On April 13, 2021 Genetron Holdings Limited ("Genetron Health" or the "Company", NASDAQ:GTH), a leading precision oncology platform company in China that specializes in molecular profiling tests, early cancer screening products and companion diagnostics development, reported the release of 22 research results at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (AACR 2021) (Press release, Genetron Health Technologies, APR 13, 2021, View Source [SID1234577985]).

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The results were from a series of studies that Genetron Health conducted with 13 leading hospitals in China. The Company leveraged original research and innovative technologies such as integrated DNA and RNA sequencing in gene fusion detection, a new MSI (microsatellite instability) detection algorithm model, its "One-Step Seq" method, and core products such as Onco Panscan and comprehensive sarcoma gene detection tests.

These studies analyzed the spread of various types of cancers throughout the Chinese population, covering lung cancer, intestinal cancer, pancreatic cancer, nervous system tumors, thymic carcinoma, and other types of cancers. More specifically, the studies focused on these cancers’ inheritance, mutation, and fusion characteristics. They paid particular attention to the validity of immunotherapy markers for various types of cancers, as well as rare cancer cases and new therapeutic treatments. These studies provided important insights that can enable the accurate diagnosis and treatment of cancer, facilitating the design of effective products in the future.

Dr. Yunfu Hu, Genetron Health’s Chief Medical Officer, said, "Genetron Health is committed to building a strong bridge between scientific research and clinical applications. The studies’ results show that the Company’s innovative technologies and products can help to further analyze the characteristics of cancer genomics for different types of cancer, optimize conventional technologies, and provide ideas for new product design, so as to promote the healthy development of translational medicine. For example, for soft tissue sarcoma (STS), the use of integrated DNA and RNA sequencing in gene fusion detection can greatly improve the detection rate of STS gene fusion, which may benefit more STS patients.

"For hereditary cancers, the screening method used to detect Li-Fraumeni syndrome will also improve cancer detection rates in these patients and provide more intervention opportunities for them; for colorectal cancer, our analysis of KMT2C/2D inactivation mutations is also pointing to more possibilities for immunotherapy patients. And lastly, our work on rare cancer cases and the experimentation of new treatments is furthering the development of diagnosis and treatment research for these various types of patients," Hu added.

Exploring Ways to Optimize Conventional Technologies

To overcome the DNA-sequencing limitations involved with detecting gene fusion, Genetron Health optimized the use of conventional technologies in Study #2288. During this study, more accurate, efficient, and low-cost detection of gene fusion mutations was achieved at the RNA sequencing level. This was evaluated and verified in a STS cohort of 142 Chinese patients. Compared with DNA detection alone, integrated DNA and RNA sequencing improved the detection rate of STS fusion by 177%, which could provide clinical benefits for more STS patients.

Study #2080 optimized the algorithm that detects MSI through next generation sequencing (NGS). The study was conducted on a large cohort of 2,523 samples with various types of cancers. According to the study results, the optimized algorithm was 99.9% consistent with PCR (polymerase chain reaction) testing – the industry’s current gold standard. The positive predictive value of MSI-H was 98.73%, and the negative predictive value of MSS was 99.92%.

Focusing on Hereditary Cancers

Two studies (#1464, #2557) provided screening methods for Li-Fraumeni syndrome, an inherited condition that is characterized by an increased risk for certain types of cancer. These methods utilized in-depth analysis of germline mutations and investigated the distribution of genetic characteristics for pancreatic cancer in the Chinese population, providing evidence and additional ideas for the diagnosis and treatment of hereditary cancers.

Investigating Gene Mutation and Fusion Characteristics

Nine studies (#2217, #2163, #2223, #2216, #2215, #2313, #2252, #2183, #2182) examined the mutation and fusion characteristics of soft tissue sarcoma, melanoma, neuroendocrine tumors, non-small cell lung cancer, thymic carcinoma, small bowel adenocarcinoma, ampullary carcinoma, etc. The studies focused on finding potential targets for precise therapeutic treatment, drug-resistant targets and effective countermeasures.

Probing Immunotherapy Markers

Four studies (#1639, #1640, #1641, #1681) investigated the predictive effects of KMT2C/D loss-of-function mutations, DDR signaling pathway-related gene mutations, ARID1A mutations, and BRCA1/2 mutations on immunotherapy treatments for a wide range of cancer types, providing further insights.

