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NOXXON PHARMA SIGNS CLINICAL IMMUNO-ONCOLOGY COLLABORATION AGREEMENT WITH MSD TO STUDY NOX-A12 COMBINED WITH KEYTRUDA® (PEMBROLIZUMAB) IN PANCREATIC AND COLORECTAL CANCER

On December 15, 2016 NOXXON Pharma N.V. (Paris:ALNOX) reported the signature of a collaboration agreement with Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the US and Canada), under which the two companies will collaborate in a phase 1/2 clinical trial of NOXXON’s anti-CXCL12 agent, NOX-A12, and MSD’s anti-PD-1 inhibitor, Keytruda (pembrolizumab), in patients with metastatic solid tumors that do not usually respond to checkpoint inhibitor monotherapy (Press release, NOXXON, DEC 15, 2016, View Source [SID1234517085]).

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The goal of the two-part, open-label phase 1/2 study is to evaluate pharmacodynamic effects and safety of NOX-A12 as a monotherapy in addition to safety and efficacy of NOX-A12 in combination with Keytruda in patients with metastatic colorectal and pancreatic cancer. A total of twenty patients will be recruited, ten of each cancer type. NOXXON will be the sponsor of the study, which will be conducted in Europe.

The design of the clinical trial was a collaborative effort between NOXXON and MSD. Part 1 of the study, in which patients will receive NOX-A12 monotherapy for up to two weeks, will evaluate immune infiltrate changes within the tumor microenvironment induced by CXCL12 inhibition with NOX-A12 by comparing pre- and post-treatment biopsy specimens as well as the safety and tolerability of NOX-A12 in patients with metastatic (stage IV) colorectal and pancreatic cancer. Part 2 of the study, in which NOX-A12 is to be combined with Keytruda, will assess the safety and tolerability of the combination in addition to the efficacy of treatment.

NOX-A12, which inhibits the key tumor microenvironment chemokine CXCL12, may be a key partner for a wide range of IO (immuno-oncology) agents. NOXXON has generated promising pre-clinical and clinical data, including recent animal data showing synergy with a checkpoint inhibitor, as well as recent phase 2a trials in multiple myeloma and a second hematological cancer that showed a safety profile that supports further development and first signs of efficacy. NOXXON believes that its planned clinical study will position the drug to be combined with multiple classes of IO approaches including those acting on or through T cells and/or NK cells.

Under the collaboration agreement, MSD will provide Keytruda to NOXXON for the conduct of the trial and has approved the trial design. Multiple paths for further development of the combination in pivotal clinical trials are envisioned in this agreement, although the agreement grants no commercial rights to either party for the other party’s compound. Additional details were not disclosed.

Aram Mangasarian, PhD, Chief Executive Officer of NOXXON commented: "This collaboration with MSD allows us to initiate a clinical trial of NOX-A12 in patients with metastatic solid tumors with the advice and support of one of the key players in the immuno-oncology space. We are pleased that MSD shares our interest in the potential of the CXCL12 pathway to modulate the tumor microenvironment to increase the efficacy of checkpoint therapy."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Cellectis Announces Recombinant DNA Advisory Committee’s (RAC) Unanimous Approval of UCART123 Phase 1 Study Protocols in AML and BPDCN

On December 15, 2016 Cellectis (Alternext: ALCLS; Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR T-cells (UCART), reported the National Institute of Health’s Recombinant DNA Advisory Committee (RAC)’s unanimous approval of two Phase 1 study protocols for Cellectis’ UCART123, the Company’s most advanced, wholly owned TALEN gene edited product candidate in patients with acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Cellectis, DEC 15, 2016, View Source [SID1234517084]).

Cellectis will host a conference call in the next coming days. The details will be communicated shortly.

The RAC hearing was held on December 14, 2016 during a session dedicated to UCART projects and TALEN based gene editing. This was the first time that allogeneic CAR T-cell programs gene edited with TALEN technology were presented during a RAC hearing.

