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Genmab Provides Update on Marketing Authorization Application for Arzerra® (ofatumumab) as Maintenance Therapy for Patients with Relapsed CLL

On June 23, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a negative opinion for the use of Arzerra (ofatumumab) as maintenance therapy for patients with relapsed chronic lymphocytic leukemia (CLL) (Press release, Genmab, JUN 23, 2016, View Source [SID:1234513520]).

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The Marketing Authorization Application (MAA) was submitted by Novartis in July 2015 under the ofatumumab collaboration between Novartis and Genmab.

"We are disappointed that we did not receive a positive recommendation for Arzerra in the maintenance CLL setting in Europe. We will continue to work with Novartis to define the best path forward for Arzerra," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The MAA was based on positive data from an interim analysis from the Phase III PROLONG study (OMB112517), which evaluated ofatumumab maintenance therapy versus no further treatment in patients with a complete or partial response after second or third line treatment for CLL.

Safety and Efficacy Data from the Phase III PROLONG study
A total of 474 patients were included in the analysis. Patients who received ofatumumab maintenance treatment lived 14.2 months longer without their disease worsening than patients who received no further treatment. Median progression free survival (PFS) as assessed by the investigators was 29.4 months for the ofatumumab treatment arm, and 15.2 months for the observation arm (Hazard Ratio 0.50; p<0.0001).

There were no unexpected safety findings. The most common adverse reactions (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection. The two most common grade 3-4 adverse events were neutropenia (22% in ofatumumab arm vs 8% in observation arm), and pneumonia (5% in ofatumumab arm vs 3% in observation arm). During the period between the first dose and 60 days after the last dose there were two patients (1%) in the ofatumumab group and five patients (2%) in the observation group who died due to adverse events.

About the Phase III PROLONG study
This Phase III study was designed to randomize up to 532 patients with relapsed CLL who have responded to treatment at relapse, to either ofatumumab maintenance treatment or no further treatment (observation). Patients in the ofatumumab arm received an initial dose of 300 mg of ofatumumab, followed one week later by a second dose of 1,000 mg, then doses of 1,000 mg every 8 weeks for up to two years, while patients in the observation treatment arm received no further treatment.

The primary endpoint of the study was PFS. Secondary objectives were evaluation of clinical benefit, overall survival, safety, tolerability, the health-related quality of life of subjects treated with ofatumumab versus no further treatment, and pharmacokinetics among relapsed CLL patients receiving maintenance therapy with ofatumumab.
About CLL

CLL is the most commonly diagnosed adult leukemia in Western countries, and accounts for approximately 1 in 4 cases of leukemia.1 Most CLL patients experience disease progression despite initial response to therapy and may require additional treatment.2

About Ofatumumab (Arzerra)
Ofatumumab is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of chronic lymphocytic leukemia (CLL) cells and normal B lymphocytes.

In the United States, Arzerra is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate and for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. In the European Union, Arzerra is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. In more than 50 countries worldwide, Arzerra is also indicated as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.

Please see full Prescribing Information, including Boxed WARNING for Arzerra (ofatumumab).
Arzerra is marketed under a collaboration agreement between Genmab and Novartis. Novartis has rights to develop ofatumumab in autoimmune indications, including multiple sclerosis.

First-in-class Immunometabolic Modulator, PAK4/NAMPT Inhibitor, to be Evaluated in Patients with Advanced Solid Malignancies or Non-Hodgkin’s Lymphoma

On June 22, 2016 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company reported dosing of the first patient in a Phase 1 clinical trial evaluating KPT-9274, an oral, first-in-class, dual-acting p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, in patients with advanced solid malignancies (including sarcoma, colon and lung cancer) or non-Hodgkin’s lymphoma (NHL) whose disease has relapsed after standard therapy(s) (NCT02702492) (Press release, Karyopharm, JUN 22, 2016, View Source [SID1234517065]).

This first-in-human, multi-center, open-label, dose-escalation trial is expected to enroll up to 175 patients. The primary endpoints of this study are to determine the recommended Phase 2 dose (RP2D) and the maximum tolerated dose (MTD) of KPT-9274 administered alone and with extended release niacin, and to evaluate safety and tolerability. The key secondary endpoint is to assess anti-tumor activity in patients predicted to be more sensitive to PAK4/NAMPT inhibition, including those with NAPRT-deficient tumors and tumors harboring IDH1 mutations.

