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Genmab Announces U.S. FDA Approval of DARZALEX® (daratumumab) in Combination with Lenalidomide and Dexamethasone in Frontline Multiple Myeloma

On June 27, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the U.S. Food and Drug Administration (U.S. FDA) has approved the use of DARZALEX (daratumumab) in combination with lenalidomide and dexamethasone (Rd) for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT) (Press release, Genmab, JUN 27, 2019, View Source [SID1234537320]). The supplemental Biologics License Application (sBLA) for this indication was submitted by Genmab’s licensing partner, Janssen Biotech, Inc., under the Real-Time Oncology Review (RTOR) pilot program. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"The combination of lenalidomide and dexamethasone is broadly used by newly diagnosed patients with multiple myeloma ineligible for ASCT in the United States. We are extremely pleased that physicians can now offer their patients the option to add DARZALEX to this regimen in the U.S.," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The approval was based on data from the Phase III MAIA (MMY3008) study of daratumumab in combination with lenalidomide and dexamethasone as treatment for patients with newly diagnosed multiple myeloma, who are not candidates for high dose chemotherapy and ASCT. Data from this study was presented as a Late-Breaking Abstract at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018.

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 was 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 treatment with lenalidomide and dexamethasone until disease progression or unacceptable toxicity. The primary endpoint of the study is progression free survival.

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) intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; 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 the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan. 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.

Adrian Rawcliffe to Succeed James Noble as Adaptimmune Chief Executive Officer

On June 24, 2019 Adaptimmune Therapeutics plc (Nasdaq:ADAP), reported that Adrian Rawcliffe, currently Chief Financial Officer (CFO) of the Company, will succeed James Noble as Chief Executive Officer (CEO) (Press release, Adaptimmune, JUN 27, 2019, View Source [SID1234537319]). This transition will occur when James retires from his executive duties and transitions to a non-executive director role on the Company’s Board on September 1, 2019. Adrian will join the Board of Directors from the same date.

"Following James’ request early last year, the Board has been planning for leadership succession. Today, I am pleased to announce Adrian’s appointment, following a rigorous global selection process," said David Mott, Adaptimmune’s Chairman of the Board. "We were very fortunate to have Adrian as a candidate, not only given his role as CFO, covering a wide range of responsibilities from manufacturing to information management, but also his previous experiences at GSK. I want to thank James for his leadership, energy and drive, which has delivered the Company’s science, current pipeline, manufacturing expertise, and strong teams. Based on these strengths, Adrian will now lead the Company towards commercialization."

"I am delighted and privileged to have been chosen to succeed James as CEO. Since I joined Adaptimmune, I have been intimately involved in building the Company working alongside the Executive Committee and the Board. The opportunity for cell therapy to transform the lives of cancer patients is profound. Over the next two months, I will work with James and the other Company leaders to ensure a smooth handover. I am excited about the future and look forward to delivering rapidly the promises of our investigational therapies, focussing on SPEARHEAD-1, our next-gen trial, and advancing our allogeneic platform" said Adrian Rawcliffe.

James Noble said: "Over the past 20 years leading Adaptimmune and its predecessor company Avidex, I am proud to have built technologies, teams and partnerships to create strong R&D platforms and a rich pipeline. Now that the Company is about to start SPEARHEAD-1 and our first next-gen trial, it is the right time to hand over the CEO role to someone to lead Adaptimmune’s next phase towards delivering our first approved product to patients. Having worked with Adrian over the past four and a half years, I have confidence that he is the best person to do this. I look forward to continuing being involved in the next steps of the Company’s journey, as a non-executive Board member."

The Company has started a global search for a new CFO, which will be the subject of a separate announcement.

Since he joined Adaptimmune as Chief Financial Officer in March 2015, Adrian has led the Company’s financial strategy and operations, as well as investor relations, corporate communications, manufacturing and supply chain, product development, information management and facilities. He currently serves as a non-executive director of WAVE Life Sciences (NASDAQ: WVE). Before joining Adaptimmune, he held various senior roles at GSK, after joining the pharmaceutical company in 1988. His most recent role at GSK was Senior Vice President, Finance of the North American Pharmaceuticals business. Other roles at GSK included Senior Vice President Worldwide Business Development and R&D Finance, where he was responsible for all business development and finance activities for GSK’s Pharmaceuticals R&D business and Managing Partner and President of SR One Ltd, GSK’s venture-capital business. Adrian qualified as a chartered accountant with PwC and holds a B.Sc. degree in Natural Sciences from the University of Durham, U.K.

After co-founding the Company, James Noble has served as Adaptimmune’s full-time Chief Executive Officer since March 2014, and part-time CEO from July 2008 to March 2014. During the same period, between July 2008 and March 2014, Mr. Noble was also CEO of Immunocore. He has 30 years of experience in the biotech industry. He has held numerous non-executive director positions, including at CuraGen Corporation, PowderJect Pharmaceuticals plc, Oxford GlycoSciences plc, MediGene AG, and Advanced Medical Solutions plc. He is also Deputy Chairman of GW Pharmaceuticals plc (NASDAQ: GWPH). He qualified as a chartered accountant with Price Waterhouse and spent seven years at the investment bank Kleinwort Benson Limited, where he became a director in 1990. He then joined British Biotech plc as Chief Financial Officer from 1990 to 1997. He was previously Chief Executive Officer of Avidex Limited, a privately held biotechnology company that was Adaptimmune’s predecessor, from 2000 to 2006. He holds an M.A. from the University of Oxford.

