On November 30, 2018 Crescendo Biologics Ltd (Crescendo), the drug developer of novel, targeted T-cell enhancing therapeutics, reported that Takeda Pharmaceutical Company Limited (Takeda), has exercised an option under its existing, multi-target collaboration and license agreement (Press release, Crescendo Biologics, NOV 30, 2018, View Source [SID1234531757]). Takeda has taken an exclusive licence to Humabodies directed to one of its oncology targets.

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 licence option exercise comes substantially earlier than planned and marks the highly successful delivery and further pre-clinical evaluation by Takeda of Humabody leads meeting its stringent criteria.

Dr Peter Pack, CEO of Crescendo, commented:

"The team at Crescendo has made great progress on our Humabody programmes, working closely with the Takeda team. To date, we have met all the technical milestones on time or earlier than planned, which is proof of our excellent collaboration. We are delighted that the option to license has been taken by Takeda ahead of schedule and look forward to further future successes."

Chris Arendt, Head, Oncology Drug Discovery Unit & Immunology Unit, Takeda, commented:

"At Takeda, we continue to research diverse modalities to bring transformative treatments to patients with cancer. Our decision to exercise the licence was based on the quality of the Humabody leads and the potential we see to develop improved and differentiated immuno-oncology therapies."

Takeda’s option is part of the existing multi-target collaboration and licence agreement announced in October 2016 where Takeda received the right to develop and commercialise Humabody-based therapeutics resulting from the collaboration. Under the agreement, Crescendo is eligible to receive clinical development, regulatory and sales-based milestone payments of up to $754 million plus royalties on Humabody-based product sales by Takeda.

On November 30, 2018 Turnstone Biologics, a clinical-stage immuno-oncology company leading the next generation of oncolytic viral therapies, reported its pre-clinical data today supporting the development of a new Vaccinia therapeutic platform at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Tumor Immunology and Immunotherapy Meeting in Miami (Press release, Turnstone Biologics, NOV 30, 2018, View Source [SID1234531756]). This platform was developed by Dr. John Bell and his colleagues at The Ottawa Hospital Research Institute and the University of Ottawa, and engineered to be potent, highly selective and immune-stimulatory. Furthermore, the versatility of the platform enables additional therapeutic agents to be encoded in the virus and produced at tumor sites. This single platform virus has the potential to create a portfolio of diverse products. Turnstone has exclusively licensed this technology.

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 proprietary Vaccinia virus can be delivered systemically and is designed to target and kill cancer cells throughout the body, modulate the tumor microenvironment and stimulate both innate and adaptive immune responses. The virus also contains a very large transgene capacity, allowing for the insertion of multiple therapeutic agents. These agents will be produced selectively at tumor sites as the virus replicates only in the tumor cells, effectively enabling a local combination therapy from a single therapeutic promoting cancer cell killing. Turnstone is conducting IND-enabling studies on TBio-6517, its lead product candidate from this platform, consisting of the Vaccinia virus expressing three potent immune modulators, and anticipates initiating clinical studies in 2019.

"The decades-long search for immunotherapies and combinations that are safe and effective for a range of cancers has proven challenging," said Dr. Bell. "While previous Vaccinia therapies have shown promise, we believe that we have selected and designed significant improvements into this platform, potentially allowing us to safely and effectively combine multiple modes of action into a single therapy."

"This is an exciting time for Turnstone as we unveil another novel viral immunotherapy platform technology in our continued pursuit to develop transformative technologies that advance the treatment of cancer," said Mike Burgess, MBChB, Ph.D., President, Research and Development at Turnstone Biologics. "We are rapidly advancing our lead candidate from this proprietary platform, TBio-6517, to the clinic with the goal of achieving effective and durable outcomes for a greater number of cancer patients."

The oral presentation entitled "Utilizing Novel Oncolytic Vaccinia Virus for Selective Expression of Immunotherapeutic Proteins in Metastatic Tumors" includes key proof-of-concept data:

Cancer Cell Selectivity: The Turnstone Vaccinia virus was shown to rapidly kill more than 80% of cancer cells across multiple cell lines while sparing normal cells, exhibiting high tumor specificity in mouse models.
Potent Oncolytic Activity: The Turnstone Vaccinia virus replicated in human lung, sarcoma, melanoma, ovarian, gastic and thymic tumor explants, and showed efficacy with improved safety in the HT29 colon cancer tumor model.
Transgene Expression: TBio-6517 demonstrated selective expression of its three encoded immunomodulators at the sites of tumors in preclinical models, with no evidence for exposure in the peripheral blood.

