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On December 11, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMmotion151 study met its co-primary endpoint of investigator-assessed progression-free survival (PFS) and demonstrated that the combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) provided a statistically significant and clinically meaningful reduction in the risk of disease worsening or death (PFS) in people whose disease expressed the PD-L1 (programmed death-ligand 1: Expression ≥1%) protein compared with sunitinib for the first-line treatment of people who have advanced or metastatic renal cell carcinoma (mRCC) (Press release, Hoffmann-La Roche, DEC 11, 2017, View Source [SID1234522504]).

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Observations of a pre-specified subgroup analysis of the Tecentriq and Avastin combination indicated that, in people whose disease expressed PD-L1, a numerical difference favouring Tecentriq was seen across all patient risk factor groups (favourable, intermed­iate and poor) compared to sunitinib; however, due to the study design these data could not be assessed for statistical significance and are descriptive only. Assessment of secondary endpoints is ongoing. Safety for the Tecentriq and Avastin combination appeared consistent with the known safety profile of the individual medicines and what was previously reported in the Phase II IMmotion150 study. No new safety signals were identified with the combination.

Results will be presented at an upcoming oncology conference in 2018. Top-line results from the co-primary endpoint of overall survival (OS) are not mature.

"We are encouraged by these results as they add to the emerging body of evidence that supports our rationale for this combination. We believe that the regimen of Tecentriq and Avastin may enhance the potential of the immune system in the initial treatment of advanced kidney cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We will discuss these data with health authorities globally and hope to bring this combination forward as a potential new treatment option to patients as soon as possible.’’
IMmotion151 is the second successive positive Phase III study of Tecentriq that includes an Avastin combination component as an initial treatment. This follows the positive Phase III non-squamous non-small cell lung cancer (NSCLC) IMpower150 study that showed Tecentriq and Avastin plus chemotherapy demonstrated a PFS advantage over Avastin plus chemotherapy.

About the IMmotion151 study
IMmotion151 is a Phase III multicentre, randomised, open-label study to evaluate the efficacy and safety of Tecentriq and Avastin versus sunitinib in people with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy. It enrolled 915 people globally who were randomised 1:1 to receive Tecentriq and Avastin, or sunitinib alone.

People in the Tecentriq and Avastin arm received Tecentriq at a fixed dose of 1200 milligrams (mg) and Avastin at a dose of 15 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 3 weeks until loss of clinical benefit or unacceptable toxicity. People in the sunitinib arm received sunitinib 50 mg orally, once daily for 4 weeks followed by 2 weeks rest until loss of clinical benefit or unacceptable toxicity.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in people whose tumours expressed PD-L1 [PD-L1 expression ≥1 percent on immune cells (IC)], and OS in the overall study population (intention-to-treat, ITT). PD-L1 expression was prospectively assessed using an immunohistochemistry (IHC) test (SP142) developed by Roche Tissue Diagnostics.
Stratification factors included the presence or absence of liver metastases; level of IC staining for PD-L1 (≥1 percent vs. <1 percent) and Memorial Sloan-Kettering Cancer Center (Motzer) risk score. The Motzer prognostic scoring system predicts for OS based upon an individual’s baseline clinical and laboratory characteristics.
Depending on the presence of one or several of five variables (risk factors), patients are classified in one of the three risk groups: ‘Favourable’ with 0 risk factors, ‘Intermediate’ with 1–2 risk factors and ‘Poor’ with ≥ 3 risk factors.

About RCC
Kidney cancer remains one of the most common cancers in the world, accounting for over 140,000 deaths worldwide each year,1 with renal cell carcinoma (RCC) accounting for approximately 90% of all cases.2 Over 300,000 people are diagnosed with RCC every year and currently only about 1 in 10 people are alive beyond 5 years following diagnosis of metastatic disease.

RCC occurs when abnormal cells develop in the tissue of the kidneys, specifically in the small tubes (also known as tubules) where our blood is filtered.4 Typically, RCC is a single tumour in one kidney but, in rare cases, there can be multiple tumours, which can occur in one or both kidneys.

Despite recent progress in the field of kidney cancer, treatment options for people with the disease remains limited.

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Tecentriq is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Avastin (bevacizumab) in RCC
Avastin (bevacizumab) is an anti-VEGF inhibitor. VEGF (vascular endothelial growth factor) is a protein that stimulates the formation and maintenance of blood vessels and has been shown to play a key role in the development of RCC.
RCC tumours are highly vascularised, meaning they have many blood vessels and also exhibit a high concentration of VEGF5. There is, therefore a strong rationale for medicines such as Avastin that block the VEGF pathway. Avastin is the only currently available treatment for patients with mRCC that directly inhibits VEGF.

