On March 6, 2017 Dynavax Technologies Corporation (NASDAQ: DVAX) reported the presentation of findings in patients with metastatic melanoma in the dose escalation phase of an ongoing Phase 1b/2 study investigating SD-101, Dynavax’s intratumoral TLR9 agonist, in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy developed by Merck, known as MSD outside the United States and Canada (Press release, Dynavax Technologies, MAR 6, 2017, View Source [SID1234518000]). Results evaluating 17 patients for efficacy and 22 patients for safety were reported. In patients naïve to anti-PD-1 treatment, responses were observed in six out of seven patients, for an Overall Response Rate (ORR) of 86%. This includes two (29%) complete responses (CR) and four (57%) partial responses (PR). Target tumor shrinkage was observed in all 7 evaluable patients. In 10 patients with progressive disease who initiated KEYTRUDA anti-PD-1 monotherapy prior to enrollment, one PR was observed and five patients had stable disease (SD) while receiving KEYTRUDA and SD-101, with four of the 10 patients experiencing target tumor shrinkage. These data are being presented by Robert Janssen, M.D., chief medical officer for Dynavax, in an oral presentation at the International Congress on Targeted Anticancer Therapies which begins today in Paris, France.

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"We are pleased with the response in the anti-PD-1 naïve group with 2 complete responses and tumor shrinkage in all 7 evaluable patients," said Dr. Janssen. "In addition, we are encouraged to have seen a partial response at the highest dose in the anti-PD-1 refractory group with little toxicity. This allows us to explore higher doses of SD-101 in anti-PD-1 refractory patients in the expansion phase to further develop the best path forward for this hard to treat population."

SD-101 in combination with KEYTRUDA generally was well-tolerated. No dose-limiting toxicities of the combination were observed in any dose cohort, and a maximum tolerated dose (MTD) was not identified. The most common treatment-emergent adverse events were injection site reactions and transient grade 1 to 2 flu-like symptoms, including fever, chills and myalgia that respond to over the counter medications such as acetaminophen. The study also includes biomarker assessments, suggesting that treatment with SD-101 and KEYTRUDA resulted in elevation of gene signatures consistent with an increase in Th1 immune cell types as well as an increase in immune cell infiltrates such as CD8+ T-cells in the tumor microenvironment.

About MEL-01 (KEYNOTE-184)
The dose-escalation and expansion study of SD-101 in combination with KEYTRUDA includes patients with histologically or cytologically confirmed unresectable Stage IIIc/IV melanoma. The primary endpoints of the trial are MTD and evaluation of the safety of intratumoral SD-101 in combination with KEYTRUDA. In addition, the trial is investigating response as assessed by the investigator according to RECIST v1.1, biomarker assessments and duration of response. Patients previously treated with anti-PD-1 and other immunotherapies are included.

About SD-101
SD-101 is Dynavax’s proprietary, second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. SD-101 is being studied for its multiple anti-tumor activities in innate immune cells and activation of plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

For information about SD-101 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

On March 6, 2017 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT:IMUC) reported an update on the Company’s ICT-107 phase 3 registration trial in newly diagnosed glioblastoma, and announced advances in its Stem-to-T-cell Research program (Press release, ImmunoCellular Therapeutics, MAR 6, 2017, View Source [SID1234517998]).

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ICT-107 Phase 3 Trial in Newly Diagnosed Glioblastoma Update

As previously disclosed, ImmunoCellular submitted an amendment of the ICT-107 phase 3 protocol to the US FDA. The key change in this amendment will enable patients to be randomized 30 days after commencing screening procedures, accelerating the time to randomization by approximately 2 months.

"We are pleased to announce that the amendment is currently being implemented at US clinical sites and that amended protocol submissions are underway in Europe and Canada," said Anthony Gringeri, PhD, ImmunoCellular President and Chief Executive Officer. "As anticipated, as a result of the protocol change, the Special Protocol Assessment (SPA) which was based on the original protocol, is no longer applicable. We will engage in further discussions with the FDA concerning the SPA in the future. The change in the status of the SPA will not materially impact the execution of the phase 3 trial, and data generated from this phase 3 study can still be used as primary evidence to support a marketing application."

