On December 7, 2021 Persephone Biosciences Inc. ("Persephone"), a privately held company investigating the human microbial ecosystem’s effect on therapeutic treatment, diagnostics and disease prevention, reported a collaboration with Janssen Research & Development, LLC, (Janssen) for the colorectal cancer (CRC) arm of Persephone’s ARGONAUT study (Press release, Janssen Research & Development, DEC 7, 2021, View Source [SID1234596580]).

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ARGONAUT is a longitudinal, prospective, observational study that will collect and analyze stool and blood samples from 4,000 advanced-stage cancer patients and healthy individuals with varying cancer risk, of diverse racial backgrounds. The data collected can be used to develop precision microbiome medicines and for the identification of clinically actionable cancer-specific biomarkers to guide therapeutic decisions.

ARGONAUT will profile four types of solid tumor cancers: non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), colorectal cancer (CRC) and pancreatic cancer. Through the agreement announced today, Persephone will work with Janssen on the CRC patient arm and additional healthy individuals with varying cancer risk enrolled in the study. Financial terms related to the agreement are not being disclosed. Persephone intends to sign additional agreements covering the study’s other arms.

The results of the ARGONAUT study could provide a better understanding of the gut microbiome’s role in patient response to cancer therapies, which could in time lead to the development of adjuvant therapeutics or a precision medicine approach to future oncology interventions, based on prior microbiome diagnostic testing. In addition, the potential discovery of biomarkers in the microbiome could enable earlier cancer detection and intervention. Importantly, the ARGONAUT study will enroll a diverse patient population, emphasizing patients from minority groups.

"We are delighted to be working with Janssen in ARGONAUT’s colorectal cancer arm in this important new area of therapeutic research," said Stephanie Culler, CEO and Co-founder of Persephone Biosciences. "Importantly, patient diversity is a key driver of enrollment for the study, and we look forward to curating a study that will encompass a large cross section of American society, with implications for future oncology interventions worldwide."

About ARGONAUT

The official title of the ARGONAUT study is: "Argonaut: Development and Analysis of a Blood, Tissue and Stool Sample Bank for Cancer Patients, Enabling the Systematic Study of Host-Gut Microbiome Interactions on the Response to Colorectal Cancer Treatment, and Analysis of Biomarkers of Cancer Risk." More information can be found at www.clinicaltrials.gov using the identifier NCT04638751.

On December 7, 2021 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the first interim analysis met the primary study endpoint of the overall survival (OS) of the Phase 3 clinical study (NCT04063163) of its innovative PD-1 inhibitor serplulimab in combination with chemotherapy in previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Shanghai Henlius Biotech, DEC 7, 2021, View Source [SID1234596579]). There is no anti-PD-1 mAb approved for the treatment of extensive-stage small cell lung cancer (ES-SCLC) worldwide.

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The study’s main purpose is to explore the efficacy and safety of serplulimab in combination with chemotherapy in previously untreated patients with ES-SCLC. Based on the results of a pre-defined interim analysis conducted by the Independent Data Monitoring Committee (IDMC), serplulimab in combination with chemotherapy showed a significant improvement in OS against chemotherapy, which met the pre-defined efficacy criteria, with good safety and no detection of a new safety signal. IDMC suggested that the company can hence communicate with healthy authority.

Professor Ying Cheng, the principal investigator of NCT04063163, Director of Jilin Department of Medical Oncology Cancer Center, Jilin Province Lung Cancer Diagnosis and Treatment Center, and Jilin Cancer Hospital Malignant Tumor Clinical Research Integrated Diagnosis and Treatment Center, said, "I’m very excited to see that the Phase 3 study of serplulimab in ES-SCLC has met its primary endpoint OS, and its efficacy and safety have been fully validated. This study is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. The favorable clinical results show China’s ability to innovate with a high clinical trial level. We are looking forward to serplulimab launching as soon as possible, which brings a drug with Chinese independent intellectual property to patients with small cell lung cancer all over the world."

IDMC Chairman of NCT04063163, and Cancer Hospital Chinese Academy of Medical Sciences, Professor Jie Wang, said, "SCLC is a type of lung cancer with strong invasion and poor prognosis, among which ES-SCLC cancer cells are prone to metastasis. At present, ES-SCLC is still mainly treated with chemotherapy or chemotherapy combined with PD-L1 inhibitors. It is easy to progress after chemotherapy, and the 5-year survival rate is generally less than 5%. The prognosis has not been improved for a long time. The results of the Phase 3 trial of serplulimab bring a new option for anti-PD-1 mAb as a first-line ES-SCLC therapy."

