On January 25, 2022 Gilead Sciences Inc. (Nasdaq: GILD) reported that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on studies evaluating the combination of magrolimab plus azacitidine due to an apparent imbalance in investigator-reported suspected unexpected serious adverse reactions (SUSARs) between study arms (Press release, Gilead Sciences, JAN 25, 2022, View Source [SID1234606787]). While no clear trend in the adverse reactions or new safety signal has been identified by Gilead at this time, the partial clinical hold is being implemented by Gilead across all ongoing magrolimab and azacitidine combination studies worldwide in the best interests of patients as additional data is gathered and analyzed to address the concerns raised by FDA.

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During the partial clinical hold, screening and enrollment of new study participants will be paused in any study investigating the combination of magrolimab with azacitidine. Patients already enrolled in these clinical studies may continue to receive magrolimab and azacitidine, or placebo, and continue to be closely monitored according to the current study protocol. Gilead is currently notifying clinical investigators and global regulatory authorities about the partial clinical hold. Other magrolimab studies, or cohorts, that are not studying the combination of magrolimab plus azacitidine, will continue without any impact by the partial clinical hold.

"The safety and well-being of people enrolled in our studies is our top priority. We will share more information with the medical and patient community as soon as we can," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "Considering the high unmet need for new medicines in myelodysplastic syndrome and acute myeloid leukemia, we will work closely with regulatory authorities worldwide to continue the magrolimab development program appropriately. We remain confident in the potential of magrolimab across a broad range of tumors, including the other, ongoing magrolimab studies. We are grateful to those participating in our studies, their families, and the investigators for their continued contributions to the clinical program for magrolimab."

Gilead is working with regulatory authorities to determine next steps to release the partial clinical hold for new patient enrollment for the affected studies.

The studies impacted by this partial clinical hold include:

Phase 3 ENHANCE study in myelodysplastic syndrome (MDS; NCT04313881)
Phase 3 ENHANCE-2 study in acute myeloid leukemia (AML; TP53 mutated patients; NCT04778397)
Phase 3 ENHANCE-3 study in unfit AML (NCT05079230)
Phase 1b study in MDS (NCT03248479)
Phase 2 study in myeloid malignancies (NCT04778410) *only the azacitidine combination cohorts
The studies not impacted include:

Phase 2 study in diffuse large B-cell lymphoma (NCT02953509)
Phase 2 study in multiple myeloma (NCT04892446)
Phase 2 study in head and neck squamous cell carcinoma (NCT04854499)
Phase 2 study in solid tumors (NCT04827576)
Phase 2 study in triple-negative breast cancer (NCT04958785)
Phase 2 study in colorectal cancer, planned and not currently recruiting
About Magrolimab

Magrolimab is a potential, first-in-class investigational monoclonal antibody against CD47 and a macrophage checkpoint inhibitor that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, with the goal of blocking the "don’t eat me" signal used by cancer cells to avoid being ingested by macrophages. Magrolimab is being developed in several hematologic cancers, including myelodysplastic syndrome (MDS), as well as solid tumor malignancies.

More information about clinical trials with magrolimab is available at www.clinicaltrials.gov.

On January 25, 2022 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 a presentation at the 2nd Annual TGFβ for Immuno-Oncology Drug Development Summit (January 25-27, 2022) (Press release, Scholar Rock, JAN 25, 2022, View Source [SID1234606786]).

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"Development of a Comprehensive Biomarker Strategy to Support DRAGON, a Phase 1 Clinical Trial of SRK-181, the latent TGFβ1 Inhibitor" will be presented on January 27th, 2022, at 11:00 AM EST. The presentation, led by Si Tuen Lee-Hoeflich, Director, Translational Sciences at Scholar Rock, will discuss the SRK-181 biomarker strategy in relation to the DRAGON Phase 1 proof-of-concept trial (NCT04291079). The goal of the trial is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SRK-181 administered alone and in combination with an anti-PD-(L)-1 in adult patients with locally advanced or metastatic solid tumors. The biomarker strategy will focus on the evaluation of biomarkers relevant to the mechanism of action of SRK-181 to facilitate the clinical development of Scholar Rock’s immuno-oncology (IO) program and to identify the next wave of IO biomarkers that correlate with anti-tumor response.

"We are excited to be presenting at the TGFβ for Immuno-Oncology Drug Development Summit on our biomarker strategy for SRK-181 in support of DRAGON," said Gregory Carven, Ph.D., Chief Scientific Officer. "Our biomarker efforts play an important role in advancing our understanding of the mechanisms of action of selective inhibition of TGFβ1 and for facilitating the development of SRK-181, which we hope will positively impact the lives of those affected by cancers that are resistant to checkpoint blockade."

