On May 16, 2018 Turnstone Biologics reported it has received U.S. Food and Drug Administration (FDA) clearance of its Investigational New Drug Application (IND) for MG1-HPV for the treatment of patients with human papillomavirus (HPV) positive solid tumors (Press release, Turnstone Biologics, MAY 16, 2018, View Source [SID1234526721]). Additionally, Turnstone reported that it has entered into a clinical supply agreement with F. Hoffmann-La Roche Ltd ("Roche") under which Roche will provide atezolizumab (Tecentriq), its anti-PDL1 antibody, for use in combination with Turnstone’s Maraba virus immunotherapy platform, MG1.

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Turnstone will investigate the safety and efficacy of MG1-HPV therapy in combination with atezolizumab across a range of HPV positive tumors in a Phase I/II clinical study expected to commence in the second quarter of 2018.

"We are committed to helping patients in need of a safe and effective treatment for HPV positive cancers. Following FDA clearance of our IND, we look forward to advancing this promising combination of therapies into the clinic," said Mike Burgess, MD, Ph.D., president of Research and Development at Turnstone. "We are excited to have the support of Roche in evaluating our novel MG1 platform in combination with atezolizumab, and believe the promise of our technology to unleash the power of T cells to treat a range of solid tumors is reinforced by this relationship."

Turnstone’s MG1 virus is the first immunotherapy engineered to function as both a selective tumor-destroying oncolytic virus and an immune stimulating T cell vaccine. MG1 directly attacks cancer cells and modifies the microenvironment to make tumor sites throughout the body susceptible to targeted killer T cell responses, also induced by the virus. Building off of recently published scientific data, Turnstone will investigate MG1-HPV (MG1 expressing four different HPV viral antigens) as a safe and effective treatment option for patients with advanced metastatic cervical, oropharyngeal, and other HPV positive solid tumors.

On May 16, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from the Phase III IMpower150 study of Tecentriq (atezolizumab) and Avastin (bevacizumab) plus carboplatin and paclitaxel (chemotherapy) for the initial (first-line) treatment of chemotherapy-naïve people with metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, MAY 16, 2018, View Source [SID1234526738]). This interim analysis showed that Tecentriq and Avastin plus carboplatin and paclitaxel helped people live significantly longer compared with Avastin plus carboplatin and paclitaxel (median overall survival [OS] = 19.2 versus 14.7 months; hazard ratio [HR] = 0.78, 95% CI: 0.64-0.96; p=0.016) in the intention-to-treat wild-type (ITT-WT) population, a co-primary endpoint of the study.1 An OS advantage was observed in all pre-specified exploratory biomarker-selected subgroups analysed, which included people with EGFR- and ALK-positive mutations who had received an appropriate targeted therapy, and those with varying levels of PD-L1 expression or with negative PD-L1 expression. People with liver metastases treated with the Tecentriq combination also had a survival advantage. The safety profile of the Tecentriq and Avastin plus carboplatin and paclitaxel combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.

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"The IMpower150 study results showed a significant survival benefit, adding to the clinical evidence supporting the combination of Tecentriq and Avastin as an initial treatment for metastatic non-squamous non-small cell lung cancer. An overall survival benefit was also observed in key populations such as people with EGFR- and ALK-positive mutations and those with liver metastases," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are working with health authorities around the world to bring this potential Tecentriq combination regimen to people living with this disease."

At this interim analysis, the combination of Tecentriq plus carboplatin and paclitaxel (Arm A) did not show a statistically significant OS benefit when compared to the combination of Avastin plus carboplatin and paclitaxel (Arm C). Arm A will continue as planned to the final analysis. Safety in the Tecentriq plus carboplatin and paclitaxel arm appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

The official data presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting will be on Monday, June 4, 2018, at 15:45 – 15:57 p.m. CDT (Abstract #9002).

The combination of Tecentriq and Avastin plus carboplatin and paclitaxel was recently granted Priority Review from the U.S. Food and Drug Administration (FDA) for the initial (first-line) treatment of chemotherapy-naïve people with metastatic non-squamous NSCLC. The FDA is expected to make a decision on approval by September 5th, 2018.

IMpower150 is one of eight Phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines. Following the IMpower150 and IMpower131 studies, three more Phase III lung cancer studies are expected to report this year.

