On May 5, 2020 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported the initiation of patient dosing in the DRAGON Phase 1 dose escalation and dose expansion clinical trial of SRK-181 in patients with locally advanced or metastatic solid tumors (Press release, Scholar Rock, MAY 5, 2020, businesswire.com/news/home/20200505005992/en/Scholar-Rock-Announces-Initiation-Patient-Dosing-Phase [SID1234557056]). SRK-181 is a potent and highly selective inhibitor of latent TGFβ1 activation and is being developed to increase responses to immunotherapy by overcoming primary resistance to anti-PD-1 or anti-PD-L1 antibody therapy.

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"Based on emerging evidence in the field from human and preclinical data implicating TGFβ1 as a key culprit in primary resistance to anti-PD-(L)1 therapy, we are excited to be investigating a rational approach to combination immunotherapy," said Yung Chyung, M.D., Chief Medical Officer of Scholar Rock. "Our team’s focus and determination to advance SRK-181 and this Phase 1 trial, particularly as the evolving COVID-19 pandemic has resulted in various challenges, has been truly impressive. We remain committed to our mission of developing important therapies for patients and the initiation of dosing in this proof-of-concept trial represents an important milestone for us and our TGFβ1 platform."

DRAGON Phase 1 Proof-of-Concept Trial

The DRAGON Phase 1 open-label, dose escalation and dose expansion clinical trial is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SRK-181 in adult patients with locally advanced or metastatic solid tumors enrolled across multiple sites in the U.S. The two-part trial consists of a dose escalation portion (Part A) for SRK-181 as both a single agent and in combination with approved anti-PD-(L)1 therapy, followed by a dose expansion portion (Part B) evaluating SRK-181 in combination with approved anti-PD-(L)1 therapy in multiple tumor-specific cohorts. Intravenous (IV) SRK-181 is administered every 3 weeks (Q3W) and additional dosing regimens may be explored.

Due to the COVID-19 pandemic and the anticipated pace of enrollment, Scholar Rock now plans to provide an update on dose escalation of SRK-181 as a single agent as well as in combination with anti-PD-(L)1 therapy in the fourth quarter of 2020. Clinical response and safety data are anticipated in 2021. Timing of data read-outs may be further impacted by COVID-19-related disruptions.

Part A Dose Escalation: Part A of the Phase 1 trial assesses SRK-181 both as a single agent and in combination with approved anti-PD-(L)1 therapy and will be conducted in a staggered fashion. The safety, PK, and activity of SRK-181 will be evaluated, including effects upon biomarkers, such as CD8 T cell infiltration, based on biopsies before and after treatment.

Part A1 evaluates SRK-181 as a single agent in patients with locally advanced or metastatic solid tumors. The dose escalation will follow a modified 3+3 design and assess doses starting at 80 mg up to 2400 mg (based on an average body weight of approximately 80 kg).

Part A2 evaluates SRK-181 in combination with anti-PD-(L)1 therapy in patients with locally advanced or metastatic solid tumors that exhibit primary resistance to anti-PD-(L)1 antibodies. Lack of response is characterized as either stable disease or progressive disease following at least three cycles of treatment with an approved anti-PD(L)1 therapy, either alone or in combination with chemotherapy. Patients must have received their most recent dose of anti-PD-(L)1 therapy within six months of enrollment. In combination with SRK-181, patients will be treated with the same anti-PD-(L)1 therapy that they had previously tried and did not experience a response. The dose escalation will follow a 3+3 design and assess doses up to 2400 mg.

Part B Dose Expansion: Part B of the trial consists of multiple parallel cohorts to evaluate the anti-tumor activity of SRK-181 in combination with anti-PD-(L)1 therapy. The target indications are expected to include non-small cell lung cancer, urothelial carcinoma, and cutaneous melanoma, amongst other solid tumor types.

Each cohort will enroll up to 40 patients with locally advanced or metastatic solid tumors for which anti-PD-(L)1 therapy is approved and have demonstrated primary resistance, characterized as a lack of response (stable or progressive disease) following at least three cycles of treatment. Patients must have received their most recent dose of anti-PD-(L)1 therapy within six months of enrollment. Similar to Part A2, patients will be treated with SRK-181 in combination with the same anti-PD-(L)1 therapy that they had previously tried and did not experience a response.