Initial Part A data from the ongoing DRAGON trial in patients with locally advanced or metastatic solid tumors were presented by Scholar Rock at the 36th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2021, supporting dose selection and advancement into Part B. Part B will assess SRK-181 in combination with an approved anti-PD-(L)1 therapy across multiple solid tumor cohorts to test proof of concept. To learn more about DRAGON, visit clinicaltrials.gov.

For Summit information, visit: www.tgf-beta-summit.com

About SRK-181

SRK-181 is a 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 tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, thereby inhibiting anti-tumor immunity (1). Scholar Rock believes SRK-181, which specifically targets the latent TGFβ1 isoform, has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. The DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) in patients with locally advanced or metastatic solid tumors is ongoing. The efficacy and safety of SRK-181 have not been established. SRK-181 has not been approved for any use by the FDA nor any other regulatory agency.

(1) Martin et al., Sci. Transl. Med. 12: 25 March 2020

On January 25, 2022 Iterative Scopes, a pioneer in the development of precision-based gastrointestinal disease technologies, reported that it has entered into a collaboration with Janssen Research & Development, LLC (Janssen) in which Iterative Scopes will work with the Janssen Data Science and Immunology teams to augment Janssen’s clinical trials for inflammatory bowel disease (IBD) with the deployment of cutting-edge artificial intelligence (AI) and computer vision tools (Press release, Janssen Research & Development, JAN 25, 2022, View Source [SID1234606785]).

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Patient recruitment and clinical trial workflow inefficiencies are ongoing challenges for gastrointestinal clinical researchers and drug developers. Through this agreement, Iterative Scopes and Janssen will work together to integrate computational gastroenterology solutions to enhance assessment and interpretation of endoscopic video images, facilitating recruitment of eligible patients for Janssen’s IBD clinical trials. This collaboration has significant potential to addressing the bottlenecks in IBD clinical research, helping identify the right patients for each trial, reducing unnecessary screening costs, and accelerating trials.

"Our team at Iterative Scopes is thrilled to be collaborating with Janssen, to help solve some of the toughest problems facing drug development for Inflammatory Bowel Disease with artificial intelligence," said Jonathan Ng, Founder and CEO of Iterative Scopes.

Johnson & Johnson Innovation – JJDC, Inc., the strategic venture capital arm of Johnson & Johnson, participated with other investors in Iterative Scopes’ $30 million Series A financing, which closed in August 2021, as well as their $150 million Series B financing, which closed in December 2021.

On January 25, 2022 Personal Genome Diagnostics Inc. (PGDx), a leader in cancer genomics, reported an update to the Proprietary Laboratory Analyses (PLA) code for its comprehensive genomic profiling test, PGDx elio tissue complete (Press release, Personal Genome Diagnostics, JAN 25, 2022, View Source [SID1234606784]). The Centers for Medicare & Medicaid Services (CMS) finalized a national reimbursement rate of $2,919.60 for the PLA code (0250U) that PGDx obtained for the test.

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"We are thrilled that CMS has responded to PGDx’s advocacy efforts, agreeing with our crosswalk recommendation for the previously obtained PLA code," said PGDx CEO Megan Bailey. "The PGDx elio tissue complete test enables rapid and actionable genomic insights for patients living with advanced cancers, and the national reimbursement rate as determined by CMS will allow for more patients to receive targeted insights and informed treatment options that could improve outcomes."

The new Medicare payment rate went into effect on January 1, 2022. More information can be found in the latest Medicare Clinical Laboratory Fee Schedule Files.

The PGDx elio tissue complete solution is an in-house comprehensive genomic profiling (CGP) test that identifies key genomic alterations and guideline supported biomarkers in solid tumors using a 500+ gene panel. PGDx elio tissue complete is the industry’s first and only NGS diagnostic kit for comprehensive tumor profiling that is FDA cleared and CE-IVD marked for use in labs worldwide.

On January 25, 2022 Lineberger Comprehensive Cancer Center reported An anonymous donor has made a $25 million gift to establish the UNC Lineberger Center for Triple Negative Breast Cancer and to support other key UNC Lineberger initiatives (Press release, Lineberger Comprehensive Cancer Center, JAN 25, 2022, View Source [SID1234606783]). This is the largest donation in UNC Lineberger’s history, and it enables the cancer center to advance its groundbreaking research on diagnosing and treating a highly aggressive breast cancer that disproportionately affects Black, Latina and young women and historically has limited research funding.