On November 30, 2018 Eureka Therapeutics, Inc., a clinical stage biopharmaceutical company with the goal of curing cancer by developing novel T-cell therapies that harness the evolutionary power of the immune system, reported that five abstracts, including four oral presentations and one poster discussion, highlighting clinical programs in multiple myeloma and NHL using binding domains developed by Eureka, have been accepted for presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 1-4 in San Diego, California (Press release, Eureka Therapeutics, NOV 30, 2018, View Source [SID1234531755]).

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 data presented at this meeting underscores the potential potency of antibodies generated from Eureka’s proprietary E-ALPHA discovery platform, which includes the human BCMA and CD19 binding domains used in the CAR-T and ARTEMIS T-cell therapies presented at ASH (Free ASH Whitepaper). The E-ALPHA platform comprises a highly diverse human-derived antibody phage library, containing over 100 billion clones with unique antibody sequences, and a robust workflow to develop highly specific antibodies against target antigens.

"We are pleased to be working with Eureka on our multiple myeloma programs," said Eric Smith, M.D., Ph.D., Director of Translational Development, Cellular Therapeutics Center at Memorial Sloan Kettering Cancer Center (MSK) and co-inventor of CARs for the targeting of multiple myeloma. "Working with Eureka to identify fully-human BCMA and other multiple myeloma targeted binding domains has the potential to avoid host anti-CAR immunity that may develop when using murine derived antibodies as binders. We look forward to continue working with Eureka on developing the next generation of T-cell therapies."

"We are delighted that data involving Eureka’s assets are being reported in many presentations at ASH (Free ASH Whitepaper) – in particular the exciting clinical data from the BCMA/multiple myeloma programs that we developed in collaboration with Memorial Sloan Kettering in 2012 and licensed to Juno Therapeutics (now Celgene) in 2016," said Dr. Cheng Liu, President and Chief Executive Officer of Eureka Therapeutics. "In addition, the updated data from the 21-patient proof-of-concept study of our ARTEMIS T-cell therapy (ET190L1 ARTEMIS) for CD19-positive r/r NHL continues to show that our ARTEMIS T-cells have been well tolerated with no observed cytokine release syndrome (CRS) or neurotoxicity, validating the potential of our ARTEMIS platform to deliver safer T-cell therapy than the currently available CAR-T therapies."

The accepted abstracts are listed below and are now available on the ASH (Free ASH Whitepaper) website.

Multiple Myeloma

CAR T Cell Therapy Targeting G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D), a Novel Target for the Immunotherapy of Multiple Myeloma
Author: Eric L. Smith, MD, PhD
Abstract #589
Oral Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Development of Novel Immunotherapeutic Approaches in Multiple Myeloma
Monday, December 3, 2018: 7:00 AM, Ballroom 20D
Clinical Responses and Pharmacokinetics of MCARH171, a Human-Derived BCMA Targeted CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma: Final Results of a Phase I Clinical Trial
Author: Sham Mailankody, MBBS
Abstract #959
Oral Session: 653. Myeloma: Therapy, excluding Transplantation: Immunotherapies in Plasma Cell Disorders
Monday, December 3, 2018: 5:30 PM, Ballroom 20A
JCARH125, Anti-BCMA CAR T-cell Therapy for Relapsed/Refractory Multiple Myeloma: Initial Proof of Concept Results from a Phase 1/2 Multicenter Study (EVOLVE)
Author: Sham Mailankody, MBBS
Abstract #957
Oral Session: 653. Myeloma: Therapy, excluding Transplantation: Immunotherapies in Plasma Cell Disorders
Monday, December 3, 2018: 5:00 PM, Ballroom 20A
Fully Human BCMA Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma
Author: Damian J. Green, MD
Abstract #1011
Oral Session: 653. Myeloma: Therapy, excluding Transplantation: Immunotherapy
Monday, December 3, 2018: 6:45 PM, Ballroom 20D
Non-Hodgkin Lymphoma

