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Novocure Initiates Phase 3 Pivotal Trial in Recurrent Ovarian Cancer

On March 22, 2019 Novocure (NASDAQ: NVCR) reported that it has initiated INNOVATE-3, a phase 3 pivotal trial testing the efficacy of Tumor Treating Fields combined with paclitaxel in patients with recurrent, platinum-resistant ovarian cancer (Press release, NovoCure, MAR 22, 2019, View Source [SID1234534559]). INNOVATE-3 is Novocure’s fourth phase 3 pivotal trial initiated to study solid tumors beyond glioblastoma.

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"Ovarian cancer is one of the most aggressive forms of cancer," said Professor Ignace Vergote, Chairman of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, European Union. "Most ovarian cancer patients are diagnosed at an advanced stage, which makes the disease difficult to treat. Current treatment options are not enough for these patients. We are pleased to begin this trial that has the potential to improve survival in recurrent ovarian cancer."

INNOVATE-3, a prospective, open-label study, will include 540 patients with recurrent, platinum-resistant ovarian cancer. Patients will be randomized to receive either weekly paclitaxel alone or weekly paclitaxel in combination with Tumor Treating Fields tuned to 200 kHz until progression. The primary endpoint is overall survival. Secondary endpoints include progression free survival, objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life. Patients may have had a maximum of two prior lines of systemic therapy following diagnosis of platinum-resistance.

Novocure developed the trial design for INNOVATE-3 after learning the results of its phase 2 pilot trial of Tumor Treating Fields in combination with weekly paclitaxel, the INNOVATE trial. In 31 evaluable patients, the INNOVATE trial suggested a more than doubling of progression free survival and an improvement in overall survival among patients who received Optune with paclitaxel compared to paclitaxel alone.

"INNOVATE-3 is Novocure’s fourth phase 3 pivotal trial beyond glioblastoma, demonstrating our commitment to developing Tumor Treating Fields for a variety of solid tumors," said Asaf Danziger, Novocure’s Chief Executive Officer. "At Novocure, we strive to extend survival in some of the most aggressive forms of cancer. Ovarian cancer has been an important area of focus for our research because of the great unmet need faced by these patients. We are now working closely with trial sites and institutional review boards to open sites and enroll patients as quickly as possible."

About Ovarian Cancer `

In the United States, ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. Ovarian cancer incidence increases with age, and the median age at time of diagnosis is 63 years old. The incidence of ovarian cancer is approximately 22,500 new cases annually in the United States, approximately 68,000 new cases annually in Europe, and approximately 10,000 new cases annually in Japan. Tumor Treating Fields is not approved for the treatment of ovarian cancer by the U.S. Food and Drug Administration. The safety and effectiveness of Tumor Treating Fields for ovarian cancer has not been established.

Genmab Announces European Regulatory Submission for Daratumumab in Combination with Lenalidomide and Dexamethasone in Frontline Multiple Myeloma

On March 22, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that Janssen Pharmaceutica NV (Janssen) has submitted a Type II variation application to the European Medicines Agency (EMA) (Press release, Genmab, MAR 22, 2019, View Source [SID1234534557]). The application seeks to broaden the existing marketing authorization for daratumumab (DARZALEX) to include use in combination with lenalidomide and dexamethasone (Rd) as treatment for newly diagnosed multiple myeloma patients who are not candidates for high dose chemotherapy and autologous stem cell transplant (ASCT) . The submission is based on data from the Phase III MAIA study of daratumumab in combination with Rd as treatment for patients with newly diagnosed multiple myeloma, who are not candidates for high dose chemotherapy and ASCT. Data from the study was presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which took place in San Diego, California in December 2018. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

"At Genmab we’re committed to improving the lives of patients by creating and developing innovative antibody products. With this potential label expansion, we are hopeful that DARZALEX will become available to an even wider group of multiple myeloma patients in the first line setting," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the MAIA (MMY3008) study
The Phase III study (NCT02252172) is a randomized, open-label, multicenter study that includes 737 newly diagnosed patients with multiple myeloma who are not candidates for high dose chemotherapy and ASCT. Patients were randomized to receive either daratumumab in combination with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid) or lenalidomide and dexamethasone alone. In the daratumumab treatment arm, patients received 16 milligrams per kilogram (mg/kg) weekly for first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide is administered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexamethasone was administered at 40 mg once a week for both treatment arms. Participants in both treatment arms will continue Rd until disease progression or unacceptable toxicity. The primary endpoint of the study is PFS.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