About the IMpower150 study
IMpower150 is a multicentre, open-label, randomised, controlled Phase III study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and paclitaxel) with or without Avastin in people with stage IV or recurrent metastatic non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease. It enrolled 1,202 people of which those with ALK and EGFR mutations were excluded from the primary ITT analysis. People were randomised (1:1:1) to receive:

Tecentriq plus carboplatin and paclitaxel (Arm A), or
Tecentriq and Avastin plus carboplatin and paclitaxel (Arm B), or
Avastin plus carboplatin and paclitaxel (Arm C, control arm).
During the treatment-induction phase, people in Arm A received Tecentriq administered intravenously at 1200 mg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. Following the induction phase, people received maintenance treatment with Tecentriq (1200 mg every 3 weeks) until loss of clinical benefit or disease progression. IMpower150 was designed to formally compare Tecentriq plus chemotherapy (Arm A) versus Avastin plus chemotherapy (Arm C), only if Tecentriq and Avastin plus chemotherapy (Arm B) is shown to improve OS in the ITT-WT population compared to Avastin plus chemotherapy (Arm C).

People in Arm B received induction treatment with Tecentriq (1200 mg) and Avastin administered intravenously at 15 mg/kg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. People then received maintenance treatment with the Tecentriq Avastin regimen until disease progression (Avastin) or loss of clinical benefit/disease progression (Tecentriq).

People in Arm C received induction treatment with Avastin administered intravenously at 15 mg/kg plus intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. This was followed by maintenance treatment with Avastin alone until disease progression.

The co-primary endpoints were PFS and OS, as determined by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The co-primary OS endpoint in IMpower150 was assessed in all randomised people without an EGFR or ALK genetic mutation (intention-to-treat wild-type). Key secondary endpoints included investigator-assessed PFS, OS and safety in the ITT population and in EGFR and ALK mutation subgroups. The study met its co-primary endpoints of OS and PFS per study protocol.

A summary of OS results is included below.

The safety profile of the Tecentriq and Avastin plus carboplatin and paclitaxel combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination. Serious adverse events (Grade 3-4) related to treatment were observed in 57% of people who received Tecentriq and Avastin plus carboplatin and paclitaxel compared to 49% of those who received Avastin plus carboplatin and paclitaxel.

About NSCLC
Lung cancer is the leading cause of cancer death globally.2 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.3 Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.3 NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope. The squamous form tends to grow near the centre of the lung, and accounts for approximately 25-30% of all NSCLC cases.4

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.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 70 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)
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasise).

About the Tecentriq (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat first-line advanced NSCLC. 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.

On May 16, 2018 LIDDS AB (publ) reported that it has signed a license agreement for Liproca Depot with Jiangsu Ambition Medical, a Chinese pharmaceutical company specializing in global collaborations and in-licensing. Liproca Depot is LIDDS injectable cancer drug candidate for local treatment of prostate cancer (Press release, Lidds, MAY 16, 2018, View Source [SID1234555918]). LIDDS is receiving a signing fee exceeding USD 1 million followed by milestone payments and royalty. A phase III clinical trial will be conducted in China and will be fully financed by the licensee.

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The strategic cooperation between Jiangsu Ambition Medical and LIDDS is expected to result in market approval for Liproca Depot in China as the first country in the world. Jiangsu Ambition Medical originates from Jiminkexin Group which ranks as one of the top 10 pharma companies in China. Jiangsu Ambition Medical has also expressed a strong interest for other drugs formulated in the NanoZolid technology platform.

LIDDS is very pleased to enter into the license agreement with Jiangsu Ambition Medical which has the highly regarded expertise to perform necessary clinical trials, and also an impressive sales organization to manage a future launch of Liproca Depot. The agreement is also a clear recognition of the international interest for the NanoZolid technology and Liproca Depot as treatment for prostate cancer, says Monica Wallter, CEO of LIDDS.

The prostate cancer market is substantial in China with around 500 000 patients being diagnosed annually. Oncology is a focus area at Jiangsu Ambition Medical and the company expects that the sales of Liproca Depot will reach yearly sales of 50 000 to70 000 treatments in 3 to 5 years after launch.

