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Progenics Announces Breakthrough Therapy Designation for Azedra in Pheochromocytoma and Paraganglioma

On July 28, 2015 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative ways to target and treat cancer, reported that the U.S. Food and Drug Administration (FDA) has designated Azedra as a Breakthrough Therapy for the treatment of patients with iobenguane-avid metastatic or recurrent pheochromocytoma and paraganglioma (Press release, Progenics Pharmaceuticals, JUL 28, 2015, View Source [SID:1234506726]).

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Azedra is currently being evaluated in a pivotal Phase 2b trial, which is being conducted under a Special Protocol Assessment Agreement (SPA), and has received Orphan Drug and Fast Track designations from the FDA.

The Breakthrough Therapy designation pathway was created by the FDA to expedite the development and review for a drug that treats a serious or life-threatening condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies.

"This Breakthrough Therapy designation for Azedra reflects the urgent need for new options for patients suffering from pheochromocytoma and paraganglioma," stated Mark Baker, CEO of Progenics. "Azedra has the potential to be the first approved therapy for patients with these rare and devastating tumors, and this designation will allow for a close collaboration between Progenics and the FDA as we complete our ongoing pivotal Phase 2b trial and, assuming a positive trial outcome, advance Azedra through the regulatory review process."

About AZEDRA

Azedra is a radio-therapeutic with FDA Fast Track status currently being studied in a phase 2 registrational trial under a SPA with the FDA using a surrogate marker as registrational endpoint. In addition to potentially treating pheochromocytoma and paraganglioma, Azedra may also have utility in treating neuroblastoma and other neuroendocrine tumors. Clinical trials for Azedra have not been completed and regulatory approvals for Azedra remain subject to the successful completion of all required studies.

About Pheochromocytoma and Paraganglioma

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors that arise from cells of the sympathetic nervous system. When pheochromocytomas are located outside the adrenal glands, they are called paragangliomas. Standard treatment options for these tumors include surgery, palliative therapy and symptom management. Malignant and recurrent pheochromocytomas and paragangliomas may result in unresectable disease with a poor prognosis, representing a significant management challenge with very limited treatment options and no approved anti-tumor therapies.

OncoMed Initiates Phase 1 Clinical Trial for Anti-RSPO3 Antibody

On July 28, 2015 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported dosing of the first patient in its anti-RSPO3 antibody (OMP-131R10) Phase 1a/1b clinical trial (Press release, OncoMed, JUL 28, 2015, View Source [SID:1234506725]). Anti-RSPO3 is the first drug in its class to target the R-spondin-LGR pathway, an important cancer stem cell pathway identified by OncoMed researchers.

"The inhibition of RSPO3 has shown robust preclinical activity against a number of solid tumor types. In this trial, we look forward to establishing a suitable dose and exploring this antibody’s safety and initial efficacy," said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer. "In addition, studies using our human tumor xenograft models have demonstrated a strong correlation between activity and RSPO3 biomarkers as well as potent activity in the colorectal cancer setting, which we will examine in the second part of this comprehensive Phase1a/1b trial."

The Phase 1a/1b clinical trial is initially enrolling patients with advanced refractory solid tumors. Patients will receive escalating doses of anti-RSPO3 until disease progression. The open-label study is designed to assess the safety, pharmacokinetics, pharmacodynamics and initial evidence of efficacy of the anti-RSPO3 antibody. Once a single-agent dose has been identified, biomarker-selected patients will be enrolled in a Phase 1a expansion arm to obtain additional preliminary information on possible anti-tumor activity. In the Phase 1b portion of the trial, anti-RSPO3 will also be tested in second-line colorectal cancer patients in combination with the chemotherapeutic standard of care in metastatic colon cancer, known as FOLFIRI (folinic acid, fluorouracil and irinotecan). The trial is being conducted at five sites in the United States.

Dr. Gail Eckhardt, Professor, Division of Medical Oncology and Stapp-Harlow Endowed Chair at the University of Colorado, is a Principal Investigator of the study who treated the first patient on the clinical trial. Dr. Eckhardt commented, "RSPO3 is an exciting new therapeutic target in solid tumors and in particular in colorectal cancer. OncoMed’s OMP-131R10 is a novel antibody approach that will hopefully provide clinical benefit and therapeutic options for cancer patients."

