On October 18, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, today provided a summary of GEN-1 immunotherapy-related presentations made during the Company’s Research and Development (R&D) Day held on Thursday, October 12, 2017 (Press release, Celsion, OCT 18, 2017, View Source [SID1234521003]). This summary is intended to provide easy access to pertinent, top line information discussed during the conference. A complete webcast of the presentations are available on Celsion’s website at www.celsion.com under the heading News & Investors / Financial Events / Featured Events – October 12, 2017 – Celsion to Host Research and Development Update.

The GEN-1 immunotherapy presentations focused on the Company’s clinical and translational research data from its OVATION Study, a Phase Ib dose escalating clinical trial combining GEN-1, the Company’s DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced Stage III/IV ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery. GEN-1 is an interleukin-IL-12 (IL-12) DNA plasmid vector formulated as a nanoparticle in a non-viral delivery system to cause the sustained local production and secretion of the IL-12 protein loco-regionally at the tumor site. The lead clinical investigator for the OVATION Study and leading immuno-oncology experts from the Roswell Park Cancer Institute presented their current experience with GEN-1 immunotherapy for the treatment of ovarian cancer.

Khursheed Anwer, Ph.D., Celsion’s Executive Vice President & Chief Scientific Officer, presented the following:
GEN-1 immunotherapy is a powerful pro-immune modulator designed to modulate the tumor microenvironment through the delivery of the potent immune agent IL-12 into the peritoneal cavity in a local and persistent manner.
IL-12 shifts the tumor microenvironment from immune suppressive to immune activation.
GEN-1 immunotherapy results in the loco-regional production of the potent cytokine IL-12 avoiding toxicities and poor pharmacokinetics associated with systemic recombinant IL-12 protein; lasts up to one week; Dosing can be repeated making GEN-1 immunotherapy ideal for long-term maintenance therapy.

Premal H. Thaker, M.D., Associate Professor in Gynecologic Oncology, Washington University School of Medicine, St. Louis, Missouri presented the final clinical data from the Phase Ib dose-escalating OVATION Study:
Neoadjuvant treatment approach to ovarian cancer has been gaining greater support over the last few years due to safety benefits; Addition of GEN-1 to neoadjuvant chemotherapy was safe and well tolerated.
The R0 margin negative resection score in 64% of patients treated in the OVATION Study appeared to be higher than what you see with neoadjuvant chemotherapy alone; R0 score of 100% in the highest dose group is impressive.

Progression Free Survival (PFS) of over 14 months in the as-treated patient population is on a positive trend since only 2 out of 16 patients have progressed to-date.
The patient population in the OVATION Study was highly advanced (94% at Stage IIIC – IV); better results are anticipated in a mixed population trial.

Richard C. Koya, M.D., Ph.D., Associate Professor of Oncology and Immunology, Director of the Vector Development & Production Facility, Associate Director of the Center for Immunotherapy, Roswell Park Cancer Institute, Center for Immunotherapy, Buffalo, NY presented the following translational research data from the OVATION Study:

GEN-1 treatment when administered in combination with standard of care increased the levels of immune-stimulatory cytokines and tumor infiltrating lymphocytes in a manner that is consistent with the known actions of IL-12.
There is evidence of GEN-1 activity on T-cell numbers as well as T-cell function. A dose-dependent increase in IFN-gamma, a strong mediator of immune response, following the treatment is impressive. Significant reduction in angiogenic growth factor, VEGF, is also a good indicator of the IL-12 treatment effect.

The decrease in immune suppressive signals and the increase in the ratio of cytotoxic CD8+ cells to immune suppressive signals suggest a shift in tumor environment in favor of immune stimulation. A highly immune suppressive tumor environment is linked with a worsening of the disease and poor treatment outcome. A shift in the tumor microenvironment in favor of immune stimulation following GEN-1 treatment is a positive indication of the IL-12 treatment effect.

The modulation of tumor microenvironment in favor of immune stimulation by GEN-1 raises its potential combination benefits with other forms of immunotherapies, especially adoptive T-cell therapy. GEN-1 pre-treatment has potential to improve the survival and potency of the engineered T-cells, a major limitation in adoptive T-cell therapies.
About the OVATION Study

The Phase Ib trial was designed to evaluate weekly intraperitoneal dosing of GEN-1 in combination with neoadjuvant chemotherapy, the standard of care for patients newly diagnosed with ovarian cancer. Concurrently with neoadjuvant chemotherapy, enrolled patients will receive escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, with interval debulking surgery to follow. The regimen was primarily evaluated for its safety and tolerability. GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation.

