On March 16, 2016 Sanofi and DiCE Molecules, a newly-launched, privately held company developing a next generation approach to small molecule drug discovery, reported a five-year global collaboration to discover potential new therapeutics for up to 12 targets that encompass all disease areas of strategic interest to Sanofi (Press release, Sanofi, MAR 16, 2016, View Source [SID:1234509606]).

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The collaboration builds upon DiCE’s unique technology platform, which leverages directed evolution to select and optimize low molecular weight compounds against any target. The platform’s capabilities include the potential to unlock protein-protein interfaces that were previously unreachable for oral therapies.

The collaboration is a part of Sanofi’s Sunrise Initiative, a strategic partnership model that seeks to invest in early stage transformative opportunities that align with Sanofi’s expert development and commercialization abilities. A joint steering committee comprised of Sanofi and DiCE representatives will oversee the initiative.

"In the past, targeting protein-protein interfaces with small molecules was not thought possible in a generalizable fashion, especially in the development of orally bioavailable drugs," said Kevin Judice, President and Chief Executive Officer of DiCE. "Our platform is uniquely positioned to overcome these historical challenges and this partnership with Sanofi reinforces the potential of our technology. DiCE’s self-financing business model and distinctive partnership approach will allow us to focus solely on advancing our development programs. We are delighted to be collaborating with Sanofi and its innovation-focused team within the Sunrise Initiative."

Collaboration Overview
The partnership between Sanofi and DiCE represents a unique R&D commitment to small molecule discovery. DiCE’s directed chemical evolution platform is anticipated to shorten drug development timelines through the rapid and efficient discovery of a greater breadth of molecules for each target in the collaboration.

The collaboration encompasses up to 12 discrete targets over the five-year period and provides funding in excess of $50 million in equity, upfront, target exclusivity, technology access fees, and research services, along with up to $184 million in research, clinical and regulatory milestone payments per target, and royalty payments based on any future annual net sales of each compound developed by Sanofi.

"We are pleased to initiate this collaboration with DiCE and its unique technology platform, which brings the power of selection and enrichment to small molecule discovery," said Dr. Kathy Bowdish, Head of Sunrise, Sanofi. "We hope this partnership will help deliver essential therapies against currently intractable disease targets, and help patients who otherwise have been unable to receive treatments outside of the inpatient setting. This initiative will allow our teams to combine their wealth of knowledge in drug discovery and further strengthens Sanofi’s commitment to open innovation."

The DiCE Difference
DiCE’s technology selects and optimizes drug-like ligands to any given target, beginning with libraries containing billions of individual molecules. Unique among currently available options, DiCE’s technology restores the libraries to their original ligand concentration after each round of screening, revealing the full landscape of binding molecules and allowing them to easily be selected for enhanced potency, selectivity, and drug-like properties through testing with proprietary assays. This novel approach may address long-standing chemistry issues and would enable monoclonal antibodies to be replaced by orally administered medicines.

DiCE’s core technology was invented by Stanford Professor Pehr Harbury, Ph.D., a recipient of the Macarthur "Genius" Award and the NIH Pioneer award. In addition to Dr. Harbury, the founding team includes John Bedbrook, Ph.D., a seasoned entrepreneur in the agricultural biotechnology space who serves as Founder and Chairman of the DiCE Board of Directors; Kevin Judice, Ph.D., who while in the lab discovered the marketed drug Telavancin and has held various leadership roles at Genentech, Theravance, Achaogen, and Cidara prior to joining DiCE as Founder and Chief Executive Officer; and Phil Patten, Ph.D., an internationally recognized expert in the field of directed evolution who held various scientific roles at Maxygen, Achaogen, and DuPont, prior to joining DiCE as Founder and Chief Scientific Officer.

On March 2016 BioInvent International (BINV) reported that the European Patent Office, EPO, has decided to grant the company’s patent EP 1 960 432, relating to the immune-oncology antibody BI-505 (Press release, BioInvent, MAR 16, 2016, View Source [SID:1234509596]). BioInvent plans to shortly initiate a Phase II trial with BI-505 in patients with multiple myeloma, with the aim to prevent or significantly delay relapse of this serious form of hematologic cancer.

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The European patent for BI-505 will enter into force on 6 April 2016 and will expire in 2026. Corresponding patents have already been granted in the US, Japan, Australia, China, South Korea and Russia, among other countries.

"The extended geographical patent protection for BI-505 increases the value of our project and underlines BioInvent’s ability to develop innovative and unique antibodies against severe cancer diseases", says Michael Oredsson, CEO of BioInvent.
During 2016, the start of clinical studies for three of BioInvent’s clinical phase drug projects are planned. In addition to the study mentioned above with BI-505, clinical studies are also expected to be initiated with BI-1206 in patients with non-Hodgkin lymphoma and chronic lymphatic leukaemia, and with TB-403 for treatment of rare but serious types of cancer in children.

