On October 16, 2017 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company developing new gene and cell-based immunotherapies for cancer, reported that the first patient has been dosed in a new Phase 1 study of Ad-RTS-hIL-12 with veledimex for the treatment of pediatric brain tumors (Press release, Ziopharm, OCT 16, 2017, View Source [SID1234520948]).

This open label study will assess the safety and tolerability of a single intratumoral injection of Ad-RTS-hIL-12, a gene therapy designed to control the expression of human interleukin 12 (hIL-12), a critical protein for stimulating a localized anti-cancer immune response. The study is conducted in two groups: the first is comprised of pediatric patients with recurrent or progressive brain tumors in the cortex, while the second is comprised of pediatric patients with diffuse intrinsic pontine glioma (DIPG).

“Studies in adults with recurrent glioblastoma have shown that Ad-RTS-hIL-12 with veledimex is not only well tolerated, but also have shown growing evidence that this treatment elicits a targeted immune response against brain tumor cells that gives rise to improvement in overall survival,” said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. “We look forward to advancing our studies in pediatric patients with brain tumors as these patients have limited-to-no therapeutic options.”

This Phase 1 study is being conducted at leading pediatric cancer centers across the United States, including Ann & Robert H. Lurie Children’s Hospital in Chicago, Dana-Farber Cancer Institute in Boston and the University of California, San Francisco. The first pediatric patient to receive Ad-RTS-hIL-12 plus veledimex is receiving care at Lurie Children’s.

“Pediatric gliomas are a devastating diagnosis for children and families, and DIPG, specifically, while rare, is extremely aggressive and always a fatal disease with no viable treatment options,” said Stewart Goldman, M.D., Division Head Hematology-Oncology, Neuro-Oncology & Stem Cell Transplantation at Lurie Children’s. “We look forward to evaluating the potential of Ad-RTS-hIL-12 plus veledimex as a treatment option for children with brain tumors.”

About Glioma

Glioblastoma (GBM) is a fast-growing, aggressive type of central nervous system tumor, with an estimated 12,390 new adult cases predicted in 2017 according to the American Brain Tumor Association. Recurrence rates for this type of cancer are near 90 percent, and prognosis for adult patients is poor with treatment often combining multiple approaches including surgery, radiation and chemotherapy i. In children, the incidence of brain cancer is approximately 4.84 per 100,000, according to the National Cancer Institute. Glioma in the cortex (cerebrum) of children is unusual and is treated along the same lines as in adults with occurrence common and survival poor. Glioma in the pontine region of the brain, or DIPG, accounts for approximately 15 percent of all cases of pediatric brain tumors, with a median survival time of less than one yearii. Because of where these tumors are situated, DIPG is inaccessible to surgery and there are no curative options.

About Ad-RTS-hIL-12 plus Veledimex

ZIOPHARM is advancing Ad-RTS-hIL-12 plus veledimex as a gene therapy for recurrent GBM (rGBM). Ad-RTS-hIL-12 is an adenoviral vector administered via a single injection into the tumor and engineered to express hIL-12, a powerful cytokine that has demonstrated the potential to stimulate a targeted, anti-tumor immune response. The expression of hIL-12 is controlled and modulated with the RheoSwitch Therapeutic System (RTS) by the small molecule veledimex, an activator ligand which has been shown to cross the blood brain barrier. The Company has recently reported that biopsies from three patients treated with Ad-RTS-hIL-12 plus veledimex provided evidence of documented pseudo-progression rather than tumor progression. Pseudo-progression may be seen in serial post-treatment imaging studies of cancers where the tumor appears larger compared to baseline, but these changes are due to infiltration of immune cells, as evidenced by subsequent biopsies. ZIOPHARM’s Phase 1 stereotactic study of Ad-RTS-hIL-12 with veledimex for the treatment of patients with brain tumors is underway. The Company also plans to initiate enrollment of adult patients with rGBM who will receive a single dose of Ad-RTS-hIL-12 plus veledimex in combination with a checkpoint inhibitor targeting programmed cell death protein 1 (PD-1) by the end of the year.

On October 16, 2017 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that new preclinical data and a patient case study for its CD47-blocking agent, TTI-621 (SIRPa-IgG1 Fc), were presented at the EORTC CLTF meeting “Cutaneous Lymphomas – Insights and Therapeutic Progress”, October 13-15, in London, England (Press release, Trillium Therapeutics, OCT 16, 2017, View Source [SID1234520947]).

