On May 19, 2022 Coinciding with Melanoma Awareness Month, the Melanoma Research Alliance (MRA), the largest non-profit funder of melanoma research, reported funding for 27 research grants totaling $13,046,774 to support new research aimed at advancing melanoma prevention, diagnosis and treatment (Press release, Melanoma Research Alliance, MAY 19, 2022, View Source [SID1234614880]). Melanoma is the deadliest form of skin cancer and the fifth most common cancer in the United States.

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The grants will support 11 Team Science Awards, 10 Young Investigator Awards, and 6 Pilot Awards. MRA grant awards back development of innovative ideas that offer the promise of rapidly improving outcomes for melanoma patients.

This year’s grant awards focus on a variety of approaches, including the use of novel cellular barcodes to identify causes – and possible treatments – of resistant disease; research focused on rare melanoma subtypes ways to improve response to existing checkpoint immunotherapies; and two pilot awards co-funded with the Michael J. Fox Foundation to study the connection between melanoma and Parkinson’s Disease.

"These scientific proposals selected this year for funding by MRA’s expert Grant Review Committee are exceptional," said MRA Chief Executive Officer Marc Hurlbert, PhD. "We are at a pivotable moment in the fight against melanoma. We are thrilled to support this critical work with the hope of benefiting all patients and families dealing with melanoma, and preventing countless more from having to do so."

2022 Melanoma Research Alliance Grant Awards

Team Science Awards

Targeting Oncogenic Gaq in Uveal Melanoma
MRA Team Science Award
Boris Bastian, MD, The University of California, San Francisco

Identification & Validation of Novel Druggable Targets in Mucosal Melanoma
MRA Team Science Award
Genevieve Boland MD, PhD, Massachusetts General Hospital

Targeting Epigenetics to Enhance Anti-Melanoma Immunity
Leveraged Finance Fights Melanoma – MRA Team Science Award
Marcus Bosenberg MD, PhD, Yale University

Targeting RNA Processing to Enhance Mucosal Melanoma Immunotherapy
MRA Team Science Award
Rotem Karni PhD, Hebrew University of Jerusalem

Harnessing B Cell Checkpoints in Melanoma
MRA Team Science Award, collaboratively funded by Brigham and Women’s Hospital and The University of Texas MD Anderson Cancer Center
Vijay Kuchroo DVM, PhD, Brigham and Women’s Hospital, Inc.

Targeting Chromothripsis to Suppress Metastasis and Therapy Resistance
MRA Team Science Award
Roger Lo MD, PhD, The University of California, Los Angeles

Cellular Barcoding to Define Melanoma Drug Resistance and Cell of Origin
MRA Team Science Award for Women in Melanoma Research
Elizabeth E. Patton PhD, University of Edinburgh

Identifying Public Neoantigens, their TCRs and their Rules of Engagement
MRA Team Science Award
Yardena Samuels PhD, Weizmann Institute of Science

Improving Immunological Memory During Anti-PD-1 Immunotherapy
MRA Team Science Award, collaboratively funded by Harvard Medical School and Dana-Farber Cancer Institute
Arlene Sharpe MD, PhD, Harvard Medical School

Noninvasive Prediction of Severe Toxicity from Immune Checkpoint Blockade
MRA Team Science Award, collaboratively funded by Yale University, Washington University, and Stanford University
Mario Sznol MD, Yale University

Team Science Academic-Industry Partnership Award

Analytical and Clinical Validation of a Multiplex IF Biomarker for Anti-PD1
MRA Team Science Academic-Industry Partnership Award
Janis Taube MD, Johns Hopkins University School of Medicine

Young Investigator Awards

New Genetic Tools to Understand the Role of M6A in Melanomagenesis
MRA Young Investigator Award
Claudio Alarcon PhD, Yale University, School of Medicine

Decipher the Epigenetic Code Regulating Cellular Dynamics in Acral Melanoma
MRA Young Investigator Award
Junyue Cao PhD, The Rockefeller University

Targeting Anti-Tumor Immunity in Anatomically Distinct Mucosal Melanomas
MRA Young Investigator Award for Women in Melanoma Research
Kasey Couts PhD, University of Colorado Denver

Investigating Lipid Kinase Pip4k2c in Regulating Anti-Tumor Immunity
Bristol Myers Squibb – MRA Young Investigator Award
Karen Dixon PhD, Brigham and Women’s Hospital

Mechanisms and Relevance of Treg Expansion after PD-1 Blockade in Melanoma
Bristol Myers Squibb – MRA Young Investigator Award
Francesco Marangoni PhD, The University of California, Irvine

Interfering with Early Cell State Transitions to Prevent Drug Tolerance
The Wayne Stinchcomb Big Orange Melanoma Foundation – MRA Young Investigator Award
Florian Rambow PhD, Essen University Hospital