Celyad to Announce Full Year 2018 Financial Results and Host Conference Call

On March 22, 2019 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, reported that the Company will report full year 2018 financial and operating results on the evening of Thursday, March 28, 2019 (Press release, Celyad, MAR 22, 2019, https://www.celyad.com/en/news/celyad-to-announce-full-year-2018-financial-results-and-host-conference-call [SID1234534556]).

Following the press release, Celyad management will host a conference call on Friday, March 29 at 1p.m. CET / 8a.m. EDT to discuss full year 2018 results and provide an update on the Company’s recent progress and upcoming milestones.

Participants may access the conference call by dialing +44 (0) 2071 928000. The conference ID for the call is 8745558. Alternatively, participants may access the conference call by dialing the following local numbers: Belgium 024009874, France 0176700794, Netherlands 0207143545 and U.S. 16315107495.

To access the subsequent archived recording, visit the "Events & Webcasts" section of the Celyad website.

bluebird bio Opens State-of-the-Art Gene and Cell Therapy Manufacturing Facility in Durham, North Carolina

On March 22, 2019 bluebird bio, Inc. (Nasdaq: BLUE) reported the official opening of its first wholly owned manufacturing facility in Durham, N.C., that will produce lentiviral vector for the company’s investigational gene and cell therapies, including: bb2121 and bb21217 for the treatment of multiple myeloma and potentially LentiGlobin for the treatment of transfusion-dependent β-thalassemia (TDT) and sickle cell disease (Press release, bluebird bio, MAR 22, 2019, View Source [SID1234534554]).

Gov. Roy Cooper, Secretary of Commerce Tony Copeland and local patient advocates will join chief bluebird Nick Leschly in a ribbon cutting ceremony at the 125,000-square-foot facility. Currently, bluebird employs approximately 50 scientists, engineers, manufacturing and operations personnel at the facility and is on track to grow to approximately 70 employees by the end of 2019.

"At bluebird bio, we view every aspect of our path to helping patients as both a privilege and a responsibility. This includes the expertise that we’ve poured into the construction and operation of our manufacturing facility, because it is a crucial step toward our mission of bringing a new generation of treatments to people living with severe genetic diseases and cancer," said Leschly. "Our teams in North Carolina and across the globe are working to deliver treatments that will make a big difference for a lot of patients and families. This is what drives our ambition to bring four gene therapies forward in the next few years."

"North Carolina is proud to bring bluebird bio’s cutting-edge work to Durham," Governor Cooper said. "bluebird is developing treatments for devastating diseases that could change the course of medicine. And, with the Triangle’s highly-skilled workforce, it will continue to be a leader in the biotech field."

bluebird bio purchased the facility in November 2017. Once completed, the company will have invested more than $80 million building a world class site equipped with multiple manufacturing suites capable of producing lentiviral vector (LVV). The facility also includes warehouse and quality control testing laboratories. The facility construction is substantially complete and equipment qualification is underway. Initially, bluebird bio expects the facility to produce clinical and commercial supply of lentiviral vector, which is a critical component of the company’s gene and cell therapies. The facility is large enough to accommodate significant future expansion, including the possibility of manufacturing commercial drug product.

The goal of gene therapy is to change or replace faulty genes with functional ones in order to prevent, treat or cure a disease. Vectors are selected parts of viruses that have been genetically modified so they can deliver new genes into cells without causing an infectious disease. Prior to gene therapy treatment, copies of functional genes are added to a vector — the delivery system — in a laboratory setting. The vector, with copies of the functional gene, is added to blood stem cells collected from the patient. The cells that now have functional copies of the gene are referred to as gene-modified cells.