Oral Presentation O-16: CD47 Blockade with TTI-621 (SIRPαFc) in Sézary Syndrome
Presenter: Dr. Oleg Akilov, University of Pittsburgh

This oral presentation highlighted that leukemic cells from patients with Sézary syndrome, a form of cutaneous T cell lymphoma (CTCL), express the CD47 “do not eat” signal at almost four times the level of normal lymphocytes and that over-expression of CD47 is associated with poor prognosis. In vitro experiments demonstrated that blockade of CD47, employing TTI-621, may constitute a promising therapeutic approach for patients with Sézary syndrome. Two clinical trials of TTI-621 that include patients with relapsed or refractory CTCL are ongoing at multiple North American sites (NCT02663518 and NCT02890368).

Poster Presentation P-10: Synergistic Effect of Successive Administration of TTI-621 (SIRPαFc) and PEGylated Interferon-α2a in a Patient with Sézary Syndrome
Presenter: Dr. Oleg Akilov, University of Pittsburgh

This case study reported local and systemic anti-tumor activity in a Sézary syndrome patient treated with a single intratumoral dose of TTI-621. Administration of PEGylated Interferon-α2a seven days after TTI-621 resulted in decreased leukemic burden and improvements in clinical symptoms. Trillium believes such a reduction is not observed regularly with standard regimens and would not be anticipated following PEGylated Interferon-α2a monotherapy, suggesting a synergistic effect of TTI-621 and PEGylated Interferon-α2a.

“CTCL patients are being treated in both our intratumoral and intravenous trials,” said Dr. Niclas Stiernholm, Trillium’s Chief Executive Officer. “Careful study of the effects of TTI-621 in CTCL patients potentially provides us with a unique opportunity to better understand the mechanism behind TTI-621’s anti-tumor activity and the role of CD47 in the overall immuno-oncology landscape, ultimately leading to targeted indications and combination therapies with sound scientific rationale.”

About Cutaneous T-Cell Lymphoma (CTCL)

CTCL is a rare type of non-Hodgkin’s lymphoma which is characterized by localization of malignant T lymphocytes to the skin. The two most common types of CTCL are mycosis fungoides and Sézary syndrome. The disease most often involves the skin, may progress to involve lymph nodes, blood, viscera and other organs, and in select cases may become leukemic.

October 16, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported initiation of a phase 1b/2 immuno-oncology trial to evaluate Genentech/Roche’s atezolizumab (TECENTRIQ) in combination with Inovio’s INO-5401, a T cell activating immunotherapy encoding multiple antigens, and INO-9012, an immune activator encoding IL-12 (Press release, Inovio, OCT 16, 2017, View Source [SID1234520944]).

The multi-center, open-label efficacy trial will be managed by Inovio, and Genentech will supply atezolizumab. The trial will evaluate the safety, immune response and clinical efficacy of the combination therapy in approximately 80 patients with advanced bladder cancer, specifically advanced unresectable or metastatic urothelial carcinoma (UC), the most common type of bladder cancer. The majority of the patients to be enrolled in the trial will have previously received and failed to demonstrate meaningful response to an anti-PD-1 or PD-L1 checkpoint inhibitor alone. Thus the study will evaluate potential benefit of a checkpoint inhibitor combined with a DNA-based immunotherapeutic and T cell activator within a bladder cancer patient population with very limited treatment options and poor outcomes. The immunologic analyses accompanying the study will provide further insight into mechanisms of checkpoint inhibition and T cell activation in bladder cancer.

Dr. Joaquim Bellmunt, MD, PhD, Director of Bladder Cancer Center, Dana-Farber Cancer Institute and Associate Professor, Harvard Medical School, said, “The unmet need for effective treatments for advanced UC patients remains very high even in the midst of approvals of multiple checkpoint inhibitors in this space — as only a small subset of patients respond to these therapies alone. Increasing evidence suggests that combinatorial approaches are needed to improve upon the initial success of checkpoint inhibitors; the benefit to this patient population may be significantly improved when combination therapies that also generate activated T cells are utilized. Furthermore, there is a very high need for effective treatment approaches in checkpoint-refractory patients.”

Dr. J. Joseph Kim, Inovio’s President and CEO, said, “Combining INO-5401 with TECENTRIQ may provide a synergistic therapeutic effect as a result of generating high levels of activated T cells and simultaneously inhibiting PD-L1. Bladder cancer has often been described as an immunogenic tumor, and here our approach is to augment the anti-PD-1/PD-L1 driven efficacy by further enhancing the T cells against the tumor in a cancer antigen-specific manner. We believe we can demonstrate the immense potential of INO-5401 as a universal cancer immunotherapy to treat patients with multiple cancers.”

