On October 30, 2018 Distributed Bio, the global leader in computational optimization of fully human monoclonal antibody libraries, reported a discovery collaboration with H3 Biomedicine, Inc. designed to help accelerate the discovery of novel cancer therapeutics (Press release, Distributed Bio, OCT 30, 2018, View Source [SID1234530430]). The collaboration will leverage Distributed Bio’s proprietary SuperHuman antibody library platform to discover therapeutic-ready, preoptimized antibodies against H3 Biomedicine targets. H3 Biomedicine is a clinical stage biopharmaceutical company specializing in the discovery and development of next-generation cancer medicines using its data science and precision chemistry product engine.

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"H3 Biomedicine is an exciting oncology company, with a novel approach to uncovering targets that could lead to new treatments for unmet needs in various types of cancer," said Jacob Glanville Ph.D., Co-founder & CSO, Distributed Bio. "What was clear to us from the outset was that H3 Biomedicine’s goals would require significant advances to the normal antibody selection process. At Distributed Bio we are uniquely positioned to provide the advanced selection, screening and engineering techniques needed to advance important discovery programs."

Under the terms of the agreement, Distributed Bio will discover antibodies by screening its SuperHuman antibody library with antigens provide by H3 Biomedicine. Multiple lead antibodies will be identified using a proprietary assay cascade. The antibodies generated through this method will be available to H3 Biomedicine to advance to clinical development. Distributed Bio will receive research funding and the opportunity for future milestone payments.

"At H3 Biomedicine, we are focused on uncovering novel cancer biology and rapidly translating those learnings to advance novel, first-in-class precision oncology medicines. As our lead clinical development programs continue to progress, we are also pursuing a broad portfolio of research programs and targets," said Andrea Gerken, Vice President, Business Development at H3 Biomedicine. "As part of those research efforts, our collaboration with Distributed Bio will enable us to explore H3’s differentiated approach to antibody drug conjugates targeting RNA splicing."

On October 30, 2018 City of Hope reported that Women with HER2-positive breast cancer that has spread to the brain need more treatment options, and City of Hope and Mustang Bio Inc. are meeting that challenge (Press release, Mustang Bio, OCT 30, 2018, View Source [SID1234530429]). A new City of Hope chimeric antigen receptor (CAR) T cell trial – the first to focus on HER2-positive breast cancer patients with brain metastases – is now enrolling potential participants.

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The phase 1 trial will be conducted in an outpatient setting and will also be the first to use intraventricular delivery of CAR T cells directly to the brains of these patients. It will test the safety and effectiveness of the CAR T cell therapy for patients who have tried other types of treatment that are no longer effective. HER2 refers to a cancer-causing protein called human epidermal growth factor receptor-2, which is found on the cell surface of breast cancer cells, as well as some lung, colon and other cancer cells, and some melanoma cells. About 20 percent of breast cancer patients are HER2-positive, according to the American Cancer Society.

"For a woman who already has breast cancer, learning that a brain tumor has developed can be a frightening diagnosis because there are few treatment options available. CAR T cell therapy may be another tool in our fight against this devastating disease," said Jana Portnow, M.D., City of Hope associate clinical professor in the Department of Medical Oncology & Therapeutics Research and associate director of the Brain Tumor Program. Portnow and Saul Priceman, Ph.D., assistant research professor in City of Hope’s T cell immunotherapy program, who conducted preclinical research that led to the trial’s development, are leading the CAR T cell trial.

"Our hope is that the HER2-specific CAR T cell therapy will target and kill HER2-positive cancer cells, and safely and effectively treat brain metastases in these patients," Priceman added.

CAR T cell therapy is a type of cell-based immunotherapy in which a patient’s own T cells are reprogrammed to actively seek out and destroy cancerous cells. For this trial, the patient’s T cells will be isolated from the blood and genetically engineered to express a CAR that allows these immune cells to target and eradicate HER2-positive cancer cells.

City of Hope, a recognized leader in CAR T cell therapies, has treated more than 200 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world – it currently has 16 ongoing CAR T clinical trials, including a trial that opened recently for patients with primary glioblastoma that expresses the HER2 protein. The institution plans to open a trial in the coming months for patients with bone metastatic prostate cancer.

