ZIOPHARM Oncology Inc. (NASDAQ:ZIOP) announced financial results for the first quarter ended March 31, 2016, and provided an update on the Company’s recent activities.
“We have solid momentum in each of our cell and gene therapy programs, with the potential to move our lead gene therapy, Ad-RTS-IL-12 + veledimex, into a pivotal study next year,” said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. “Ad-RTS-IL-12 + veledimex continues to yield encouraging results as we recruit additional patients into an ongoing dose-escalation study in recurrent glioblastoma, and we look forward to presenting this data to the American Society of Clinical Oncology (ASCO) at its annual meeting in June of this year. Given the dire outcomes in this patient population, a potential therapeutic benefit may be quickly assessed and, if these results remain durable, our goal would be to move into a registration study, following discussions with regulators.”
Dr. Cooper added: “As this promising program moves forward, we continue to test the potential of our cell therapy platform and technologies in collaboration with leading partners in industry and academia. This includes clinical-stage platforms unique to ZIOPHARM, such as the non-viralSleeping Beauty (SB) system, that are fundamental to making immune cell therapy a cost-effective, widely-available treatment modality. These technologies are particularly important in leveraging T-cell receptors (TCRs) to target neoantigens in solid tumors which requires individualizing this immunotherapy, an approach that is possible with our customizable, easy-to-manufacture non-viral gene transfer system. We expect to initiate or continue prosecuting up to six clinical trials across multiple platforms in 2016 and look forward to sharing data and outcomes from these trials throughout the year.”
The SB transposon-transposase is a unique non-viral system for introducing genes encoding CARs and TCRs into lymphocytes and is exclusively licensed by Intrexon Corporation (NYSE:XON) through MD Anderson and accessed as part of ZIOPHARM’s collaboration with Intrexon. This non-viral approach has several potential advantages over viral-based delivery systems, including a lower cost of generating genetically modified T cells as well as the ability to generate T cells with minimal ex vivo processing and can serve as a conduit to targeting solid tumor neoantigens using TCRs.
Ad-RTS-hIL-12 + veledimex is a gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a critical protein for stimulating an anti-cancer immune response, using the RheoSwitch Therapeutic System® (RTS®) gene switch. ZIOPHARM is currently enrolling patients in two studies of Ad-RTS-hIL-12 + veledimex: a multi-center Phase 1 study in patients with recurrent or progressive glioblastoma multiforme (GBM), an aggressive form of brain cancer, and a Phase 1b/2 study for the treatment of patients with locally advanced or metastatic breast cancer following standard chemotherapy.
- Preclinical studies combining Ad-RTS-IL-12 + veledimex and checkpoint inhibitors in brain tumor models presented at ASGCT. In an oral presentation, ZIOPHARM presented data from preclinical studies of Ad-RTS-IL-12 + veledimex combined with immune checkpoint inhibitors (iCPI) in GBM mouse models at the 2016 Meeting of the American Society of Gene and Cell Therapy (ASGCT) in Washington D.C. held last week. Results demonstrated that survival of mice treated with Ad-RTS-IL-12 + veledimex and anti-PD-1 therapy was superior to either treatment alone, with a combination showing 100% survival. Because Ad-RTS-IL-12 and anti-PD-1 are clinically available, these data provide impetus for evaluating this combination immunotherapy in humans. ZIOPHARM plans to initiate a combination study in 2016 and is currently in discussion with partners to provide anti-PD-1 therapy.
- Encouraging data from Phase 1 brain tumor study to be presented at ASCO. ZIOPHARM expects to present data from a multicenter, Phase 1 gene therapy study of Ad-RTS-IL-12 in patients with recurrent or progressive GBM or Grade III malignant glioma at the 2016 ASCO Annual Meeting in June. Following reporting of encouraging data from the first cohort of the study at the initial dosing of Ad-RTS-IL-12 + veledimex, the Company announced last March that the first patient had been enrolled in the study’s second dose cohort. The Company continues to enroll patients in the study and remains encouraged by the survival results observed to date.
Adoptive Cell Therapies
ZIOPHARM is developing various immuno-oncology programs, including chimeric antigen receptor T-cell (CAR-T), TCR, and natural killer (NK) adoptive cell-based therapies. These programs are being advanced in collaboration with Intrexon, MD Anderson Cancer Center, and the biopharmaceutical business of Merck KGaA, Darmstadt, Germany (CAR-T only).
- Preclinical study showing evolution of the Sleeping Beauty (SB) non-viral transposon-transposase system in a mouse model of leukemia presented at ASGCT. In an oral presentation, MD Anderson researchers in collaboration with ZIOPHARM presented data from preclinical studies demonstrating the ability to address the challenges of streamlining the manufacture of cell based therapy by leveraging the non-viral SB system to reduce cell culture time. The results were presented at the 2016 Meeting of the ASGCT in Washington D.C. held last week. These data also demonstrated an improvement in the anti-tumor activity of the CD19-specific CAR by modifying the “stalk” of the CAR.
