On June 28, 2017 Kite Pharma, Inc., (Nasdaq:KITE), a leading cell therapy company, reported that the United States Patent and Trademark Office (USPTO) has provided a Notice of Intent to issue an Ex Parte Reexamination Certificate that confirms the patentability of amended claims presented in U.S. Patent No. 7,741,465, known as the Eshhar ‘465 patent (Press release, Kite Pharma, JUN 28, 2017, View Source [SID1234519709]). The Eshhar ‘465 patent, exclusively licensed by Kite in 2013, protects the axicabtagene ciloleucel franchise and may impact competitive CAR-T therapies.

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"This notice by the USPTO outlining its intent to confirm the Eshhar patent further asserts the pioneering role of Dr. Zelig Eshhar in developing CAR-T technology," said Arie Belldegrun, MD, FACS, Chairman, President and Chief Executive Officer of Kite. "Our significant patent portfolio, combined with our positive data and industry-leading manufacturing process, reinforces our position as one of the foremost companies in cell therapy."

The Eshhar ‘465 patent term continues to June 2027, not including certain potential extensions. Kite’s growing intellectual property portfolio now encompasses more than 200 patent assets relating to its broad cell therapy pipeline and manufacturing excellence.

Axicabtagene ciloleucel is the first engineered cell therapy to be reviewed by the U.S. Food and Drug Administration (FDA) in aggressive non-Hodgkin’s lymphoma (NHL). The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of November 29, 2017.

About axicabtagene ciloleucel

Kite’s lead product candidate, axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

On June 28, 2017 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported the initiation of enrollment in the stereotactic arm of its Phase 1 multicenter study of Ad-RTS-hIL-12 + veledimex, a gene therapy for controlled expression of IL-12, in patients with recurrent glioblastoma multiforme (rGBM) (Press release, Ziopharm, JUN 28, 2017, View Source [SID1234519708]). The stereotactic cohort will include rGBM patients that are not scheduled to undergo surgical resection to assess the safety and tolerability of a single dose of Ad-RTS-hIL-12 administered via injection and activated with orally-administered veledimex (20 mg QD, days 1-14).

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"Supported by strong clinical data highlighting the potential for controlled immune activation to affect survival outcomes in recurrent GBM, we are expanding our innovative Ad-RTS-hIL-12 + veledimex gene therapy into new treatment settings and combinations," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "By introducing stereotactic administration, we broaden the population of patients who may be eligible for treatment, including pediatric patients with diffuse intrinsic pontine glioma, a rapidly fatal and inoperable form of brain cancer. Additionally, preclinical studies of this tunable IL-12 gene therapy in combination with an immune checkpoint inhibitor have yielded promising results, notably a 100 percent survival rate of treated mice, and we look forward to bringing this approach into the clinic."

Following an observation period, the Company expects to immediately:

Initiate enrollment in a study of adult patients with rGBM who will receive a single dose of Ad-RTS-hIL-12 + veledimex in combination with a checkpoint inhibitor targeting programmed cell death protein 1 (PD-1);
Initiate enrollment in a study of pediatric patients with recurrent/progressive glioma who will receive a single dose of Ad-RTS-hIL-12 + veledimex. The Company anticipates children with diffuse intrinsic pontine glioma (DIPG) will be eligible for enrollment.
At the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held in June, the Company reported encouraging results from patients receiving intratumoral Ad-RTS-hIL-12 with 20 mg of orally-administered veledimex (n = 15) following craniotomy, with a median overall survival (mOS) of 12.5 months comparing favorably to historical controls. Based on the observed ratio of CD8+/FOXP3+ (effector/suppressor) T cells, overall survival appears directly correlated with IL-12-mediated cellular immune activation. Furthermore, patients who received low dose steroids have a much better survival rate than those who received elevated systemic steroids, as the latter presumably interferes with immune activation. The Company continues to progress towards a registration study for Ad-RTS-hIL-12 + veledimex for rGBM to start in 2017 and is also evaluating partnership opportunities for this promising treatment candidate.

"Stereotactic treatment serves as a runway into our next phase of development for Ad-RTS-hIL-12 + veledimex including combination therapy and pediatric studies," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology. "We anticipate translating the combination approach to patients imminently and further leveraging initial observations on the survival benefit of IL-12-driven immune activation. As a pediatric oncologist, I know full well the devastating impact of DIPG and am also looking forward to seeing the effect of controlling IL-12 in this difficult-to-treat disease."