About SRK-181

SRK-181 is a potent and highly selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on analyses of human tumors that are resistant to anti-PD-(L)1 therapy, data suggests TGFβ1 is a key contributor to excluding immune cell entry into the tumor microenvironment, thereby preventing normal immune function. By overcoming this immune cell exclusion, Scholar Rock believes SRK-181 has the potential to induce tumor regression when administered in combination with anti-PD-(L)1 therapy. A Phase 1 proof-of-concept clinical trial in patients with locally advanced or metastatic solid tumors is ongoing. The effectiveness and safety of SRK-181 have not been established and SRK-181 has not been approved for any use by the FDA or any other regulatory agency.

On May 5, 2020 PierianDx, the leading clinical genomics informatics company, and University Hospital of Augsburg reported a strategic development partnership to optimize an interpretation and reporting workflow based on the PierianDx Clinical Genomics Workspace platform for the AmpliSeq for Illumina Myeloid and Focus assays (Press release, PierianDx, MAY 5, 2020, View Source [SID1234557055]). Under the agreement, University Hospital of Augsburg will use the PierianDx Clinical Genomics Workspace to create an out-of-the-box bioinformatics and clinical genomics reporting workflow optimized for these AmpliSeq assays and tailored to the specific needs of the European market.

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The AmpliSeq Myeloid and Focus assays accommodate DNA or RNA samples and investigate a number of genes, gene fusions, or expression levels with known relevance to solid- and blood-based cancers. These assays, already in use by University Hospital of Augsburg, are a key part of the hospital’s overall plan to expand its NGS testing program to offer precision medicine treatments to the community it serves.

As assays become more sophisticated, interpretation and reporting have usurped library preparation and sequencing as the most complex portion of the workflow. Manually interpreting each case is simply not scalable, especially with frequently changing literature, guidelines, and clinical trials.

To address these challenges, University Hospital of Augsburg will use the PierianDx Clinical Genomics Workspace, which includes a highly curated, rules-based knowledgebase and clinical sharing network for the rapid classification of variants. Concurrent to its use of Clinical Genomics Workspace, University Hospital of Augsburg will work with PierianDx on an ongoing basis to refine a European market-specific reporting workflow for the AmpliSeq assays. The result will be a refined clinical genomics report, complete with assay-specific variant filters, that is optimized with European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) guidelines, EMA drug labels, and active and recruiting European clinical trials, all of which have been included in the PierianDx platform since 2019.

Sebastian Dintner, Head of Molecular Pathology, University Hospital of Augsburg, states: "We are happy to work with PierianDx to optimize the workflow and pioneer one of the first region-specific reporting solutions for the AmpliSeq assays. By doing so, we will be able to accomplish our mission of expanding our precision medicine offerings to provide advanced cancer care for our patients."

"As we provide streamlined interpretation and supporting solutions for leading assay manufacturers, it’s imperative that we acknowledge region-specific needs of the market," states Rakesh Nagarajan, Founder, President, and Chief Technology and Visionary Officer of PierianDx. "We are excited to partner with University Hospital of Augsburg because it helps us refine our system for the European market."

On May 5, 2020 Bayer reported the launch of Test4TRK program in collaboration with NeoGenomics, Inc. to offer genomic cancer testing for NTRK gene fusions at no cost for patients with RAI-refractory (RAI-R) differentiated thyroid carcinoma (DTC) and metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H) (Press release, Bayer, MAY 5, 2020, View Source [SID1234557054]). NTRK gene fusions, which have been shown to drive tumor growth, are more commonly found in patients with MSI-H mCRC and RAI-R DTC and may play a role in disease management.1-3 Bayer will cover the full cost of the test regardless of the results, treatment decision and patient’s insurance coverage. All eligible patients who enroll and opt-in to the program will receive an RNA-based next-generation sequencing (NGS) test, NTRK NGS Fusion Profile. Patients with an adequate tissue sample will also receive a Pan-Tropomyosin receptor kinase (Pan-TRK) Immunohistochemistry (IHC) test.

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Healthcare professionals and patients can visit www.Test4TRK.com to learn more and download the test request form or call Bayer Medical Communications at +1-888-84BAYER (+1-888-842-2937) for questions on NTRK gene fusions and TRK fusion cancer.

"The results of a genomic cancer test may be a deciding factor in treatment selection, especially for patients with differentiated thyroid cancer who have limited options," said Marcia S. Brose, M.D., Ph.D., Director of the Center for Rare Cancers and Personalized Therapy at the Abramson Cancer Center of the University of Pennsylvania and an Associate Professor in Otorhinolaryngology: Head and Neck Surgery at Penn’s Perelman School of Medicine, who collaborated on the development of the testing platform. "If we implement comprehensive genomic testing early upon diagnosis to uncover NTRK gene fusions, we may have a deeper understanding of patients’ tumors in aiding treatment decisions."