- Molecular Therapy Publication Highlights the Potential of Sleeping Beauty to Personalize TCR Gene Therapy. In March, the Company announced the publication of an article describing the use of SB non-viral gene transfer technology to genetically modify T cells to target neoantigens present within solid tumors. This approach unlocks the potential for rapid and individualized TCR gene therapy aimed at unique mutations within each patient’s cancer cells. The article, titled “Stable, non-viral expression of mutated tumor neoantigen-specific T-cell receptors using the Sleeping Beauty transposon/transposase system,” was published in the journal Molecular Therapy (5 March 2016, doi:10.1038/mt.2016.51), and is available online.
- First patient enrolled in Phase 1 study of second generation non-viral CD19-specific CAR T-cell therapy for advanced lymphoid malignancies. In February 2016, ZIOPHARM announced that the first patient was enrolled in a new Phase 1 clinical study of its second generation non-viral CD19-specific CAR modified T-cell therapy in patients with advanced lymphoid malignancies (ClinicalTrials.gov Identifier: NCT02529813). T cells were modified using the SB system to stably express a CAR targeting CD19. This second-generation study at MD Anderson employs a CAR construct with a stalk revised to improve persistence and anti-tumor response over the first generation therapy. This investigational treatment is independent of hematopoietic stem-cell transplantation and includes patients with advanced disease.
- Sleeping Beauty non-viral gene transfer technology featured in Nature Medicine. In January 2016, the SB non-viral gene transfer technology was featured in a perspectives article in the journal Nature Medicine (Volume 22, Number 1, 26-36), titled “Prospects for gene-engineered T cell immunotherapy for solid cancers.” The article describes how adoptive transfer of TCR-engineered T cells for solid tumors may come from the “arduous task of targeting the unique set of mutations that cause each patient’s cancer.” Because of the challenges of achieving this goal, the authors note that non-viral integration systems will likely be considerably cheaper to manufacture and easier to implement for single-use applications compared with viral vectors and that, among non-viral platforms, SB has advanced furthest in clinical development.
ZIOPHARM expects the following milestones to occur in 2016:
- Intra-tumoral IL-12 RheoSwitch® programs:
- Clinical update at ASCO 2016 for Phase 1 study of GBM
- Update at ASCO 2016 for Phase 1/2 study in breast cancer with standard of care
- CAR-T programs:
- Continuation of CD19 CAR+ T-cell clinical study
- Initiate a CAR+ T-cell clinical study for myeloid malignancies
- Initiate CAR+ T-cell preclinical studies for other hematological malignancies and solid tumors
- Initiate preclinical studies of allogeneic, off-the-shelf (OTS) T-cell studies in 2016
- TCR-T programs
- Initiate TCR-modified T-cell preclinical studies
- NK cell programs
- Initiate a Phase 1 study of OTS NK cells for AML
- GvHD programs
- Initiate preclinical studies
The Company is also evaluating additional potential preclinical candidates and continuing discovery efforts aimed at identifying other potential product candidates under its Exclusive Channel Agreement with Intrexon. In addition, the Company may seek to enhance its pipeline in immuno-oncology through focused strategic transactions, which may include acquisitions, partnerships and in-licensing activities.
First-Quarter 2016 Financial Results
- Net loss for the first quarter of 2016 was $12.0 million, or $(0.09) per share, compared to a net loss of $78.2 million, or $(0.69) per share, for the first quarter of 2015. During the first quarter ended 2015, the company incurred a one-time non-cash charge of $67.3 million, or $(0.59) per share, related to a license agreement with The University of Texas M.D. Anderson Cancer Center.
- Research and development expenses were $10.2 million for the first quarter of 2016 compared to $74.2 million for the first quarter of 2015. The decrease in research and development expenses in the current year primarily relates to a one-time charge of $67.3 million related to the M.D. Anderson license agreement in 2015.
- General and administrative expenses were $3.8 million for the first quarter of 2016 compared to $4.3 million for the first quarter of 2015. The decrease was primarily due to a reduction in contracted outside service costs in 2016.
- The Company ended the quarter with cash and cash equivalents of approximately $124.8 million, which the Company believes will be sufficient to fund its currently planned activities into the fourth quarter of 2017. (Original Source)
Shares of Ziopharm closed today at $7.48, up $0.07 or 0.94%. ZIOP has a 1-year high of $14.93 and a 1-year low of $4.56. The stock’s 50-day moving average is $7.86 and its 200-day moving average is $8.60.
On the ratings front, Ziopharm has been the subject of a number of recent research reports. In a report issued on January 25, Mizuho analyst Eric Criscuolo reiterated a Hold rating on ZIOP, with a price target of $6, which reflects a potential downside of -19.8% from last closing price. Separately, on January 14, J.P. Morgan’s Whitney Ijem reiterated a Hold rating on the stock .
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Eric Criscuolo and Whitney Ijem have a total average return of -8.9% and -9.8% respectively. Criscuolo has a success rate of 36% and is ranked #3374 out of 3828 analysts, while Ijem also has a success rate of 36% and is ranked #3244.
ZIOPHARM Oncology, Inc. is a biopharmaceutical company currently in developmental stage that seeks to acquire, develop and commercialize, on its own or with commercial partners, a diverse portfolio of cancer therapies. It is focused on two clinical stage product candidates: Ad-RTS-IL-12 + veledimex and DC-RTS-IL-12 + veledimex. Ziopharm Oncology was founded on September 9, 2003 and is headquartered in Boston, MA.