Brain tumors

Recurrent GBM represents approximately 15% of all primary adult brain tumors and remains a high unmet clinical need that affects roughly 74,000 people worldwide annually.i,ii GBM is an aggressive form of brain cancer with recurrence rates near 90%, and prognosis for patients is poor with treatment often combining multiple approaches including surgery, radiation, and chemotherapy. Patients with recurrent GBM typically have a mOS of 6-7 months, and overall survival in patients who have failed temozolomide, bevacizumab or equivalent salvage chemotherapy, is approximately 3-5 months.iii,iv DIPG is a rapidly progressive brain tumor of children with tragically near universal fatal outcomes and a median survival less than 12 months.v

On June 28, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported that CA4P in combination with a checkpoint inhibitor significantly reduced tumor size in a CT-26 colon cancer animal model (Press release, Mateon Therapeutics, JUN 28, 2017, View Source [SID1234519707]).

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Mateon evaluated its lead investigational drug CA4P, which is also currently being studied in a phase 2/3 clinical trial in platinum-resistant ovarian cancer, in a syngeneic mouse model in combination with a checkpoint inhibitor. In order to assess the effects of CA4P on more advanced and difficult-to-treat tumors, tumors in this study were allowed to grow for 13 days prior to treatment. Consequently, beginning tumor sizes were approximately three times larger than those generally evaluated in preclinical studies. Results following two weeks of treatment are as follows:



Treatment Baseline
Tumor Size Day 14
Tumor Size Day 14 Survival Survival
p-values
Vehicle 159 mm3 2005 mm3 0 / 8 Not applicable
CA4P 159 mm3 1265 mm3 2 / 8 Not significant
Anti-CTLA-4 156 mm3 1016 mm3 4 / 8 0.048
CA4P + Anti-CTLA-4 157 mm3 229 mm3 8 / 8 0.001 *
* p=0.032, Anti-CTLA-4 vs. CA4P and anti-CTLA-4

"CA4P increases the effects of checkpoint inhibitors because it rapidly causes tumor cell death, which likely increases tumor antigen presentation and T-cell activation and the overall immunologic response," said William D. Schwieterman, M.D., President and Chief Executive Officer. "These new results reinforce similar results observed in other studies and, importantly, the animals in the combination CA4P and anti-CTLA-4 antibody treatment group are continuing to show declines in tumor volume beyond Day 14. We look forward to additional data from this study and other on-going preclinical work over the next several months."

Mean Tumor Volume in CT-26 Colorectal Mouse Model
Mean Tumor Volume in CT-26 Colorectal Mouse Model


An infographic accompanying this announcement is available at View Source
This is the second study and tumor type to demonstrate robust complementary effects when Mateon’s CA4P is provided in combination with a checkpoint inhibitor; results obtained approximately four months ago in a smaller tumor EMT-6 mammary model also showed strong synergy when anti-CTLA-4 antibodies were combined with CA4P.

On June 28, 2017 Halozyme Therapeutics (NASDAQ: HALO) reported that Phase 2 randomized, multi-center clinical trial in pancreas cancer patients were shared today in two oral presentations at the European Society for Medical Oncology’s 19th World Congress on Gastrointestinal Cancer (Press release, Halozyme, JUN 28, 2017, View Source [SID1234519706]).

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The HALO-202 study represents the first clinical trial of a molecularly targeted drug in pancreatic ductal adenocarcinoma and the results support hyaluronan (HA) as a potential biomarker to predict those patients who could benefit from Halozyme’s investigational new drug PEGPH20 (pegvorhyaluronidase alfa) when added to standard chemotherapy.

As previously reported, the study met its primary efficacy and safety endpoints and the key secondary endpoint of progression-free survival (PFS) in HA-High patients. PEGPH20 plus standard chemotherapy of ABRAXANE (nab-paclitaxel) and gemcitabine improved median PFS by 77 percent over chemotherapy alone in HA-High patients.

Dr. Andrew Hendifar, the medical oncology lead for the Gastrointestinal Disease Research Group at Cedars-Sinai and co-director of Pancreas Oncology delivered the presentation, "PEGPH20 Improves PFS in Patients With Metastatic Pancreatic Ductal Adenocarcinoma: A Randomized Phase 2 Study in Combination With nab-Paclitaxel/Gemcitabine."

Dr. Andrea Bullock, attending physician in Gastrointestinal Oncology at Beth Israel Deaconess Medical Center and an Instructor in Medicine at Harvard University delivered the presentation, "Tumor Hyaluronan May Predict Benefit From PEGPH20 When Added to nab-Paclitaxel/Gemcitabine in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (mPDA)."

New safety data reported today show bleeding events were balanced between the two arms after the introduction of low molecular weight heparin in stage 2 of the study.

"The results of HALO-202 are encouraging and continue to support our ongoing HALO-301 phase 3 study in HA-High pancreas cancer patients," said Dr. Helen Torley, president and chief executive officer. "HALO-301 is now open for screening and enrollment at more than 200 centers in over 20 countries."

