INXN-2001

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.”

Shares of Ziopharm Oncology, Inc. are still sliding after the company announced it was pausing its planned Phase III trial for its lead gene therapy product designed to treat patients with recurrent glioblastoma (rGBM) as a monotherapy and in combination with an immune checkpoint inhibitor. Shares of ZIOPHARM Oncology, Inc . are still sliding after the company announced it was pausing its planned Phase III trial for its lead gene therapy product designed to treat patients with recurrent glioblastoma (rGBM) as a monotherapy and in combination with an immune checkpoint inhibitor. On Friday Boston-based Ziopharm said before the trial can continue it must resolve previously disclosed technical requirements related to Chemistry and Manufacturing Control (CMC) in order to make the asset ready for the Phase III trial in rGBM. This is the second delay the company has initiated for this particular study. Last year the program was pushed back several months and expected to start this year. Ziopharm did not provide a timeline for the Phase III trial to begin. The company said it intends to advance Ad-RTS-hIL-12 plus veledimex as a treatment for rGBM, but before it does so, the company said it intends to “focus its resources on studies of Controlled IL-12 in additional tumor types to demonstrate the value of this platform technology.” That was the reason cited by the company for the delay in its first quarter financial report. During a conference call with investors and analysts David Mauney, Ziopharm’s chief business development officer and interim Chief operating officer, said the company wants to focus on expanding its IL-12 program into new tumor types and with new combinations. “…the idea here is to make immunologically cold tumors hot by calling in the bodies T cells via the tunable control of IL-12. Once these cold tumors are flush with cancer-fighting T cells, the gates are now open to turbo-charge the effects by adding in combination therapies like checkpoint inhibitors,” Mauney said during the call, according to transcripts . “Additionally, from a business perspective, we’ve seen several recent transactions that suggest having an ability to make cold tumors hot across multiple tumor types. Even with just Phase 1 data drives tremendous value relative to pursuing just one indication. We’re now executing on a revised clinical plan for this technology, which is focused on delivering clinical data in multiple tumor types and in combination with checkpoint inhibitors as quickly and cash efficiently as possible.” Mauney framed the decision to pause the glioblastoma trial as a business move that could potentially provide the company with a greater revenue stream. With Eli Lilly ’s recent $1.6 billion acquisition of ARMO BioSciences and its cytokine programs, Ziopharm could be seeing the potential for lucrative partnerships. “This effort greatly expands our addressable markets. It aligns us with what potential partners want to see in terms of clinical data, and have the additional benefit of tremendous cost savings in the near-term. We view this as a positive pivot point for this platform and executing on this plan will provide the information needed in the shortest time possible and for a fraction of the cost of a randomized controlled pivotal trial,” Mauney said in a statement. While Ziopharm is indefinitely pausing the glioblastoma trial, the company said it is moving forward with its combination trial of Ad-RTS-hIL-12 and Opdivo, Bristol-Myers Squibb ’s blockbuster checkpoint inhibitor. Ziopharm said it expects the first patient to be dosed in this trial in the second quarter. The company is also focused on its Sleeping Beauty program to speed up the manufacture of CAR-T cells. The company said it anticipates driving this program into the clinic in the second half of this year. The Sleeping Beauty program is designed to manufacture the CAR-T cells in two days, a move the company believes will address concerns of high cost to patients.