1stOncology™: Cancer Intelligence Service – Page 16222 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

FDA Accepts Genentech’s Biologics License Application For Subcutaneous Formulation Of Rituximab

On November 3, 2016 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that the U.S. Food and Drug Administration (FDA) has accepted Genentech’s Biologics License Application for a subcutaneous formulation of rituximab in multiple blood cancer indications (Press release, Halozyme, NOV 3, 2016, View Source [SID1234516224]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

This is a co-formulation with Halozyme’s proprietary recombinant human hyaluronidase enzyme (ENHANZE platform), approved and marketed under the MabThera SC brand in countries outside the U.S. "We are excited to see Genentech and Roche taking steps to bring a subcutaneous formulation of rituximab to patients in the United States," said Dr. Helen Torley, president and chief executive officer. "If approved, this formulation has the potential to reduce administration time for patients and health care practitioners." Including all approved indications, Roche reported total 2015 sales of rituximab in the United States of 3.76 billion CHF.

BioLineRx Discloses Positive Correlative Data from Phase 2a AML Study and Mechanism-of-Action Data for BL-8040 Oncology Platform at ASH 2016

On November 3, 2016 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported positive Phase 2a correlative data, as well as detailed mechanism-of-action data, for BL-8040, the Company’s leading oncology platform, that will be presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exhibition in San Diego, California, taking place December 3-6, 2016.

In a poster titled, "The Selective Anti Leukemic Effect of BL-8040, a Peptidic CXCR4 Antagonist, is Mediated by Induction of Leukemic Blast Mobilization, Differentiation and Apoptosis: Results of Correlative Studies from a Ph2a Trial in Acute Myeloid Leukemia", BioLineRx reports the final correlative results from its Phase 2a trial in acute myeloid leukemia (AML). The trial consisted of 45 AML patients receiving BL-8040 monotherapy on days 1-2, followed by the same dose of BL-8040 plus chemotherapy (Cytarabine) on days 3-7. All patients had poor-risk disease and had been heavily pretreated, with 19% having relapsed after a short first remission (≤12 months), 17% having 2 or more relapses, while 45% were refractory to 1-2 induction treatments.

As previously reported, the composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving BL-8040 dose ≥1.0 mg/kg (n=39). In the 1.5 mg/kg dose selected for the expansion phase of the study (n=22), the composite complete remission rate was 41%. These response rates are superior to the historical response rate of approximately 20% reported for high-risk AML patients treated with Cytarabine alone. The ongoing follow-up of responding patients (n=19) showed median Event Free Survival of 9.3 months (range of 4.3-12.8 months).

Results further show that BL-8040 monotherapy had a substantial therapeutic effect. Treatment with BL-8040 as a single agent triggered robust mobilization of AML blasts from the bone marrow to the peripheral blood stream, and the extent of mobilization was correlated with a positive response to treatment. The preferential mobilization of AML blasts over normal cells (4.7-fold vs. 1.4-fold, respectively) was further confirmed by FISH analysis in a subset of patients. In addition, BL-8040 monotherapy resulted in a 40% increase in AML blast apoptosis.

In an oral presentation at ASH (Free ASH Whitepaper), entitled "The High Affinity CXCR4 Inhibitor, BL-8040, Induces Apoptosis of AML Blasts and their Terminal Differentiation by Blocking AKT/ERK Survival Signals and Downregulating BCL-2, MCL-1 and Cyclin-D1 through Regulation of miR-15a/16-1 Expression", delivered by Prof. Amnon Peled from the Hadassah Medical Center and Biokine Therapeutics, BioLineRx reports detailed data on the mechanism-of-action by which BL-8040 directly induces apoptosis of AML cells. The data presented are from in vitro studies using human AML cell lines and human primary AML samples, as well as in vivo studies using human primary AML cells engrafted in NOD scid gamma (NSG) mice.

The results of the pre-clinical studies show that BL-8040 treatment in vivo triggered mobilization of AML blasts from their protective bone marrow microenvironment and induced their terminal differentiation, further supporting the data presented by BioLineRx at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual conference earlier this year.

In addition, the studies illustrate how BL-8040 increases the expression and activity of a special class of microRNA precursors termed miR-15a/16-1. These microRNA molecules have been previously linked to cancer, and shown to suppress the activity of several tumor-related pro-survival proteins. Therefore, by increasing the expression of miR-15a/16-1 microRNA molecules, BL-8040 decreases the expression of tumor-survival proteins and promotes tumor cell death. Importantly, in both in vitro and in vivo experiments, BL-8040 was found to synergize with a selective Bcl-2 inhibitor (Venetoclax) and an FLT3 inhibitor (Quizartinib, also known as AC220) in inducing AML cell death, pointing at potential drug combination treatments.