"Our first-in-class, oral, small molecule PAK4 and NAMPT modulator, KPT-9274, has synergistic anti-tumor effects through several mechanisms including immune cell activation by inhibiting ß-catenin, reduction of NAD levels which tumor cells use as a key energy source, blockade of DNA damage repair mechanisms, and induction of tumor cell apoptosis," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We are encouraged by the preclinical profile of KPT-9274, highlighted at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) and 2016 American Association of Cancer Research annual meetings, which support the novel mechanism and demonstrated encouraging preclinical anti-tumor activity. To our knowledge, we are the only company with a compound in clinical development that directly targets both PAK4 and NAMPT. This important Phase 1 study will continue to build upon the body of scientific evidence supporting KPT-9274’s safety and efficacy, and we look forward to reporting top-line data next year."

This Phase 1 clinical study is supported by extensive preclinical data demonstrating KPT-9274’s anti-cancer activity against hematological and solid tumors while showing minimal toxicity to normal cells in vitro. Preclinical studies demonstrate that by blocking PAK4, KPT-9274 potently inhibits ß-catenin as well as certain Ras oncogene-dependent pathways. ß-catenin is believed to be a key mediator of immune suppression, including resistance to immune-activating therapies. In addition, both ß-catenin and Ras are key growth signaling pathways for many common tumors such as colon and lung cancers. NAMPT, which can be found in a complex with PAK4 within the cell, is a pleiotropic protein with intra- and extra-cellular functions as an enzyme, cytokine, growth factor and hormone, and is thought to play a role in cellular energy metabolism. Hematologic and solid tumor cells become dependent on both PAK4 and NAMPT pathways and are therefore susceptible to single-agent cytotoxicity by KPT-9274. In mouse and rat xenograft studies, orally administered KPT-9274 showed robust anti-cancer activity with favorable tolerability. Based on in vitro and in vivo activity, Karyopharm believes KPT-9274 holds significant potential for the treatment of a wide variety of both solid and hematological cancers.

About KPT-9274

KPT-9274 is a first-in-class, orally bioavailable, small molecule immunometabolic modulator that works through non-competitive dual inhibition of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). Co-inhibition of these targets is believed to lead to synergistic anti-tumor effects through suppression of ß-catenin by blocking PAK4, leading to both immune cell activation and inhibition of tumor growth, energy depletion through NAMPT inhibition, blockade of DNA repair, cell cycle arrest and ultimately apoptosis. KPT-9274 may therefore have both immune-activating and direct antitumor effects. In contrast, normal cells are less sensitive to inhibition by KPT-9274 due in part to their relative genomic stability and lower metabolic demands.

Nymox Reports Long-Term Prostate Cancer Results in 7 Year Prospective Study of 995 U.S. Middle-Aged and Elderly Men Without Cancer

On June 22, 2016 Nymox Pharmaceutical Corporation (NASDAQ:NYMX) reported results from the Company’s 7 year prospective placebo controlled double blind studies of treatment of 995 U.S. men with the Company’s lead drug fexapotide (Press release, Nymox, JUN 22, 2016, View Source;fvtc=4&fvtv=6907 [SID:1234513492]). Men who received fexapotide showed a major reduction in the incidence of prostate cancer, compared to placebo and compared to the known and expected normal incidence of the disease.

The men in the study received fexapotide or placebo for the treatment of their prostate enlargement (BPH) symptoms. All men were thoroughly evaluated to exclude any prostate cancer prior to qualifying for enrollment in the studies. The participants were enrolled at over 70 top well-known U.S. urological investigational centers, and were followed for up to 7 years (median of 5 years) after treatment. The study analyzed all cases of prostate cancer that were subsequently diagnosed. The expected rate of new prostate cancer in the U.S. general male population in this age group is in the 5-20% range after 7 years. In the BPH population in published large trials of drugs for the prevention of prostate cancer, the incidence of new prostate cancer cases after 4-7 years has been reported in major studies to be 20-25%. The new data analysis from the Nymox fexapotide study has now shown the statistically significant and very low incidence of 1.3% for prostate cancer in this comparable fexapotide treated BPH population.