On October 18, 2017 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported that Genentech, a member of the Roche Group, has commenced a Phase 1b/2 study for the treatment of gastric cancer with BL-8040 in combination with atezolizumab (TECENTRIQ), Genentech’s anti-PDL1 cancer immunotherapy agent (Press release, BioLineRx, OCT 18, 2017, View Source [SID1234521002]).

Up to 40 patients are planned to be enrolled in this multicenter, randomized, controlled, open-label study to evaluate the clinical response, safety and tolerability, as well as multiple pharmacodynamic parameters, of BL-8040 in combination with atezolizumab. Initially, patients will receive BL-8040 injections as priming monotherapy, after which they will receive both BL-8040 and atezolizumab, and continue with multiple treatment cycles for up to two years or, until disease progression, clinical deterioration or unacceptable toxicity.

The clinical study collaboration between BioLineRx and Genentech is part of MORPHEUS, Roche’s novel cancer immunotherapy development platform. MORPHEUS is a phase 1b/2 adaptive platform to develop combinations of cancer immunotherapies more rapidly and efficiently.

Philip Serlin, Chief Executive Officer of BioLineRx, stated, “This is the third trial to commence under our collaboration with Genentech for the combination of our CXCR4 inhibitor lead oncology platform and their anti-PDL1 inhibitor, following initiation of a pancreatic cancer study in July and initiation of an AML study in September. We are therefore hopeful that combining atezolizumab with BL-8040 can lead to a significant advancement in the treatment of gastric cancer, and of other solid tumors that are difficult to treat. BL-8040 has shown to induce robust mobilization of immune cells, improve the infiltration of T cells into solid tumors, and affect the immunosuppressive tumor micro-environment. We look forward to the results of this trial and the initiation of an additional combination study under this collaboration, planned for later this year.”

This study is being carried out as part of BioLineRx’s cancer immunotherapy collaboration with Genentech, which includes several Phase 1b/2 studies investigating BL-8040 in combination with atezolizumab in multiple cancer indications, announced in September 2016.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in clinical trials to be a robust mobilizer of immune cells and to be effective in inducing direct tumor cell death. Additional findings suggest that BL-8040 may be effective in inducing the migration of anti-tumor T cells into the tumor micro-environment, as well as improving the infiltration of T cells into solid tumors. Atezolizumab is a humanized monoclonal antibody designed to bind to PD-L1 in tumor cells and tumor infiltrating immune cells and blocks interactions with the PD-1 and B7.1 receptors. Through this interaction, atezolizumab may enable the activation of T cells, whose migration into the tumor may be enhanced by BL-8040.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On October 18, 2017 Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading hepatitis B virus (HBV) therapeutic solutions company, and Gritstone Oncology, a leader in personalized cancer immunotherapies, reported a collaboration and license agreement (Press release, Arbutus Biopharma, OCT 18, 2017, View Source [SID1234520997]). Arbutus is deploying its proprietary lipid nanoparticle (LNP) technology to deliver Gritstone’s RNA-based neoantigen immunotherapy products.

Under the terms of this license agreement, Gritstone obtains worldwide access to Arbutus’ portfolio of proprietary and clinically validated LNP products and associated intellectual property. Gritstone will pay Arbutus an upfront payment, payments for achievement of development, regulatory, and commercial milestones, as well as royalties. In addition, Gritstone will reimburse Arbutus for conducting technology development and providing manufacturing and regulatory support for Gritstone’s product candidates. The license is specifically directed to the novel RNA-based platform for neoantigen immunotherapies.

“The recent phase III validation of Arbutus’ LNP platform makes them the natural partner for Gritstone as we drive our proprietary two-component immunotherapy program into the clinic in mid-2018,” said Andrew Allen, M.D., Ph.D., President and CEO of Gritstone Oncology. “Successful exploratory preclinical work with Arbutus fueled a strong bilateral desire to formalize and extend our relationship. We’re excited to continue our work with the team at Arbutus and its LNP technology as we advance our pipeline of immunotherapy product candidates.”

“This agreement again represents validation of our industry-leading LNP technology. We are excited to be working with Gritstone to advance their innovative personalized immunotherapies for the treatment of cancer,” said Dr. Mark J. Murray, Arbutus’ President and CEO. “This transaction is part of realizing the value of our LNP platform, which has broad potential to deliver nucleic acid-based products including mRNA and gene editing therapeutics, and enable Arbutus to continue to focus on development of curative therapies for HBV.”

