On September 27, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that the first patient has been dosed in the Phase 1 clinical trial (see www.clinicaltrials.gov, identifier NCT03189030) designed to evaluate the safety and tolerability of a personalized live, attenuated double-deleted Listeria monocytogenes (pLADD) immunotherapy for adults with metastatic colorectal cancer that is microsatellite stable (MSS) (Press release, Aduro Biotech, SEP 27, 2017, View Source [SID1234520656]). The personalized immunotherapy has been engineered with patient-specific neoantigens that were identified and selected using state-of-the-art neoantigen identification technology developed by Hanlee Ji, M.D., associate professor of medicine at the Stanford University School of Medicine.

“Our pLADD program leverages our extensive capabilities relating to the use of Listeria as a delivery mechanism for cancer antigens and Dr. Ji’s innovative neoantigen technology used to identify immunogenic antigens specific for an individual patient,” said Natalie Sacks, M.D., chief medical officer of Aduro Biotech. “Together, we believe these two cutting edge technologies represent a new approach to treating patients who have relapsed following prior chemotherapy. We look forward to evaluating initial proof-of-concept in this Phase 1 clinical trial.”

Clinical Design of Phase 1 PLADD Trial in Adults with Metastatic Corlorectal Cancer
The Phase 1 clincial single-arm trial is designed to evaluate the safety and tolerability of a personalized immunotherapy made using patient-specific antigens and Aduro’s proprietary live, attenuated, double-deleted Listeria monocytogenes platform technology. The trial is seeking to enroll approximately 10 patients with metastatic colorectal cancer that is MSS. Patients will receive their patient-specific immunotherapy once every three weeks.

About pLADD
Personalized LADD, or pLADD, is a second-generation LADD technology that is designed to leverage the immune-activating activity of the Listeria bacterial vector in combination with neoantigens, which are unique, patient-specific tumor markers exclusively expressed in an individual’s tumor cells. Once administered, pLADD therapies are expected to mobilize the immune system in two ways–first, through the immediate recognition of the presence of Listeria as being foreign, and subsequently, through a specific and customized immune attack on cells containing the tumor neoantigens presented by pLADD.

To create a patient-specific pLADD therapy, a physician begins by removing tumor cells from the patient. These cells are analyzed in order to molecularly characterize (sequence) the tumor, including any mutations that are unique to the patient’s own tumor cells. Predictive algorithms for antigen processing are run to identify pertinent tumor antigens. Aduro then creates a LADD strain engineered to enable the presentation of multiple selected neoantigens in dendritic cells, with the aim of inducing a targeted, robust anti-cancer immune response.

Preclinical Data with pLADD
Preclinical data showed that mouse pLADD strains targeting tumor-specific neoepitopes induced a robust immune response, including induction of cytokines, chemokines, and antigen-specific CD8+ T cells. In preclinical models of pLADD, remodeling of the tumor microenvironment with an increase in the CD8:Treg ratio was observed. The combination of pLADD with an anti PD-1 agent led to a sustained immune response and significantly improved efficacy in these mouse tumor models.

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.

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.

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.

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