R-spondin proteins bind to or activate leucine-rich repeat containing G-coupled receptors (LGRs) and blocking this activity has been shown to inhibit tumor growth. In preclinical studies OncoMed’s anti-RSPO3 antibody demonstrated robust in vivo anti-tumor efficacy as a single agent and in combination with standard of care across a range of solid tumors, including colon, lung, ovarian, and pancreatic cancers, among others. The anti-RSPO3 antibody delayed tumor recurrence following termination of chemotherapy, and decreased the frequency of cancer stem cells.

The anti-RSPO3 antibody represents the third drug in the clinic that is part of OncoMed’s collaboration with Celgene.

Aeterna Zentaris Grants Option to Develop and Commercialize Oral Allogenic Cancer Vaccine Technology

On July 28, 2015 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") reported that it has granted to German life sciences entrepreneurs with a proven track-record of funding the development and commercialization of biotechnology (collectively, the "Optionee"), an option to license the Company’s live recombinant oral allogenic tumor vaccine technology (the "Technology"), including AEZS-120, the most advanced product candidate for prostate cancer which is ready to enter a Phase 1 clinical trial (Press release, AEterna Zentaris, JUL 28, 2015, View Source [SID:1234506719]).

This option is granted to the Optionee worldwide, for a period of twelve months, in exchange for an upfront fee.

Pursuant to the option agreement, the Optionee has the right to obtain a worldwide exclusive license to develop, use and sell products relating to the Technology and AEZS-120, in exchange for milestone payments and royalties on net sales of any product developed from the Technology and an equity interest in the company formed to develop the Technology. At the present time, Aeterna Zentaris holds worldwide rights to the Technology, including AEZS-120.

David A. Dodd, Chairman and CEO of Aeterna Zentaris, commented, "This agreement is part of our strategy of leveraging some of our promising early-stage drug candidates in order to generate potential long-term value without having to invest in their development. Our live recombinant oral allogenic cancer vaccine is a novel approach to treating cancer and could prove to be a beneficial option for the millions of people suffering from different types of cancer."

About AEZS-120

AEZS-120 is a live recombinant oral allogenic cancer vaccine candidate based on Salmonella typhi Ty21a as a carrier strain. Salmonella typhi Ty21a is an approved oral typhoid vaccine which has been safely applied in more than 250 million doses. The principle of AEZS-120 is based on the recombinant expression of prostate specific antigen fused to the B subunit of cholera toxin and a secretion signal in the presence of the Escherichia coli type I hemolysin secretion system. The proprietary system allows the secretion of the antigen, together with an immunological adjuvant which has been demonstrated to be required for optimal induction of CD8 T-cell responses by recombinant Salmonella based bacterial vaccines. The proof-of-concept was demonstrated for the mouse homologue of AEZS-120 in a mouse tumor-challenge model. In general, by varying the antigen and/or the carrier, this proprietary platform technology should be suitable for virtually any therapeutic or prophylactic vaccine indication with a favorable cost of goods expectation in large scale.

Merck Enhances Immuno-Oncology Portfolio with Acquisition of cCAM Biotherapeutics

On July 28, 2015 Merck (NYSE:MRK), known as MSD outside the United States and Canada, and cCAM Biotherapeutics reported that the companies have signed a definitive agreement under which Merck will acquire cCAM Biotherapeutics, a privately held biopharmaceutical company focused on the discovery and development of novel cancer immunotherapies (Press release, Merck & Co, JUL 28, 2015, View Source [SID:1234506714]).

Under terms of the agreement, Merck, through a subsidiary, will acquire all outstanding stock of cCAM in exchange for an upfront payment of $95 million in cash. In addition, cCAM shareholders of record are eligible to receive a total of up to $510 million associated with the attainment of certain clinical development, regulatory and commercial milestones. The transaction is subject to certain closing conditions.

"We continue to strengthen our portfolio of immunotherapeutic candidates through strategic collaborations and acquisitions," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "The acquisition of cCAM supports our objective to advance the care of patients with cancer by stimulating tumor-directed immune responses."

The acquisition provides Merck with several early immunotherapy candidates including cCAM Biotherapeutics’ lead pipeline candidate, CM-24 – a novel monoclonal antibody (mAb) targeting the immune checkpoint protein CEACAM1 that is currently being evaluated in a Phase 1 study for the treatment of advanced or recurrent malignancies, including melanoma, non-small-cell lung, bladder, gastric, colorectal, and ovarian cancers. Based on the transaction, cCAM Biotherapeutics, domiciled in Israel, will become a wholly owned subsidiary of Merck and continue to advance the development of CM-24 in its ongoing Phase 1 clinical trial. cCam was originally established under the Israeli Office of Chief Scientist’s incubators program.