About BI-505
BI-505 is a human antibody against ICAM-1 developed by BioInvent, which will be clinically tested in cooperation with researchers at Penn Medicine as an immuno-oncological therapy to prevent or delay relapse in patients with multiple myeloma (a form of bone marrow cancer) undergoing stem-cell transplantation. Preclinical data indicates improved activity against myeloma when BI-505 is administered in combination with Velcade or Revlimid. BI-505’s favourable safety profile has been demonstrated in a previous phase I trial. This and the unique mechanism of action, "flagging" remaining myeloma cells for elimination by actively recruited macrophages, as well as the potential to inhibit ICAM-1 dependent survival signals between myeloma cells and tumour stroma, indicate a unique possibility of improving the therapeutic effect of stem-cell transplantation.

On March 16, 2016 Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, reported that its preclinical data for GEN-1 in combination with Avastin and Doxil for the treatment of ovarian cancer will be presented at the upcoming AACR (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans (Press release, Celsion, MAR 16, 2016, View Source [SID:1234509587]).

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The presentation will be held on Monday, April 18, 2016 (1:00 pm to 5:00 pm) and will summarize results from preclinical studies demonstrating significant synergistic anti-cancer effects when GEN-1 is combined with Avastin and Doxil, a current Standard of Care (SoC) for platinum resistant ovarian cancer patients. GEN-1 is an IL-12 DNA plasmid vector formulated into a nanoparticle with a non-viral delivery system to cause the sustained local production and secretion of the Interleukin-12 (IL-12) protein loco-regionally to the tumor site. These data will be used by the Company to support a comprehensive IND protocol filing for a Phase I/II clinical trial evaluating the combination in recurrent ovarian cancer later this year.

"The immune stimulating nature of GEN-1 in combination with Avastin and Doxil, two of the most widely used cancer therapies, makes for an ideal therapy, bolstering the anti-cancer effect beyond what has been observed when used alone," said Nicholas Borys, M.D., senior vice president and chief medical officer of Celsion. "Results from this important study are highly encouraging and suggest that when these therapies are combined, they offer the potential to significantly reduce tumor burden and disease progression in this highly aggressive cancer in patients who have failed first line platinum-based therapies."

Data is emerging on how SoC chemotherapy treatments influence the immune response in cancers that they are targeting. Chemotherapy stimulates the immune system by (i) making the dying tumor cells more visible to the body’s immune system through the release of tumor antigens; (ii) destroying the immune suppression caused by the tumor; and (iii) directly or indirectly affecting immune cells and immune modulators.

Chemotherapy treatments may be a good candidate for combination with immune-mediating therapies like GEN-1. Doxorubicin increases not only T-cell and natural killer (NK) cell production, but also B cells (anti-tumor antibodies) in ovarian cancer. IL-12 is a highly active cytokine that can induce a potent anti-cancer immunity mediated through the activation of cytotoxic T-lymphocytes and NK cells and the inhibition of immune-suppressing regulatory T-cells.

Clinical data supporting the combination of GEN-1 with SoC chemotherapies

GEN-1 has already demonstrated encouraging safety and efficacy clinical data in combination with PEGylated liposomal doxorubicin (Doxil) in patients with platinum-resistant ovarian cancer. Results from a Phase Ib clinical trial in platinum resistant ovarian cancer patients have shown that intraperitoneal delivery of GEN-1 in combination with Doxil produced an overall clinical benefit of 57.1% (PR=21.4%; SD=35.7%) in patients with measurable disease. The highest percentage of PRs were found at the highest dose level (28.6%) along with the highest percentage of patients achieving SD (57.1%) producing an overall clinical response rate (CR+PD+SD) of 86% at the highest GEN-1 dose cohort, which, despite a small study size, is highly encouraging considering the poor outcome with Doxil alone in this patient population.

GEN-1 has also produced encouraging data in combination with Avastin alone in earlier preclinical studies in a model of ovarian cancer, leading to a significant reduction in tumor burden and disease progression. The inhibition of VEGF by IL-12 through the secretion of interferon-gamma may help explain the impressive synergies between GEN-1 and SoC anti-angiogenic agents like Avastin. These findings open up an additional combination therapy of Avastin with an immune-based therapy like GEN-1.

Preclinical data supporting the combination of GEN-1 with SoC Chemotherapy + Avastin

Results from comprehensive studies confirmed remarkable, statistically significant initial GEN-1 + Avastin findings. Recent studies now show convincingly that GEN-1 when combined with Avastin and Doxil demonstrated a greater than 98% reduction in tumor burden when compared to the untreated control group. The findings represent a statistically significant reduction in tumor burden and disease progression when compared to the combination of Avastin and Doxil in a SKOV3 human cell line implanted into immunocompromised (nude) mice. Analysis of serum chemistry and hematology suggested no overt toxicities associated with the combined treatments. The preclinical data are consistent with the mechanism of action for GEN-1, which exhibits certain anti-angiogenic properties in addition to its well-characterized immunomodulatory activities.

