On December 7, 2021 HiberCell, a clinical-stage biotechnology company developing therapeutics to address therapeutic resistance, cancer relapse and metastasis, reported that it will present new data from the ongoing phase 2 open-label clinical trial evaluating the company’s odetiglucan (Imprime PGG), in combination with Merck’s anti-PD-1 therapy pembrolizumab, in patients with metastatic breast cancer at the 2021 San Antonio Breast Cancer Symposium (SABCS) from December 7-10, 2021 (Press release, HiberCell, DEC 7, 2021, View Source;utm_medium=rss&utm_campaign=hibercell-to-present-new-data-on-odetiglucan-plus-pembrolizumab-in-ongoing-phase-2-metastatic-breast-cancer-trial-at-san-antonio-breast-cancer-symposium [SID1234596551]).

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Odetiglucan is a Dectin-1, pattern recognition receptor agonist that has been observed to drive a coordinated innate and adaptive anti-cancer immune cell response in metastatic hormone receptor-positive, HER2-negative breast cancers (mBCA). Hibercell’s prior data supports its belief that combining odetiglucan with pembrolizumab will enhance mBCA patient sensitivity to checkpoint inhibitors (CPI) in those patients who have progressed through hormonal therapy with a CDK4/6 inhibitor. The World Health Organization assigned "odetiglucan" as the International Nonproprietary Name (INN) for Imprime PGG as of November 2021.

Odetiglucan plus pembrolizumab has shown encouraging results in preclinical studies and a prior phase 2 clinical trial, called IMPRIME 1. The ongoing phase 2 clinical trial is now recruiting patients at the SUNY Stony Brook Cancer Center, while actively opening additional clinical trial sites in the U.S.

Presentation number: OT1-18-05
Title: A Multicenter, Open-label, Phase 2 Study of Imprime PGG and Pembrolizumab in Patients with Metastatic Breast Cancer (mBCA) Who Have Progressed Through Prior Hormonal Therapy
Presenter: Alison Stopek, M.D., Stony Brook Cancer Center
Time/Date: Wednesday, December 8, 2021: 5:00 pm – 6:30 pm CT
For more information about HiberCell’s clinical trials, visit the website at www.HiberCell.com.

On December 7, 2021 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of synthetic DNA using its silicon platform, reported the launch of the Twist cfDNA Pan-cancer Reference Standards, a high-quality standardized control for use in the development and continuous monitoring of liquid biopsy tests to detect cancer from blood samples (Press release, Twist Bioscience, DEC 7, 2021, View Source [SID1234596571]).

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Liquid biopsy tests, which rely on NGS-based circulating tumor DNA (ctDNA) analysis, are a promising and growing area in clinical oncology. Liquid biopsy assays can accurately identify a single tumor variant in the presence of thousands of healthy cells. The most sought-after applications in the ctDNA field include early detection of disease, personalization of therapy, monitoring response to therapy, and monitoring for relapse of disease. Developing and standardizing these ultra-sensitive yet accurate ctDNA-based assays is paramount to ensure the resulting analysis from the test informs clinical decisions reliably.

"As the number of clinical validations of liquid biopsies increase, a true ctDNA pan-cancer reference standard, beyond the few variants that are widely available today, will increase liquid biopsies’ accuracy in detecting specific oncogenes and variants," said Florian Battke, director of development at CeGaT GmbH. "There is an obvious benefit of using a synthetic approach like the Twist ctDNA standards, as they are very high quality and closely mimic the properties of real samples without the instability."

The Twist cfDNA Pan-cancer Reference Standards material consists of synthetically designed variant sequences that mimic ctDNA combined with background DNA that is derived from, and closely mimics, human-derived cell-free DNA (cfDNA).

This reference standard can be used by researchers to assist in the development of liquid biopsy assays to establish the analytical limit of detection (LoD) for specific cancer variants and as a control to track the quality of an NGS assay workflow to ensure the fidelity of the assay process.

The Twist cfDNA Pan-cancer Reference Standards can be used within the liquid biopsy workflow, which includes Twist Library Preparation Kit and the Twist Mechanical Fragmentation Kit, for maximum efficacy and provides a large and diverse number of clinically relevant variants, combining best in class methods for variant synthesis with unrivaled control over the specific target allele frequencies in a format which closely mimics the size distribution and fragmentation profile of cfDNA. In contrast, traditional reference standards are limited in the number and variation of variants and typically use cell line-derived DNA which can carry unwanted sequence variations and variable fragment length.

