First patient enrolled into phase I clinical trial of Oncolytic Virus HF10 against pancreatic cancer in Japan

On September 27, 2017 Takara Bio Inc. (Takara Bio), reported that the first patient with pancreatic cancer has been enrolled into Oncolytic Virus HF10(TBI-1401) phase I clinical trial in Japan on September　26, 2017 (Press release, Takara Bio, SEP 27, 2017, View Source [SID1234520647]).

This clinical trial will be conducted in patients with unresectable advanced pancreatic cancer to evaluate safety of HF10 in combination with existing chemotherapeutic drug.

In this clinical trial, the HF10 manufactured at Center for Gene and Cell Therapy, Takara Bio’s facility, will be used.
Regarding domestic development and sales of oncolytic virus HF10, Takara Bio has an exclusive licensing agreement with Otsuka Pharmaceutical Co., Ltd., and both companies will consult with each other and aim for the early approval of HF10 in Japan.

Pelican Therapeutics Announces Manufacturing Agreement with KBI Biopharma to Advance Cancer-targeting Immunotherapies

On September 27, 2017 Pelican Therapeutics (“Pelican”), a subsidiary of Heat Biologics, Inc. (“Heat”) (Nasdaq: HTBX), entered into a manufacturing agreement with KBI Biopharma, Inc., a global biopharmaceutical contract development and manufacturing organization, for cGMP production of its PTX-35 antibody and PTX-15 fusion protein (Press release, Heat Biologics, SEP 27, 2017, View Source [SID1234520646]). PTX-35 and PTX-15 have the potential to improve clinical response in combination with Heat’s ImPACT therapeutic platform and other immunotherapy drugs by simulating the production of antigen-specific T-cells.

“We selected KBI as our manufacturing partner because, based on our assessment, they have strong development capabilities, and possess the agility and flexibility to help Pelican prepare for early development of both our Phase 1 and 2 clinical trials,” said Rahul Jasuja, CEO of Pelican.

Under the agreement, KBI Biopharma will offer comprehensive development and manufacturing services, which Pelican expects will offer advantages such as speed, productivity, stability and flexibility over traditional approaches to cell line development.

In May 2016, Pelican was awarded a $15.2 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to support these manufacturing efforts, as well as to complete a 70-patient, Phase 1 clinical trial incorporating one or more of these compounds.

Genmab Announces Approval of DARZALEX® (daratumumab) for Relapsed or Refractory Multiple Myeloma in Japan

On September 27, 2017 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the Ministry of Health, Labor and Welfare (MHLW) in Japan has approved the use of DARZALEX (daratumumab) in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is being developed under an August 2012 agreement in which Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize the product (Press release, Genmab, SEP 27, 2017, View Source [SID1234520645]). Genmab will earn milestone payments of USD 25 million from Janssen upon the first commercial sale of DARZALEX in Japan in the coming months. As the first commercial sale could take place in either late 2017 or early 2018, Genmab is not updating its financial guidance for 2017. If the first commercial sale is achieved prior to year end, Genmab expects to update its financial guidance at that time.

“Multiple myeloma is one of the most common forms of blood cancer in Japan and we are very pleased that DARZALEX will soon also become available for Japanese multiple myeloma patients who have failed other treatments,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The approval is based on two pivotal studies: the Phase III CASTOR study (MMY3004), published in The New England Journal of Medicine in August 2016; the Phase III POLLUX study (MMY3003), published in The New England Journal of Medicine in October 2016; and supported by several other studies, including two safety studies (MMY1002 and MMY1005) in Japanese patients with relapsed or refractory multiple myeloma.

About multiple myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in Japan, after leukemia and lymphoma.2 Approximately 8,700 new patients were expected to be diagnosed with multiple myeloma and approximately 4,200 people were expected to die from the disease in Japan in 2016.2 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.3 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.4 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.5

About DARZALEX (daratumumab)

DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death). 6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, NKT-cell lymphoma, amyloidosis, myelodysplastic syndromes and solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

“ALAGLIO® Divided Granules 1.5g,” a Photodynamic Diagnostic Agent Obtained Manufacture and Marketing Approval

On September 27, 2017 SBI Pharmaceuticals Co., Ltd., (Head office: Minato-ku, Tokyo; Representative Director & President: Yoshitaka Kitao; “SBI Pharma”), a subsidiary of SBI Holdings, Inc., engaged in the research and development of medicines using 5-ALA (5-Aminolevulinic acid) (*1) and Chugai Pharmaceutical Co., Ltd. (Head office: Chuo-ku, Tokyo; Chairman & CEO: Osamu Nagayama; “Chugai”) hereby reported that the manufacture and marketing approval of a photodynamic diagnostic agent, “ALAGLIO Divided Granules 1.5g” (Generic name: Aminolevulinic acid hydrochloride; “this Agent”) has been obtained from the Ministry of Health, Labour and Welfare for the indication of diagnostic agent to visualize non-muscle invasive bladder cancer at the operation of its transurethral resection (Press release, Chugai, SEP 27, 2017, View Source [SID1234520643]).

