On June 2, 2015 Amgen reported a collaboration with Roche on a Phase 1b study to evaluate the safety and efficacy of talimogene laherparepvec, Amgen’s investigational oncolytic immunotherapy, in combination with Roche’s investigational anti-PDL1 therapy, atezolizumab (also known as MPDL3280A), in patients with triple-negative breast cancer and colorectal cancer with liver metastases (Press release, Amgen, JUN 2, 2015, View Source [SID:1234505188]). Schedule your 30 min Free 1stOncology Demo! Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells. Atezolizumab is an investigational monoclonal antibody designed to interfere with the PD-L1 protein.
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The rationale for combining these two investigational agents is to activate an anti-tumor immune response with talimogene laherparepvec and to block inhibitory T cell checkpoints with atezolizumab, to potentially increase the anti-tumor activity relative to each agent alone.
"We believe that talimogene laherparepvec has potential to help patients in several cancer types based on its mechanism of action to promote tumor antigen release and presentation, important steps in activating a systemic immune response," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This further builds our alliance network in oncology and we look forward to collaborating with Roche on this study as part of our increasing efforts in immuno-oncology."
"Atezolizumab is our most advanced cancer immunotherapy with 10 ongoing Phase 3 pivotal trials across lung, bladder, breast and kidney cancers," said Sandra Horning, M.D., chief medical officer and head of Global Product Development at Roche. "We are looking forward to working with Amgen on this trial, which can inform potential future treatment options for patients affected by very difficult-to-treat tumor types."
About Talimogene Laherparepvec
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Talimogene laherparepvec was designed to work in two important and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor’s cells causing the cell to rupture and die in a process called lysis. Then, the rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, that can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body.
Amgen has initiated a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.
About Atezolizumab (also known as MPDL3280A)
Atezolizumab is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumor cells.
Author: [email protected]
Amphivena Therapeutics Presents Positive Data on Novel Acute Myeloid Leukemia (AML) Immunotherapy at 2015 ASCO Annual Meeting
On Jun 1, 2015 Amphivena Therapeutics, Inc., a developer of cancer immunotherapies, reported positive data from several preclinical studies characterizing the company’s proprietary T-cell redirecting bispecific CD33/CD3-targeting antibodies as potential immunotherapeutics for the treatment of acute myeloid leukemia (AML) (Press release, Amphivena Therapeutics, JUN 1/, 2015, View Source [SID:SID1234515580]). Study findings, which demonstrated potent and specific anti-AML activity for the novel antibodies, were presented at the 2015 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Amphivena also announced selection of a development candidate, AMV-564, based on these compelling preclinical data.
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A diverse collection of Amphivena’s novel T-cell redirecting, tetravalent, bispecific CD33/CD3-targeting antibodies were evaluated across a rigorous panel of in vitro and in vivo systems in order to identify an optimal candidate for clinical development. The studies, conducted in collaboration with leading researchers at the Fred Hutchinson Cancer Research Center and the Washington University School of Medicine, were designed to examine the antibodies’ stability properties, affinity for CD33 and CD3, and impact on T-cell activation and cytotoxicity against CD33+ AML cells. The ASCO (Free ASCO Whitepaper) poster presentations (abstracts: 3057, 7067 and 7071) can be found on Amphivena’s website at www.amphivena.com.
Key study findings for Amphivena’s CD33/CD3-targeting antibodies included:
Mechanism-based, T-cell activation and proliferation was induced by the tetravalent, bispecific CD33/CD3-targeting antibodies. Importantly, the presence of CD33+ target cells was required for the T-cell activities, demonstrating the potential for minimal off-target safety issues for this antibody platform.
Potent and selective cytotoxic activity against CD33+ AML cell lines and 27 primary CD33+ AML specimens was observed at pM antibody concentrations. This activity was observed in newly diagnosed and relapsed or refractory AML samples, and was independent of disease stage. For the most potent CD33/CD3 antibodies, activity was independent of the level of CD33 expression.
Robust tumor growth inhibition and delay in prophylactic and established AML xenograft models using human cancer cell lines and donor T-cells.
Impressive activity in an AML patient-derived xenograft model with nearly complete elimination of leukemic blasts from all compartments, including bone marrow and spleen, despite the very low number of T-cells present in the patient sample.
"These preclinical studies identified T-cell redirecting bispecific CD33/CD3-targeting antibodies that meet our initial, pre-specified activity and safety profile for an immunotherapeutic clinical candidate for treating AML. Particularly exciting is the breadth and potency of the activity seen in AML patient samples from work done under the direction of Roland B Walter, M.D., Ph.D. at the Fred Hutchinson Cancer Research Center and the impressive level of activity observed in the AML patient-derived xenograft model in research conducted under the direction of John DiPersio, M.D., Ph.D., at the Washington University School of Medicine. Drs. DiPersio and Walter are two prominent, highly-regarded key opinion leaders in the area of hematologic oncology research and having their work support and validate our internal efforts is gratifying," said Jeanmarie Guenot, Ph.D., president and chief executive officer of Amphivena Therapeutics. "These positive preclinical results represent a key milestone for Amphivena, and we are happy to announce selection of a therapeutic candidate, AMV-564, for clinical development. While these studies highlighted promising therapeutic profiles for a number of our novel antibodies, we believe that AMV-564 provides the most rapid opportunity for successful development."