CB-839 (Calithera Biosciences) Drug Overview 2019: CB-839 will be the First Glutaminase Inhibitor Approved for the Treatment of Renal Cell Carcinoma

On June 27, 2019 Calithera Biosciences reported that Cancer cells are known to rely on glycolysis as an energy source (Press release, Calithera Biosciences, JUN 27, 2019, View Source [SID1234537318]). CB-839 (Calithera Biosciences) inhibits the glutaminase enzyme, reducing the ability of cancer cells to utilize glutamine in this biochemical pathway, thereby reducing cell proliferation and tumor growth.

If approved, CB-839 will be the first glutaminase inhibitor approved for the treatment of renal cell carcinoma (RCC). This novel mechanism of action could place CB-839 in a unique position in the RCC market and provide physicians with an alternative treatment option.

CB-839 is being investigated in combination with either Afinitor (everolimus; Novartis) or Cabometyx (cabozantinib; Exelixis/Ipsen/Takeda) for previously treated advanced RCC patients, suggesting it will not compete with the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) therapies being developed for first-line use.

CB-839 is being developed by Calithera Biosciences, a company that is yet to bring an oncology product to market. Due to Calithera’s limited geographic scope, the author expects the company to look for partners to market CB-839 in Japan and the EU.

Key Topics Covered:

OVERVIEW

Drug Overview
Product Profiles
CB-839 : Renal cell carcinoma (RCC)
LIST OF FIGURES

CB-839 for RCC – SWOT analysis
The authors drug assessment summary of CB-839 for RCC
CB-839 sales for RCC in the US, 2017-26
LIST OF TABLES

CB-839 drug profile
CB-839 Phase II trials in RCC
CB-839 sales for RCC in the US ($m), 2017-26
For more information about this report visit View Source

Mirati Therapeutics Announces Closing Of Public Offering Of Common Stock And Full Exercise Of Underwriters’ Option To Purchase Additional Shares

On June 27, 2019 Mirati Therapeutics, Inc. (Nasdaq: MRTX) reported the closing of its previously reported underwritten public offering of 2,415,000 shares of its common stock at a public offering price of $97.00 per share (Press release, Mirati, JUN 27, 2019, View Source [SID1234537315]). This includes the exercise in full by the underwriters of their option to purchase up to 315,000 additional shares of common stock. The aggregate gross proceeds to Mirati from this offering were approximately $234.3 million, before deducting underwriting discounts and commissions and estimated offering expenses payable by Mirati.

Cowen, Credit Suisse and Barclays acted as joint book-running managers in the offering. Guggenheim Securities and Oppenheimer & Co. acted as co-lead managers and H.C. Wainwright & Co. acted as co-manager in the offering.

The shares of common stock described above were offered by Mirati pursuant to a shelf registration statement filed by Mirati with the Securities and Exchange Commission ("SEC") that became automatically effective upon filing. A final prospectus supplement and accompanying prospectus relating to the offering were filed with the SEC and are available on the SEC’s website located at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained from Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY,11717, Attn: Prospectus Department, or by telephone: (631) 592-5973, or by emailing [email protected]; from Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, Eleven Madison Avenue, 3rd floor, New York, NY 10010, or by telephone: (800) 221-1037, or by emailing [email protected]; or from Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by calling (888) 603-5847, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

TriSalus Life Sciences Forms World-Class Scientific Advisory Board to Accelerate Advancement of Strategy to Deliver Therapeutics to Solid Tumors

On June 27, 2019 TriSalus Life Sciences, an oncology company focused on overcoming infusion barriers to improve patient outcomes, reported the creation of a world-class scientific advisory board (SAB) to support advancement of the company’s strategy to deliver therapeutics more effectively into solid tumors (Press release, TriSalus Life Sciences, JUN 27, 2019, View Source [SID1234537314]). The aim of integrating targeted therapeutics and delivery using the company’s proprietary Pressure-Enabled Drug Delivery (PEDD) is to provide therapeutic benefit by overcoming dense tumor stroma, improving the functionality of the poor vasculature, and activating the immune system to target tumor cells in pancreatic and liver cancers.

The new SAB is composed of preeminent experts across medical, surgical and radiation oncology, and immunology. The SAB will collaborate with TriSalus in all aspects of research, including preclinical, clinical, and commercial evaluation of new therapeutics, and in assessing the combining of PEDD with currently approved cytotoxic and immuno-oncology (I-O) regimens.

"We are deeply gratified to have attracted some of the most renowned thought leaders, healthcare providers, and visionaries in oncology who, like TriSalus, are fully committed to finding and validating more effective treatments for solid tumors," said Mary T. Szela, CEO and president of TriSalus Life Sciences. "The collective clinical and scientific expertise of the SAB members provides a powerful resource to identify more effective methods for treating solid tumors and will help accelerate our efforts to change the outcomes of certain cancers."