This Agent is the world-first orally administered formulation for photodynamic diagnosis (PDD) for the purpose of visualizing the non-muscle invasive bladder cancer (*3) at the operation of the transurethral resection of the bladder tumor (TURBT) (*2) and designated as an orphan drug. The Phase II/III clinical trials of this Agent were conducted at 5 medical institutions with the central role of Kochi University as Investigator-Initiated Clinical Trials of Clinical Research Promotion Program supported by the Center for Clinical Trials, Japan Medical Association. (The results of the follow-up Phase III clinical trials conducted at the same medical institutions were shown on the news of SBI Pharma dated April 24, 2017.)

This Agent is dissolved in water and orally administered to the patient 3 hours (Range: 2-4 hours) before the insertion of a cystoscope to the bladder, and then blue light is irradiated inside the bladder. This procedure emits red fluorescence at the site of tumor lesion and elevates the visibility of the lesion. This is thought to make it easy to distinguish even minute cancer and flat cancer that cannot easily be visible by the conventional method with white light source only. Resecting tumor lesion as much as possible at the initial treatment of the non-invasive bladder cancer is expected to be clinically useful to prevent progression and recurrence of bladder cancer after the operation.

Chugai has been granted the exclusive marketing rights on this Agent in Japan by SBI Pharma, which obtained the manufacture and marketing approval of this Agent. (Please refer to the news dated March 13, 2017.)

SBI Pharma and Chugai join and further strengthen the efforts to speed up the availability of ALAGLIO Divided Granules 1.5g, a new therapeutic option, for patients fighting against the bladder cancer and healthcare professionals.

(*1) 5-aminolevulinic acid (5-ALA): An amino acid produced in mitochondria. It is an important substance that serves as a functional molecule related to energy production in the form of heme and cytochromes, and its productivity is known to decrease with age. 5-ALA is contained in food such as shochu lees, red wine and Asian ginseng. It is also known as a material forming chloroplasts in plants.

(*2) Transurethral resection of the bladder tumor (TURBT): TURBT is an abbreviation of Transurethral Resection of the Bladder Tumor. A method to insert a surgical endoscope (cystoscope) from the urethra without laparotomy, and resect the tumor while preserving the bladder function.

(*3) Non-muscle invasive bladder cancer: The bladder cancer of a relatively early stage, without invading muscular layer of urinary bladder. It accounts for about 70% of all types of the bladder cancer*. The initial treatment for this type of cancer is primarily TURBT, aiming at the preservation of the bladder function. However, TURBT with a conventional white light source only results in the recurrence with the ratio of 31-78% within 5 years after the operation**.

* Guideline for the Diagnosis and Treatment of the Bladder Cancer 2015 (Edited by The Japanese Urological Association) Igakutosho-shuppan Ltd.; p25
** Sylvester RJ, et al. (2006) Eur Urol; 49: 466-77

Asterias Receives Regulatory Clearance to Initiate Clinical Study of AST-VAC2 in Subjects with Early and Late Stage Non-Small Cell Lung Cancer

On September 26, 2017 Asterias Biotherapeutics, Inc. (NYSE MKT:AST), a biotechnology company pioneering the field of regenerative medicine, reported that the Medicines and Healthcare Products Regulatory Agency (MHRA) and the NHS Research Ethics Committee (REC) have provided the necessary approvals to initiate the first-in-human (FIH) clinical trial of AST-VAC2 in the United Kingdom (UK) (Press release, Asterias Biotherapeutics, SEP 26, 2017, View Source;p=RssLanding&cat=news&id=2302817 [SID1234520634]). The trial, which is being sponsored and managed by Cancer Research UK, will examine the safety, tolerability, immunogenicity and activity of AST-VAC2 in non-small cell lung cancer (NSCLC) patients and is expected to be initiated later this year.

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AST-VAC2 is a "first-in-class" allogeneic cancer immunotherapy that is composed of mature dendritic cells which are designed to kill tumor cells by stimulating immune responses to telomerase, a tumor antigen expressed by over 85% of malignant tumor cells. AST-VAC2 is available for "on demand" patient use because it is produced from allogeneic pluripotent stem cells that can be manufactured in scale and then cryopreserved. The AST-VAC2 to be used in this trial has been manufactured by Cancer Research UK’s Biotherapeutics Development Unit.

AST-VAC2 is a platform cancer immunotherapy that could be investigated as a potential therapeutic for many cancer indications and for targeting of many antigens. The results from the clinical trial sponsored by Cancer Research UK could be used to support advanced clinical studies in one or more of the following areas:

Non-small cell lung cancer
Other indications showing high levels of telomerase activity and susceptibility to immunotherapy
In combination with check point or immune pathway inhibitors
In combination with additional antigens, including those arising from the exciting new field of tumor neoantigens
"The recently announced acquisition of Kite Pharma by Gilead for $11.9 billion provides strong validation for the cell therapy industry generally and especially in oncology," said Mike Mulroy, President and Chief Executive Officer. "With its potential as a ready-to-administer, off-the-shelf cancer immunotherapy, AST-VAC2 represents an exciting opportunity for Asterias in the rapidly evolving immuno-oncology sector and the approvals received from MHRA and REC to commence clinical testing represent an important milestone in the development of AST-VAC2."

