On October 18, 2017 Eli Lilly and Company (NYSE: LLY) and CureVac AG reported a global immuno-oncology collaboration focused on the development and commercialization of up to five potential cancer vaccine products based on CureVac’s proprietary RNActive technology (Press release, Eli Lilly, OCT 18, 2017, View Source [SID1234521004]). The companies will use messenger RNA (mRNA) technology that targets tumor neoantigens for a more robust anti-cancer immune response.

“We are excited to be collaborating with CureVac to discover what could potentially be the next frontier of cancer medicines,” said Greg Plowman, M.D., Ph.D., vice president of oncology research at Lilly. “This collaboration reinforces Lilly’s commitment to delivering life-changing medicines to treat and cure people living with cancer around the world.”

Ingmar Hoerr, Ph.D., co-founder and CEO of CureVac, stated, “This new collaboration with Lilly is a testimony to the progress and sophistication of CureVac’s RNActive technology and the potential of mRNA-based therapeutics. We now have the opportunity to combine forces to further expand the exciting space of immuno-oncology with the next generation of cancer therapies. We are thrilled to work with the Lilly team and hope to advance this new treatment paradigm into the clinic and ultimately to the market.”

Under the terms of the agreement, CureVac will receive an upfront payment of $50 million and an equity investment of €45 million. CureVac is also eligible to receive more than $1.7 billion in development and commercialization milestones if all five vaccines are successfully developed, plus tiered royalties on product sales. Lilly is responsible for target identification, clinical development and commercialization. CureVac will be responsible for mRNA design, formulation and manufacturing of clinical supply and retains the option to co-promote the vaccine products in Germany.

CureVac’s proprietary RNActive technology will be used to deliver mRNA that ultimately directs the human immune system to target the encoded neoantigens. These tumor-specific neoantigens instruct the patient’s existing immune system to mount a selective and potent response to eradicate the cancer.

This transaction is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions. Subject to the closing of this transaction, Lilly expects to incur an acquired in-process research and development charge to earnings of approximately $0.03 per share.

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.”