On May 26, 2020 Bio-Techne (NASDAQ:TECH), a global life sciences company providing innovative tools and bioactive reagents for the research and clinical diagnostic communities and Leica Biosystems, a global leader in workflow solutions and automation, reported the European launch of the CE-IVD marked RNAscope In Situ Hybridization Detection Kit for automation on the BOND-III platform (Press release, Bio-Techne, MAY 26, 2020, View Source [SID1234558437]). The combination of Bio-Techne’s RNAscope and Leica’s BOND-III will provide pathologists access to an unprecedented number of leading applications to support their diagnostics labs.

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Tissue-based diagnostics are growing in globally and there is a demand for high throughput, streamlined workflows that enable visualization of genomic expression at the individual cell level. RNAscope, a leading RNA ISH technology, improves on traditional ISH methodologies through higher target sensitivity and specificity. This combined with the automation of the Leica BOND-III, will optimize and streamline the applications in diagnostic labs.

"We are excited to expand our Leica partnership with the launch of our CE-IVD marked detection kit in Europe. Diagnostic labs will now have access to the fully automated RNAscope technology, providing pathologists with a powerful new tool to evaluate biomarkers involved in cancer, infection, and other important human diseases," said Kim Kelderman, President, Diagnostics and Genomics Segment of Bio-Techne.

"During these difficult times and ever-changing world due to COVID-19, we are excited about this innovative product as it delivers the benefit of improved workflow, reduced hands on time and provides our European pathology partners an additional tool in their IVD tool box against various diseases," said Colin White, Global Vice President, Advanced Staining and Imaging at Leica Biosystems.

The RNAscope In Situ Hybridization Detection Kit and Probes are a robust technology that identifies RNA expression patterns and localization at the single cell level with spatial and morphologic context. The RNAscope technology is highly sensitive, and specific due to its double Z probe design, resulting in an extremely high signal-to-noise ratio of staining in various tissues types, allowing diagnostic pathologists to visualize, localize, and quantify biomarker expression simultaneously.

Building on its legacy of excellence in advanced staining technology and pathology processes the new BOND-III makes it easier for labs to quickly and consistently deliver complete cases to pathologists. With optimal patient care depending on an accurate and timely diagnosis, the latest advance to the BOND-III stainer incorporates a unique set of productivity innovations to support pathology labs’ drive for procedural efficiency and diagnostic confidence.

On May 26, 2020 AstraZeneca reported that it will collaborate with ArcherDX, a genomic analysis company focused on precision oncology, to use personalised cancer monitoring to detect minimal residual disease (MRD) in patients with early-stage non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, MAY 26, 2020, View Source [SID1234558436]).

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ArcherDX’s personalised assay will be used in AstraZeneca’s recently launched Phase III MERMAID-1 trial to evaluate the effect of adjuvant treatment with Imfinzi (durvalumab) plus chemotherapy versus chemotherapy alone on disease-free survival (DFS). The trial is in patients with completely resected, Stage II and III NSCLC who show evidence of MRD suggesting a high risk of relapse.

MRD describes a very small number of otherwise undetectable cancer cells that shed circulating tumour DNA (ctDNA) in the blood. Monitoring for the presence of MRD using ctDNA may provide valuable information on how well a treatment is working, inform prognosis, and detect if a patient’s cancer has returned. Ultimately, MRD detection may enable physicians to intervene earlier and tailor the best treatment options for individual cancer patients.
Charles Swanton, MD, PhD, Professor at UCL and the Francis Crick Institute, Chief Clinician at Cancer Research UK, leader of Tracking Cancer Evolution through Therapy (Rx) (TRACERx) and international coordinating investigator in the MERMAID-1 trial, said: "MERMAID-1 is a novel randomised trial using ctDNA to identify patients at high risk of recurrence after surgery who may benefit from intervention with immunotherapy. We hope this approach will lead to better patient outcomes by intensifying treatment for patients most likely to relapse, while avoiding additional chemotherapy after surgery when not needed."

José Baselga, Executive Vice President of Oncology R&D, said: "While detecting and monitoring for minimal residual disease has proven challenging in solid tumours, the MERMAID-1 trial and this partnership stand to break new ground in lung cancer. This innovative endeavour is reflective of our strategy to improve cancer outcomes by treating patients as early as possible. It is in this early setting that the chance of cure is higher and identifying personalised, effective treatments could increase survival and improve quality of life."

Jason Myers, Chief Executive Officer and co-founder of ArcherDX, said: "While there has been progress in improving adoption of precision oncology for patients with late-stage cancers, there is a pressing need to accelerate access to precision oncology for all patients diagnosed with cancer regardless of the stage or location of the care setting. AstraZeneca shares this critical mission, and we are pleased to partner with them in the development of biomarker-driven therapies and the expansion of personalised cancer monitoring for all patients."