"Merck’s excellence and leadership in immuno-oncology provides a strong foundation for advancing CM-24, for the treatment of people with cancer," said Pini Orbach, Ph.D., Chairman of the Board, cCAM Biotherapeutics and Head of Pharma at Arkin Holdings. "This is a significant achievement for cCAM Biotherapeutics, as well as a vote of confidence in the Israeli innovative biotech industry as a whole."

About CEACAM1 and CM-24

CM-24 is a humanized monoclonal antibody directed against CEACAM1, an immune checkpoint protein belonging to the Human CEA (Carcino-Embryonic Antigen) protein family. Evidence has shown that CEACAM1 is expressed on tumor lymphocytes, and is up-regulated in several cancer types. Preclinical studies have shown evidence that CM-24 enhances the cytotoxic activity of tumor-infiltrating lymphocytes (TILs) against various CEACAM1-positive tumor cell lines. CM-24 is being developed for multiple oncological indications according to the expression pattern of its target protein.

About cCAM Biotherapeutics

Founded in 2010 and led by Tehila Ben-Moshe, Ph.D., cCAM is a biopharmaceutical company focused on the discovery and development of novel immunotherapies to treat cancer. Its lead product, CM-24, is a first-in-class humanized anti-CEACAM1 monoclonal antibody undergoing Phase 1 clinical trials. CM-24 is based on the research of Professor Gal Markel, Head of Research, Ella Institute of Melanoma, at Sheba Academic Medical Center Hospital, Israel. Main and equal Investors in the Company include: Arkin Holdings, OrbiMed and Pontifax. For more information, please visit View Source

MGD011 Advances Into Clinical Development

On July 28, 2015 MacroGenics, Inc. (Nasdaq:MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as various autoimmune disorders and infectious diseases, reported that its partner, Janssen Biotech, Inc. ("Janssen"), has initiated dosing in a Phase 1 trial of MGD011 (also known as JNJ-64052781) (Press release, MacroGenics, JUL 28, 2015, View Source [SID:1234506713]).

MGD011 incorporates MacroGenics’ proprietary platform for Dual-Affinity Re-Targeting (DART) to simultaneously target CD19 and CD3 for the potential treatment of B-cell malignancies. Achievement of this milestone triggers a $10 million payment to MacroGenics by Janssen.

The purpose of this first-in-human, open-label study is to evaluate the safety, tolerability and preliminary clinical activity of MGD011 when administered to patients with relapsed or refractory B-cell malignancies, including diffuse-large B cell lymphoma, follicular lymphoma, mantle-cell lymphoma, chronic lymphocytic leukemia and acute lymphoblastic leukemia.

"Janssen’s use of the DART platform for targeting CD19 provides important validation of our technology," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We continue to be impressed with Janssen’s track record of successfully developing potentially transformative oncology therapies and look forward to the future progress of MGD011 in this Phase 1 study."

About MGD011/JNJ-64052781

MGD011 (also known as JNJ-64052781), a humanized CD19 x CD3 bispecific DART protein, is being developed for the treatment of B-cell hematological malignancies. CD19, a lymphocyte-specific marker expressed from early B-lymphocyte development through mature memory B cells, is highly represented in B-cell malignancies. This makes it attractive for targeted interventions. MGD011 is designed to redirect T cells, via their CD3 component, to eliminate CD19-expressing cells. MGD011 has been engineered to address half-life challenges posed by other programs targeting CD19 and CD3. This product candidate incorporates an Fc domain, which allows for extended pharmacokinetic properties and convenient dosing at an interval of once-every-two-weeks. In addition, MGD011 and MacroGenics’ other DART molecules that redirect T cells against cancer targets are manufactured using a conventional antibody platform without the complexity of having to genetically modify T cells from individual patients as required by cell-based approaches such as chimeric antigen receptor (CAR) T-cells.

About the MGD011 Collaboration and License Agreement with Janssen

In December 2014, MacroGenics entered into a collaboration agreement with Janssen. Under this collaboration, MacroGenics licensed MGD011 to Janssen and received a $50 million upfront license fee and a $75 million equity investment by Johnson & Johnson Innovation – JJDC, Inc. Janssen is fully responsible for developing MGD011. Beyond the upfront consideration and recent $10 million clinical milestone, MacroGenics is eligible to receive up to an additional $565 million in clinical, regulatory and commercialization milestone payments. MacroGenics may elect to fund a portion of late-stage clinical development in exchange for a profit share in the U.S. and Canada. If commercialized, MacroGenics would be eligible to receive double-digit royalties on any global net sales and has the option to co-promote the molecule with Janssen in the U.S.