On November 7, 2019 AvantGen, Inc., a biotechnology company with its array of technology platforms for antibody discovery, optimization, and novel NK cell engager generation, reported a strategic collaboration with an undisclosed biopharmaceutical company for the purpose of generating multiple novel bi-specific NK cell engaging therapeutic antibody product candidates (Press release, AvantGen, NOV 7, 2019, View Source [SID1234550673]).

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!

Under the terms of the agreement, AvantGen will be responsible for engineering bi-specific variants of specified molecules using its proprietary NK cell engager platform and the biopharmaceutical company’s antibodies against a novel disease target. The biopharmaceutical company will receive worldwide rights on an exclusive basis with respect to its proprietary target to develop and commercialize product candidates arising from the collaboration. AvantGen receives upfront payments and is eligible to receive milestone payments and royalties associated with the development and sale of any products derived from the collaboration.

"We are pleased to collaborate with a team of talented leaders in the field of immuno-oncology to generate a novel class of anti-cancer molecules with superior efficacy. Our cutting-edge NK cell engager platform is comprised of binders that are exquisitely specific for CD16a, an activating receptor expressed on NK cells, but do not cross-react with the highly homologous CD16b receptor which is expressed on neutrophils. These attributes are intended to greatly enhance desirable NK cell-mediated antibody dependent cellular cytotoxicity (ADCC) activity against cancer cells while minimizing the undesirable inhibitory effects of neutrophil-mediated ADCC functions," said Xiaomin Fan, Ph.D., founder and president of AvantGen. Dr. Fan continued, "Our platform is further differentiated by designing the NK cell engagers to activate NK cells only in the presence of cancer cells that are recognized by the tumor targeting moiety of the engager and in a manner that is not affected by high concentrations of human IgG. We welcome the opportunity to generate novel product candidates for our biopharmaceutical company partner under this collaboration, and look forward to entering similar arrangements with others on a cancer target-exclusive basis."

On November 7, 2019 Tizona Therapeutics, Inc., a clinical stage, privately held company developing first-in-class cancer immunotherapies, reported the online publication of an article in Cancer Discovery describing novel mechanisms to more potently modulate the adenosine pathway and activate anti-tumor immune responses using antibodies that block CD39 (Press release, Tizona Therapeutics, NOV 7, 2019, View Source [SID1234550672]).

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!

The paper, "Targeting CD39 in Cancer Reveals an Extracellular ATP and Inflammasome-driven Tumor Immunity", found that blocking CD39 enzymatic activity with an anti-CD39 antibody facilitated immune cell infiltration into T cell-poor tumors and rescued anti-PD-1 resistance. This activity was shown to be mediated by ATP’s signaling of the P2X7 receptor and consequent stimulation of the inflammasome. Stimulating inflammasome-driven anti-tumor immunity through the preservation of ATP coupled with preventing the production of immune suppressive adenosine is only achieved through targeting CD39.

TTX-030, a first-in-class anti-CD39 antibody discovered at Tizona, is currently being evaluated in collaboration with AbbVie in a Phase 1/1b clinical study as a monotherapy and in combination with an approved anti-PD-1 agent and standard chemotherapy in adults with advanced cancer (NCT03884556).

"Targeting CD39 is a promising approach to modulate the adenosine pathway within the tumor microenvironment to both stimulate the immune system and counter immune suppression," said Scott Clarke, CEO of Tizona. "This paper provides additional evidence that CD39 is a key immune regulatory switch in the TME, and we are excited to develop TTX-030, our first-in-class anti-CD39 antibody, with the potential to transform outcomes for people with cancer."

About TTX-030, the Adenosine Axis, and the Tumor Microenvironment

TTX-030 is a monoclonal antibody that inhibits the activity of CD39, a cell surface enzyme upregulated on tumors, exhausted T cells, as well as many suppressive cell types. It catalyzes the conversion of ATP to AMP, the first step in the generation of adenosine. By blocking the action of CD39, TTX-030 prevents the formation of immune suppressive extracellular adenosine, which would otherwise inhibit effector cells in the TME. In addition to preventing the formation of suppressive adenosine, TTX-030 also prevents the degradation of ATP, preserving ATP’s ability to stimulate dendritic and myeloid-derived cells responsible for innate immunity and the immune cell priming necessary for adaptive immunity.

On November 7, 2019 Targos Molecular Pathology GmbH, a market leader in clinical biomarker services reported a technology partnership with Ultivue, the innovation leader in multiplex tissue biomarker assays, to offer the biopharmaceutical industry new capabilities to improve the characterization of cancer patients’ samples selected for clinical research programs (Press release, Targos Molecular Pathology, NOV 7, 2019, View Source [SID1234550671]). UltiMapper multiplex immuno-histochemistry assays enable the precise identification of cellular phenotypes that can be associated to drug efficacy and further used to develop a companion diagnostic assay.

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!

"UltiMapper assays are very modular by design, allowing for various levels of multiplexing and throughput, and supporting same day staining-to-data workflows," stated Dr. Thomas Henkel, CEO of Targos. "The adoption of highly standardized multiplex tissue biomarker assays is a strategic fit with our mission to continuously improve the success of clinical trials and deliver exceptional value to our biopharma partners."