In recently presented preclinical and clinical data at the American Association of Immunologists’ annual meeting, targeted regional delivery of chimeric antigen receptor T cell (CAR-T) and checkpoint inhibitors into solid tumors using PEDD significantly increased therapeutic effect compared with low-pressure delivery. Importantly, there was no increase in liver inflammation or toxicity, which are known adverse side effects associated with some systemic treatments.

Scientific Advisory Board Members

Vincent Picozzi, MD

Dr. Picozzi is the director of the Pancreatic Center of Excellence at the Digestive Disease Institute at Seattle’s Virginia Mason Medical Center, and also serves as a practicing physician in Virginia Mason’s division of Hematology-Oncology. Dr. Picozzi has received numerous clinician accolades and directs an active clinical research program. He has published more than 100 papers and abstracts and is a featured speaker at virtually every national clinical oncology meeting. Dr. Picozzi is also chair of the Precision Promise℠ Clinical Trial Consortium while managing one of the largest U.S. pancreaticobiliary oncology practices.

Christopher Crane, MD

Dr. Crane serves as vice chair for the Department of Radiation Oncology at New York’s Memorial Sloan Kettering Cancer Center, where he specializes in gastrointestinal (GI) cancers. Previously, he was program director and chief of the GI section of the Radiation Oncology division at MD Anderson Cancer Center. Dr. Crane leads and conducts clinical trials in GI cancers focused on combining molecular targeted therapies with radiotherapy. In addition, he focuses on the role of radiation dose escalation using novel technologies in the curative treatment of liver and pancreatic cancers, and has helped develop novel technologies to treat GI malignancies, particularly pancreatic cancer.

Philip A. Philip, MD

Dr. Philip is a professor of Oncology, Pharmacology, and Medicine and the Kathryn E. Cramer, MD, Endowed Chair for Cancer Research in the Department of Oncology at the Karmanos Cancer Institute at Wayne State University School of Medicine. He leads the gastrointestinal and neuroendocrine cancers team and is the vice president of Medical Affairs. He also chairs the gastrointestinal cancers committee at the Southwest Oncology Group (SWOG) and sits on the GI Steering Committee that oversees gastrointestinal cancer research nationally. Dr. Philip has been the principal investigator of many Phase I-III trials. He is a frequent national and international lecturer, and has authored more than 200 manuscripts, review articles, and editorials, in addition to co-editing a book on pancreatic cancer and another on GI cancers. Dr. Philip’s major research interest lies in the development of new therapies for GI and neuroendocrine cancers, with a special focus on pancreatic cancer.

Gabriela Plesa, MD, Ph.D.

Dr. Plesa is director of Translational Research Operations and deputy director of the Clinical Cell and Vaccine Production Facility (CVPF) at the University of Pennsylvania. Dr. Plesa has been part of the group led by preeminent immunologist/oncologist Dr. Carl June for 15 years, where she acquired extensive translational research experience largely focused on adoptive immunotherapy with genetically engineered human cells. She has led the effort of opening multiple new investigational cell therapy studies at UPenn, focusing on development of IND-enabling data, clinical approaches, GMP manufacturing processes, and regulatory strategy for launching Phase I and II clinical trials with novel cellular therapeutic approaches. Dr. Plesa is experienced in alliance management as well as federal, university, and regulatory approval requirements for initiating and implementing clinical trials for cellular biologics.

Aravind Arepally, MD

Dr. Arepally is section chief for vascular and interventional radiology at Piedmont Radiology, an affiliate of Piedmont Healthcare. Formerly, he served as clinical director for the Center for Bioengineering Innovation and Design at Johns Hopkins. Dr. Arepally is a co-founder of TriSalus Life Sciences’ predecessor Surefire Medical, Inc. and has coordinated with research labs at Duke University and Johns Hopkins to develop new embolic platforms, including advanced catheter systems for targeted delivery of embolics. He holds multiple patents and has authored more than 150 papers, books, and abstracts. Dr. Arepally was principal investigator of multiple National Institutes of Health (NIH) grants and other grants and is the recipient of numerous national awards for his research in the field of MRI, device development, and embolization applications. He also lectures internationally on minimally invasive procedures.

Steven Katz, MD

Chairman, Scientific Advisory Board

Dr. Katz is director of the Complex Surgical Oncology Fellowship Program and Office of Therapeutic Development at Roger Williams Medical Center. He also serves as associate professor of Surgery at Boston University School of Medicine. A surgeon with expertise in liver and pancreatic surgery, Dr. Katz’s research focuses on immunotherapy for liver metastases and sarcoma. He has served as principal investigator of four Hepatic Immunotherapy for Metastases (HITM) trials testing regional infusion of CAR-T cells for liver metastases, and he also leads the Immunotherapy for Peritoneal Carcinomatosis (IPC) program, investigating CAR-T infusions for stage IV abdominal cancers. In addition, Dr. Katz serves as a reviewer for several scientific and clinical journals and is a member of the Cancer Gene Therapy editorial board, among others.