Genomic cancer testing helps detect changes in a tumor’s DNA, called genomic alterations, that can determine how the cancer behaves and why it grows or spreads.4 30-49 percent of patients who undergo genomic cancer testing may have actionable genomic alterations, meaning the alterations can be matched to treatments that have been approved or are in clinical trials.5,6

"After receiving a cancer diagnosis, patients and their loved ones critically need information that can help guide the course of their treatment journey," said Anjee Davis, president of Fight Colorectal Cancer (Fight CRC). "The Test4TRK program aligns with our commitment to empowering patients with educational resources. Colorectal cancer patients need to be armed with biomarker testing because their biomarkers can have an impact on treatment decisions, especially MSI-H. This can inform treatment plans and reduce financial barriers that could prevent some patients from receiving personalized care."

Bayer has developed this program in collaboration with patient organizations Thyroid Cancer Survivors’ Association, Inc. (ThyCa) and Fight CRC as well as Marcia S. Brose, MD, PhD of the University of Pennsylvania. Dr. Brose serves in an advisory role for Bayer and receives honoraria and funding for research support.

The Test4TRK program provides testing for an NTRK gene fusion, which occurs when an NTRK gene joins together, or fuses, with a different, unrelated gene. The NTRK gene fusion creates certain proteins (TRK fusion proteins) that can cause cancer cells to multiply and form a tumor.1 Cancers with NTRK gene fusions can occur in tumors that originate in different sites in the body in varying frequencies and are called TRK fusion cancers.7

"It is critical cancer patients have access to genomic testing for NTRK gene fusions to inform treatment decisions," said Joseph Germino, M.D., Vice President of Medical Affairs, Oncology at Bayer. "Bayer is providing the Test4TRK program as part of our continued efforts to empower the community and help increase the accuracy of cancer diagnoses to improve patient outcomes."

About the Test4TRK Program
Test4TRK is a Bayer-sponsored program offering laboratory testing for NTRK gene fusions (histology and molecular subject to tissue availability) at no cost to eligible patients with RAI-refractory (RAI-R) differentiated thyroid carcinoma (DTC) and metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H). The test results provide information on whether the tumor harbors an NTRK gene fusion to aid in the treatment decision. Bayer will cover the full cost of the test regardless of the test results, treatment decision and patient’s insurance coverage for up to 500 patients in the U.S. Bayer will not cover the associated costs of extracting a viable tumor specimen. For more information, visit www.Test4TRK.com.

About Genomic Cancer Testing
It is important for patients diagnosed with cancer to discuss genomic cancer testing with their healthcare provider (HCP). Genomic cancer testing can identify DNA alterations, or changes, within cancer cells that determine how a tumor behaves or why it grows.4 Genomic cancer testing may help HCPs match patients to approved or investigational therapies based on the specific alteration identified.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now expands to six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On May 5, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the publication of a clinical utility model for its cutaneous squamous cell carcinoma (SCC) prognostic test, DecisionDx-SCC, for patients diagnosed with high-risk cutaneous SCC (Press release, Castle Biosciences, MAY 5, 2020, View Source [SID1234557053]). The test is expected to launch commercially in the second half of 2020.

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The article titled, "Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management," was published in the peer-reviewed journal, Current Medical Research and Opinion (CMRO).

This publication proposes a framework for integration of DecisionDx-SCC into existing management pathways for a risk-appropriate approach in high-risk cutaneous SCC patients (as defined by having one or more high-risk factors and consistent with the National Comprehensive Cancer Network (NCCN) guidelines).

"Castle’s DecisionDx-SCC test is designed to stratify risk of regional or distant metastasis in high-risk cutaneous SCC patients," said Aaron Farberg, M.D., first author, Icahn School of Medicine at Mount Sinai, New York and Arkansas Dermatology Skin Cancer Center, Little Rock, Arkansas. "This manuscript proposes a framework for clinical use of this test, along with current risk stratification tools within established management pathways. The expectation is that the test will enable more informed clinical decisions about adjuvant therapy and other management options."