ET190L1-ARTEMIS T Cell Therapy Results in Durable Disease Remissions with No Cytokine Release Syndrome or Neurotoxicity in Patients with Relapsed and Refractory B-Cell Lymphoma
Author: Zhitao Ying, MD, PhD
Abstract #1689
Poster Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster I
Saturday, December 1, 2018, 6:15 PM-8:15 PM, Hall GH
About E-ALPHA Antibody Discovery Platform
Eureka’s proprietary E-ALPHA antibody discovery platform is composed of a highly diverse human-derived antibody phage library, containing over 100 billion clones with unique antibody sequences, and a robust workflow with specificity screens designed to develop highly specific antibodies against target antigens. The E-ALPHA platform is designed to enable Eureka to rapidly discover, iterate upon and improve our antibodies. Eureka’s E-ALPHA platform enables Eureka to develop highly specific antibodies for both conventional targets, such as cell surface markets, and T-cell receptor targets, such as intracellular peptides displayed by the major histocompatibility complex, with the goal of addressing solid tumors.

About ARTEMIS T-cell Receptor Platform
Eureka’s proprietary ARTEMIS T-cell receptor platform was designed to create potentially safer and more effective T-cell therapies. In pre-clinical studies against CD19-positive malignancies, Eureka’s ARTEMIS T-cells matched the cancer killing potency of currently available CAR-T therapies but with a dramatic reduction in the levels of inflammatory cytokines released. Cytokine release syndrome (CRS) and neurotoxicity are serious side effects associated with currently available CAR-T therapies.

On November 30, 2018 bluebird bio, Inc. (Nasdaq: BLUE) reported that the company will host a live webcast of an investor and analyst event being held on Monday, December 3, 2018, during the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, bluebird bio, NOV 30, 2018, View Source [SID1234531754]). Speaker presentations will begin at 8:30 p.m. PST (11:30 p.m. EST) and will review the company’s data being presented at the ASH (Free ASH Whitepaper) meeting.

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!

To access the live webcast of bluebird bio’s presentation, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source A replay of the webcast will be available on the bluebird bio website for 90 days following the event.

On November 30, 2018 Adaptive Biotechnologies and its collaborators reported it will present 28 studies, including a late-breaker presentation, at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego, December 1-4, 2018 (Press release, Adaptive Biotechnologies, NOV 30, 2018, View Source [SID1234531753]). The data presented at ASH (Free ASH Whitepaper) builds on the recent FDA clearance of the clonoSEQ Assay to detect and monitor minimal residual disease (MRD) in patients with multiple myeloma or B-cell acute lymphoblastic leukemia (ALL), using DNA from a patient’s bone marrow sample.

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!

Among the 28 clonoSEQ studies at ASH (Free ASH Whitepaper), new research supports expanded use in myeloma and ALL, efficacy in other blood cancers like chronic lymphocytic leukemia (CLL) and Non-Hodgkin’s Lymphoma (NHL), and ability to detect MRD in blood-based samples. New data generated using clonoSEQ will be presented that demonstrate the value of a highly sensitive, standardized next-generation sequencing MRD test to determine early response to treatment and predict potential relapse in myeloma and ALL patients. Data will also be presented that look at the sensitivity of clonoSEQ and other technologies to assess MRD.

"This year has been a landmark year for minimal residual disease. It’s one of the first new endpoints we’ve seen in hematology clinical trials since progression-free survival," said Chad Robins, chief executive officer and co-founder of Adaptive Biotechnologies. "The volume and the quality of MRD data being presented at ASH (Free ASH Whitepaper) establish that MRD has firmly taken root as a clinical trial endpoint and biomarker that can help predict patient outcomes. With greater reliance on MRD in clinical trials, as well as a growing focus on monitoring MRD to inform patient care, having access to a highly sensitive, standardized test like clonoSEQ is paramount."

clonoSEQ, the first clinical application of Adaptive’s pioneering immune profiling platform, will be featured in a late-breaker presentation, 12 oral presentations and 15 posters. Data on approved, investigational and research uses will be presented across a range of cancers – 14 multiple myeloma, 4 ALL, 4 CLL, 4 mantle cell lymphoma, 1 diffuse large B-cell lymphoma, and 1 Hodgkin’s lymphoma.