In addition to the Durham facility, bluebird bio also has multi-year agreements with three manufacturing partners in the United States and Europe: Brammer Bio (Cambridge, Mass.), Novasep (Gosselies, Belgium) and MilliporeSigma, the Life Science business of Merck KGaA (Carlsbad, Calif.). Each of these partners is collaborating with bluebird bio on production of lentiviral vector across all programs. bluebird bio also partners with Lonza (Houston, Texas) and apceth Biopharma (Munich, Germany) to produce drug product for Lenti-D and LentiGlobin.

bluebird will receive an Economic Development Award from NCBiotech upon meeting job creation targets in North Carolina and will also receive life-sciences-specific employee training support through the North Carolina Community College System’s Customized Training Program.

SELLAS Life Sciences Reports 2018 Financial Results and Provides Business Update

On March 22, 2019 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported financial results for the year ended December 31, 2018 and provided a business update (Press release, Sellas Life Sciences, MAR 22, 2019, View Source [SID1234534552]).

"In February, we initiated a review of a wide range of strategic alternatives to maximize shareholder value, such as a sale of the Company, a merger, or a strategic investment or financing," stated Dr. Angelos M. Stergiou, M.D., ScD h.c., President and Chief Executive Officer of SELLAS. "We are currently actively exploring these alternatives with the goal of identifying a plan that will enhance shareholder value while advancing our novel cancer immunotherapy clinical pipeline."

2018 and Recent Business Highlights

Corporate Developments

In February 2019, the Company announced that its Board of Directors is conducting a review of strategic options focusing on maximizing shareholder value. SELLAS has engaged Cantor Fitzgerald & Co. to act as its strategic and financial advisor for this process.
In March 2019, the Company entered into a warrant exchange agreement with a single investor, the proceeds of which are being used by the Company to further its development programs and business operations during the strategic alternatives evaluation process.
Clinical Pipeline

Galinpepimut-S (GPS)

In November 2018, following discussion with the U.S. Food and Drug Administration (FDA), the Company announced a streamlined clinical trial design and biostatistical plan for a Phase 3 registrational study for GPS in acute myeloid leukemia (AML). The planned Phase 3 registrational study will be a 1:1 randomized, open-label study comparing GPS in the maintenance setting to investigators’ choice of best available treatment in adult AML patients who have achieved hematologic complete remission, with or without thrombocytopenia (CR2/CR2p), after second-line antileukemic therapy and who are deemed ineligible for or unable to undergo allogeneic stem-cell transplantation. The primary endpoint is overall survival and secondary endpoints include leukemia-free survival, antigen-specific T-cell immune response dynamics over time and rates of achievement of measurable residual disease negativity. The study will have a planned interim safety and futility analysis after 80 events (deaths). The Phase 3 study is expected to enroll approximately 116 patients at approximately 50 clinical sites in the United States and Europe. The Company is completing preparations for the initiation of this study which is subject to the receipt of sufficient funding. This study is being led by Drs. Hagop Kantarjian of MD Anderson Cancer Center and Gert Ossenkoppele of Amsterdam University Medical Center (VUMC) and the HOVON network.
In December 2018, SELLAS initiated enrollment of the Phase 1/2 open-label, non-comparative, multicenter, multi-arm study of GPS in combination with Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) in patients with selected WT1-positive advanced cancers, including both hematologic malignancies and solid tumors. This study, which is being conducted under a Clinical Trial Collaboration and Supply Agreement with Merck (known as MSD outside the United States and Canada), will assess the efficacy and safety of the combination, with exploratory long-term follow-up for overall survival and safety, and is expected to enroll approximately 90 patients at up to 20 sites in the United States. The initial tumor types to be treated will be AML (patients unable to attain deeper morphological response than partial on hypomethylating agents and who are not eligible for allogeneic hematopoietic stem cell transplant) and ovarian cancer (second or third line), to be followed by triple negative breast cancer (TNBC) (second line), small cell lung cancer (second line), and colorectal cancer (third or fourth line). The study is being led by Drs. Richard Maziarz of Oregon Health and Science University and Roisin O’Cearbhaill of Memorial Sloan Kettering Cancer Center.
Nelipepimut-S (NPS)