Disease and Study Background

Approximately 1 million patients are diagnosed with SCC of the skin in the U.S. each year, and the incidence continues to grow; while the majority of patients have a favorable prognosis, approximately 200,000 patients are identified as high risk.
NCCN guidelines for SCC define treatment pathways based on risk of local recurrence or metastasis. For SCC, there are two clinicopathologically defined categories: low risk and high risk. NCCN defines high risk as SCC patients with one or more of several high-risk clinicopathologic features.
The study objective was to integrate gene expression profiling into the management of high-risk SCC within NCCN guidelines to improve risk-aligned management recommendations.
DecisionDx-SCC stratifies patients into three categories based on risk of metastasis: Class 1 (low-risk), Class 2A (high-risk) and Class 2B (highest-risk).This study was designed to evaluate possible changes in management for 300 NCCN high-risk cutaneous SCC patients, when considering DecisionDx-SCC test results.
Study Findings

Combining DecisionDx-SCC class with American Joint Committee on Cancer T stage identified a group of 159 low-risk patients (Class 1, T1-T2) with a 7.5% rate of metastasis. Similarly, combining test results with Brigham and Women’s Hospital staging identified 173 patients with a metastasis rate of 8.1%. Rates in both groups approached the metastasis rate of 6% observed for the general cutaneous SCC patient population.
By comparison, Class 2B patients in the study (n=24) had rates of metastasis equal to or surpassing 50%, regardless of the staging system with which the Class 2B result was combined, a rate that may warrant an NCCN-defined, high intensity management plan.
Following incorporation of DecisionDx-SCC results with T stage for 300 patients with NCCN high-risk features, more than 50% would have been recommended a low intensity management plan, while 34-39% would be recommended for a moderate intensity plan and only 8% for a high intensity plan.
The DecisionDx-SCC test is the second skin cancer test discovered, developed and validated by Castle Biosciences.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers. Approximately 1 million patients are diagnosed with SCC each year in the U.S. While the majority of patients have a favorable prognosis, approximately 200,000 patients are identified as high risk. National guidelines provide for broad, aggressive treatment plan recommendations relative to low-risk patients. Traditional clinicopathologic based risk-factor staging systems suffer from low positive predictive value; meaning many more patients are classified as high risk than actually develop metastatic disease. This may lead to over- and under-treatment of a substantial number of cutaneous SCC patients. To address this clinical need, Castle Biosciences has developed a gene expression profile test designed to improve upon current staging systems and identify patients with cutaneous SCC at high risk for metastasis, in order to enable more informed, objective clinical decisions regarding adjuvant therapy and other management options.

On May 5, 2020 LifeMax Laboratories, Inc. ("LifeMax"), a private company focused on developing first-in-class or best-in-class therapeutics for the treatment of orphan diseases with few or no therapeutic options, reported the appointment of Michael Huang, MD, as its Chief Medical Officer (Press release, LifeMax Laboratories, MAY 5, 2020, View Source [SID1234557052]). LifeMax has several clinical stage programs. LM-030, licensed from Novartis and with fast track designation, rare pediatric disease designation and orphan drug designation, is in a Phase 2/3 trial for the treatment of Netherton syndrome. AMB-051, licensed from Amgen through AmMax, its majority-owned subsidiary, and delivered via a patented technology, is in development as a best-in-class, well-differentiated and broadly applicable treatment for tenosynovial giant cell tumor.

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"We are very pleased to have Dr. Huang on board. Dr. Huang brings with him a wealth of experience in drug development including both small and large molecules across a diverse range of therapeutic indications, especially in orphan indications. Dr. Huang’s expertise fits very well with our portfolio of first-in-class or best-in-class therapies for orphan diseases," said Larry Hsu, LifeMax’s Co-founder and CEO, an industry veteran who previously founded and built Impax Laboratories into a publicly traded multi-billion-dollar company.

"I am delighted to join LifeMax at such an exciting time. I am very impressed with LifeMax’s management team, its strategy, and robust science-driven portfolio focused on orphan diseases that address significant unmet medical needs. I look forward to working with the team to advance our portfolio towards regulatory approval and commercialization," said Dr. Huang.

Dr. Huang was most recently Chief Medical Officer of Spruce Biosciences. He is an experienced biopharmaceutical industry executive who has successfully advanced therapeutics across modalities through all phases of development to regulatory approval. He is the author or co-author of numerous peer-reviewed journal articles, abstracts, and scientific publications. Dr. Huang received his bachelor’s degree in molecular and cell biology from the University of California at Berkeley, his medical degree from the Chicago Medical School, and his post-graduate internship and residency training from the University of California at Irvine.