On October 18, 2017 AbbVie (NYSE: ABBV), a global biopharmaceutical company, and Harpoon Therapeutics, a biotechnology company developing novel T-cell recruiting biologic therapies, reported that they have entered an immuno-oncology research collaboration (Press release, AbbVie, OCT 18, 2017, View Source [SID1234520996]). The goal of the collaboration is to incorporate Harpoon’s tri-specific T-cell activating construct (TriTAC) platform with AbbVie’s research-stage immuno-oncology targets to develop novel cancer therapeutics.

Under the terms of the agreement, Harpoon will engineer TriTAC molecules directed against selected cancer targets using its proprietary platform, evaluate the molecules for pharmacologic properties, and provide AbbVie the right to pursue further development and commercialization of these molecules. Financial terms were not disclosed.

“This collaboration is the first for Harpoon and highlights the high level of industry interest in best-in-class platform technologies. We are excited about partnering with AbbVie to help generate novel T-cell engagers for the treatment of cancer based on the combination of T-cell receptors with TriTACs,” said Jerry McMahon, Ph.D., chief executive officer, Harpoon Therapeutics.

“T-cell therapies represent the next wave of innovation in cancer treatment,” said Tom Hudson, M.D., vice president, oncology early discovery and development, AbbVie. “Harpoon’s technology offers the potential for a unique approach to engage the immune system through AbbVie’s investigational therapies in development.”

On October 18, 2017 Provectus Biopharmaceuticals, Inc. (OTCQB: PVCT, www.provectusbio.com) (“Provectus” or the “Company”), a clinical-stage biotechnology company leading the development of the first small molecule oncolytic immunotherapy, intralesional (“IL”) PV-10, as a single agent for locally advanced disease as well as in combination with another agent for widely metastatic disease, both for multiple cancer indications, reported results from the Company’s ongoing Phase 1b/2 study of IL PV-10 in combination with KEYTRUDA (pembrolizumab), Merck’s systemic anti-PD-1 (programmed death receptor-1) antibody agent, were presented at the Society for Melanoma Research 2017 Congress, held in Brisbane, Australia from October 18-21 (Press release, Provectus Biopharmaceuticals, OCT 18, 2017, View Source [SID1234520993]). IL injection of PV-10 induces immunogenic cell death that results in tumor-specific reactivity in circulating CD8+ T cells.

The Phase 1b portion of the study continues to enroll patients with metastatic melanoma at clinical sites in the U.S. and Australia (NCT02557321); Stage IV patients with at least one injectable lesion who are candidates for KEYTRUDA are eligible. A total of up to 24 patients would receive the combination of IL PV-10 and KEYTRUDA every three weeks for five cycles (i.e., for up to 12 weeks, with no further PV-10 administered after week 12), followed by only KEYTRUDA every three weeks for up to 24 months. The primary endpoint for the Phase 1b trial is safety and tolerability; objective response rate and progression-free survival are key secondary endpoints (both assessed via RECIST 1.1 after five treatment cycles, and then every 12 weeks thereafter).

IL PV-10 Results from the Phase 1b Trial Presented at SMR:

● Baseline characteristics (safety population, N=12): 92% men; median age of 71.5 years (range 28-81), 67% > 65 years; 67% Stage IV M1b/c.

● Subject characteristics (safety population): 2.5 median number of cutaneous/subcutaneous lesions (range 1-40); patients had substantial non-injected systemic disease burden in addition to their injectable cutaneous and/or subcutaneous lesions; patients received a median of 5 cycles of PV-10 (mean 3.8, range 1-5); PV-10 was not administered after week 12.

● Preliminary safety (safety population): adverse events were consistent with the established patterns for each drug; there were no unexpected toxicities or evidence of compounded toxicity.

● Preliminary target lesion efficacy (efficacy evaluable population, N=10): 50% complete response; 80% objective response; maximum response.

● Preliminary overall efficacy (efficacy evaluable population): 10% complete response; 50% objective response; 60% clinical benefit; highest responses observed in M1c patients; per RECIST 1.1.

Dominic Rodrigues, Chairman of the Company’s Board of Directors, said, “These preliminary results highlight the safety characteristics of the combination of intralesional PV-10 and checkpoint inhibition. The data confirm an almost complete absence of correlation of adverse events between the two drugs, which we refer to as ‘orthogonality.’ This outcome is very different from when oncolytic viruses or other biologics are used in combination with checkpoint inhibitors.”

Mr. Rodrigues added, “There also was promising clinical benefit after minimal PV-10 intervention, especially in those patients with Stage IV M1c disease. These data support the advancement of the combination of PV-10 and checkpoint inhibition in the clinical study of metastatic melanoma.”

A copy of the poster presentation is currently available on Provectus’ website at View Source