Cellectis expects to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) by the end of 2016 and, pending FDA clearance, plans to initiate Phase 1 clinical trials in the first half of 2017. These programs will be the first therapeutic applications of a gene edited allogeneic "off-the-shelf" product candidate in the U.S.

UCART123 is a gene edited T-cell product candidate that targets CD123, an antigen that is located on CD123-expressing leukemic cells in AML, as well as in leukemic and other tumoral cells in BPDCN.

AML is a devastating clonal hematopoietic stem cell neoplasm that is characterized by uncontrolled proliferation and accumulation of leukemic blasts in bone marrow, peripheral blood and, occasionally, in other tissues. These cells disrupt normal hematopoiesis and rapidly cause bone marrow failure and death. In the U.S. alone, there are an estimated 19,950 new AML cases per year, with 10,430 estimated deaths per year.

The clinical research at Weill Cornell will be led by principal investigator Dr. Gail J. Roboz, Director of the Clinical and Translational Leukemia Programs and Professor of Medicine.

BPDCN is a very rare and aggressive hematological malignancy that is derived from plasmacytoid dendritic cell precursors. BPDCN is primarily a disease of bone marrow and blood cells but also often affects skin and lymph nodes.

The UCART123 clinical program at MD Anderson will be led by Professor Hagop Kantarjian, MD, Department Chair, Department of Leukemia, Division of Cancer Medicine and Professor Naveen Pemmaraju, MD, Assistant Professor.

Cellectis’ allogeneic CAR T-cell product line, Universal CARTs or UCARTs, yields frozen, off-the-shelf, engineered CAR T-cells. UCARTs are meant to be readily available CAR T-cells for a large patient population. Their production can be industrialized and standardized with defined pharmaceutical release criteria.

About RAC

The Recombinant DNA Advisory Committee (RAC) is a federal advisory committee that provides recommendations to the NIH Director related to basic and clinical research involving recombinant or synthetic nucleic acid molecules. The NIH, through the RAC, reviews the most innovative clinical study protocols involving a gene therapy product.

Aptevo Therapeutics Amends Collaboration Agreement with MorphoSys AG for Novel Immunotherapeutic, MOR209/ES414

On December 15, 2016 Aptevo Therapeutics Inc. (Nasdaq:APVO) a biotechnology company focused on developing novel oncology and hematology therapeutics, reported that it has amended the terms of its collaboration agreement with MorphoSys AG, originally executed in August 2014, for the joint worldwide development and commercialization of MOR209/ES414, a novel bispecific immuno-oncology therapeutic currently being evaluated in a Phase 1 clinical study for the treatment of metastatic castration-resistant prostate cancer (mCRPC.) (Press release, Aptevo Therapeutics, DEC 15, 2016, View Source [SID1234517083]).

Aptevo and MorphoSys agreed to modify their collaboration agreement to, among other things, adjust the allocation of certain manufacturing and development costs and extend MorphoSys’ convenience termination rights. Under the amendment, the timeframe for a one-time right to terminate the collaboration agreement by MorphoSys has been extended from December 31, 2016 to June 30, 2017, or after review of clinical data from the first 6 patients enrolled and dosed in the MOR209/ES414 Phase I clinical trial. In addition, the companies have agreed that Aptevo will be responsible for 75% of the development costs of the program through June 30, 2017 with MorphoSys responsible for the remaining 25%, after which time the cost-sharing ratio shifts to 49% for Aptevo and 51% for MorphoSys through 2018, and subsequently 36% for Aptevo and 64% for MorphoSys in 2019 and thereafter.