Philip Serlin, CEO of BioLineRx, commented, "We are pleased to be presenting additional positive results about BL-8040, our lead oncology platform. In particular, clinical studies show that BL-8040 acts selectively on chemotherapy-resistant cells, which may be beneficial in reduction of residual disease and supports the incorporation of BL-8040 in front-line treatment settings such as AML consolidation. Such studies are currently ongoing. We are also encouraged to see, in pre-clinical models, a synergistic effect between BL-8040 and Venetoclax, and between BL-8040 and Quizartinib, drugs which are also being investigated as AML treatments. Given the high percentage of patients experiencing a relapse or that are refractory to available treatments, we anticipate that BL-8040, in combination with a growing repertoire of drugs, will be able to offer hope to AML patients around the world."

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. Furthermore, scientific findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with immune checkpoint inhibitors, BL-8040 has the potential to enable activated T cells to better reach tumor cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

http://www.medivir.com/investors/press-releases/2016/medivir-strengthens-its-clinical-pipeline-by-entering-into-agreement-to-acquire-a-portfolio-of-clinical-stage-oncology-programs

November 2, 2016 Medivir AB (Nasdaq Stockholm: MVIR) reported that it has entered into an agreement to acquire two clinical stage oncology programs from Tetralogic Pharmaceuticals Corporation (Nasdaq: TLOG), advancing and expanding its clinical pipeline (Press release, Medivir, NOV 2, 2016, View Source [SID1234528400]). The acquisition includes remetinostat, a skin-directed HDAC inhibitor, and birinapant, a bivalent SMAC mimetic, and all intellectual property and data associated with Tetralogic’s HDAC inhibitor and SMAC mimetic projects.

Remetinostat Clinical Program
Remetinostat is a topical, skin-directed inhibitor of histone deacetylases (HDACs) and has a strong link to Medivir´s existing expertise in protease inhibition. The compound was designed to effectively inhibit HDACs within cutaneous lesions, but to be rapidly broken down in the bloodstream, preventing the side effects associated with systemically administered HDAC inhibitors.

Remetinostat is currently in a late phase II program aimed to treat early stage cutaneous T-cell lymphoma (CTCL), a chronic, orphan hematologic cancer that presents in the skin. There are few drugs available for the treatment of the disease, and those currently available have generally poor tolerability. As a result, patients are in need of safe and effective new treatment options which remetinostat may represent. The estimated addressable market for early-stage CTCL in the US alone is approximately USD 900m annually.

Medivir currently plans to start a phase III trial with remetinostat in the second half of 2017.

Birinapant Clinical Program
Birinapant is a bivalent, second mitochondrial activator of caspases (SMAC) mimetic that binds cellular inhibitor of apoptosis proteins (cIAPs) and induces their degradation. cIAPs are part of the ubiquitin proteasome system, and birinapant therefore ties in well to Medivir’s existing interests in modulators of protein ubiquitination. Medivir currently plans to start two different clinical studies with birinapant:

A phase I study in combination with KeytrudaTM(pembrolizumab), a PD-1 inhibitor from Merck & Co., Inc. (MSD outside of the US and Canada, "MSD"), in patients with solid tumours, subject to transfer to Medivir of the clinical trial agreement between Tetralogic and MSD and receipt of KeytrudaTMsupply. Preclinical studies have shown that SMAC mimetics such as birinapant are able to enhance the response of T-cells to tumour antigens, and the objective of the planned phase I study is to investigate the safety of the combination and the potential of birinapant to enhance response rates seen with KeytrudaTMalone. PD-1 inhibitors such as KeytrudaTMare immuno-oncology products that have substantially improved treatment outcomes for patients with solid tumours. Revenues of PD-1 inhibitors as reported by MSD and Bristol-Myers Squibb in the last twelve months have totalled approximately USD 3.2b. The PD-1 inhibitor market is expected to continue to grow from increasing use and expansion of the number of indications for which they are approved.
A phase II program, to investigate birinapant in combination with platinum-based chemotherapy for the treatment for high-grade serous carcinomas (HGSCs), including ovarian cancer, in collaboration with clinical investigators at UCLA. The UCLA team have identified that platinum-resistant cells in HGSCs are highly susceptible to birinapant-platinum co-therapy in approximately half of patients, and have developed a bioassay to enable patient selection. High-grade serous carcinomas are tumours that are believed to be derived from cells in the fallopian tube and can present as ovarian, endometrial, tubal or peritoneal cancer. The majority of ovarian cancer cases are high-grade serous carcinomas and these patients have a very poor survival rate. The ovarian cancer market size overall is estimated to be USD 840m, with those patients resistant to platinum treatments representing the group with highest unmet need.
Financial Consideration and Third-Party Arrangements
The acquisition has been structured to provide an upfront cash payment, but with the majority of financial consideration tied to successful clinical development, regulatory approvals and sales milestones. Medivir will also assume agreements or certain obligations with other third parties, including the MSD agreement regarding KeytrudaTM, subject to confirmation from MSD.