Interrogating Epigenetic Regulation of PD1 in Melanoma-Infiltrating T Cells
Leveraged Finance Fights Melanoma – MRA Young Investigator Award in memory of Michael Konigsberg
Debattama Sen PhD, Massachusetts General Hospital

Tumor-Stroma Metabolic Crosstalk in Melanoma Brain Metastases
Tara Miller Melanoma Foundation – MRA Young Investigator Award
Inna Smalley PhD, H. Lee Moffitt Cancer Center & Research Institute

Investigating the role of FGL1/LAG-3 Axis in Melanoma Immunity
Bristol Myers Squibb – MRA Young Investigator Award
Jun Wang PhD, New York University School of Medicine

mRNA-Based Re-Programming of Terminally Differentiated TILs
MRA Young Investigator Award
Yochai Wolf PhD, The Sheba Fund for Health Service and Research

Pilot Awards

A Strategy to Identify the Basis of Melanoma and Parkinson’s Comorbidity
The Michael J. Fox Foundation – MRA Pilot Award
Deanna L. Benson PhD, Icahn School of Medicine at Mount Sinai

Investigating ARID2 as a Suppressor of Melanoma Metastasis
MRA Pilot Award for Women in Melanoma Research
Emily Bernstein PhD, Icahn School of Medicine at Mount Sinai

Combined Intrathecal Immunotherapeutic Strategies for Melanoma LMD
MRA Pilot Award
Sherise Ferguson MD, University of Texas MD Anderson Cancer Center

Novel Mouse Models of Uveal Melanoma
MRA Pilot Award
Florian Karreth PhD, H. Lee Moffitt Cancer Center & Research Institute, Inc

The Role of APC Mutations in Melanoma Brain Metastasis
Leveraged Finance Fights Melanoma – MRA Pilot Award
James Robinson PhD, The University of Minnesota, Twin Cities

Alpha-Synuclein’s Role in Melanoma Formation and Metastasis
The Michael J. Fox Foundation – MRA Pilot Award
Vivek Unni MD, PhD, Oregon Health & Science University

On May 19, 2022 Brainlab reported that clinicians at UZ Brussel are the first to treat patients with the company’s new Deep Inspiration Breath Hold (DIBH)* technology designed to streamline image guided and surface guided radiation therapy (IGRT and SGRT) and deliver the highest quality of care for breast cancer patients (Press release, Brainlab, MAY 19, 2022, View Source [SID1234614879]). UZ Brussel is a university hospital at the Vrije Universiteit Brussel with 721 hospital beds and almost 4,000 employees. UZ Brussel successfully validated the technology and presented research at the Novalis Circle Symposium at ESTRO on May 8, 2022. The research demonstrates that Brainlab ExacTrac Dynamic DIBH streamlines the process and increases positioning confidence through "on-the-fly" X-Ray confirmation. Internal anatomy verification at the breath hold level may increase confidence in dose sparing of critical structures like the heart.

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Deep Inspiration Breath Hold is a well-established technique and standard of care in treating breast cancer with radiation therapy. When a patient takes a deep breath, the distance between the heart and the chest cavity is increased, reducing the risk of cardiac toxicity during breast cancer treatment. The new Brainlab technology takes traditional surface tracking methodology and augments it with a thermal signature, delivering a fourth dimension to reduce ambiguities otherwise associated with surface tracking systems. Adding synchronized X-ray images to the workflow increases accuracy and clinician confidence by incorporating insights derived from internal bony anatomy. Brainlab DIBH workflow is CE marked and FDA cleared.

"The incorporation of ‘on-the-fly’ X-Ray confirmation streamlines the process and delivers the confidence that the heart is outside of the treatment beam," said Stefan Vilsmeier, President and CEO, Brainlab. "This solution delivers correlation between internal and external anatomy in one shot, revealing any misalignment that would otherwise remain undetected and could result in delivering excess dose to the heart. Partnering with UZ Brussel on new technologies demonstrates our combined interest in expanding personalized digital treatment innovation to other indications requiring high precision radiotherapy."

"This is next generation technology and UZ Brussel is proud to work in close collaboration with our long-time partner Brainlab to validate and present our findings showing the superior speed, innovative postural patient positioning and seamless integration into our therapeutic radiation program," said Prof. Mark de Ridder, Head of the Radiotherapy Department at UZ Brussel. "We’re excited to be the first to use this game changing positioning and breath hold control in breast cancer patients without skin marks. The positive effect on reducing cardiotoxicity on population level is significant. This becomes even more important with the increasing incorporation of neo-adjuvant chemotherapy and new HER2-directed monoclonal antibodies in the treatment strategy."