Key highlights include:

Abstract Title Date, Time, Location
Multiple myeloma and ALL
Abstract #LBA-2, Late-Breaker Presentation

LBA-2: Phase 3 Randomized Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA) Tuesday, December 4, 7:30 AM PT, Hall AB, San Diego Convention Center
Abstract #156, Oral Presentation

One-Year Update of a Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Patients (Pts) with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM): Alcyone Saturday, December 1, 1:15 PM PT, Grand Ballroom 7, Marriott Marquis San Diego Marina
Abstract #123, Oral Presentation

Ixazomib-Lenalidomide-Dexamethasone (IRd) Consolidation Following Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Large Multi-Center Phase II Trial Saturday, December 1, 10:00 AM PT, Grand Hall C, Manchester Grand Hyatt San Diego
Abstract #281, Oral Presentation

Multivariable Modeling of Disease and Treatment Characteristics of Adults with B-ALL in MRD-Negative CR after CD19 CAR-T Cells Identifies Factors Impacting Disease-Free Survival Sunday, December 2, 8:30 AM PT, Ballroom 20D, San Diego Convention Center
Abstract #1551, Poster Presentation

Molecular Detection of Minimal Residual Disease Precedes Morphological Relapse and Could be Used to Identify Relapse in Pediatric and Young Adult B-Cell Acute Lymphoblastic Leukemia Patients Treated with Tisagenlecleucel Saturday, December 1,
6:15 PM PT, Hall GH, San Diego Convention Center

Abstract #3272, Poster Presentation

Evaluation of Sustained Minimal Residual Disease (MRD) Negativity in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Treated with Daratumumab in Combination with Lenalidomide Plus Dexamethasone (D-Rd) or Bortezomib Plus Dexamethasone (D-Vd): Analysis of Pollux and Castor Sunday, December 2, 6:00 PM PT, Hall GH, San Diego Convention Center
Blood-based MRD Monitoring
Abstract #147, Oral Presentation

Circulating Tumor DNA Dynamics during Therapy Predict Outcomes in Mantle Cell Lymphoma Saturday, December 1, 12:30 PM PT, Pacific Ballroom 20, Marriott Marquis San Diego Marina
Abstract #3137, Poster Presentation

Undetectable-Minimal Residual Disease (U-MRD6) (10-6 sensitivity) Is Associated with Best Progression-Free Survival for Patients Who Achieve Bone Marrow Undetectable MRD4 (10-4 sensitivity) with First-Line FCR Sunday, December 2, 6:00 PM PT, Hall GH, San Diego Convention Center
About Minimal Residual Disease

Minimal residual disease (MRD), also referred to as measurable residual disease, refers to cancer cells that remain in the body after treatment for patients with lymphoid cancers. These cells can be present at levels undetectable by traditional morphologic methods, microscopic examination of blood, or a bone marrow or a lymph node biopsy.

MRD is used by physicians to detect and monitor disease burden in patients and to inform their treatment decisions. Clinical practice guidelines recommend assessing MRD at multiple time points during treatment and maintenance in MM and ALL, and guidelines for both diseases include NGS as a recommended testing method. The prognostic value of MRD assessment has been demonstrated in multiple lymphoid cancers. Controlled trials have shown that even small amounts of disease are profoundly significant for predicting a patient’s long-term clinical outcomes. Therefore, highly sensitive, standardized molecular technologies are needed for reliable detection of MRD.

Measurement of MRD is currently being evaluated as a way to measure efficacy in drug trials, with the potential to expedite the approval of emerging therapies.

About the clonoSEQ Assay

The Adaptive Biotechnologies clonoSEQ Assay has been granted De Novo designation by the FDA as an in vitro diagnostic (IVD) to detect and monitor minimal residual disease (MRD) in patients with multiple myeloma (MM) and B-cell acute lymphoblastic leukemia (ALL) using DNA from bone marrow samples. It identifies and quantifies specific DNA sequences found in malignant cells, allowing clinicians to monitor patients for changes in disease burden during and after treatment. This robust assay provides sensitive and accurate measurement of residual disease that allows physicians to predict patient outcomes, assess response to therapy over time, monitor patients during remission and detect potential relapse. The clonoSEQ Assay is a single-site assay performed at Adaptive Biotechnologies. It is also available as a CLIA-regulated laboratory developed test (LDT) service for use in other lymphoid cancers.

clonoSEQ was reviewed under the FDA’s De Novo premarket review pathway, a regulatory pathway for some low- to moderate-risk novel devices for which there is no legally marketed predicate device.

For important information about the FDA-cleared uses of clonoSEQ, including the full intended use, limitations, and detailed performance characteristics, please visit www.clonoSEQ.com/technical-summary