Emily Leproust, CEO and co-founder of Twist Bioscience said, "Building on the success of our SARS-CoV-2 positive controls that are now used in COVID-19 tests worldwide, we believe having precise standard cancer reference controls that can be used in a validated workflow will be a gamechanger to confirm clinical insights from genetic information. While it is possible to create cell-based controls specific to each test, using a robust, precise control set that detects variation in test assays will be pivotal in both development and ongoing monitoring of a wide variety of liquid biopsy assays."

Applying the right reference materials is essential to benchmark the complexity and biological content of DNA found in liquid biopsy samples for assay development and validation. The Twist ctDNA reference material contains over 400 variants, including SNVs, indels, fusions and structural variants, as well as more than 140 clinically relevant variants. All variants are offered with a unique tiling design, which accurately mimics the pattern of naturally derived ctDNAs. All of these features make the Twist ctDNA reference a high-quality standard for the ctDNA variants that cancer liquid biopsy assays are designed to detect.

To demonstrate the limit of detection (LoD) of an ultra sensitive NGS-based liquid biopsy assay, using an accurately quantified ctDNA control is key. Twist’s silicon platform provides an advantage by specifically writing individual variants of interests, thus preventing any interference caused by contaminants derived from cell culture-based methods. Twist’s ctDNA reference material is also well-characterized and quantified, using industry-standard and proprietary methods (NGS, ddPCR, and fluorescence-based quantification).

On December 7, 2021 Crown Bioscience, a JSR Life Sciences company and leading contract research organization (CRO) in preclinical and translational drug development services, reported that it has completed the expansion and renovation of its Crown Bioscience United Kingdom facility (Press release, Crown Bioscience, DEC 7, 2021, View Source [SID1234596590]). The additional laboratory and office space will increase capacity and expand the company’s current in vivo offering by 30 percent and provide dedicated space for a newly acquired high frequency ultrasound unit – a specialized high-resolution imaging device designed to increase the utility of two- and three-dimensional imaging without the need for cell line-tagging, coupled with high precision guided inoculation/dosing of orthotopic and metastatic models.

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"This expansion is a critical step in our ability to provide additional imaging modalities to better visualize and understand tumor progression and response to potential therapies," said Yinfei Yin, PhD, General Manager at Crown Bioscience UK. "This additional imaging platform allows us to perform cutting-edge preclinical studies, offering our customers advanced insights on potential drug candidates before they enter clinical trials."

The Company’s UK site leverages more than 15 years of experience in in vivo optical imaging, including bioluminescence, fluorescence and microCT modalities. Specifically, the addition of high frequency ultrasound will enable better longitudinal evaluation of tumor growth and earlier, more detailed analytics on the tumor microenvironment.

"This site expansion is driven by increased customer demand for access to Crown Bioscience’s in vivo services from the UK and mainland Europe, and allows us to build upon our innovative foundation to develop additional industry-leading technologies," said Armin Spura, PhD, Chief Executive Officer of Crown Bioscience. "Following our recent acquisition of OcellO B.V. and launch of our 3D Ex Vivo Patient Tissue Platform, this milestone enables Crown Bioscience to continue to use the power of partnership to unlock breakthroughs in drug discovery and, ultimately, to provide patients with better treatment options."

Crown Bioscience UK serves customers advancing preclinical and clinical oncology and immuno-oncology studies. The site offers a comprehensive suite of in vivo models, including PDX, CDX and syngeneic portfolios incorporating orthotopic, metastatic, and systemic variations, as well as in vitro and ex vivo services, such as cell viability, invasion/migration assays, immunoassays, 3D-TGA and combination studies/analysis.

On December 7, 2021 AstraZeneca reported that it has entered into a new global development and commercialisation agreement with Ionis Pharmaceuticals, Inc. (Ionis) for eplontersen, formerly known as IONIS-TTR-LRX (Press release, AstraZeneca, DEC 7, 2021, View Source [SID1234596552]). Eplontersen is a ligand-conjugated antisense investigational medicine currently in Phase III clinical trials for amyloid transthyretin cardiomyopathy (ATTR-CM) and amyloid transthyretin polyneuropathy (ATTR-PN). It is designed to reduce the production of transthyretin (TTR protein) to treat both hereditary and non-hereditary forms of TTR amyloidosis (ATTR).