There is a strong scientific rationale to support further investigation of Tecentriq and Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat first-line advanced NSCLC and mRCC. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.
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On December 11, 2017 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that IND-enabling production of FT500 has commenced at University of Minnesota, Molecular and Cellular Therapeutics, a state-of-the-art, FDA-registered Good Manufacturing Practice (GMP) facility (Press release, Fate Therapeutics, DEC 11, 2017, View Source [SID1234526859]). Jeffrey S. Miller, M.D., Professor of Medicine, Deputy Director of the Masonic Cancer Center, University of Minnesota presented an overview today at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition of the clinical translation of FT500, a first-of-kind natural killer (NK) cell cancer immunotherapy generated from a self-renewing clonal master pluripotent cell line (MPCL). The clonal MPCL was created from a single induced pluripotent stem cell (iPSC) using the Company’s proprietary iPSC product platform. The Company expects to file an Investigation New Drug (IND) application in the first quarter of 2018 for the clinical testing of multiple dosing cycles of FT500 in combination with FDA-approved checkpoint inhibitor therapies for advanced solid tumors in the outpatient setting.

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"Preclinical studies demonstrate that FT500 has direct anti-tumor activity and the capacity to secrete inflammatory cytokines and chemokines upon activation. This enables the cell product to potentially exploit both innate and adaptive immunity and elicit a broad, multi-targeted immune response against tumor cells by engaging a diverse set of stress ligands, recruiting a polyclonal T-cell population to the tumor site and augmenting T-cell activation in the tumor microenvironment," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "While checkpoint inhibitors have transformed the cancer therapy landscape by inducing long term remissions in multiple solid tumor indications, many tumor subtypes are resistant to checkpoint blockade therapy and non-responsiveness remains a significant concern. We thank the FDA for considering the unique therapeutic value of FT500 in combination with checkpoint inhibitors and its supportive feedback on our ongoing clinical translation and planned 1Q18 IND submission."

In November 2017, Fate Therapeutics received a Type B Pre-IND meeting written response from U.S. Food & Drug Administration (FDA) for FT500. The written response and subsequent FDA correspondence aligned the Company’s approach to safety testing, product manufacture, quality assessment and clinical trial design in support of IND submission. FT500 is manufactured in a first-of-kind paradigm that uses a clonal MPCL as a renewable cell source for large-scale, cost-effective manufacture of a homogeneous NK cell product that can be reliably administered as a multi-dose, off-the-shelf cell product without patient matching restrictions. The Company estimates that a single manufacturing campaign conducted in one cGMP suite can yield hundreds of doses of up to 1×109 NK cells per dose. This novel approach to cell therapy has the potential to mediate safer, more effective pharmacologic activity, including in combination with cycles of other cancer treatments.

In preclinical studies conducted by the Company, FT500 displays multiple potential mechanisms by which it may synergize with T cells to activate the immune system in patients with tumors that are non-responsive to checkpoint inhibitors alone. FT500 has shown augmented secretion of cytokines and chemokines capable of enhancing T-cell activation in vitro. In addition, localized administration of FT500 into the peritoneal cavity results in the migration of circulating T cells into the peritoneal cavity. Finally, utilizing a three-dimensional tumor spheroid model in vitro, infiltration of activated T cells into tumor spheroids was significantly enhanced in the presence of FT500.

Fate Therapeutics has built an extensive intellectual property portfolio broadly covering the genomic engineering of iPSCs and off-the-shelf NK and T-cell cancer immunotherapies. Its proprietary portfolio includes compositions and methods for engineering iPSCs to modify their biological properties using CRISPR and other nucleases, and for manufacturing cells of all hematopoietic lineages from iPSCs including NK cells. In addition, the Company has an exclusive license from the University of Minnesota covering iPSC-derived NK cells expressing targeting receptors, including modified CD16 Fc receptors and chimeric antigen receptors for human therapeutic use.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables large-scale generation of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event, and selecting a single iPSC for maintenance as a clonal master pluripotent cell line (MPCL). Similar to master cell lines used for the manufacture of monoclonal antibodies, clonal MPCLs can serve as a renewable cell source for the consistent and repeated manufacture of homogeneous cell products with the potential to treat many different diseases and many thousands of patients in an off-the-shelf manner. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 90 issued patents and 100 pending patent applications.

On December 11, 2017 RXi Pharmaceuticals Corporation (NASDAQ: RXII) reported that it has entered into a research collaboration with Medigene AG (MDG1, Frankfurt, Prime Standard, TecDAX) to explore potential synergies of using RXi’s self-delivering RNAi technology (sd-rxRNA) in combination with Medigene’s recombinant TCRs to develop modified T cells with enhanced efficacy and/or safety (Press release, RXi Pharmaceuticals, DEC 11, 2017, View Source [SID1234522533]). The preclinical research program will examine the applicability of RXi’s sd-rxRNA technology to be integrated into Medigene’s process to produce receptor-modified T cells with the ultimate goal to further improve Medigene’s T cell therapies for the treatment of cancer patients.