"Bispecific antibodies represent an emerging new class of protein therapeutics that holds promise as an important new immunotherapeutic approach to cancer treatment," commented Marvin L. White, President and Chief Executive Officer of Aptevo. "We are pleased to have the opportunity to collaborate with MorphoSys on the development of MOR209/ES414 and look forward to the results of the ongoing Phase I dose escalation study."

argenx launches Phase I/II study of ARGX-110 in combination with azacitidine in newly diagnosed AML patients

On December 15, 20166 argenx (Euronext Brussels: ARGX), a clinical-stage biopharmaceutical company focused on creating and developing differentiated therapeutic antibodies for the treatment of cancer and severe autoimmune diseases, reported the initiation of a Phase I/II clinical trial of ARGX-110 in combination with azacitidine in newly diagnosed, elderly acute myeloid leukemia (AML) patients (Press release, arGEN-X, DEC 15, 2016, View Source [SID1234517082]). ARGX-110 is the Company’s SIMPLE Antibody targeting CD70. Azacitidine is a hypomethylating agent that upregulates CD70 expression on AML blasts, and is currently the standard of care treatment for elderly AML patients.

"AML blasts and leukemic stem cells of newly diagnosed AML patients strongly overexpress CD70, regardless genetic factors or risk class. Targeting CD70 has proven to be a very promising therapeutic approach in various preclinical models of AML. The idea of combining ARGX-110 with the current standard of care azacitidine, which seems to sensitize cancer cells to a CD70 treatment, is an exciting one since it allows us to go into the first-line therapy setting," commented Tim Van Hauwermeiren, CEO of argenx. "This trial marks the first combination study for ARGX-110. We believe that combination therapies for cancer will be a mainstay approach to enhance synergistic mechanisms and we are eager to see how ARGX-110 and azacitidine may support this hypothesis in newly diagnosed AML patients."

The Phase I/II trial is an open-label, dose-escalating study (Phase I) with a proof-of-concept cohort (Phase II). In this Phase I study safety and tolerability will be determined whilst for the Phase II efficacy will be assessed in up to 42 newly diagnosed AML patients in total. Top-line data from the dose escalation are expected in about 18 months.

About ARGX-110

ARGX-110 is a SIMPLE Antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors and severe autoimmune diseases. ARGX-110 works in three ways: i) blocks growth of tumor cells, ii) kills cancer cells and iii) restores immune surveillance against tumors (Silence K. et al. mAbs 2014; 6 (2):523-532). ARGX-110 is currently being evaluated in hematological and solid tumors. Preclinical work on ARGX-110 in AML was done in collaboration with the Tumor Immunology Lab of Prof. A. F. Ochsenbein at the University of Bern, who won together with Prof Manz from the University Hospital of Zürich, the prestigious 2016 Otto Naegeli Prize for his breakthrough research on CD70/CD27 signaling with therapeutic potential for cancer patients.

Otsuka Signs Japan-Exclusive License Agreement with Takara Bio for the Investigational Cancer Treatment HF10, an Oncolytic Virus

On December 15, 2016 Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Takara Bio Inc. (Takara Bio) reported that it entered into an exclusive license agreement on December 15 for the joint development and commercialization in Japan of Takara’s investigational oncolytic virus HF10 therapy (HF10) for the treatment of pancreatic cancer, melanoma and other tumors (Press release, Otsuka, DEC 15, 2016, View Source [SID1234517079]).

HF10 is an attenuated strain of Herpes Simplex Virus type 1 (HSV-1) *1, an oncolytic virus which in clinical trials to date has demonstrated antitumor activity when injected into cancerous areas. Oncolytic viruses, which rarely proliferate in normal cells, destroy cancer cells directly by proliferating inside them.

Under the terms of the agreement, Otsuka and Takara Bio are to jointly pursue remaining clinical development of HF10 in Japan. Otsuka is to pay Takara Bio an up-front milestone payment and development progression milestone payments (up to approximately 3 billion yen).

Otsuka is to hold exclusive commercialization rights in Japan. Related to this, Otsuka is to make up to two milestone payments to Takara Bio based on the attainment of specified sales targets.

Takara Bio is to manufacture the product for use in clinical trials and for post-approval supply in return for unspecified fees to be paid by Otsuka.

Assuming HF10 receives regulatory approvals, the aim is launch HF10 in Japan as an oncolytic virotherapy for melanoma, pancreatic cancer and other tumors.