"These results are astonishingly good. Other drug treatments and controls tested in similar studies have been associated with a prostate cancer incidence 10 times higher than the results reported today by Nymox for fexapotide. This is truly good news. The data strongly indicate that in addition to benefit for BPH symptoms, fexapotide will also help to prevent cancer in these patients," said Dr. Ronald Tutrone, one of the Principal Investigators in the Nymox Fexapotide Prostate Cancer and BPH studies. Dr. Tutrone is Chief of the Division of Urology, Greater Baltimore Medical Center; Medical Director of Chesapeake Urology Research Associates and Chairman of the William E. Kalhert Endowment for Urological Research.

Fexapotide is a safe and painless single injection treatment given in the urologist’s office. The drug is in Phase 3 for BPH and Phase 2 for prostate cancer. It has been tested in over 1700 drug and placebo treatment administrations in the U.S. As a treatment for BPH, fexapotide shows long-term efficacy without the safety risk and side effect concerns or added cancer risk associated with currently approved BPH treatments. As a treatment for prostate cancer fexapotide was found to lead to highly statistically significant reduction in disease progression in a large 147 patient multi-year Phase 2 study of U.S. men with low grade cancer.

Dr. Paul Averback, CEO of Nymox said, "The new results now add a third dimension to fexapotide utility: clinical prostate cancer prevention. The drug has now demonstrated statistically significant prospective long-term outcome data showing dramatic reduction in the incidence of newly diagnosed prostate cancer after minimal BPH treatment with fexapotide. Nymox announced in Q3 last year that it will seek regulatory approvals for fexapotide for BPH based on the long-term BPH safety and efficacy data announced Q3 last year. We believe that the exciting new prostate cancer prevention results reported today will add to the evidence in fexapotide’s favor towards our goal of widespread major benefit for middle-aged and elderly men."

Dr. Averback added, "We are extremely grateful to the thousands of people who have been part of these clinical trials. The Company also thankfully acknowledges our shareholders for their long-term commitment that supports these studies."

IFM Therapeutics Raises $27 Million Series A Financing Led by Atlas Venture and Abingworth

On June 22, 2016 IFM Therapeutics, a biopharmaceutical company developing a portfolio of first-in-class small molecules targeting the innate immune system, reported the closing of a $27 million Series A financing led by Atlas Venture and
Abingworth, with participation from Novartis. In conjunction with the funding Jean-François Formela and Vincent Miles, Partners at Atlas and Abingworth respectively, have joined IFM’s CEO, Gary D. Glick, on the board of directors, with Dr. Formela serving as chair of the board (Press release, IFM Therapeutics, JUN 22, 2016, View Source [SID1234520287]).

IFM Therapeutics, incubated as a part of the Atlas Venture seed program, is developing modulators of novel targets that either enhance innate immune responses for treating cancer, or dampen certain immune responses that drive many inflammatory diseases. The company
will use the proceeds of the financing to advance and expand its early-stage portfolio and begin clinical development of its most advanced product candidate, a selective activator of a novel target, for treating solid tumors.

"While proteins in the innate immune system represent an attractive landscape of therapeutic targets, they have been notoriously difficult to drug," said Dr. Formela from Atlas. "During the brief period since its founding, IFM has made excellent progress on several of these targets, reflecting its exceptional team of experienced scientists and executives, possessing expertise in medicinal chemistry, a deep understanding of the relevant biology, and relationships with academic thought leaders in the areas of immunology and immune oncology."

"IFM’s programs have the potential to make a major difference in the lives of patients with serious, and sometimes fatal, diseases," said Abingworth’s Dr. Miles. "We look forward to helping the team build on their strong start to advance these programs into clinical development."

"This financing is an important validation of the IFM team and technology," said Dr. Glick, IFM’s Co-founder and CEO. "The company is fortunate to be working with a talented and experienced group of investors. Their expertise in building world-class biopharmaceutical
companies will be invaluable as we grow the company."

OGD2 Pharma and Green Cross Lab Cell start collaboration for developing NK-cell therapeutics targeting the O-acetyl-GD2 cancer antigen

On 22 June 2016, OGD2 Pharma SAS, a biotechnology company developing innovative anti-cancer therapies targeting the O-acetylated form of the GD2 ga nglioside (OAcGD2), today announces a collaboration with Green Cross Lab Cell (GCLC), a subsidiary of Green Cross Corporation, a leading South Korean biopharmaceutical company that delivers life-saving and life-sustaining protein therapeutics and vaccines (Press release, OGD2 Pharma, JUN 22, 2016, View Source [SID1234519565]).