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Research teams at Medigene will closely work together with the scientists at RXi to explore potential advantages of transient down regulation of certain genes ("knock down") to prevent negative regulation of T cells expressing a recombinant TCR directed against a predefined tumor antigen. The two complementing technologies could lead to synergistic effects that might further sharpen and improve the therapeutic effects of Medigene’s receptor-modified T cells.

Markus Dangl, Senior Vice President Research and Preclinical Development of Medigene AG, comments: "We are very happy that we found a partner that is fully aligned with our vision to further improve our adoptive T cell therapy approach. We are convinced that this technology can help us to develop the next generation of recombinant T cells that are highly efficacious, also in challenging solid tumor environments. These T cells will contain features that have the potential to further enhance the efficacy and safety of our approach to bring highly beneficial cellular therapies to the market."

Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals, adds: "We are excited to start this new collaboration. Medigene’s adoptive cell therapy, using their TCR platform, is a very attractive and promising development in immuno-oncology; and we are pleased with their decision to use our sd-rxRNA technology in combination with their TCR approach. The use of our immuno-oncology sd-rxRNA compounds with their receptor-modified T cells could potentially create a next generation of very powerful adoptive cell therapies against serious cancers that currently are difficult to target."

About Medigene’s TCR technology: The TCR technology aims at arming the patient’s own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex vivo).

TCR therapy is developed to utilize a higher number of potential tumor antigens than other T cell-based immunotherapies, such as chimeric antigen receptor T cell (CAR T) therapy. Medigene is preparing the clinical development of its first TCR candidates and is establishing a pipeline of recombinant T-cell receptors, and has established Good Manufacturing Practice (GMP)-compliant processes for their combination with patient-derived T cells.

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, TecDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development.

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On December 11, 2017 Innovation Pharmaceuticals, (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, reported successful topline results from the Company’s randomized, double-blind, placebo-controlled, Phase 2 clinical trial of Brilacidin (see NCT02324335) for the prevention and control of Oral Mucositis (OM) in patients receiving chemoradiation for treatment of Head and Neck Cancer (Press release, Innovation Pharmaceuticals, DEC 11, 2017, View Source [SID1234522527]). Brilacidin-OM is being developed under an FDA Fast Track designation for this indication.

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Summary of Topline Results from the Placebo-Controlled Phase 2 Trial

· Brilacidin met primary endpoint of reduced incidence of severe OM experienced by patients during radiation therapy.
· Incidence of severe OM in Modified Intent to Treat (mITT) Population: Brilacidin 42.9%, Placebo 60.0%.
· Incidence of severe OM in Per Protocol (PP) Population: Brilacidin 36.8%, Placebo 60.0%.
· Trial results support continued and expedited development of Brilacidin-OM.

Clinical Trial Background

In this trial, Head and Neck Cancer patients self-administered Brilacidin (45 mg/15 ml oral rinse—"swish and spit") or placebo three times daily across 7 consecutive weeks (49 days). Of the 61 patients randomized, 46 patients met the cumulative radiation dose criteria of at least 55 Gy—the minimum treatment threshold for inclusion in the efficacy population—and 39 of these patients met more strict criteria for inclusion in the "per protocol" study population. The trial’s primary endpoint was established as reduced incidence of severe OM (defined as Grade ≥ 3 on the WHO Oral Mucositis scale) experienced by patients during radiation therapy.

Topline results reveal a clear reduction in the incidence of severe OM (WHO Grade ≥ 3) in patients treated with Brilacidin-OM as compared to those on placebo. Brilacidin also appeared generally safe and well-tolerated across all treated patients (the safety population).

Primary Efficacy Results: Incidence of severe OM (WHO Grade ≥ 3)

Active (Brilacidin) Control (Placebo)

Modified Intent to Treat 9 of 21 patients (42.9 %) 15 of 25 patients (60.0%)
(mITT) Population (n=46)
Per Protocol
(PP) Population (n=39) 7 of 19 patients (36.8%) 12 of 20 patients (60.0%)

Overall reduction in observed severe Oral Mucositis (WHO Grade ≥ 3) in the Brilacidin-OM treatment group from that seen in the control group ([incidence control – incidence active]/incidence control) was: 28.5% (mITT population) and 38.7% (PP population).