Ultivue technologies and UltiMapper assays are widely used in tumor immune-profiling research strategies by the biomedical community to demonstrate the clinical utility of panels of markers. "Through our collaboration with Targos, the same panels can seamlessly be used in their existing setup to create a very effective continuum of translational and clinical research," said Philippe Mourere, SVP Commercial Operations at Ultivue. "Targos also offers highly customizable UltiMapper panels that can be used in combination with the company’s broad menu of additional assays and end-to-end quality services."

Additional details on the partnership will be communicated at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting at the Gaylord National Resort & Convention Center in National Harbor, MD on November 8 and 9, 2019 at the Ultivue booth #428.

On November 7, 2019 Amphivena Therapeutics, Inc., a private clinical stage immuno-oncology company developing T cell engager therapeutics for cancer, reported that it will present at the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) Annual Meeting on November 7 new understandings of the mechanism of action of its T cell engager clinical candidate, AMV564 (Press release, Amphivena Therapeutics, NOV 7, 2019, View Source [SID1234550670]). Specifically, Amphivena said that AMV564, a bivalent CD33/CD3 T cell engager, selectively depletes myeloid-derived suppressor cells (MDSC) in patients, sparing normal neutrophils and monocytes. The company announced in October initiation of a Phase 1 trial to evaluate the effect of AMV564 on these immune suppressive cells and the potential therapeutic benefit of relieving this important source of T cell suppression in patients with solid tumors.

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!

Vitoria Smith Ph.D., Chief Scientific Officer, who will make the oral presentation, noted, "AMV564 selectively reduces MDSC in the bone marrow and periphery in acute myeloid leukemia and myelodysplastic syndrome patients. In addition, we observed that T cell activation on therapy can lead to rapid increases in MDSC. However, this can be modulated by AMV564 due to avid binding of activated CD33 on MDSC. We believe that with application of a continuous dosing regimen we may control immune-suppressive MDSC and promote anti-tumor immunity."

The oral presentation (071) is scheduled for 2:25 pm ET in Potomac Ballroom CD.

Amphivena will also present a "Trials in Progress" poster summarizing the study design and objectives of its ongoing study AMV564-301 "Phase 1 Dose Escalation with Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of AMV564 in Patients with Advanced Solid Tumors" (NCT04128423). The multi-center Phase 1 study is currently open for enrollment at NEXT Oncology (PI: Raghad Karim) in San Antonio, TX, MD Anderson Cancer Center (PI: Sarina Piha-Paul) and Peninsula Cancer Institute (PI: Alexander Starodub) in Newport News, VA. AMV564 is being administered to solid tumor patients by subcutaneous injection.

The poster presentation (P416) is scheduled for 7:00 pm – 8:30 pm ET in Prince George’s Exhibition Hall AB.

About AMV564

AMV564 is a bivalent, bispecific (2:2) T cell engager that binds CD33 and CD3. To date, over 50 patients have received AMV564 in two Phase 1 clinical trials for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). It is currently being evaluated in a First-in-Human Phase 1 trial in patients with relapsed/refractory AML at Washington University School of Medicine, MD Anderson Cancer Center, New York-Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine, Fred Hutchinson Cancer Research Center, The Ohio State University Wexner Medical Center, University of Pennsylvania Medical Center, Northwestern Memorial Hospital, and The Johns Hopkins Hospital.

The safety, efficacy and selectivity of AMV564 was highlighted most recently at both the 24th European Hematology Association (EHA) (Free EHA Whitepaper) meeting in Amsterdam (Abstract S877) and at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, CA last December. Amphivena believes that AMV564 has demonstrated novel clinical activity by rapidly and selectively eliminating leukemic blasts and rare immature, granulocytic and monocytic MDSCs while sparing normal CD33-expressing cells, including neutrophils and monocytes.

On November 7, 2019 Renowned South Korean healthcare company, Yuhan Pharmaceuticals (Yuhan) and Cyclica Inc. (Cyclica), a leading neo biotechnology company reported a collaboration to apply Cyclica’s proprietary AI-integrated drug discovery platform in two separate R&D programs (Press release, YuHan, NOV 7, 2019, View Source [SID1234550669]). Yuhan is keen on implementing innovative technologies to enhance drug development efforts and will utilize Cyclica’s unique end-to-end AI-integrated drug discovery platform across diverse therapeutic areas to develop novel advanced lead-like molecules with desired chemical properties against the targets of interest determined by Yuhan’s R&D priorities.

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!

Yuhan will leverage Cyclica’s integrated drug discovery platform, Ligand DesignTM and Ligand Express to generate novel chemical entities with desired polypharmacological, physicochemical, and ADMET properties while providing insights into systems biology and structural pharmacogenomics.

Cyclica will receive an upfront payment as well as receive milestone payments upon the completion of specific objectives. Through this collaboration, Yuhan and Cyclica envision a long-term relationship to enhance future R&D and drug discovery efforts to identify novel solutions for unaddressed therapeutic needs.

Yuhan CEO and President Jung Hee Lee said, "We are very pleased to be collaborating with Cyclica to apply its proprietary AI-integrated drug discovery platform in our R&D programs, and hope to expand our partnership upon the success of the collaboration. Yuhan is dedicated to offering first-in-class to the patients within a short time by applying new computational methods, including AI and Big Data that can shorten the time and the cost required for drug development."

"It’s an honour to collaborate with Yuhan, a visionary company that is thinking deeply about the future of the discovery of better medicines, and the application of new computational methods, including machine and deep learning. I am confident that this collaboration, and the future relationship with Yuhan and Cyclica will benefit patients waiting for new and better medicines." said Naheed Kurji, President and CEO of Cyclica.