Under the terms of the agreement, ArcherDX will perform whole exome sequencing of NSCLC patient samples and generate highly sensitive, personalised ctDNA assays to test for MRD that remains after a patient’s successful surgery. The ongoing development of these assays is informed by the TRACERx study, funded by Cancer Research UK and led by UCL and the Francis Crick Institute.

Imfinzi is being tested in an extensive development programme in lung cancer with several ongoing Phase III trials in earlier stages of NSCLC in potentially curative settings.

Lung cancer

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% classified as NSCLC.2 Approximately 39% of patients with NSCLC present with localized or regional lung cancer, where surgery (complete resection) may be an option.3 Among Stage II-III patients who undergo surgery, up to 60% eventually develop recurrence.4

MERMAID-1

MERMAID-1 is a randomized, multi-centre, double-blind, placebo-controlled Phase III trial evaluating adjuvant Imfinzi in combination with chemotherapy versus standard-of-care chemotherapy in approximately 330 patients diagnosed with resectable (Stage II-III) NSCLC who have undergone complete resection of the primary tumour. The primary endpoint is DFS for patients who show evidence of MRD, which will be tested using a highly sensitive, personalised ctDNA assay based on whole exome sequencing of patient samples.

Collaboration between AstraZeneca and ArcherDX

ArcherDX’s personalised cancer monitoring (PCM) technology is intended to detect MRD in early-stage cancer patients following surgery, and it has received a Breakthrough Device Designation from the US Food and Drug Administration. ArcherDX plans to leverage the PCM assays to develop companion diagnostics for AstraZeneca’s selected medicines, and together, the companies plan to seek regulatory approval if clinical trials are completed successfully. The assays are currently for investigational use only.

PCM, TRACERx and Cancer Research UK

TRACERx (Tracking Cancer Evolution through therapy (Rx)), which informs the ongoing development of the ArcherDX PCM assay, is the single biggest investment in lung cancer research by Cancer Research UK. Taking place over nine years, the translational research programme is the first study to look at the evolution of cancer in real time and immense detail. Researchers follow patients with lung cancer all the way from diagnosis through to either disease relapse or cure after surgery, tracking and analysing how their cancer develops. TRACERx is led by University College London and the Francis Crick Institute via the Cancer Research UK Lung Cancer Centre of Excellence and also supported by the National Institute for Health Research, University College London Hospitals Biomedical Research Centre and the Rosetrees Trust.

Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the Phase III PACIFIC trial. Imfinzi is approved for the 1st-line treatment of extensive-stage SCLC in combination with SoC chemotherapy in the US and Singapore. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumours.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action. AstraZeneca aims to address the unmet needs of patients with EGFRm tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with the approved medicines Iressa (gefitinib) and Tagrisso, and its ongoing Phase III trials LAURA, and FLAURA2.5-7

AstraZeneca is committed to addressing tumour mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD which test Tagrisso in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines. Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate is in development for metastatic non-squamous HER2-overexpressing or HER2-mutated NSCLC including trials in combination with other anticancer treatments.

An extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a targetable genetic mutation which represents up to three-quarters of all patients with lung cancer.8 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON and PEARL) and for patients in earlier stages of disease including potentially curative settings (Phase III trials MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in combination with tremelimumab and/or chemotherapy. Imfinzi is also in development in the Phase II combination trials NeoCOAST, COAST and HUDSON in combination with potential new medicines from the early-stage pipeline.

AstraZeneca in Immuno-Oncology

Immuno-oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca’s Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With six new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On May 25, 2020 Nail Imune Biotech Co., Ltd. (Location: Minato-ku, Tokyo, hereinafter "Noil Imune") and C4U Co., Ltd. (Location: Suita, Osaka Prefecture, hereinafter "C4U") are now editing the next-generation genome of C4U (Press release, Noile-Immune Biotech, MAY 25, 2020, View Source [SID1234561509]). Combining the CRISPR/Cas3 technology, which is a technology, with the PRIME (Proliferation inducing and migration enhancing) technology for adapting genetically modified immune cell therapies such as CAR-T and TCR-T possessed by Noil Imune to solid cancer We would like to inform you that we have signed an agreement for joint research and commercialization of cross-type allogeneic genetically modified immune cell therapy technology.

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The CRISPR/Cas3 technology, which is the basic technology of C4U, is the research result of Prof. Tomoshi Mashita of the Institute of Medical Science, University of Tokyo, who is the founding member of C4U and advisor of science and technology, and Professor Junji Takeda of the Institute of Microbial Diseases, Osaka University. A new genome editing technology using the CRISPR/Cas3 system developed based on It is a technology that can counter the CRISPR/Cas9 system, which is currently being researched all over the world, and is attracting attention as a promising genome editing technology that is not affected by the complicated patent situation regarding Cas9.

