Ziopharm Oncology Posts Letter to Stockholders
Dear Fellow Stockholders,
With the 37th Annual
As we begin 2019, Ziopharm is already better. We are executing as a new company, focusing on our own programs with a concentrated corporate strategy. We have evolved, proven and validated Sleeping Beauty as a leading non-viral gene transfer platform and we have treated more than 100 patients with our Controlled IL-12 platform delivering more than 1,250 doses of the activating ligand, veledimex. We are focused on advancing three programs into the clinic in 2019: Sleeping Beauty TCR-T, Sleeping Beauty CD19 CAR-T, and Controlled IL-12, all of which will be tested in five clinical trials.
NCI Expected to Begin Treating Patients with Solid Tumors with TCR-T Therapy in Mid-2019
One of the hottest areas in immunotherapy is centered on the use of T-cell receptors, or TCRs, to target neoantigens for the treatment of solid tumors, the leading cause of cancer deaths in
The field is in development stages with significant investment emerging in the TCR-T space as companies increasingly focus on the value of targeting neoantigens. We could not be better positioned with our unique and technically-advanced program. We are different from others in this space as we aim to be the first non-viral approach to generating multiple TCRs directed at multiple neoantigen targets to serve as therapy for individual patients. It is our belief that a viral-based approach to manufacturing patient-specific TCRs will not be commercially feasible. In contrast, we have the most advanced non-viral genetic engineering solution to generate T cells at scale tailored to be specific for solid tumors.
We believe that unless you can deliver a commercially-viable product efficiently and at a reasonable cost, a T-cell program will struggle to scale to meet needs and thus get off the ground. We see this with commercialization efforts for single-target CD19-specific CAR-T therapies and these issues will be magnified significantly for multiple-target TCR-T cell therapies. Our Sleeping Beauty platform provides a low-cost and less complex manufacturing solution for T cells expressing a battery of TCRs that is paramount to commercializing a TCR-T therapy.
Simply put, we believe infusing T cells designed to target neoantigens offers the best hope for any patient with metastatic solid tumors. To be successful in this arena, we have to provide a solution to two major challenges. The first is the ability to express different TCRs for different patients as the neoantigen targets are most often unique to each cancer patient. The second is to prevent relapse by targeting multiple neoantigens for each patient as, unlike CD19, there is no one target that is expressed by all cancer cells within a solid tumor. Our Sleeping Beauty platform can address both challenges as it can be scaled to deliver unique TCRs, so multiple patients with a variety of solid tumors can benefit, and it can be scaled to deliver multiple TCRs in a patient’s T cells, so the recipient has the best chance of an anti-tumor effect.
Sleeping Beauty to Overcome Commercialization Hurdles of CAR-T Therapy
The headwinds of cost and complexity continue to limit commercial success of approved CAR-T therapies, despite the billions of dollars invested to date to develop and commercialize these technologies. Our Sleeping Beauty system, designed to express CD19-specific CAR with membrane-bound interleukin 15 (mbIL15), was adapted for the very rapid manufacture of patient-derived T cells in two days or less, which should result in a dramatic cost savings and increase the number of patients who benefit. When resetting our relationship with
Using our Sleeping Beauty platform, we believe we can solve ongoing commercialization hurdles by manufacturing CAR-T faster and at a fraction of the expense compared to viral vectors, thereby dramatically expanding patient access. We have made considerable progress in achieving T-cell viability needed to obtain regulatory clearance for our clinical trial. We plan to begin using this approach to treat patients at MD Anderson in the second half of 2019 with CD19-specific CAR-T therapies (with mbIL15 and a kill switch) manufactured in two days or less following gene transfer. Also, our new joint venture, Eden BioCell, will appropriate the same Sleeping Beauty platform to undertake very rapid manufacturing in the
Controlled IL-12 under RheoSwitch with Low-dose Steroids Provides Survival Benefit for Patients with
IL-12 is likely the most potent immune stimulator in the cytokine family that leads to profound anti-tumor effects. In our clinical studies, we have demonstrated that IL-12 recruits and sustains a significant and long-term T-cell response and an upregulation of checkpoints, such as PD-1.
We believe our technology provides the precision to safely harness IL-12 which will enable us to turn it into a potent drug. IL-12 experts have stated that the first company to turn this exquisitely powerful cytokine into a controllable drug will have untapped a new and sizeable market, and we are on the verge of doing just that. In addition, we have witnessed the importance and value of genetic switches when reviewing comparable technologies in the marketplace. Our RheoSwitch appears to be the most validated transcriptional switch in development for oncology and our data show that IL-12 can be efficiently turned up and down, on and off.
Our experience administering Controlled IL-12 (Ad-RTS-hIL-12 plus veledimex) as a monotherapy for recurrent glioblastoma (rGBM) has produced compelling clinical data, with a subset of patients in a phase 1 trial, who received low-dose steroids along with 20 mg of veledimex, achieving a remarkable 17.8 months median overall survival (OS) when compared with 5 to 8 months OS established in historical controls. We are building on these data with an expansion cohort of an additional 25 patients taking 20 mg of veledimex, which is on track to be fully enrolled this week with 65 percent of enrolled patients having received low-dose steroids. We have growing interest from potential new trial sites and accrual is occurring faster than ever before for our IL-12 trials.
After the administration of IL-12 as a single agent, we demonstrated through biopsies that the invading T cells within rGBM had upregulated PD-1. This provided a convincing justification for combining Controlled IL-12 with PD-1 inhibitors, which is why we expect to show the value of Controlled IL-12 in combination with checkpoint inhibitors in two trials in 2019. Enrollment in our existing combination trial with the PD-1 inhibitor OPDIVO® (nivolumab) is expected to be complete in 2Q2019. Our new partnership with Regeneron, which validates our commitment to this promising platform, is advancing into a phase 2 trial to evaluate Controlled IL-12 in combination with Regeneron’s PD-1 antibody, Libtayo® (cemiplimab-rwlc), later this year.
Building upon momentum
After completing a significant transformation in 2018, we have the right assets, resources, supporters, and partners to deliver life-saving cell and gene immunotherapies to patients with cancer. We cleaned up our balance sheet, we are fully funded into 2Q2020 without debt, and we are advancing Sleeping Beauty CD19-specific CAR T and Controlled IL-12. These two programs in and of themselves hold tremendous value, and furthermore, we believe our TCR program stands alone in a new class of T-cell therapeutics which offers the best chance of having a profound impact on the lives of patients with solid tumors.
We appreciate your support and confidence and on behalf of everyone at Ziopharm, we wish you all a happy, healthy and prosperous 2019.
Ziopharm Chief Executive Officer
Forward-Looking Statements Disclaimer
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding the Company's business and strategic plans, the availability of cash resources, and the progress and timing of the development of Ziopharm’s research and development programs, including the timing for the initiation and completion of its clinical trials. Although Ziopharm’s management team believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Ziopharm, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, changes in our operating plans that may impact our cash expenditures, the uncertainties inherent in research and development, future clinical data and analysis, including whether any of Ziopharm’s product candidates will advance further in the preclinical research or clinical trial process, including receiving clearance from the
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Source: ZIOPHARM Oncology Inc