"The potent in vitro and in vivo activity of AMV-564 suggests this tetravalent, bispecific antibody may soon be ready for early phase clinical trials," said Dr. DiPersio, M.D., Ph.D., Chief, Division of Oncology, Deputy Director, Siteman Cancer Center, Washington University School of Medicine.
Dr. Walter, M.D., Ph.D., is Assistant Member, Clinical Research Division at the Fred Hutchinson Cancer Research Center and Associate Professor Medicine, Division of Hematology at the University of Washington.
Under terms of Amphivena’s ongoing agreement with Janssen Biotech, Inc. (Janssen), Janssen has the exclusive right to acquire Amphivena following approval of an Investigational New Drug (IND) application. As part of the agreement, Janssen has provided Amphivena with an initial upfront payment, as well as contingent payments to Amphivena based on achievement of predetermined milestones.
About AMV-564
AMV-564 is one of Amphivena’s proprietary first-in-class, tetravalent, bispecific TandAb antibodies. The novel immunotherapy recruits T-cells to eliminate cancer cells that express CD33, a receptor that is expressed on the majority of acute myeloid leukemias (AMLs) and is present on other hematologic malignancies. AMV-564 is bivalent for both CD33 on AML cells and CD3 on T-cells, forming a T-cell activating complex in the presence of target cancer cells. By maintaining the avidity for antigen as found in typical monoclonal antibodies, AMV-564 mediates potent and efficient tumor cell lysis. AMV-564 also offers pharmacokinetic advantages over smaller, monovalent bispecific constructs due to a molecule size that exceeds renal clearance limits. Amphivena is currently completing IND-enabling studies to advance AMV-564 into clinical development as a treatment for AML.
BioInvent enters into third research collaboration with University of Southampton
On June 1, 2015 BioInvent International (OMXS: BINV) reported a three-year research collaboration with the University of Southampton (UoS), one of the world’s leading antibody research groups, under the direction of Professor Mark Cragg, BSc, PhD, Professor of Experimental Cancer Research and Director of the Cancer Pathway Integrated Postgraduate Programme (Press release, BioInvent, JUN 1, 2015, http://www.bioinvent.com/media-centre/press-releases/release/?ReleaseID=0E5DCBBC28836A0F [SID:1234506557]).
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The collaboration, also involving Professor Martin Glennie and Dr Stephen Beers is aimed at developing new immunotherapy treatments for cancer by targeting regulatory T cells (T regs). The program builds on the clinical successes of antibodies to so called T cell checkpoint inhibitors. The collaboration aims to develop novel antibodies and targets that are more specific for the cancer-associated T regs.
This collaboration is separate from two existing research programs in place between the University of Southampton and BioInvent.
Terms of the collaboration are not disclosed, noting that BioInvent will have the option to license any promising results for further development and commercialization. Under the agreement, both parties will contribute to intellectual property generation.
BioInvent has the capacity, through the F.I.R.S.T. platform, to generate a large number of T cell depleting antibodies. UoS has unique capabilities to test and evaluate potential lead candidates in several advanced in vitro and in vivo models. The collaboration between BioInvent and UoS around n-CoDeR antibodies targeting human T regs for cancer therapy utilizes the strengths from both groups.
Professor Cragg commented, "We look forward to building on the strength of our collaborative relationship with BioInvent, which should allow us to remain at the cutting edge of antibody immunotherapy for the benefit of cancer patients worldwide. Both clinical and preclinical data suggests that depletion of T regs can result in efficient anti-tumor T cell responses and tumor eradication. However, current T cell targeting therapeutic antibodies and checkpoint inhibitors were developed based on their abilities to block inhibitory signals. Novel, as yet unidentified targets with broad expression on regulatory T cells in different cancers, such as melanoma, lung cancer etc. and antibody formats with superior T reg depleting activity may have greater activity. We look forward to working with BioInvent’s extensive antibody library and its novel targeting platform to establish several lead candidates for clinical development in this very important area of cancer research."
"We are especially pleased to be undertaking this additional research collaboration with the team at the University of Southampton. This esteemed research center and its renowned clinicians are experts in the fields of immunology and oncology and are at the forefront of unlocking the potential of therapeutic antibodies," said Björn Frendéus, PhD, Chief Scientific Officer of BioInvent and honorary Professor at the University of Southampton. "BioInvent’s phenotypic target and mAb discovery platform, F.I.R.S.T., are ideally suited to identify a great diversity of human mAb with cancer T reg depleting or modulating activity. In collaboration with our colleagues in Southampton, we aim to generate more efficacious and safer immune modulatory antibodies for cancer treatments."