Mustang Bio Inc. (NASDAQ: MBIO), a company focused on the development of novel immunotherapies based on proprietary CAR T technology and gene therapies for rare diseases, licensed the HER2 technology from City of Hope in 2017.

The HER2 trial meets a crucial need – it is estimated that nearly half of all women with HER2-positive breast cancer will eventually develop brain metastases. The current standard of care for treating brain metastases uses HER2-targeted drugs and/or radiation.

"Targeted agents don’t always work because of the blood-brain barrier, a semipermeable membrane that often prevents easy access of potentially effective therapeutic drugs to the tumors," Portnow said. "Likewise, radiation has its limitations in durably controlling disease. These patients are in desperate need of safe and more effective therapies."

City of Hope researchers were the first to use intraventricular delivery of CAR T cells in patients with glioblastoma, one of the deadliest types of brain tumors. They found that injecting engineered CAR T cells locally into a patient’s brain, or regionally through infusion in the ventricular system, has the potential to eradicate brain tumors.

"Because this type of CAR T cell delivery was found to be safe, City of Hope will now also use this route of administration for patients on this trial," Priceman added.

The trial’s key investigators also include Stephen J. Forman, M.D., the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation; Christine Brown, Ph.D., the Heritage Provider Network Professor in Immunotherapy; and Behnam Badie, M.D., chief of City of Hope’s Division of Neurosurgery and director of its Brain Tumor Program.

On October 30, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported that the Company will present data from the dose escalation portion of its Phase 1 trial of SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, in advanced solid tumor patients in an oral plenary session at the 30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium taking place November 13-16 in Dublin (Press release, Syros Pharmaceuticals, OCT 30, 2018, View Source [SID1234530428]). The presentation will include data on safety, pharmacokinetics and proof-of-mechanism. These data will be the first clinical data presented on a selective CDK7 inhibitor, marking a significant milestone in the development of selective CDK7 inhibitors for the treatment of cancer.

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In additional poster presentations, Syros will present new preclinical data on the mechanistic rationale for SY-1365 in combination with carboplatin in ovarian cancer; the first preclinical data on its oral CDK7 inhibitor program; and the discovery of drug targets and patient subsets from its analysis of the super-enhancer landscape in ovarian cancer.

The abstract for the oral presentation on SY-1365 will remain under embargo until the day of the presentation. The abstracts for the poster presentations are now available online on the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) conference website at View Source

Details on the oral presentation are as follows:

Presentation Title: Proof-of-Mechanism Based on Target Engagement and Modulation of Gene Expression Following Treatment with SY-1365, a First-in-Class Selective CDK7 Inhibitor in Phase 1 Patients with Advanced Cancer
Session Date & Time: Thursday, November 15, 14:30-15:45 GMT (9:30-10:45 a.m. ET)
Presentation Time: 15:30-15:45 GMT (10:30-10:45 a.m. ET)
Session Title: Plenary Session 6: Proffered Papers
Presenter: Dejan Juric, M.D., Massachusetts General Hospital
Abstract Number: 11
Location: Auditorium, The Convention Centre Dublin

Details on the poster presentations are as follows:

Presentation Title: SY-1365, a selective CDK7 inhibitor, enhances carboplatin activity in ovarian cancer cell lines and xenografts, and transcriptionally inhibits homologous recombination repair (HRR) genes
Date & Time: Tuesday, November 13, 12:00-19:00 GMT (7:00 a.m.-2:00 p.m. ET)
Session Title: Poster Session: DNA Repair Modulation
Presenter: Liv Johannessen, Ph.D., Syros
Abstract Number: 50
Location: PB-001, Exhibition Hall, The Convention Centre Dublin

Presentation Title: An oral and selective CDK7 inhibitor demonstrates substantial anti-tumor effect in breast and ovarian cancer models
Date & Time: Tuesday, November 13, from 12:00-19:00 GMT (7:00 a.m.-2:00 p.m. ET)
Session Title: Poster Session: Molecular Targeted Agents – PART 1
Presenter: Claudio Chuaqui, Ph.D., Syros
Abstract Number: 96
Location: PB-047, Exhibition Hall, The Convention Centre Dublin