Advances in the Stem-to-T-Cell Research Program

ImmunoCellular reported successful completion of the first milestone for the Company’s Stem-to-T-cell program, the sequencing of a selected T cell receptor (TCR) gene. When inserted into a blood stem cell, this TCR gene is expected to enhance patients’ immune systems to produce killer T cells programmed to attack tumors. This Stem-to-T-cell therapeutic strategy has the potential to provide a safer, sustainable and more specific immune treatment for cancer.

"We are excited that our Stem-to-T-cell program is advancing well and look forward to working with our collaborators at The University of Texas MD Anderson Cancer Center to develop antigen-specific killer T cells. This approach potentially represents a major advance in cancer immunotherapy and may overcome the challenge of short-lived T cell responses seen with the present forms of T cell and CAR-T therapies," said Steven J. Swanson, PhD, ImmunoCellular’s Senior Vice President, Research.

Achieving this milestone required completion of several critical steps: the collection and analysis of multiple clones of cells containing the target TCR genes, harvesting the plasmids with the TCR gene, and then sequencing that gene. Next, ImmunoCellular Therapeutics will initiate development of the gene therapy component. This phase entails loading the TCR gene sequence into a viral vector (such as a lentivirus) for delivery into the patient’s hematopoietic stem cells which could become, in essence, an internal factory producing antigen-specific killer T cells. Once these fundamental elements are in place, a product candidate for testing in cell lines and suitable preclinical models may be generated. Successful testing would potentially lead to human clinical trials.

In November 2015, ImmunoCellular entered into a sponsored research agreement with MD Anderson, with Dr. Cassian Yee as principal investigator, which focused on identifying T cells that find and kill tumor cells expressing a target antigen. The ultimate goal of this work is to establish a clinical program based on hematopoietic stem cells that are isolated from the patient, modified with the TCR gene sequence, and then returned to the patient. These modified stem cells would continually produce antigen-specific killer T cells that target and kill the tumor.

ImmunoCellular plans to provide a more detailed update on the ICT-107 phase 3 trial and the Stem-to-T-cell program when it reports fourth quarter and full year 2016 financial results in March.

About ImmunoCellular’s Stem-to-T-Cell Program

ImmunoCellular’s Stem-to-T-cell program seeks to create antigen-specific cytotoxic or "killer" T cells that attack tumors in patients. Autologous hematopoietic stem cells (HSCs) are collected from cancer patients and transfected using a T cell receptor sequence that recognizes the patient’s tumor. After transfection, the HSCs would be administered to the patient. These transfected HSCs, now containing the T cell receptor gene, would migrate to the patient’s bone marrow and re-establish residence. In addition to replicating transformed HSCs, these cells would begin producing cytotoxic T cells specifically targeting the patient’s tumor. These cytotoxic T cells would migrate to the tumor location and begin the process of tumor destruction. This renewable population of killer T cells provides ongoing surveillance to prevent disease recurrence.

ImmunoCellular’s collaboration with the University of Maryland, established in January 2016, is designed to enhance the Company’s dendritic cell (DC) and stem cell technology platforms. It is comprised of three projects currently underway. In the first project, collaborators have screened and identified FDA approved small molecule drugs that behave effectively like checkpoint inhibitors, and potentially preventing cancer cells from evading the immune system. These small molecules appear to down-regulate important tumor features, such as the PD-1 ligand on the surface of the tumor cells, and also up-regulate the display of tumor specific antigens. If successfully developed, they could be used in combination with ImmunoCellular’s DC or Stem-to-T-cell therapies, augmenting their ability to recognize and kill tumors cells.

A second project represents new ways to engineer T cells for combination with DC immunotherapy by amplifying T cell properties directed toward tumor antigens. A third project focuses on modifying antigens for enhanced DC immunotherapy, including novel peptide configurations for use in DC-based products to induce enhanced T cell responses.