In 2018, the Company announced positive data from a prospective, randomized, single-blinded, controlled Phase 2b independent investigator-sponsored clinical trial of the combination of NPS (NeuVax) + trastuzumab (Herceptin) targeting HER2 low-expressing breast cancer patient cohorts. In the study, NPS + trastuzumab demonstrated clinically and statistically significant efficacy in the cohort of patients with TNBC, with a p-value of 0.013 and a 75.2% reduction in risk of relapse or death.
A preplanned secondary efficacy analysis across human leukocyte antigen (HLA) allele subgroups from the Phase 2b study confirmed the therapeutic potential of NPS in patients with early-stage TNBC in the adjuvant setting across HLA types A-02, -03, -24 and -26, which cover approximately 80-85% of the North American/European populations and 86-90% of Asian/Pacific basin populations. Additional positive data from the Phase 2b study showed a clinically meaningful and statistically significant decrease in the number of clinically detectable relapses in the TNBC cohort with the combination of NPS + trastuzumab (7.5%) vs. trastuzumab alone (27.3%) (p=0.004). In addition, four pre-defined subgroups of TNBC patients in the NPS +trastuzumab arm demonstrated an average decrease of 84.2% in relative risk of relapse or death at 24 months (p=0.004-0.014).
Based on the Phase 2b data presented in 2018, as well as the unanimous recommendation of the Data Safety Monitoring Board to expeditiously seek regulatory guidance from the FDA for further development of NPS + trastuzumab in TNBC, SELLAS is currently in continuing active discussions with the FDA.
View Source End 2018 Financial Results

Cash Position: As of December 31, 2018, cash and cash equivalents were $5.3 million, compared to $2.3 million as of December 31, 2017. Net cash used in operating activities was $30.4 million for the year ended December 31, 2018, compared to $11.0 million for the year ended December 31, 2017. Net cash provided by financing activities was $23.1 million for the year ended December 31, 2018, primarily attributable to $31.5 million in net proceeds from the sale of equity securities, partially offset by $7.6 million in principal payments on previously outstanding debt. Net cash provided by financing activities for the year ended December 31, 2017 was $5.5 million, primarily attributable to $6 million in net proceeds from the sale of equity securities, partially offset by $0.5 million on previously outstanding long-term debt.

R&D Expenses: Research and development expenses were $8.8 million for the year ended December 31, 2018, as compared to $6.1 million for the year ended December 31, 2017. The $2.7 million increase was primarily due to increases in clinical and regulatory consulting and other clinical expenses related to startup costs for the Phase 1/2 basket trial of GPS in combination with pembrolizumab (Keytruda) in multiple tumor types during 2018, and ongoing costs incurred related to the Phase 2b trial of NPS in combination with trastuzumab (Herceptin). These increases were partially offset by decreases in compensation and benefits, including stock-based compensation, and manufacturing expenses.

G&A Expenses: General and administrative expenses were $12.8 million for the year ended December 31, 2018, as compared to $15.1 million for the year ended December 31, 2017. The $2.3 million decrease was primarily driven by a decrease in compensation and employee benefits, including stock-based compensation, and in banking and advisory fees partially offset by increases in outside services and public company costs, rebates and returns of former commercial products, and insurance premiums.

Net Loss: Net loss for the year ended December 31, 2018 was $27.7 million and loss attributable to common stockholders was $41.3 million, or a basic and diluted loss per share to common stockholders of $3.15, as compared to a net loss of $23.8 million and loss attributable to common stockholders of $24.4 million for the year ended December 31, 2017, or a basic and diluted loss per share to common stockholders of $10.44. Net loss and loss attributable to common stockholders for the year ended December 31, 2018 includes a $9.6 million one-time non-cash impairment charge of in-process research and development associated with the termination of a license agreement for anagrelide CR formulation (GALE-401).

Keytruda and Herceptin are registered trademarks of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA, and Genentech, Inc., respectively, and are not trademarks of SELLAS. The manufacturers of these brands are not affiliated with and do not endorse SELLAS or its products.