In addition, PRIME technology, which is the basic technology of Noyle Immune, is the scientific founder and director of Noyle Immune, and Professor Koji Tamada of the Graduate School of Medicine, Yamaguchi University (Professor, Gene and Cell Therapy Center, Institute of Medical Science, University of Tokyo). It is a technology related to cancer immune cell therapy such as CAR-T developed by et al. CAR-T is a technology that not only enhances the functions of CAR-T, etc. by producing cytokines and chemokines, but also causes cancer injury by cancer patients’ own endogenous immune cells.

"I am very pleased to be able to form a business alliance with C4U, which has excellent genome editing technology of its own." In this project, we will combine the PRIME CAR-T technology of Noil Imune and the genome editing technology of C4U. By combining these, we will promote the development of highly active CAR-T cells that utilize immune cells derived from alleles.The combination of domestic technologies is highly versatile and can exert therapeutic effects even on solid cancers. We hope that next-generation CAR-T cells will be developed and a treatment method that will save more patients will be created.This project is based on the Ministry of Education, Culture, Sports, Science and Technology subsidy project "Regional Innovation Ecosystem Formation Program". We are aiming to develop the world’s most advanced cancer immunotherapy with the help of various researches including the beginning."

In addition, C4U’s Satoshi Mashita said, "The PRIME CAR-T technology possessed by Noyle Imune is a wonderful technology that can be proud of in the world, which has successfully overcome the effects of CAR-T cells on solid cancer, which was a weak point, and the sustainability of the effects. By adding our newly developed CRISPR/Cas3 genome editing technology to this technology, it is possible to achieve a more inexpensive, more effective and superior allogeneic CAR-T cell therapy compared to the existing CAR-T cell therapy. I am confident that we will be able to provide to many suffering patients."

Neil Imune and C4U will collaborate on allogeneic genetically modified immune cell therapy under this partnership. Neil Imune will bear part of the costs necessary to carry out this joint research. In addition, both companies have the right to commercialize the results obtained by this joint research, and the right to mutually receive royalties based on the contract. Noil Imune will pay the access fee for the basic technology of C4U when commercializing. Further details of the contract are not disclosed.

On May 25, 2020 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported that in an abstract at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, it will release updated results from the CS1001-101 study of the Company’s anti-PD-L1 monoclonal antibody CS1001 (Press release, CStone Pharmaceauticals, MAY 25, 2020, View Source [SID1234558551]).

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"We are pleased that CS1001 in combination with platinum-based chemotherapy has demonstrated promising anti-tumor activity and good safety, and that the PoC data supports its development," said Dr. Jason Yang, Chief Medical Officer of CStone. "CStone has already completed subject enrollment for the Phase III study of CS1001, in which CS1001 will be used in combination with platinum-based chemotherapy for first-line treatment of advanced NSCLC. The top-line data from the Phase III trial are expected to be published in the coming months. It is worth mentioning that this trial is the first Phase III study in China targeting first-line NSCLC treatment with both squamous and non-squamous sub-populations involved; hence, its results are highly anticipated."

About the CS1001-101 study

The CS1001-101 study is a Phase I study designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of CS1001 in patients with advanced solid tumors or lymphomas. The results of CS1001-101 study to be released at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting are efficacy data from the Phase Ib cohort study, which is a proof of concept (POC) study aiming to assess the efficacy and safety of CS1001 in combination with platinum-based chemotherapy for first-line treatment of NSCLC.

Phase Ⅰb Study Results

21 and 20 patients were respectively enrolled in the non-squamous and squamous NSCLC cohorts.

Efficacy data

• As of July 1, 2019, 10 patients from each of the two cohorts had reached partial response (PR), resulting in an ORR of 47.6% for the non-squamous NSCLC cohort, and 58.8% for the squamous NSCLC cohort. The median duration of response (mDoR) and median progression-free survival (mPFS) endpoints were not reached due to the short median follow-up duration prior to the data cutoff (non-squamous NSCLC: 5.4 months; squamous NSCLC: 3.9 months).

• Updated efficacy data collected during the most recent follow-up period (the median follow-up duration as of February 19, 2020: non-squamous NSCLC: 13.4 months; squamous NSCLC: 11.3 months) are shown in the table below.