Safety and Tolerability Profile

Brilacidin administered as an oral rinse was generally well-tolerated by patients. Safety findings were typical for patients with Head and Neck Cancer being treated with chemoradiation, with all treated patients reporting at least one Treatment-Emergent Adverse Event (TEAE). Of the TEAEs categorized as serious (SAEs), 13 patients (8 in the Brilacidin group, and 5 in the Placebo group) experienced at least one SAE. No SAEs reported led to death. None of the SAEs were classified by the Investigator as related to Brilacidin.

Management Comments

Additional study endpoint analyses are ongoing, with outputs expected in the coming weeks. These endpoints are important in building a deeper knowledge base around Brilacidin-OM, further informing other aspects of efficacy and helping to plan the next stage of clinical development.

"The completion of the Phase 2 trial of Brilacidin-OM is a major milestone for the Company, particularly given the successful topline study results. In a broader context, these mid-phase study results represent a watershed moment in the management of OM, as there has been negligible prior innovation in safely mitigating the onset of the severest stages of the disease," commented Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals. "We believe that we now occupy a leadership position with this drug candidate in the prevention and treatment of severe OM in Head and Neck Cancer patients. Considering the global unmet medical need in treating severe OM, we anticipate leveraging these promising data, both in securing potential partnership opportunities and establishing an early competitive market position. In combination with other promising clinical data on Brilacidin, we are building a strong case that our novel defensin-mimetic pipeline can safely address an array of diseases and conditions by showing meaningful clinical responses. We now look forward to discussing our plans with the FDA to best align and prepare for the expedient advancement of the Brilacidin-OM program."

"Based on these data, we are confident Brilacidin-OM has potential to improve significantly the treatment paradigm for OM," said Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "To see a clear beneficial clinical response is what clinicians hope for—a viable drug candidate bettering the lives of patients in dire need of newer treatment options. Further, today’s news is added validation of the Brilacidin Franchise, now anchored in three distinct clinical indications—OM, inflammatory bowel disease and serious skin infections. Brilacidin is an extremely unique drug candidate that we look forward to continuing to explore and advance across its many therapeutic applications."

About Brilacidin

Brilacidin is Innovation Pharmaceuticals’ lead drug candidate in its defensin mimetic franchise. Modeled after Host Defense Proteins (HDPs), the "front-line" of defense in the immune system, it is a small, non-peptidic, synthetic molecule that kills pathogens swiftly and thoroughly. Just as importantly, Brilacidin also functions in a robust immunomodulatory capacity, lessening inflammation and promoting healing. Due to its unique properties, the Company is studying Brilacidin’s effect on Oral Mucositis (under Fast Track designation) and on Ulcerative Proctitis / Proctosigmoiditis (UP/UPS) in Phase 2 trials. Additional trials of Brilacidin are planned in other conditions, including: Atopic Dermatitis, Hidradenitis Suppurativa and Acne. Brilacidin is also being developed under FDA’s Qualified Infectious Disease Product (QIDP) designation as an antibacterial product for Acute Bacterial Skin and Skin Structure Infection (ABSSSI)—qualifying it for Fast Track and possible Priority FDA Review and an extra 5 years of United States market exclusivity upon drug approval.

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About Brilacidin-OM

Innovation Pharmaceutical’s first-in-class immunomodulatory drug candidate, Brilacidin, targets the prevention of severe Oral Mucositis (OM)—a common and debilitating side-effect of receiving chemoradiation therapy—in Head and Neck Cancer. Each year, OM affects hundreds of thousands of patients worldwide. Only a limited number of OM treatments are available, most of which are palliative in nature. A Phase 2 randomized, placebo-controlled clinical trial of Brilacidin-OM (see NCT02324335) has been recently completed in which topline results demonstrate a reduced rate of severe OM (WHO Grade >3) in patients treated with Brilacidin-OM compared to those on placebo.

About Oral Mucositis

Oral Mucositis (OM) is a frequent, painful and debilitating complication of chemoradiation. Head and Neck Cancer (HNC) patients—comprising an estimated 65,000 newly diagnosed cases in the U.S. alone in 2017, and an estimated 700,000 worldwide (source: GLOBOCAN)—are at the greatest risk of developing OM (a 90 to 100 percent rate of occurrence). By 2030, the global incidence of HNC cases is expected to exceed 1 million per year. Moreover, between 25 and 60 percent of cancer patients, regardless of cancer type, also will experience OM. Characterized by inflammation and ulceration, patients suffering from OM are often unable to speak and eat (requiring the insertion of a feeding tube) and are more susceptible to infections, with severe cases leading to hospitalization at increased treatment costs of up to $25,000. There currently are no approved medications for the prevention of OM in the HNC population, with only limited palliative care options available. Worldwide, the potential market for OM is expected to exceed $1 billion in the next few years.