The clinical trial will administer AST-VAC2 in up to twenty-four patients in two cohorts. In the first cohort, up to 12 patients with advanced non-small cell lung cancer and a specific immunological marker called HLA-A2 will receive AST-VAC2, and will be followed for safety, immune responses to telomerase, and overall clinical survival. The second cohort will evaluate AST-VAC2 in up to 12 patients with the HLA-A2 marker who have had successful resection of their tumor with no evidence of metastasis and each patient will be followed for safety, immune responses to telomerase, overall clinical survival and time to relapse. Both cohorts will have a control group consisting of patients that meet all inclusion/exclusion criteria for the study except those patients do not have the HLA-A2 marker.

"The design of the trial will allow us to assess many features of AST-VAC2 and how to best position its use in future trials," said Jane Lebkowski, Chief Scientific Officer. "We will be testing immune responses invoked by AST-VAC2 in the settings of advanced disease and resected disease and perform intermediate assessments of immune response during the course of AST-VAC2 dosing. Clinical outcome and immune response data will help confirm whether AST-VAC2 is most beneficial for patients in an active or minimal residual disease setting and inform determination of the optimal dosing regimen for future trials. The trial will also have a concurrent control group to provide real-time assessment of the safety and activity of the product. We are very excited to begin the clinical development of AST-VAC2 which could become a cornerstone agent in the immunotherapy of cancer."

"The AST-VAC2 study is an exciting step towards improving our tools in cancer immunotherapy," said Professor Christian Ottensmeier, the study’s principal investigator. "Not only does the Asterias approach already have a track record in Acute Myeloid Leukemia (AML), but an ‘off the shelf’ dendritic cell vaccine opens the path towards making dendritic cell vaccination easily deliverable in the clinic. We are very excited to be working towards opening this study in the second half of 2017."

The partnership between Asterias and Cancer Research UK is being conducted under Cancer Research UK’s Clinical Development Partnerships (CDP) scheme, which allows the first clinical trial of AST-VAC2 to be initiated without significant Asterias resources being allocated to the trial and the manufacturing of the product. On completion of the clinical trial, Asterias will have an exclusive first option to acquire the data from the trial.

About AST-VAC2

AST-VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. These non-patient specific (allogeneic) AST-VAC2 cells are engineered to express a modified form of telomerase, a protein widely expressed in tumor cells, but rarely found in normal cells. The modified form of telomerase invokes enhanced stimulation of immune responses to the protein. Similar to an earlier, Asterias-sponsored, hematological cancer program which provided proof-of-concept data, the AST-VAC2 dendritic cells instruct the immune system to generate responses against telomerase which will target tumor cells. AST-VAC2 is based on a specific mode of action that is complementary to and potentially synergistic with other immune therapies such as checkpoint inhibitors or other immune pathway inhibitors.

About Non-Small Cell Lung Cancer and the AST-VAC2 Trial

Lung cancer (both small cell and non-small cell) is the leading cause of cancer-related death, accounting for about one-quarter of all cancer deaths and more than colorectal, breast, and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of lung cancers, according to the American Cancer Society. The three main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The American Cancer Society’s estimates for lung cancer in the United States for 2017 are: about 222,500 new cases of lung cancer, and about 155,870 deaths from lung cancer. Despite the large number of people afflicted by non-small cell lung cancer, patients remain vastly underserved due to a scarcity of effective treatments. According to statistics published by Cancer Research UK, the five year survival rate for lung cancer patients in England and Wales is less than 10%.

The AST-VAC2 clinical trial will enroll up to twenty-four patients into one of two cohorts, depending on the stage of their non-small cell lung cancer. The first cohort will evaluate AST-VAC2 in up to 12 patients with advanced non-small cell lung cancer for whom only palliative treatments are available. Subjects in this cohort, who carry the major histocompatibility gene, HLA-A2, will receive six weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase, impact on tumor burden and overall clinical survival. These safety and activity results will be compared directly to a control group who meet all of the other inclusion/exclusion criteria but do not possess the HLA-A2 gene. Assuming safety is demonstrated in the first cohort, enrollment will advance to a second cohort. In the second cohort, early stage patients who have had successful resection of their tumor with no evidence of metastasis will be enrolled. Up to 12 subjects in this second cohort who carry the major histocompatibility allele HLA-A2 will receive six, weekly injections of AST-VAC2 and will be followed for safety, immune responses to telomerase, and relapse. These safety and activity results will again be compared directly to a control group who meet all of the inclusion/exclusion criteria of cohort 2 but are not HLA-A2+. For their key endpoints, patients will be followed for one year.