Jiangsu Ambition Medical views NanoZolid technology and specifically the Liproca Depot product as a very promising treatment for prostate cancer, a disease that is also very common in China. We are very happy to enter the agreement with LIDDS and will immediately start to prepare for conducting the Liproca Depot clinical trial in China. We hope to extend the partnership and get other products based on the NanoZolid technology into our pipeline, says Mr. Mark Dai, CEO of Jiangsu Ambition Medical.

Jiangsu Ambition Medical has its own regulatory and clinical departments and a highly recognized marketing and sales organization. Being deeply connected with the Chinese regulatory authorities and key clinical opinion leaders, their sales network covers 1,130 large scale public hospitals and an additional 4,592 hospitals in China. The sales team has launched four different drug products with an annual revenue of more than RMB 1.5 billion each and three drug products with revenues of RMB 1 billion respectively. LIDDS and Jiangsu Ambition Medical will work together to optimise the time to market for launching Liproca Depot in China.

On May 16, 2018 FogPharma reported the closing of a $66 million Series B financing (Press release, FogPharma, MAY 16, 2018, View Source [SID1234552458]). The round was led by 6 Dimensions Capital, with participation by additional new investors, including GV (formerly Google Ventures), Blue Pool Capital, Horizons Ventures, Nan Fung Group, and Leerink Partners. All existing investors participated in the round including Deerfield Management, Boyu Capital, WuXi AppTec Corporate Ventures, and a prominent international group of non-institutional investors.

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FogPharma was founded by renowned scientist-entrepreneur Dr. Gregory Verdine, whose Harvard lab invented cell-penetrating miniproteins and who coined the term "drugging the undruggable" to describe his life’s mission. FogPharma’s research and development strategy is unique in that it pairs a broadly-enabling new drug class, designed to access the cell interior, with a massively parallelized engine to discover – rapidly and on-demand – drugs that engage the most intractable of disease targets. FogPharma’s drug discovery engine has been configured to deliver multiple new medicines in rapid succession, with clinical entry for the first product, a first-in-class beta-catenin antagonist, by the end of 2019, followed by a steady stream of first-in-class clinical product candidates addressing other intractable targets.

While FogPharma’s approach has many therapeutic applications, the company’s early focus is on drugging the major, intractable drivers of cancer and on pharmacological management of the immune response.

"One of the most important challenges of our time is making actionable the enormous, inactionable trove of biological data on human disease targets. FogPharma is addressing this challenge by bringing forward a new class of medicines that combine the cell-penetrating ability of small molecules with the broad, target power of biologics, and by learning how to discover these medicines better, faster and smarter," said Verdine, chief executive officer and chief scientific officer, FogPharma.

Added Verdine, "We are thrilled to have such an incredible group of investors who share our vision of fundamentally advancing the treatment of cancer and other serious diseases with few if any current treatment options. We are excited at the opportunity provided by this financing to propel our programs and drug discovery engine forward."

Proceeds from the Series B raise will enable the company to advance its first-in-class beta-catenin inhibitor (iCat) program into Phase 2 development for cancer indications involving Wnt pathway activation. The financing will also be used to advance clinical development of its first-in-class Cbl-b inhibitor program and a third as-yet-undisclosed program through IND-enabling studies, and FogPharma’s drug discovery platform for three additional, distinct and differentiated forms of cell-penetrating miniproteins.

In association with the Series B financing, FogPharma has appointed to its board of directors: Dr. Leon Chen, chief executive officer, 6 Dimensions Capital; Dr. Krishna Yeshwant, general partner, GV; and Dr. Rick Klausner, founder and director, Juno Therapeutics, GRAIL and Mindstrong.

"There is substantial and persistent interest in tackling targets like beta-catenin and Cbl-b, which are clearly important biologically and medically, but untouchable by conventional therapeutics. I was captivated by the FogPharma team’s unprecedented ability to go after these and other intractable targets," said Klausner, formerly director of the National Cancer Institute and executive director of the Bill and Melinda Gates Foundation.

"The opportunity in the near term to bring cell-penetrating miniproteins to the 20-25 percent of cancer patients whose disease is driven by the Wnt pathway is tremendous, and the opportunity beyond that to be the first to drug Cbl-b for immuno-oncology indications, is extraordinary. On behalf of 6 Dimensions Capital, I am thrilled to have led this exceptional investor syndicate and foster FogPharma’s mission," said Chen, chief executive officer, 6 Dimensons Capital, and member of the FogPharma board of directors.