CEL-SCI REPORTS MAY PATIENT ENROLLMENT IN ITS PHASE 3 HEAD AND NECK CANCER TRIAL
On June 1, 2015 CEL-SCI Corporation (NYSE MKT: CVM)("CEL SCI" or the "Company") reported that in May it has enrolled 26 patients in its ongoing Phase III trial of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) in patients with advanced primary squamous cell carcinoma of the oral cavity/soft palate, a type of head and neck cancer (Press release, Cel-Sci, JUN 1, 2015, View Source [SID:1234506551]). Over 463 patients have been enrolled as of May 31, 2015 in the world’s largest Phase 3 study in head and neck cancer.
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"With over half of patients enrolled, we have reached a milestone, as we look forward to completing enrollment by the first quarter of 2016," stated CEL-SCI Chief Executive Officer Geert Kersten. "We are now cleared to enroll patients in 23 countries and a number of additional clinical sites are expected to become active soon."
A total of 880 patients are expected to be enrolled, through approximately 100 clinical centers in about 25 countries.
About the Multikine Phase 3 Study
The Multikine Phase 3 study is enrolling patients with advanced primary squamous cell carcinoma of the head and neck. The objective of the study is to demonstrate a statistically significant improvement in the overall survival of enrolled patients who are treated with the Multikine treatment regimen plus standard of care ("SOC") vs. subjects who are treated with SOC only.
About Multikine
Multikine (Leukocyte Interleukin, Injection) is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line (right after diagnosis, before surgery) treatment for advanced primary squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.
Multikine is also being tested in a Phase 1 study under a Cooperative Research and Development Agreement ("CRADA") with the U.S. Naval Medical Center, San Diego, as a potential treatment for peri-anal warts in HIV/HPV co-infected men and women. CEL-SCI has also entered into two co-development agreements with Ergomed Clinical Research Limited to further the development of Multikine for cervical dysplasia/neoplasia in women who are co-infected with HIV and HPV and for peri-anal warts in men and women who are co-infected with HIV and HPV.
Baxter Ventures, Mayo Clinic and Velocity Pharmaceutical Development announce the formation of Vitesse Biologics, LLC, a company structured to accelerate therapeutic innovation.
On June 1, 2015 Baxter Ventures, the venture arm of Baxter International Inc. (NYSE:BAX), the Mayo Clinic and Velocity Pharmaceutical Development, LLC ("VPD") reported the formation of Vitesse Biologics, LLC, ("Vitesse") (Press release, Velocity Pharmaceutical Development, JUN 1, 2015, View Source [SID:1234506532]). Vitesse is a unique collaboration model initiated by Baxter Ventures to focus on the development of antibody and protein-based therapeutics in the areas of immunology, hematology, and oncology. Following the spin-off of Baxter BioScience as Baxalta Incorporated, anticipated to take place by mid-2015, the Vitesse relationship will be managed by the planned venture arm, Baxalta Ventures, for the new company.
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The collaboration model, which represents a new method of drug development, was designed to incent each partner to advance promising therapies quickly through the development process. Each partner will provide its recognized expertise to enhance the target selection, target optimization, expression and product development process. Baxter BioScience will provide global commercialization, antibody and protein development and manufacturing capabilities; Mayo Clinic researchers will execute the Phase I clinical trials; VPD will be responsible for target identification, selection of early stage drug candidates and will lead the design and execution of pre-clinical and clinical protocols.
"Delivering innovative treatments to address unmet patient needs is at the very core of everything we do and drives our ongoing R&D focus," said Ludwig N. Hantson, Ph.D., president of Baxter BioScience. "By creating Vitesse, our business is executing on a new concept in early stage R&D by leveraging the expertise of industry-leading partners to accelerate the identification and development of novel biologic treatments that could eventually contribute to unmet patient needs while enhancing the Baxalta commercial portfolio."
Vitesse will develop treatments in the fields of hematology, oncology and immunology, which aligns strongly with Baxter BioScience’s therapeutic focus. This innovative model enables Baxter to serve as a hands-on partner in the pursuit of innovative treatments, as Baxter BioScience will be involved in the early-stages of development for all products identified by Vitesse and has an exclusive option to acquire each such product following the completion of the applicable Phase I trials.
"We are excited about the possibilities for this new collaboration, and particularly for this new model for early stage drug development," said Greg Gores, M.D., executive dean for research at Mayo Clinic. "Our goal is to identify new, useful therapeutics to address the unmet needs of our patients."
David Collier, M.D., CEO of VPD, said, "We are fortunate to have world-class partners in this project. We believe that the combination of the development and manufacturing expertise offered by Baxter BioScience and the clinical capabilities of the Mayo Clinic, working in conjunction with our team at VPD, will produce a series of very promising new therapeutics developed in a more rapid and cost-efficient manner."
With research as a key priority of the Destination Medical Center (DMC) initiative, Mayo Clinic is building upon the clinical and research infrastructure further accelerating Mayo Clinic’s ability to conduct some of the most important medical research, eventually to translate these discoveries into therapies for patients from across the globe.
ABOUT VITESSE BIOLOGICS, LLC Vitesse Biologics, LLC, a Delaware Corporation based in South San Francisco, CA, develops antibody and protein-based therapeutics in the areas of immunology, hematology, and oncology.