Professor Giorgio Scagliotti from the Medical Oncology, University of Turin in Italy, one of IDMC members, said, "There are limited choices for SCLC clinical treatment, especially in anti-PD-1 mAb. Currently, the first-line treatment is chemotherapy or anti-PD-L1 mAb combined with chemotherapy according to the NCCN guidelines. This international multi-center Phase 3 clinical study on ES-SCLC has been carried out in many countries in Asia and Europe, witmore than 580 subjects worldwide. It is believed that by means of international multi-center clinical data, serplulimab will enter the international market and benefit more patients worldwide."

Mr. Jason Zhu, President of Henlius, said, "Serplulimab is an innovative mAb independently developed by Henlius, and the company has carried out a comprehensive first-line treatment layout for lung cancer. Based on the large number of unmet clinical needs, the company has invested in SCLC. The excellent results of this Phase 3 study are expected to contribute serplulimab in becoming the first anti-PD-1 mAb for the first-line treatment of SCLC, which will significantly improve the overall prognosis. Henlius focuses on high-incidence cancers both globally and in China. In the future, we will proactively promote the combination immunotherapy of serplulimab and international clinical research, benefiting more patients around the world."

SCLC is highly malignant, and the available treatment is limited

According to GLOBOCAN data, lung cancer (LC) is the second commonly diagnosed cancer globally and accounts for 11.4% of the global cancer incidence in 2020. It is estimated that there are 810,000 new cases with LC in China in 2020, and LC is the leading cause of cancer incidence and mortality. SCLC accounts for 15%-20% among LC, and is the most aggressive subtype of LC, which is divided into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. Most patients are already in extensive stage when diagnosed. Patients with ES-SCLC always have rapid tumour growth and poor prognosis. Some of them have shorter survival due to extensive tumor metastasis and poor physical status only with supportive care.

Over 20 years, etoposide plus carboplatin/cisplatin is still the standard of care for ES-SCLC, but 80% of patients with limited stage disease and almost all patients with extensive stage disease relapse within one year, with a median survival of only 4 to 5 months after relapse. The emergence of immune checkpoint inhibitors provides a new option. At present, anti-PD-L1 mAb combined with chemotherapy has been recommended by the latest NCCN guidelines and CSCO guidelines as the first-line treatment for ES-SCLC. However, the application of immunotherapy in ES-SCLC still faces challenges. In recent years, a number of PD-1 mAbs have failed in the area. Therefore, more effective first-line treatment of PD-1 inhibitors is urgently needed.

Centering on the unmet needs of patients, covering the first-line treatment of all types of lung cancer

Henlius has adopted a differentiated "Combo+Global" strategy on serplulimab. Currently, serplulimab has been approved for clinical trials in China, the United States, the European Union and other countries and regions. A total of 10 immuo-oncology therapies clinical trials of serplulimab are ongoing to evaluate its safety and efficacy in a wide variety of solid tumors that cover LC, hepatocellular carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer etc. Up to date, about 2300 patients have been enrolled worldwide, proving that the quality of serplulimab has built trust in foreign markets. In April, the New Drug Application (NDA) of serplulimab for the treatment of MSI-H solid tumours was accepted by the National Medical Products Administration (NMPA) and granted priority review, which is expected to be approved in the first half of 2022.

According to the characteristics of cancer patients both globally and in China, the company focus on lung cancer and gastrointestinal cancer with serplulimab as the backbone. Henlius has achieved a comprehensive first-line clinical layout of LC, and has carried out trials on serplulimab in sqNSCLC, non-squamous non-small cell lung cancer and SCLC, covering more than 90% of lung cancer patients. Based on a randomized, double-blind, international multi-center Phase 3 clinical trials conducted in previously untreated patients with locally advanced or metastatic sqNSCLC, the NDA of serplulimab for first-line treatment of locally advanced or metastatic sqNSCLC has been accepted by the NMPA. In the future, with abundant international clinical research data, Henlius will continue expanding the international distribution of serplulimab and benefit more patients around the world.

On December 7, 2021 LiquidLung, Inc., a biotechnology company dedicated to radically improving the detection, diagnosis and treatment of pulmonary disease, reported that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for its patent application No. 17/003,775 for claims related to the non-invasive diagnosis of lung cancer (Press release, LiquidLung, DEC 7, 2021, View Source [SID1234596578]).