Through seed and Series A financing, FogPharma previously secured $11 million bringing the company’s total funding to-date to $77 million.

In addition to FogPharma, Verdine founded and leads LifeMine Therapeutics, which has buit a first-of-its-kind, genomically-enabled drug discovery platform that can rapidly develop new drugs from fungi. Both LifeMine Therapeutics and FogPharma are headquartered in Cambridge, Mass. and were established operationally in 2016. Verdine is highly regarded for having moved seamlessly between successful roles as life scientist, entrepreneur, investor, and chief executive throughout his career. He is Erving Professor at Harvard University and Harvard Medical School and has founded multiple NASDAQ-listed biotech companies including Wave Life Sciences, Enanta, Eleven Bio, Variagenics, Tokai, Aileron, and a private company, Gloucester Pharmaceuticals, acquired by Celgene in 2010.

On May 16, 2018 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported the Company has gained access to additional intellectual property from Memorial Sloan Kettering Cancer Center (MSK) that enables the development of gene-edited T-cell immunotherapies (Press release, Fate Therapeutics, MAY 16, 2018, View Source [SID1234526687]). The newly-licensed portfolio of intellectual property covers new chimeric antigen receptor (CAR) constructs as well as off-the-shelf CAR T cells, including the use of CRISPR and other innovative technologies for their production.

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Fate Therapeutics is utilizing gene editing under its ongoing collaboration for the research and development of off-the-shelf CAR T-cell immunotherapies with Michel Sadelain, M.D., Ph.D., Director of the Center for Cell Engineering and the Stephen and Barbara Friedman Chair at MSK. At the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting, Dr. Sadelain will present preclinical data on FT819, an off-the-shelf, TCR-less, CD19 CAR T-cell product manufactured from a clonal master induced pluripotent stem cell (iPSC) line.

"Engineering stem cells and using master iPSC lines for the renewable production of off-the-shelf CAR T cells has the potential to advance the cancer immunotherapy landscape," said Dr. Sadelain. "We are pleased with the breakthrough discoveries accomplished under our ongoing collaboration with Fate Therapeutics, and look forward to continuing our advancement together of off-the-shelf CAR T-cell products toward clinical development."

The use of clonal master iPSC lines can overcome the complexity, heterogeneity and substantial costs associated with using cells from a patient or an allogeneic donor. Instead, iPSC-derived T-cell immunotherapies can be consistently and repeatedly mass produced and delivered in an off-the-shelf manner, significantly reducing the cost of, and time to, patient treatment.

"The use of a gene-edited master iPSC line for the manufacture of off-the-shelf T-cell immunotherapies ensures complete removal of endogenous TCR expression, which is critical to avoid the life-threatening complication of graft-versus-host disease that is seen in allogeneic T-cell therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "The incorporation of these latest MSK technologies into our development of FT819 and our iPSC product platform advances our leadership position in developing off-the-shelf T-cell immunotherapies with improved safety, enhanced potency and expanded therapeutic reach."

Fate Therapeutics has exclusively licensed from MSK intellectual property covering the production and composition of iPSC-derived T cells for human therapeutic use. In addition, Fate Therapeutics owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

About FT819
FT819 is a universal, off-the-shelf, dual-targeted CAR T-cell product that is manufactured from a clonal master iPSC line. The line is engineered to completely eliminate expression of the T-cell receptor, to preferentially regulate CAR19 expression by inserting the CAR into the T-cell receptor constant (TRAC) locus, and to uniquely express a recombinant CD16 Fc receptor. In preclinical studies, FT819 exhibits a target-specific T-cell response in vitro when challenged with CD19-positive tumor cells and displays enhanced production of effector cytokines and cytolytic proteins. In addition, FT819 uniquely elicits antibody-dependent cell-mediated cytotoxicity in vitro against CD19-negative, CD20-positive tumor cells with rituximab, a monoclonal antibody targeting CD20. This dual-targeted approach of FT819 can substantially broaden the cell product’s therapeutic reach and overcome CD19 antigen escape through combination with other proven cancer treatments.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary iPSC product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity, including in combination with cycles of other cancer treatments. 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 iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for consistently and repeatedly manufacturing homogeneous cell products in quantities that support the treatment of many thousands of patients in a cost-effective, 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.