Spotlight on Rare Cancer Cases and New Treatment Therapies

Five studies (#0803, #0422, #1209, #1199, #0625) detected special molecular abnormalities in patients with Lynch syndrome-related lung cancer, metastatic melanoma, anaplastic thyroid carcinoma, papillary thyroid carcinoma and liposarcoma, respectively. In these studies, scientists used molecular detection to diagnose and classify such cancers, and new, targeted therapy and immunotherapy schemes were adopted for these patients, benefiting them in the long run.

Abstract#

Title

1464

Enrichment and screening of LFS patients by analyzing TP53 germline mutations of a Chinese cancer cohort

2252

Genome profiling of thymic carcinoma identifies putative driver mutations in the NF-κB signaling pathway

2557

Germline mutation landscape in a large cohort of Chinese pancreatic cancer patients

0803

Molecular diagnosis and immunotherapy of a rare lung carcinoma patient associated with PMS2 c.1144+1G>A mutation-driven Lynch syndrome

0422

Sequential targeted therapy and immunotherapy of a BRAF positive metastatic melanoma patient with BRAF inhibitor vemurafenib, MEK inhibitor cobimetnib and a novel PD-1 antibody Sintilimab

2183

Genomic profiling of small bowel adenocarcinoma reveals targetable mutations in multiple signaling pathways

2217

More somatic mutations can be detected in cerebrospinal fluid ctDNA of NSCLC patients with brain metastases

2182

Evaluation of somatic and germline mutations in ampullary carcinoma reveals actionable targets in multiple signaling pathways

1209

An effective treatment for recurrent and inoperable anaplastic thyroid carcinoma using sintilimab and anlotinib: a case report

1681

Correlation of BRCA1/2 mutations with response to immune checkpoint inhibitors in colorectal cancer

1641

The predictive values of ARID1A mutations for response to immune checkpoint inhibitors are varied in different types of solid tumors

1639

Correlation of KMT2C/D loss-of-function mutations with PD-L1 expression and response to immune checkpoint inhibitors in solid tumors

1640

Correlations of DNA damage response gene alterations with response to immune checkpoint inhibitors are different in solid tumors

2288

Identification of gene fusions in soft tissue sarcoma improved by integrative DNA and RNA sequencing

2163

Molecular characteristics of CDK4 and/or MDM2 amplification in Chinese soft tissue sarcoma (STS) patients

0625

Co-amplification of CDK4 and MDM2 plus HMGA2 fusion in a patient with myogenic differentiation dedifferentiated liposarcoma

2223

Distinct genomic features of cutaneous, acral and mucosal melanomas in a Chinese retrospective cohort

2216

Exploration of the genomic features of pan-neuroendocrine tumors in a Chinese retrospective analysis

2215

Landscape of RET fusion identified by next‑generation sequencing in a Chinese multi-cancer retrospective analysis

1199

Mosaic KRAS G12S mutation associates with poor outcome in papillary thyroid carcinoma: A case report

2080

Tumor microsatellite instability detection method using paired tumor-normal sequence data

2313

The characteristics of ERBB2 exon 20 insertion in a large cohort of Chinese NSCLC patients

On April 13, 2021 Purple Biotech Ltd. ("Purple Biotech" ", or the "Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies by overcoming tumor immune evasion and drug resistance, reported that additional preclinical data supporting the mechanism of action of NT219, a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3, were presented in a poster entitled "Adaptation of colorectal cancer cells to the brain microenvironment: The role of IRS2," at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting (Press release, Purple Biotech, APR 13, 2021, View Source [SID1234577984]). These data update and expand on the results previously reported by the Company from its collaboration with Professor Ido Wolf, Head of the Oncology Division at Tel Aviv Sourasky Medical Center.

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Colorectal cancer (CRC) represents the fourth most frequent cause of brain metastasis, which is the most common brain tumor. The study included an analysis of more than 16,000 human CRC local and metastasis samples, and revealed increased amplification of IRS2 in brain metastases.

In an in vitro system mimicking the brain microenvironment, IRS2-overexpressed CRC cells showed prolonged survival. Importantly, transcriptomic analysis demonstrated significant enrichment of the oxidative phosphorylation (OXPHOS) pathway by IRS2. CRC cells expressing IRS2 showed increased mitochondrial activity and glycolysis-independent viability. Inhibition of IRS2 using NT219 dose-dependently inhibited IRS2-expressing cells viability and OXPHOS genes expression.