Presentation Title: Super-enhancer landscapes of ovarian cancer reveal novel epigenomic subtypes and targets
Date & Time: Friday, November 16, from 10:00-14:00 GMT (5:00-9:00 a.m. ET)
Session Title: Poster Session: Molecular Targeted Agents – PART II
Presenter: Matthew Eaton, Ph.D., Syros
Abstract Number: 400
Location: PB-063, Exhibition Hall, The Convention Centre Dublin

On October 30, 2018 Castle Biosciences, Inc., the skin cancer diagnostics company providing molecular diagnostics to improve cancer management decisions, reported the presentation of data highlighting how the accuracy of the DecisionDx-Melanoma gene expression profile (GEP) test in patients with Stage II and IIIA melanoma can improve adjuvant clinical trial design at the 2018 Society for Melanoma Research International Congress held in Manchester, England from October 24-27 (Press release, Castle Biosciences, OCT 30, 2018, View Source [SID1234530427]).

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The study titled, "Implications of a 31-gene expression profile test for cutaneous melanoma on AJCC-based risk assessment and adjuvant therapy trial design," was presented as a poster at the meeting.

Study Background

The adjuvant treatment setting for melanoma has experienced significant advances in recent years. While therapies provide clear benefits for a subset of melanoma patients, they also can be associated with significant adverse effects. Accurate assessment of individual patient risk is increasingly important to guide treatment decisions, especially for those with no evidence of disease.
The analysis focused on the use of the DecisionDx-Melanoma test to inform which Stage II and IIIA melanoma patients are at high risk of recurrence and could benefit from adjuvant therapy. Adjuvant therapy trials are being considered or underway for Stage II and Stage IIIA patients, but recurrence rates in this population make trials in this population challenging.
The study assessed whether the DecisionDx-Melanoma test could have a role in patient selection for future adjuvant therapy clinical trials, and evaluated the potential cost savings associated with patient enrollment based on risk assessment.
Study Details and Key Findings

The DecisionDx-Melanoma test was previously validated in a cohort of 690 patients from 18 centers to accurately predict 5-year risk of recurrence for patients with melanoma (Class 1A lowest risk; Class 2B highest risk).
This analysis included a subset of 173 patients who had Stage II or IIIA melanoma (restaged using American Joint Committee on Cancer [AJCC] 8th edition).
Patients in the Stage II-IIIA cohort who had a Class 1A DecisionDx-Melanoma test result had a 5-year melanoma-specific survival (MSS) rate of 100%, similar to the risk of patients with Stage 1A melanoma. Stage II-IIIA patients who had a Class 2B result had an MSS of 85%, similar to a Stage IIIB risk.
Similarly, 5-year recurrence-free survival for patients in the Stage II-IIIA cohort who had a Class 2B DecisionDx-Melanoma test result was 39% and distant metastasis-free survival was 54%, significantly lower than those for patients with a Class 1A result.
Study results showed that using the DecisionDx-Melanoma test to select patients for a clinical trial, sample size could be reduced by 36% with an overall reduction in trial costs if enrollment focused on patients with a high risk of recurrence as determined by a DecisionDx-Melanoma Class 2B result.
"Optimization of adjuvant clinical trial enrollment for melanoma is increasingly important given the adverse effects that are associated with current targeted and immune checkpoint therapies," said Sancy Leachman M.D., Ph.D., Professor and chair, Department of Dermatology and Director, Melanoma Research Program, Oregon Health & Science University. "These data support application of the DecisionDx-Melanoma test to identify Stage II-IIIA patients who are at higher risk for recurrence and metastasis and are therefore appropriate candidates for adjuvant therapy consideration in a clinical trial."

The poster is available on the www.SkinMelanoma.com website.

About DecisionDx-Melanoma

The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including 702 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included over 1,400 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in multi-center and single-center studies. More information about the test and disease can be found at www.SkinMelanoma.com.

On October 30, 2018 CymaBay Therapeutics, Inc. (Nasdaq: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported that it will host a conference call and live audio webcast on Tuesday, November 6, 2018 at 4:30 p.m. Eastern Time to discuss financial results for the third quarter and nine months ended September 30, 2018 and to provide a business update (Press release, CymaBay Therapeutics, OCT 30, 2018, View Source [SID1234530420]).

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Conference Call Details
To access the live conference call, please dial 877-407-0784 from the U.S. and Canada, or 201-689-8560 internationally, Conference ID# 13683385. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company’s website at View Source