In 2020, Brainlab installed new ExacTrac Dynamic Patient Positioning and Monitoring systems at UZ Brussel. The system’s deep integration with most linear accelerators enables thermal-surface triggered beam gating and repositioning. ExacTrac IGRT has always been the gold standard in frameless cranial, and high-precision spine stereotactic radiosurgery, enabling ablative treatments with minimal target margins.

With the introduction of the DIBH workflow, Brainlab is delivering the power of integrated IGRT to radiation therapy treatments for breast cancer patients. "We implemented this new workflow over the course of a few days," explained Prof. Thierry Gevaert, Coordinator of the Medical Physics Radiotherapy Department at UZ Brussel. "The use of surface guided technology generates a more stable breathing curve compared to traditional surrogate marker technology. And the system’s X-Ray imaging allows for fast and low-dose internal anatomy verification at breath hold. The accurate triggering and correlation of anatomical verification with ExacTrac kV imaging will be the key differentiator to further margin reduction in breast radiotherapy."

Please access the Dr. de Ridder presentation here and the Dr. Gevaert presentation here.

*Not yet commercially available in all countries. Please contact your sales representative.

On May 19, 2022 Be Biopharma, Inc. ("Be Bio") and National Resilience, Inc. (Resilience) reported a strategic collaboration to advance initial programs in Be Bio’s rare disease pipeline. Be Bio’s proprietary engineered B Cell Medicines (BeCM) platform is harnessing the power of the human B cell to create a new class of autologous and allogeneic cellular medicines that durably and redosably produce therapeutic proteins in vivo without toxic pre-conditioning (Press release, Be Biopharma, MAY 19, 2022, View Source [SID1234614878]).

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The two companies are investing to drive innovation and reliability in cell therapy manufacturing, a critical success factor for broad and meaningful patient impact. As part of this unique partnership, Resilience will dedicate personnel solely to produce and supply Good Manufacturing Practices (GMP)-grade viral vector and cell therapy drug product for the initial programs in Be Bio’s rare disease pipeline. Through a creative cost and risk-sharing model, Resilience will be responsible for manufacturing costs and receive potential future milestones and royalties.

"Over the past year, Be Bio has built a strong foundation with our BeCM platform, pipeline, team, and recent $130 million financing. Manufacturing is critical to rapidly progress our BeCMs to the clinic and we have built non-GMP manufacturing capabilities in our Cambridge facility. This deal allows us to drive GMP manufacturing with an outstanding partner, and in a capital efficient manner," said Joanne Smith-Farrell, Ph.D., Chief Executive Officer at Be Bio. "Resilience’s broad manufacturing capabilities, strong collaborative spirit and dedicated resources to our platform, make them an ideal partner for our BeCM programs."

Resilience will lead clinical GMP manufacturing of both the viral vector and the cell therapy drug product for Be Bio’s initial rare disease programs to support first-in-human clinical trials. Resilience will apply its pioneering bioprocessing solutions and network of cell therapy sites, including facilities in Research Triangle Park, NC, Philadelphia, PA, Waltham, MA and Marlborough, MA to conduct the work.

"This collaboration shows our excitement for the promising science of Be Bio’s proprietary BeCM platforms, and our confidence in their expertise to deliver transformative cell therapies," said Rahul Singhvi, Sc.D., Chief Executive Officer of Resilience. "By working alongside Be Bio early in the drug development process, we aim to accelerate the development of their B cell medicines with the potential to unlock a pipeline of product candidates across a variety of serious diseases."

About B Cells – A New Class of Cellular Medicines

Imagine what could "Be?" In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BeCM). BeCMs have the potential to be durable, allogeneic, redosable and administered without toxic conditioning. The promise of BeCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.

On May 19, 2022 Alchemab Therapeutics, a biotechnology company focused on the discovery and development of naturally-occurring protective antibodies and immune repertoire-based patient stratification tools, reported the publication of research demonstrating the potential of AntiBERTa (Antibody-specific Bi-directional Encoder Representation and Transformers), a transformer neural network that reads the components of an antibody amino acid sequence, to deeply understand the structure and function of antibody sequences (Press release, Alchemab Therapeutics, MAY 19, 2022, View Source [SID1234614877]). The article, titled "Deciphering the language of antibodies using self-supervised learning" has been published online in the journal Patterns. AntiBERTa is a 12-layer transformer model that provides a contextualized numeric representation of antibody sequences and learns biologically relevant information.

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"AntiBERTa forms the basis of Alchemab’s machine learning platform, providing a pre-trained model which is primed for multiple downstream tasks relevant to antibody drug discovery," said Jake Galson, Ph.D., Head of Technology at Alchemab. "We have already demonstrated the utility of AntiBERTa for binding-site prediction, and this is helping us to better identify convergent antibodies associated with disease resilience. We are excited to further progress our research and leverage our expertise to develop pioneering ways of treating diseases in the field of immunotherapy."