The acquisition includes the following potential payments to Tetralogic and other third party licensees:

Upfront cash consideration of USD 12m;
Remetinostat development milestones through regulatory filings of up to USD 20m;
Remetinostat regulatory approval milestones of up to USD 45m;
Remetinostat tiered royalties capped at an aggregate of 13%;
Additional remetinostat commercialization milestones of up to USD 31m, primarily based on substantial sales achievement levels;
Birinapant development milestones and research support of up to USD 20m;
Birinapant tiered royalties capped at an aggregate of 10%; and
Additional birinapant commercialization milestones of up to USD 110m, primarily based on substantial sales achievement levels.
Strategic Overview
"This is a transformative transaction for Medivir and an important part of our strategy to expand our pipeline with programs in later stage clinical phases, shifting the balance from research to clinical development. The acquisition enables Medivir to build critical mass in development and secures visible value generation, with expected near-term and continuous news flow from multiple studies. These assets are complementary to our oncology efforts in early phases. Both programs have an excellent fit with the Medivir scientific platforms and we are uniquely positioned to recognize the value of both of Tetralogic’s clinical assets." says Niklas Prager, CEO & President of Medivir.

Richard Bethell, CSO of Medivir continues, "We are excited to have acquired these two projects, both of which have the potential to meaningfully advance the care of cancer patients. Medivir has a track record of discovering and developing drugs that are targeted to specific tissues, so we are well placed to rapidly progress remetinostat for the treatment of early-stage CTCL. Many patients with this disease are urgently in need of new treatments that are both safe and effective. We also believe that birinapant, through its effects on both immune and tumour cells, offers the potential to improve the treatment of a number of different cancers. We look forward to rapidly advancing both of these agents into the next round of clinical studies."

Closing Conditions
The transaction is subject to confirmation by MSD of agreement transfer to Medivir, the consent of the Tetralogic Senior Noteholders, approval of the Tetralogic shareholders and other customary closing conditions. Medivir expects the transaction to close by year end 2016.

10-Q – Quarterly report [Sections 13 or 15(d)]

Aduro Biotech has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Aduro BioTech, NOV 2, 2016, View Source [SID1234516172]).

Anti-tumor cell therapies, signed an agreement with Bellicum Pharmaceutical

On November 2, 2016 Bellicum Pharmaceuticals and Hospital Bambino Gesù , the European reference point for the care and in pediatric research, announced the beginning of an extended collaboration centered on the development of new therapies with genetically modified cells for treating onco-hematological diseases (Press release, OPBG, NOV 2, 2016, View Source [SID1234516577]).

In detail, the arrangement concerns the preclinical and clinical development of products advanced cell therapy engineered with the suicide gene new CaspaCIDe of Bellicum, for the production of lymphocytes through modified chimeric and T-lymphocyte receptors artificial receptor (CAR T and TCR) specific for certain antigens , including CD19.

The two entities will jointly develop T cells modified with chimeric receptors (CAR T) and other cellular therapies developed by the Child Jesus and engineered with the safety switch CaspaCIDe of Bellicum, designed to reduce or eliminate the cells, when necessary, that is, presence of possible side effects related to the same cells.

Under the agreement, Bellicum will provide the necessary financial support in exchange for worldwide commercialization rights to certain developed cell therapies, while the Baby Jesus will keep the rights for the purpose of ricerc a. The Hospital of the Holy See will perform clinical research and studies for the application of advanced cell therapies in pediatric patients, initially through two clinical trials based on the use of genetically modified lymphocytes with specific chimeric receptors and CD19 antigens GD2 , respectively, in patients pediatric suffering from acute lymphoblastic leukemia, and neuroblastoma.

The trial will begin in the first half of 2017 . In addition, the Baby Jesus will produce, within its pharmaceutical plant, genetically modified cells necessary for European experiments , including T lymphocytes transduced with PRAME (Preferentially Expressed Protein in Melanoma) and employable in patients with acute myeloid leukemia or bone cancer.