Nearly 430,000 new cases of urinary bladder cancer are diagnosed each year worldwide; it accounts for about 165,000 deaths worldwide annually. Advanced unresectable or metastatic UC remains a high unmet medical need as survival remains poor for most patients who experience disease progression or intolerance to treatment during or after platinum-containing chemotherapy. The approval of several checkpoint inhibitors for advanced unresectable or metastatic UC has improved response and survival rates for some patients, however, the majority of patients do not experience meaningful clinical responses to checkpoint inhibitor monotherapy.

Inovio’s INO-5401, an immunotherapy encoding multiple cancer antigens (HTERT, PSMA, and WT1), is designed to generate and activate T cells to many cancer types including bladder cancer. INO-9012, a DNA-based immune activator encoding IL-12, is designed to amplify and accelerate T cell immune responses to INO-5401. Combining INO-5401/INO-9012 with atezolizumab may provide a synergistic therapeutic effect as a result of generating higher levels of activated T cells and simultaneously inhibiting PD-L1. Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.

About Metastatic Urothelial Carcinoma (UC)

The prognosis for patients with advanced unresectable or metastatic UC is poor, with limited treatment options. It is a disease that has seen no major advances for more than 30 years until the approvals of checkpoint inhibitors. Expected survival is generally less than 12 months; in the U.S., five-year survival of patients with distant metastasis is 5%. In the US, an estimated 79,000 new cases of urinary bladder cancer are expected in 2017.

About INO-5401

INO-5401 includes Inovio’s SynCon antigens for WT1, hTERT and PSMA and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted WT1, hTERT and PSMA among a list of attractive cancer antigens, designating them as high priorities for cancer immunotherapy development and placing WT1 at the top of the antigen list. The hTERT antigen is expressed in 85% of cancers; the WT1 and PSMA antigens are also widely prevalent in many cancers. In addition, INO-5401 is being evaluated for the treatment of GBM in combination with a checkpoint inhibitor.

On October 16, 2017 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has completed the safety review of its investigational new drug (IND) application for IMGN632 in patients with CD123-positive hematological malignancies, including acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, ImmunoGen, OCT 16, 2017, View Source [SID1234520942]). Filed in mid-September, the IND is now in effect and ImmunoGen plans to open a Phase 1 study to enrollment before the end of the year.

“IMGN632 is the second ADC from our pipeline to use one of ImmunoGen’s indolino-benzodiazepine cancer-killing agents known as IGNs”
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“IMGN632 is the second ADC from our pipeline to use one of ImmunoGen’s indolino-benzodiazepine cancer-killing agents known as IGNs,” said Richard Gregory, Ph.D., Executive Vice President and Chief Scientific Officer of ImmunoGen. “Our IGN payloads were designed to meet the dual challenges of achieving high potency against target cells, while having a tolerability profile that can enable continued patient treatment. Based on the encouraging preclinical findings, IMGN632 represents a potentially promising therapeutic approach for a range of hematological malignancies and we are working to transition this compound rapidly into clinical development before the end of the year.”

IMGN632 uses ImmunoGen’s novel DGN549 IGN payload, linker, and antibody technology and in preclinical models has demonstrated an impressive therapeutic window against CD123-positive malignancies. Preclinical findings reported at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting show that IMGN632, which alkylates DNA, had potent selective activity against AML cells with lower cytotoxicity to normal myeloid progenitor cells than an ADC designed to crosslink DNA activity. These data suggest IMGN632 has the potential to be a highly effective, yet tolerable ADC for AML patients. Supporting preclinical data for IMGN632 showed compelling activity in AML xenograft models.

About IMGN632
IMGN632 is a humanized anti-CD123 antibody-drug conjugate that is a potential treatment for AML, BPDCN, myelodysplastic syndrome, B-cell acute lymphocytic leukemia, and other CD123-positive malignancies. IMGN632 uses a novel IGN payload, linker and antibody technology and in AML xenograft models has demonstrated a large therapeutic index.1

About IGNs
Indolino-benzodiazepine cancer-killing agents, or IGNs, are a new class of cancer-killing agent developed by ImmunoGen for use in ADCs. These ultra-potent, DNA-acting IGNs alkylate DNA without crosslinking, which preclinically has resulted in potent anti-leukemia activity with relative sparing of normal hematopoietic progenitor cells.2,3 IMGN779, a CD33-targeting ADC in Phase 1 testing for AML, was the first IGN ADC to enter clinical testing.

About Acute Myeloid Leukemia (AML)
AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems and anemia.

It is estimated that, in the U.S. alone, 21,380 patients will be diagnosed with AML this year and 10,590 patients will die from the disease.