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The companies will jointly develop and commercialise eplontersen in the US, while AstraZeneca will develop and commercialise it in the rest of the world, except in Latin America.

ATTR-CM is a systemic, progressive and fatal condition that leads to progressive heart failure and death within four years from diagnosis.1 It remains underdiagnosed and its prevalence is thought to be underestimated due to a lack of disease awareness and the heterogeneity of symptoms.2 Hereditary ATTR-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade.3

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Eplontersen has the potential to halt the progression of TTR-mediated amyloidosis, irrespective of whether it’s caused by genetic mutations or aging. Thanks to its precise liver-targeting properties, it also has the potential to be a best-in-class treatment for patients suffering from this devastating disease and who currently have limited options."

Hereditary ATTR-PN is expected to be the first indication for which the companies will seek regulatory approval for eplontersen, with the potential to file a new drug application with the US Food and Drug Administration by the end of 2022.

Financial considerations
AstraZeneca will pay Ionis an upfront payment of $200m and additional conditional payments of up to $485m following regulatory approvals. It will also pay up to $2.9bn of sales-related milestones based on sales thresholds between $500m and $6bn, plus royalties in the range of low double-digit to mid-twenties percentage depending on the region. The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions.

The transaction will be funded with cash and is expected to be neutral to Core earnings in 2021. It will be accounted for as an intangible asset acquisition, recognised initially at the upfront amount, with any potential future milestone payments capitalised into the intangible asset as they are recognised.

Ionis will continue to manufacture and supply eplontersen for the existing clinical studies and process qualification. AstraZeneca will be responsible for commercial supply, with transition timing to be agreed by both parties. AstraZeneca will book all sales generated under the agreement.

The transaction is expected to close in the fourth quarter of 2021, subject to customary closing conditions and regulatory clearances. The transaction does not impact the AstraZeneca’s financial guidance for 2021.

Notes

Eplontersen
Eplontersen is a ligand-conjugated antisense (LICA) investigational medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of ATTR, a systemic, progressive and fatal disease.

TTR Amyloidosis (ATTR)
Cardiomyopathy and polyneuropathy due to ATTR are caused by aging or genetic mutations resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium and peripheral nerves, respectively. In patients with ATTR, both the mutant and wild type TTR protein builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death. Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM4,5 and 10,000 – 40,000 patients with ATTR-PN2.

On December 7, 2021 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global, clinical-stage biotechnology company developing and manufacturing novel therapies, reported that it will host a hybrid event featuring key opinion leaders (KOLs) in multiple myeloma on Monday, December 13 at 8pm ET (Press release, Legend Biotech, DEC 7, 2021, View Source [SID1234596573]).

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The meeting will detail new and updated data from the CARTITUDE Clinical Development Program for ciltacabtagene autoleucel (cilta-cel). Cilta-cel is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy being studied for the treatment of patients with relapsed and/or refractory multiple myeloma. The meeting will follow the oral and poster presentations of the studies at the 63rd ASH (Free ASH Whitepaper) Annual Meeting & Exposition.

The event participants will include Ying Huang, PhD, CEO and CFO of Legend Biotech, and the following professionals in hematology and oncology:

Sundar Jagannath, MD, Professor of Medicine, Hematology and Medical Oncology, Mount Sinai School of Medicine; Director, Multiple Myeloma Program at Mount Sinai Hospital
Saad Usmani, MD, Professor of Medicine, Weill Cornell Medical College; Chief of Myeloma Service, Memorial Sloan Kettering Cancer Center of New York
This meeting will be available to investors and other interested parties by accessing the Legend Biotech website at Events and Presentations.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.1 Although treatment may result in remission, unfortunately, patients will most likely relapse.2 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.3 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy.4,5 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.6 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.7

About Cilta-cel
Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy, formerly identified as JNJ-4528 in the U.S. and Europe and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In December 2017, Legend Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel. In addition to a Breakthrough Therapy Designation (BTD) granted in the U.S. in December 2019, cilta-cel received a Priority Medicines (PRiME) designation from the European Commission in April 2019, and a BTD in China in August 2020. In addition, Orphan Drug Designation was granted for cilta-cel by the U.S. FDA in February 2019, and by the European Commission in February 2020. A Biologics License Application seeking approval of cilta-cel was submitted to the U.S. FDA and a Marketing Authorization Application was submitted to the European Medicines Agency.