ORR (%)

mPFS (months), 95% CI

mDoR (months), 95% CI

Non-squamous NSCLC cohort of the CS1001 Phase Ib study (N=21)

47.6 6.5 (4.40, 11.7)
8.7 (1.77, -)
Squamous NSCLC cohort of the CS1001 Phase Ib study (N=20)

75.0 8.4 (8.18, -)
6.4 (6.24, -)
Safety data

• As of the data cutoff on July 1, 2019, 18 patients (85.7%) in the non-squamous NSCLC cohort reported CS1001-related AEs, and 6 patients (28.6%) reported TRAEs of Grade 3 or higher. 5 patients reported immune-related AEs (irAEs), with the most common irAEs being elevated alanine aminotransferase (ALT) levels (N=4, Grade ≤2) and elevated aspartate aminotransferase (AST) levels (N=3, Grade ≤2).

• In the squamous NSCLC cohort, 18 patients (90.0%) reported TRAEs, of which 5 patients (25%) had TRAEs of Grade 3 or higher. IrAEs occurred in 3 patients with rash (N=2, Grade ≤2) being the most common irAE.

• There were no TRAEs leading to study withdrawal.

***

About CS1001

CS1001 is an investigational monoclonal antibody directed against PD-L1, currently being developed by CStone. Authorized by the U.S. based Ligand Corporation, CS1001 is developed by the OMT transgenic animal platform, which can generate fully human antibodies in one step. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 mirrors natural G-type immunoglobulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities in patients, potentially representing a unique advantage over similar drugs.

CS1001 has completed a Phase I dose-escalation study in China, in which it demonstrated good tolerability and produced sustained clinical benefits during the Phase Ia stage of the study.

CS1001 is being investigated in a number of ongoing clinical trials, including one Phase I bridging study in the U.S., one multi-arm Phase Ib study, two Phase II registrational studies, and four Phase III studies in China, for several tumor types.

On May 25, 2020 Sanofi reported its intent to sell its equity investment in Regeneron (NASDAQ: REGN) through a registered public offering and related share repurchase by Regeneron (Press release, Sanofi, MAY 25, 2020, View Source [SID1234558465]). The registered offering and share repurchase will have no impact on the ongoing collaboration between Sanofi and Regeneron.

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A preliminary prospectus supplement relating to the offering of Regeneron’s shares will be filed with the U.S. Securities and Exchange Commission. Sanofi currently holds approximately 23.2 million shares of Regeneron’s common stock, representing approximately 20.6% ownership.

Regeneron has agreed to repurchase $5 billion of its stock from Sanofi conditional on completion of the proposed public offering. If the offering and repurchase are completed and the underwriters fully exercise their option to purchase additional shares1, Sanofi will continue to own approximately 400,000 shares of Regeneron’s common stock, which Sanofi is retaining in support of the ongoing collaboration with Regeneron.

"Sanofi and Regeneron’s collaboration has been one of the most productive in the industry, creating significant value for both companies but more importantly, resulting in five important medicines for patients. Sanofi remains committed to continuing our collaboration with Regeneron which remains an integral part of our overall strategy, and this decision was fully aligned with Regeneron, said Paul Hudson, Chief Executive Officer, Sanofi. "The decision to divest our holdings is consistent with our efforts to enhance value creation for our shareholders. We believe the proceeds from this transaction will help further our ability to execute on our strategy to drive innovation and growth."

Following completion of the proposed public offering and share repurchase, Sanofi will discontinue accounting for its ownership in Regeneron’s common shares under the equity method. After restatement of Sanofi previously reported non-GAAP indicator (Business Net Income) and change of its definition to exclude the effect of equity method accounting for Regeneron investment, Sanofi business EPS is expected to grow by approximately +5% in 2020 at constant exchange rate compared to 2019 restated business EPS of €5.64, which is in line with Sanofi’s 2020 business EPS growth guidance.

In connection with the offering, the underwriters will have an option to purchase up to an additional 10% of Regeneron’s shares offered, exercisable within 30 days following the pricing of the offering.

The Companies have had a successful and long-standing clinical and commercial collaboration dating back to 2003 that has resulted in five approved treatments to date with additional candidates currently in clinical development. Sanofi originally purchased a shareholding in Regeneron in 2004. Sanofi’s decision to sell its Regeneron common shares was made in consultation with Regeneron and the contemplated structure will allow both companies to achieve their mutual objectives.

The transaction has been approved by Sanofi and Regeneron’s Boards of Directors.

The public offering will occur simultaneously in the United States and internationally through underwriters led by BofA Securities and Goldman Sachs as joint book-running managers.

The shares offered to the public are being offered pursuant to an existing effective shelf registration statement (including a base prospectus) that has been filed by Regeneron with the U.S. Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement relating to and describing the terms of the offering will be filed by Regeneron with the SEC and will be available on the SEC website at www.sec.gov. Alternatively, any underwriter or any dealer participating in the offering will arrange to send you the prospectus and the prospectus supplement, when available, if you request them by contacting: (1) BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department or by email at [email protected], or (2) Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, via telephone: 1-866-471-2526, or via email: [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities described herein, nor shall there be any offer or sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.