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The gift was made in gratitude for the care a family member received while being treated for cancer at UNC, and to help expand and expedite the cutting-edge cancer research being conducted at UNC Lineberger. Specifically, the donor designated their investment to help women and men with all types of breast cancer, especially triple negative breast cancer because of its poor prognosis. In addition, the gift will support research directed toward developing more effective treatments for metastatic disease, improving pediatric cancer care, and eliminating racial disparities in cancer treatment outcomes.

Lisa A. Carey, MD, MSc, FASCO, will serve as the inaugural director of the UNC Triple Negative Breast Cancer Center. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research and a medical oncologist who specializes in treating breast cancer patients, said it is hard to overestimate the gift’s potential impact on advancing triple negative breast cancer research and care.

"While research advances the past 30 years have led to new and more effective treatments for many types of breast cancer, this isn’t the case with triple negative breast cancer," said Carey, who, in addition to her clinical responsibilities, is the deputy director of clinical sciences and co-leader of the breast cancer research program at UNC Lineberger. "The good news is this gift will be a game changer. It provides the cancer center with the resources to expand and speed the pace of our research focused on generating insights that lead to better treatments and outcomes for women with triple negative breast cancer."

Accounting for roughly 10-20% of breast cancer cases in the United States, triple negative breast cancer is so named because it lacks the estrogen, progesterone and HER2 protein receptors commonly associated with other breast cancers. It is an aggressive, fast-growing cancer that has a high risk of spreading beyond the breast and of recurring despite treatment. It has significantly poorer outcomes than other breast cancers, and it disproportionally affects Black, Latina and young women. The only current standard of care involves chemotherapy.

In addition to establishing this new research center, the money will create multiple professorships and accelerate three strategic research initiatives that build on existing UNC Lineberger strengths:

Developing new treatments particularly those that harness a patient’s immune system, including chimeric antigen receptor t-cell (CAR-T) immunotherapy. The objective is more personalized, more effective and less toxic treatment than currently available;
Expanding the genetic understanding and classification of cancer types to improve diagnostics and uncover new targets and modes of therapy;
And creating greater knowledge of nutrition and metabolism and their impact on disease prevention and more holistic treatment options.
"Our world-class researchers at the UNC Lineberger Comprehensive Cancer Center are applying innovative approaches to solving some of the grand challenges of our time," said UNC-Chapel Hill Chancellor Kevin M. Guskiewicz. "Our experts have done foundational work, especially in the space of triple negative breast cancer. Under Lisa Carey’s leadership, they are uniquely positioned to make the most of this generous gift and find life-saving treatments that improve health outcomes for patients in North Carolina and beyond."

Foundational research at UNC Lineberger

UNC Lineberger is internationally recognized for its foundational discoveries that have advanced the field of triple negative breast cancer research.

In 2000, Charles Perou, PhD, the May Goldman Shaw Distinguished Professor of Molecular Oncology and co-leader of the UNC Lineberger breast cancer research program, published a groundbreaking paper identifying the molecular subtypes of breast cancer and demonstrating that breast cancer was not one disease but a collection of diseases with different prognoses. Specifically, the findings defined and characterized the dominant biology underlying triple negative breast cancer.

In 2001, Carey and her UNC Lineberger colleagues launched the first clinical trial in the U.S. that targeted triple negative breast cancers. Through its longstanding population-based study, the Carolina Breast Cancer Study, UNC Lineberger researchers also were the first to demonstrate that triple negative breast cancer disproportionately affected Black women, particularly young black women.

"UNC Lineberger has a world-leading record of advancing understanding of triple negative breast cancer and its therapy," said H. Shelton Earp, MD, UNC Lineberger director. "This remarkable gift will enable us to create an unmatched national hub of research excellence combining and enhancing our expertise in genomics, immunotherapy, and cancer nutrition towards more effective and less toxic therapy for advanced triple negative breast cancer, and with the knowledge gained and our world class community engagement team, better prevention, early detection, and timely therapy for all North Carolina’s rural and urban populations."

"This magnanimous gift is both inspiring and transformative, and it will be life-saving," said A. Wesley Burks, MD, dean of the UNC School of Medicine, vice chancellor for medical affairs, and CEO of UNC Health. "In addition to building on the depth of our expertise in cancer research and care, this gift enables us to focus on uncovering what makes some cancers so difficult to treat and identifying the drivers of racial disparities in cancer treatment outcomes. This is critically important work."