The Wnt/β-catenin pathway was among the most significantly enriched pathways in the brain metastasis, as IRS2-expressing cells showed increased transcriptional activity of the β-catenin. In addition, NT219 decreased the transcriptional activity of β-catenin in IRS2-expressing CRC cells to a greater extent than AKT and PI3K inhibitors, and most significantly suggested relevance of IRS2 in activating β-catenin. It was further shown that 5-FU, a chemotherapy approved for treating CRC, elevated β-catenin expression, and that NT219 diminished both 5FU-induced and the basal level of the β-catenin expression. Utilizing an intracranial animal model, it was also demonstrated that while 5-FU alone had no significant effect, the combination of 5-FU and NT219 significantly inhibited the formation of brain metastasis and extended survival rates of the study mice.

"We are excited about these highly encouraging study results," said Bertrand Liang, M.D., Ph.D., Chief Medical Officer of Purple Biotech. "These compelling data provide important insights regarding the role of IRS2 in promoting CRC brain metastasis, and suggest that novel agents such as NT219 have the potential to effectively inhibit the development of brain metastasis. Our ongoing Phase 1/2 clinical trial of NT219 as monotherapy for the treatment of solid tumors, followed by a dose escalation of NT219 in combination with cetuximab, an epithelial growth factor receptor (EGFR) blocking monoclonal antibody, for the treatment of recurrent and/or metastatic solid tumors and squamous cell carcinoma of the head and neck cancer, is proceeding with enrollment as planned and we continue to expect the availability of top-line data from the first part of this study in the second half of this year."

The poster presentation is available at View Source

On April 13, 2021 Zymeworks Inc. (NYSE:ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported that the Company will present at the upcoming 2021 Bloom Burton Healthcare Investor Conferencetaking place April 20-21, 2021 (Press release, Zymeworks, APR 13, 2021, View Source [SID1234577982]).

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The Company’s presentation will be on Tuesday, April 20, 2021 at 11:30 a.m. ET.

Interested parties can access a live webcast of the presentation via a link from Zymeworks’ website at View Source, which will also host a recorded replay available afterwards.

On April 13, 2021 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) and Novocure (NASDAQ: NVCR) reported an update regarding its phase 3 pivotal LUNAR trial of Tumor Treating Fields (TTFields) in stage 4 non-small cell lung cancer (NSCLC) following platinum failure (Press release, Zai Laboratory, APR 13, 2021, View Source [SID1234577981]). Following a routine review of the study by an independent data monitoring committee (DMC), Novocure was informed that the pre-specified interim analysis for the LUNAR trial would be accelerated given the length of accrual and the number of events observed, to date. The interim analysis included data from 210 patients accrued to the LUNAR trial through February 2021. After review of the interim analysis report, the DMC concluded that the LUNAR trial should continue with no evidence of increased systemic toxicity.

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The DMC also stated that it is likely unnecessary and possibly unethical for patients randomized to the control arm to continue accrual to 534 patients with 18 months follow-up. The DMC recommended a reduced sample size of approximately 276 patients with 12 months follow-up which it believes will provide sufficient overall power for both primary and secondary endpoints. The DMC recommended no other changes to the design of the trial. Novocure remains blinded to all data.

The primary endpoint of the LUNAR trial is superior overall survival when patients are treated with TTFields plus immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone. The final analysis will also include an analysis of overall survival in the immune checkpoint inhibitor and docetaxel treatment subgroups.

Novocure has notified the U.S. Food and Drug Administration (FDA) of the DMC recommendations and of its intent to submit an Investigational Device Exemption (IDE) supplement incorporating the recommended protocol adjustments.

"We are very pleased with the DMC recommendations, which we believe support the potential for TTFields to make a significant difference in treatment outcomes for patients with non-small cell lung cancer, whether used together with immune checkpoint inhibitors or docetaxel," said William Doyle, Novocure’s Executive Chairman. "The accelerated interim analysis with an encouraging outcome adds to the accumulating evidence of Tumor Treating Fields’ broad potential across a range of hard-to-treat cancers."

"Combination therapy is a cornerstone of cancer care, and we believe using TTFields together with other cancer treatments, including immunotherapies, may lead to better outcomes for some patients," continued Mr. Doyle. "We are very encouraged that, consistent with our expectations, the DMC concluded that TTFields exhibited no systemic toxicity. We will continue to develop TTFields as a limited toxicity backbone therapy upon which other standard-of-care and emerging cancer treatments can be added."