"We believe that the synergy provided to the tumor micro-environment by GEN-1 is responsible for our remarkable preclinical findings," said Michael Tardugno, chairman, chief executive officer and president of Celsion. "Local cellular production and secretion of highly-tolerable endogenous IL-12, a multi-mechanistic anti-cancer agent, both supports doxorubicin’s immune system activating potential as well as reinforces the anti-angiogenic properties of one of the world’s most prescribed anti-cancer biologics, Avastin. We are excited to move forward into clinical trials with the potential for a ground breaking therapeutic approach."

The Company is currently enrolling patients in the OVATION Study, a Phase 1b dose escalating trial combining GEN-1 with neo-adjuvant therapies in newly diagnosed ovarian cancer patients which will provide a starting dose for the follow-on Phase 1/2 study combining GEN-1 with Avastin and Doxil. The Phase 1/2 combination trial is expected to begin in mid-2016.

About GEN-1 Immunotherapy

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. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer. GEN-1 has also demonstrated preclinical activity in glioblastoma multiforme (brain cancer) and the Company plans to initiate a Phase I study in this indication in the second half of 2015.

On March 16, 2016 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported the first patient has been dosed in its Halo-301 | Pancreatic study, a Phase 3 clinical trial in previously untreated metastatic pancreatic cancer patients (Press release, Halozyme, MAR 16, 2016, View Source [SID:1234509581]).

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The global, randomized, double-blind, placebo controlled trial will study Halozyme’s investigational drug, PEGPH20, in combination with ABRAXANE (nab-paclitaxel) and gemcitabine in patients identified to have tumors that accumulate high levels of hyaluronan (HA). HA is a glycosaminoglycan, or chain of natural sugars that may impede access of drugs targeting the tumor. Halozyme’s PEGPH20 temporarily degrades HA and has been shown in animal models to increase the concentration of co-administered therapies in the targeted tumor.

Halozyme also announced that the investigational device exemption (IDE) submitted to the FDA last month by Halozyme’s partner Ventana Medical Systems has been approved. This IDE allows Halozyme to use the Ventana HA CDx Assay as the companion diagnostic in Halo-301 to prospectively identify HA-High patients for inclusion in the study.

"The initiation of our Phase 3 study of PEGPH20 in HA-High pancreatic cancer patients marks a key milestone for the Halozyme team and the PEGPH20 development program," said Dr. Helen Torley, President and CEO of Halozyme.

Dr. Margaret Tempero, Director of the Pancreas Center at University of California, San Francisco and one of the Principle Investigators of the study, said, "High levels of HA have been associated with a worse prognosis in certain cancers, notably pancreas cancer. We have assembled a team of expert investigators at nearly 200 global sites to further study this potential link with the hope of bringing new treatment options to an area of high unmet need."

Halo-301 has an enrollment target of 420 HA-high patients and seeks to improve progression-free survival and overall survival in the patients receiving PEGPH20 plus ABRAXANE and gemcitabine compared to those receiving placebo plus ABRAXANE and gemcitabine.

The FDA granted orphan drug designation to PEGPH20 for the treatment of pancreatic cancer and fast track designation for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 as an orphan medicinal product for the treatment of pancreatic cancer.

On March 16, 2016 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or "The Company"), reported that the protocol for its phase 3 clinical trial for PV-10 as an investigational treatment for melanoma has been amended to reflect current and evolving standards of care and applicable patient population for a global study in melanoma (Filing, 8-K, Provectus Pharmaceuticals, MAR 16, 2016, View Source [SID:1234509578]).

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Major amendments to the protocol include the addition of talimogene laherparepvec (ImlygicTM) as an option for use as comparator. The amended protocol also extends eligibility to include Stage IV M1a patients having no active nodal or distant cutaneous or subcutaneous metastatic disease. These patients have disease characteristics and prognosis similar to that of the Stage IIIB and IIIC patients that initially defined the study patient population.

In addition, the updated protocol clarifies eligibility for patients not having access to immune checkpoint inhibitors due to standard of care and those not having access to targeted therapy due to standard of care, as well as inclusion of patients who have failed targeted therapy. In the latter case, patients who have failed targeted therapy but meet study eligibility criteria have similar disease manifestations to the remaining study population but have limited treatment options.

Dr. Eric Wachter, CTO of Provectus, said, "These kinds of amendments are commonplace in phase 3 studies and serve to fine-tune the patient population and study procedures to match changing care standards for a large global study. They are the direct result of current and emerging options for these patients and have been developed with extensive input from global leading melanoma investigators. In particular, the most obvious amendment addresses approval in late October of Imlygic by the FDA as the first and only oncolytic viral therapy. As we implement the amended protocol we will assess potential impact on study timelines."

For further information about the study, please visit View Source