In addition to the oral presentations, Halozyme and its investigators are presenting three posters pertaining to the study of PEGPH20, including:

Musculoskeletal Adverse Events with PEGPH20 Treatment and Management in Patients with Previously Untreated Metastatic PDA (HALO-202), presented by Dr. Bullock;
Global, Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of PEGPH20 + nab-Paclitaxel & Gemcitabine in Pts with Previously Untreated, HA-High, Stage IV PDA (HALO-301), presented by Dr. E. Von Cutsem, a principal investigator in the study; and
A Systematic Review Examining the Relationship Between PFS and OS Survival In Adults With Untreated Metastatic Pancreatic Cancer, presented by Halozyme.
Pancreas cancer is the third-leading cause of cancer related death in the United States, and more than 65,000 people in the U.S. and top five European countries are diagnosed annually with advanced cases of the disease.

About HALO-301 and HALO-202
HALO-301 is a phase 3 global, randomized, double-blind placebo controlled clinical trial evaluating investigational new drug PEGPH20 as a first-line therapy for potential treatment of patients with metastatic pancreas cancer. The trial will be conducted at approximately 200 sites with two primary endpoints, progression free survival and overall survival in patients receiving investigational new drug PEGPH20 in combination with gemcitabine and ABRAXANE (nab-paclitaxel) compared to gemcitabine and nab-paclitaxel alone. Secondary endpoints also include objective response rate and overall survival. More information may be found at clinicaltrials.gov (search HALO 301 or trial identifier NCT02715804) or www.HALO301.com.

HALO-202 (Halo 109-202) is a phase 2 multi-center, randomized clinical trial evaluating investigational new drug PEGPH20 as a first-line therapy for potential treatment of patients with metastatic pancreas cancer. The primary outcome of the trial is to measure improvement in progression-free survival in patients receiving investigational new drug PEGPH20 in combination with gemcitabine and nab-paclitaxel compared to gemcitabine and nab-paclitaxel alone. A second primary endpoint assesses the thromboembolic event rate in the PEGPH20 treatment arm. Secondary endpoints also include objective response rate and overall survival.

About PEGPH20 (pegvorhyaluronidase alfa)
PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan. PEGPH20 is an enzyme that temporarily degrades HA, a dense component of the tumor microenvironment that can accumulate in higher concentrations around certain cancer cells, potentially constricting blood vessels and impeding the access of other therapies.

FDA granted orphan drug designation to PEGPH20 for treatment of pancreas cancer and fast track designation for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreas cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreas cancer.

On June 28, 2017 CytomX Therapeutics, Inc. (Nasdaq:CTMX), a biopharmaceutical company developing investigational Probody therapeutics for the treatment of cancer, reported the treatment of the first patient in the PROCLAIM-CX-2009 study (Probody Clinical Assessment In Man), a Phase 1/2 clinical trial evaluating CX-2009 as monotherapy in patients with select advanced solid tumors (Press release, CytomX Therapeutics, JUN 28, 2017, View Source [SID1234519705]). CX-2009 is a Probody drug conjugate (PDC) that targets CD-166, an antigen that is broadly and highly expressed in many types of cancers and is the first PDC to enter the clinic.

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"The unique targeting ability of our Probody platform allows us to pursue targets not accessible to conventional antibody drug conjugates. With CX-2009, we are leveraging the high levels of CD-166 on many types of cancer cells despite its presence on normal tissue," said Sean McCarthy, D.Phil., president and chief executive officer of CytomX Therapeutics. "By targeting CD-166 and localizing the activity of the CX-2009 Probody therapeutic to the tumor, we could potentially treat a number of cancers for which few, if any, treatment options exist."

About CX-2009 and the PROCLAIM-CX-2009 Trial
CX-2009, a PDC that targets cell surface protein CD-166, is being developed for the treatment of solid tumors. CD-166 is highly and homogeneously expressed on multiple tumor types, such as breast cancer, endometrial cancer and prostate cancer. CytomX has demonstrated that CD-166 effectively internalizes antibody-drug conjugates resulting in potent cell killing in-vitro. CX-2009 is designed to target CD-166 specifically in the tumor microenvironment and deliver the tubulin-destabilizing maytansine payload, DM4, to cancer cells. In 2014, CytomX entered into a license agreement with ImmunoGen, Inc. to develop PDCs against a defined number of targets, bringing together CytomX’s proprietary antibody masking technology and tumor-selective protease substrates with ImmunoGen’s highly potent antibody drug conjugate cell-killing agents and engineered linkers. CX-2009 is wholly owned by CytomX.

CX-2009 is being studied within PROCLAIM, CytomX’s international modular umbrella clinical trial program that encompasses the Phase 1/2 development of multiple Probody therapeutics. PROCLAIM-CX-2009 is a dose-finding Phase 1/2 study evaluating CX-2009 as monotherapy in patients with select cancer types, including non-small cell lung cancer, breast cancer, ovarian cancer, endometrial cancer, cholangiocarcinoma (bile duct cancer), head and neck cancer and castration-resistant prostate cancer. The objectives of the study are to establish the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of CX-2009.

More information about the trial is available at ClinicalTrials.gov.