Lung cancer is the most common cause of cancer-related death worldwide, and NSCLC accounts for approximately 85% of all lung cancers. It is estimated that approximately 193,000 patients are diagnosed with NSCLC each year in the U.S. and approximately 46,000 patients receive second-line treatment for stage 4 NSCLC each year in the U.S. Physicians use different combinations of surgery, radiation and pharmacological therapies to treat NSCLC, depending on the stage of the disease. TTFields is intended principally for use together with other standard-of-care treatments, and LUNAR was designed to generate data that contemplates multiple outcomes, all of which Novocure believes will be clinically meaningful.

"The completion of the LUNAR interim analysis is an important milestone for Novocure," said Asaf Danziger, Novocure’s CEO. "We are grateful to the DMC members for their diligence, guidance and support, and are looking forward to working closely with the FDA on amendments to the protocol given the DMC’s recommendations. Pending regulatory approval, the recommended protocol adjustments could accelerate trial completion by more than a year. We look forward to sharing final data from the LUNAR trial as quickly as possible."

About NSCLC in China

Lung cancer consists of NSCLC in approximately 85% of cases and small cell lung cancer (SCLC) in approximately 15% of cases. Lung cancer has the highest total incidence of any cancer in China. According to the World Health Organization, the incidence of lung cancer in China in 2020 was 815,563 cases, with 714,699 deaths. In China, the five-year survival rate of lung cancer is estimated to be about 20%.

About LUNAR

LUNAR is a phase 3 pivotal trial testing the effectiveness of TTFields in combination with immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone for patients with stage 4 NSCLC who progressed during or after platinum-based therapy. It is estimated that approximately 46,000 patients receive second-line treatment for stage 4 NSCLC each year in the U.S. The primary endpoint is superior overall survival of patients treated with TTFields plus immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone. TTFields is intended principally for use in combination with other standard-of-care treatments, and LUNAR was designed to generate data that contemplates multiple outcomes, all of which Novocure believes will be clinically meaningful.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a broad range of clinical trials across all phases, included four phase 3 pivotal trials in a variety of tumor types. To date, more than 18,000 patients have been treated with TTFields.

Use of Tumor Treating Fields for the treatment of NSCLC is investigational only.

On April 13, 2021 PerkinElmer, Inc. (NYSE: PKI), a global leader committed to innovating for a healthier world, reported that it anticipates reported and organic revenue growth of 98% and 90%, respectively, for the first quarter ended April 4, 2021 (Press release, PerkinElmer, APR 13, 2021, View Source [SID1234577980]).

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PerkinElmer’s strong revenue performance was driven by broad-based momentum across the portfolio. In total, non-COVID-19, or core, demand increased approximately 10% organically year-over-year, and COVID-19 related solutions contributed approximately $535 million of revenue in the first quarter.

PerkinElmer will release its first quarter 2021 financial results after market close on Tuesday, May 4, 2021. The Company will host a conference call the same day at 5:00 p.m. ET to discuss these results. Prahlad Singh, president and chief executive officer, and Jamey Mock, senior vice president and chief financial officer, will host the conference call.

To access the call, please dial (720) 405-2250 prior to the scheduled conference call time and provide the access code 7294952. A live audio webcast of the call will also be available on the Investors section of the Company’s Web site at www.perkinelmer.com.

A replay of the webcast will be available beginning at 7:00 p.m. ET, Tuesday, May 4, 2021 through the Investors section of the Company’s website at www.perkinelmer.com.

In addition, PerkinElmer announced today that Steve Willoughby will be named vice president of investor relations effective May 5, 2021. Mr. Willoughby will assume this role from Bryan Kipp, who has transitioned into the role of vice president and general manager of Life Sciences integration.

Steve Willoughby joins PerkinElmer from Cleveland Research Company (CRC), an independent equity and market research firm with an exceptional reputation for ground-level intelligence. Most recently, Mr. Willoughby served as partner and senior analyst at CRC, providing detailed research, analysis and financial models on the Life Sciences and Managed Care industries to institutional investors across the United States and Europe. In 2018, Thomson Reuters StarMine named Mr. Willoughby the number-one analyst in the Life Science tools sector.