The U.S. Food and Drug Administration (FDA) placed a clinical hold on Boston-based Ziopharm Oncology’s Phase I trial of its Sleeping Beauty CAR-T therapy.
The U.S. Food and Drug Administration (FDA) placed a clinical hold on Boston-based ZIOPHARM Oncology’s Phase I trial of its Sleeping Beauty CAR-T therapy.
Ziopharm is a wholly-owned subsidiary of Intrexon Corporation and The University of Texas MD Anderson Cancer Center. The two companies are sponsoring a Phase I clinical trial to evaluate CAR-T cells manufactured with their Sleeping Beauty technology for patients with relapsed or refractory, CD19+ leukemias and lymphomas. The CAR-T cells are “very-rapidly” manufactured with the technology are designed to co-express CD19-specific chimeric antigen receptor (CAR) membrane-bound interleukin 15 and a safety switch.
The FDA requested additional information about Chemistry, Manufacturing and Controls. Ziopharm and its partners plan to address the FDA’s requests, which may cause the initiation of the clinical trial to be delayed.
Ziopharm’s lead asset is Ad-RTS-hIL-12 plus veledimex. It has shown in clinical trials the potential to control interleukin-12, which appears to cause an infiltration of T-cells that fight brain cancer.
The company is using two broad approaches, one is Controlled IL-12 and Sleeping Beauty. Sleeping Beauty is a non-viral approach to genetically modify CAR+ and T-cell receptor (TCR+) T cells. These target specific antigens in blood cancers and neoantigens in solid tumors. The company states, “Sleeping Beauty is designed using the Company’s point-of-care technology, a shortened manufacturing process which potentially can be developed as a decentralized manufacturing processed based in hospitals. These programs are being advanced in collaboration with Precigen and with MD Anderson Cancer Center, the National Cancer Institute and Merck KGaA, Darmstadt, Germany.”
Laurence Cooper, Ziopharm’s chief executive officer, said in a statement, “We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner. We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very-rapidly manufacture CD19-specific T cells within two days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”
The company doesn’t believe the feedback from the FDA will affect timelines for its planned clinical trial at the National Cancer Institute. And it indicates that its second-generation trial of Sleeping Beauty-manufactured CD19-specific CAR-T cells will continue enrolling and infusing patients at MD Anderson.
Company shares are down 12 percent in premarket trading on the news. The stock had climbed 16 percent in May, which is an up-and-down ride that’s been seen often in the last four months.
The Sleeping Beauty program is focused on engineering T-cells to fight cancer at point of care. Keith Speights, writing for The Motley Fool, reports, “Current chimeric antigen receptor T cell (CAR-T) therapies require T cells to be modified using gene therapy and multiplied outside the patient’s body. Ziopharm’s goal with Sleeping Beauty is to eliminate the need to grow T cells outside the body. This would speed up the treatment and reduce the costs. Sleeping Beauty currently includes two clinical-stage programs: a CAR-T therapy, and a T cell receptor (TCR) therapy.”
The company had delayed its pivotal Phase III clinical trial of its controlled IL-12 therapy in May, pending resolving some technical manufacturing problems.
These difficulties likely explain the stock’s volatility. Speights writes, “There’s plenty of pessimism about Ziopharm’s chances. Over 28 percent of the stock’s float is currently sold short. That reflects some big bets that the stock will continue to go down rather than move higher.”
Some of that pessimism is possibly related to company finances. At the end of March, it reported cash and cash equivalent of $51.1 million, which it thinks will fund operations into the second quarter of 2019. Speights writes, “However, Ziopharm won’t be able to wait until then to raise more cash. That means it’s highly likely, if not inevitable, that the company will issue more shares, which could dilute the value of existing shares.”
Speights’ bottom line on a buy? Intriguing and filled with potential in an area of unmet medical need. “Controlled IL-12 holds the promise of extending survival for patients with GBM. Ziopharm’s point-of-care therapies could be game-changers if they’re successful. The reality, though, is that there’s a long way to go—and Ziopharm doesn’t have enough cash to reach the finish line.”
