-ranging deal replaced with a single licensing agreement to a technology from Precigen used in Ziopharm’s R&D programs.

Ziopharm will now concentrate exclusively on its controlled IL-12 and sleeping beauty (SB) driven TCR-T and CAR-T platforms, including its lead CD19-directed CAR-T, which CEO Laurence Cooper, M.D., Ph.D., said represent the “best market opportunity” for the company.

SB uses a nonviral gene transfer system modify T cells so they target neoantigens, while the controlled IL-12 platform is designed to activate so-called ‘cold’ tumors that exhibit little or no immune system activity.

Precigen walks away with exclusive rights for all other SBs, including a CD33-directed program partnered with Germany’s Merck KGaA. It will also be in line for reduced milestones and capped royalties on Ziopharm’s projects, while the latter retains a capped royalty interest in Precigen’s SB portfolio.

The move “establishes Precigen as a therapeutics company concentrating on immuno-oncology, autoimmune and infectious disease therapies,” according to Ziopharm, which said “both companies will be better positioned to independently focus on their respective platforms and markets” as a result.

The decision comes after a trial of the CD19-directed CAR-T was placed under a clinical hold earlier this year, delaying the start of dosing, while a planned phase 3 trial of lead controlled IL-12 candidate Ad-RTS-hIL-12 was put on pause due to a chemistry, manufacturing and control problem.

“The new Ziopharm now has full autonomy … and exclusive rights to these platform technologies,” said Cooper on a conference call. He said the move was a “turning point” for the company.

Giving an update on Ziopharm’s programs, Cooper said that Ad-RTS-hIL-12 is currently being evaluated in brain tumors as monotherapy and in combination with Bristol-Myers Squibb’s immune checkpoint inhibitor Opdivo (nivolumab). The drug is administered into the tumor during surgery and an oral agent (veledimex) is then used to switch local production of IL-12 on and off.

Meanwhile, Ziopharm is also just about to file for approval to start trials of an SB program for a TCR-T cell therapy in solid tumors in collaboration with the National Cancer Institute. While CAR-Ts are directed at cell surface antigens TCR-Ts can go after antigens within the cell, and Cooper said this is the key to targeting solid tumors.

In CAR-T, which Cooper said is now Ziopharm’s smallest technology platform, the CD19 project for leukemia/lymphoma “is very much intact” and moving forward with partner MD Anderson, with a new application for trials due in the second half of 2019.

A second CAR-T program with an undisclosed target in blood cancers should be submitted for clinical testing before the end of 2019. Both are designed to be manufactured within two days, allowing for treatment at the point of care, and that could provide a speed and cost boost over approved CAR-T products.

The new arrangement means around $157 million-worth of Ziopharm preferred stock held by Intrexon has been retired, and Intrexon CEO Randal Kirk will step down from Ziopharm’s board.