With this collaboration, OGD2 Pharma and GCLC will explore the potential of targeting NK-cells to the OAcGD2 antigen using humanized antibody and chimeric antigen receptors (CAR) for fighting against solid tumors.

"Thanks to this collaboration OGD2 Pharma speed s-up the development of its anti-OAcGD2 CAR platform. We highly value Green Cross leadership in allogenic NK-cell therapy and their proven ability to develop and to market cell therapy products " said Jean-Marc Le Doussal, President at OGD2 Pharma. " OGD2 Pharma will continue building strategic partnerships wit h academic groups and private companies in other fields of cell therapies. " he added.

Bok-Soo Park, Chief Executive Officer of Green Cross LabCell commented " To work with OGD2 Pharma as our partner for the development and future commercialization of cancer immunotherap y products targeting the OAcGD2 antigen is exciting, given their world-leading expertise in cancer immunotherapies against solid tumor. This collaboration underscores our commitment to maximise the value of our technologies and accelerat e their progress to the market through partnering with industry leaders. We chose to work with OGD2 Pharma as we believe they are best positioned to accelerate development of these programs and are fully committed to their success. We look forward to worki ng with the team at OGD2 Pharma to bring desperately needed new treatment options to cancer to patients all around the world".

About Greencross Labcell: www.greencross.com
Green Cross LabCell is a subsidiary of Green Cross Corp, a leading Korean pharmaceutical company with its headquarters in Seoul. Green Cross Corp. has annual sales of more than $1 billion across 14 marketed prescription products. The Company has been actively developing a nu mber of new technologies and products in the emerging cell therapy industry. Its subsidiary, Green Cross LabCell is focused on clinical development of MG4101, a random donor PBMC-derived, ex vivo expanded and activated NK cell product in a number of Phase II clinical trials in Korea, as well as developing next generation gene-modified NK cell therapeutics. Green Cross LabCell operates its own GMP facilities in Korea for production of NK cell based therapeutics. Its proprietary production platform enables al logeneic supply of therapeutic NK cells for multiple clinical trials. This technology platform holds the promise to dramatically reduce the cost of gene-modified cell therapies for cancer, while also aiding the quality control and industrial scale producti on of NK cell products.

About OGD2 Pharma: www.ogd2pharma.com
OGD2 Pharma SAS, headquartered in Nantes, France, is a pre-clinical stage privately-held biotechnology company. Our mission is to research, develop and c ommercialize, with pharmaceutical partners, safe and efficacious cancer immunotherapies targeting the O-acetylated form of the GD2 ganglioside (OAcGD2). Pipeline includes OGD201 humanized monoclonal antibody (EMA Orphan Drug Designation for neuroblastoma), chimeric antigen receptors (CAR), antibody drug conjugates and companion diagnostic products.

About O-acetylated-GD2
As its first cousin GD2, the OAcGD2 glycolipid is expressed at high copy numbers in the membrane of tumor cells in many types of pe diatric cancers (such as neuroblastoma) and adult cancers (such as glioblastoma, melanoma, sarcoma, breast cancer, etc.) and on cancer stem cells. Remarkably, and by contrast to GD2, OAcGD2 is not expressed by normal nerves and brain tissues.

About MG4101
MG4101 is a clinical stage cell-based product developed by Green Cross LabCell based on ex vivo expanded and activated NK cells derived from peripheral blood mononuclear cells from random healthy donors. MG4101 has completed a Phase I study in patients with a variety of terminal stage solid tumours and recurrent lymphoma patients (NCT01212341, Cancer Immunol Res. 2016 Mar;4(3):215-24.), a Phase II study in hepatocellular carcinoma (HCC) after resection (NCT02008929), and a Phase II study in paediatric solid tumours (NCT01807468). Another Phase II study in HCC after transarterial chemoembolization (TACE) will be start in Q3 2016. MG4101 and its associated production process provide the basis for the next generation of NK cell therapeutics being jointly developed by Green Cross LabCell and OGD2 Pharma