The study found that the B cell receptor (BCR) sequence representations separate according to mutational load and the underlying BCR V gene segments used. Importantly, there is distinct partitioning of BCRs derived from naïve versus memory B cells, suggesting that functionally important information is captured by the model. Finally, the model recognized pairs of positions within the BCR sequence that form contacts in three-dimensional space. These data demonstrate that AntiBERTa learns various characteristics of the BCRs, such as B cell origin, activation level, immunogenicity, and structure.

Dr. Jane Osbourn, PhD, Co-founder and Chief Scientific Officer of Alchemab, commented: "Our AntiBERTa technology has the potential to transform our ability to understand antibody structure and function and will inform our understanding of antibody paratopes, or the amino acid sequences comprising the site at which antibodies bind to antigens. It will also enable Alchemab to continue to build its unbiased platform to identify novel oncology and neurodegenerative targets. Alchemab’s novel approach learns from nature and naturally optimized antibodies and works backwards to uncover the most important targets and pathways involved in disease modulation. This approach has been very successful, leading to the identification of several novel oncology and neurodegenerative disease drug targets."

On Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported new data showing that DecisionDx-SCC can independently risk-stratify patients with cutaneous squamous cell carcinoma (SCC) and one or more risk factors according to their biologic risk of metastasis, consistent with findings in previous development and validation studies.1,2 The poster was presented at the 2022 American College of Mohs Surgery (ACMS) Annual Meeting (Press release, Castle Biosciences, MAY 19, 2022, View Source [SID1234614876]).

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DecisionDx-SCC is Castle’s prognostic 40-gene expression profile (GEP) test designed to use a patient’s tumor biology to predict individual risk of metastasis for patients diagnosed with SCC who have one or more high-risk factors. The test stratifies patients into one of three classes based on their biologic risk of metastasis: Class 1 (low risk), Class 2A (moderate risk) or Class 2B (high risk).

"Identifying which patients are at an increased risk of disease progression and metastasis is a challenge for clinicians who may see hundreds of cutaneous squamous cell carcinoma cases in their practices each year," said study author Sarah T. Arron, M.D., Ph.D., Mohs surgeon and dermatologist at Peninsula Dermatology in Burlingame, California. "Using DecisionDx-SCC to add a patient’s biologic risk to our existing clinical and pathologic risk-assessment methods can improve our decision-making and help us to personalize treatment for our patients."

The poster, titled "Performance of the prognostic 40-gene expression profile (40-GEP) test for high-risk cutaneous squamous cell carcinoma (cSCC) in a second independent cohort," highlights data from a second, independent, multi-center study of high-risk SCC patients, consisting of 598 novel patient samples from 43 contributing centers. The poster can be viewed here. With the cohort of patients in this study, combined with the cohort of patients from the first validation study (n=420), the ability of DecisionDx-SCC to independently stratify risk has been confirmed in a total of 1,018 patients.

Kaplan-Meier analysis showed a statistically significant difference in metastasis-free survival (MFS) rates between DecisionDx-SCC Class 1, Class 2A and Class 2B results (p<0.0001, log-rank), demonstrating the ability of the test to risk-stratify patients according to their biologic metastatic risk. As demonstrated by univariate Cox regression analysis, DecisionDx-SCC Class 2A, Class 2B, traditional high-risk clinicopathologic risk factors, American Joint Committee on Cancer Eighth Edition (AJCC8) T3/T4 stages and Brigham and Women’s Hospital (BWH) T2b/T3 stages were all statistically associated with metastatic risk. A DecisionDx-SCC Class 2B result had the highest hazard ratio, 10.71, which was the strongest predictor of metastasis among the analyses. Further, multivariate Cox regression analysis demonstrated that DecisionDx-SCC independently and significantly contributed to risk stratification of patients when combined with traditional high-risk clinicopathologic factors (p<0.05 for Class 2A and 2B), BWH (p<0.001 for Class 2A and p<0.002 for Class 2B) or AJCC8 (p<0.001 for Class 2A and 2B) staging. This reinforces that the test’s results provide risk-stratification value on their own and can add clinical value when used as a complement to other risk-prediction systems.

Overall, the study data confirm what previous development and validation studies1,2 have substantiated: DecisionDx-SCC can accurately classify risk for metastasis in SCC patients with one or more risk factors and provides significant prognostic information independent from current risk prediction methods. Additionally, the study data further support the use of DecisionDx-SCC test results in combination with other risk-assessment and staging systems to guide more refined and risk-aligned patient care.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

More information about the test and disease can be found at www.CastleTestInfo.com.