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The technology, which is centered around a comprehensive portfolio of novel RNA biomarkers, developed in concert with Liquid Biosciences, a leading bio-analytics provider and dedicated partner to LiquidLung. The technology utilizes various mathematical gene expression signatures that uniquely span early detection and confirmatory diagnosis of lung cancer, both pre- and post-imaging, as well as the diagnostic classification of several prevalent histological subtypes of the disease.

In an independent validation study the lung cancer technology was applied to a blood-based dataset comprised of fully adjudicated in vivo patient samples consisting of patients with confirmed lung cancer and those without lung cancer, the technology achieved 97% sensitivity and 85% specificity for lung cancer detection.

Further, the technology correctly detected 100% of patients with stage I, 89.9% with stage II, 100% with stage III and 100% with stage IV. In addition to detecting lung cancer generally across all stages of disease, the technology also achieved strong sensitivity and specificity for distinguishing between small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Notably, all cited performance was derived from the biomarkers alone, with absolutely no mathematical or scientific value being derived from patient demographics, nodule information, smoking history or any other clinical risk factors, which introduces a defined opportunity to improve upon the already impressive early data with little investment in R&D.

"Imagine a non-invasive testing platform that can rule more high-risk patients with lung cancer into LDCT imaging for further evaluation earlier, reduce negative biopsy procedures for patients with suspicious pulmonary nodules discovered incidentally or through routine screening, and also accelerate the time to life-saving interventions and personalized treatments," stated Founder and Chairman, Marty Keiser. "The comprehensive nature of our to-be patented technology enables us to accurately and efficiently unlock value for patients across the entire care continuum for lung cancer, all while fitting nicely into existing workflows and standards of care."

LiquidLung is one of three companies created out of IV BioHoldings (IVBH), a bio innovation studio known for its progressive approach to R&D, company creation, productization and commercialization. IVBH made headlines in October when it aligned the public debut of its first-in-category pipeline of RNA technologies with the announcement of a strategic lab partnership with P4 Diagnostix, intended to accelerate clinical development and validation of the IVBH assets within lung cancer, non-alcoholic fatty liver disease (NAFLD) and breast cancer.

"The recent worldwide recognition and appreciation for the clinical utility of RNA, from prevention to detection to treatment, has created a timely tailwind for IVBH as we begin to publicly unveil the vast intellectual property portfolio that we have been quietly and strategically amassing since 2018," stated IVBH Chief Commercial Officer, Elizabeth Cormier-May, who also leads the studio’s women’s health company, Mammogen. "The USPTO decision is a significant milestone for LiquidLung and further establishes IVBH’s position as a leader in the rapidly accelerating RNA revolution," Cormier-May continued.

IVBH is currently scaling operationally to support the lung cancer, NAFLD and breast cancer programs through near-term clinical milestones with multiple phases of clinical data generation expected throughout 2022 across all programs.

On December 7, 2021 Immunicom, Inc., a clinical-stage biotech pioneering subtractive therapies for advanced cancers, reported that promising preliminary data from a clinical trial investigating Immunopheresis therapy for resistant melanoma and other solid cancers at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2021’s 36th annual meeting (Press release, Immunicom, DEC 7, 2021, View Source [SID1234596577]). The clinical trial is being conducted at Sheba Medical Center and uses Immunicom’s proprietary, subtractive LW-02 column to selectively remove immunosuppressive soluble tumor necrosis factor receptors (sTNF-Rs) via apheresis. By depleting TNF receptors from plasma, this therapy is designed to free the cytokine TNF-alpha, thereby unleashing its potent anti-cancer effects.

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The basket oncology clinical trial (NCT04142931; n =30 patients), which is being conducted under the direction of Dr. Ronnie Shapira, MD, and Prof. Gal Markel, MD PhD, is evaluating the safety and the clinical effectiveness of Immunopheresis as a monotherapy, and in combination with Bristol Myers Squibb’s anti-PD-1 immune checkpoint inhibitor, OPDIVO (nivolumab), in heavily pretreated patients. Preliminary data were presented from Part A (Immunopheresis therapy alone) from six patients—three with melanoma, and three with triple negative breast cancer (TNBC)—who have failed multiple prior lines of standard chemo and immunotherapies. Of these six heavily pretreated patients, three completed the 12-week study regimen, and three were withdrawn due to clinical progression. Two patients are still alive after a year (median overall survival 26.6 weeks). Immunopheresis therapy was well-tolerated in these late-stage patients, and no treatment-related serious adverse events were reported. The therapy was demonstrated to significantly reduce the levels of sTNF-Rs in plasma. Immune profiling of blood and tumor specimens showed evidence of upregulation of protein biomarkers and cell populations that are associated with improved activity of the immune system. Specifically, the tumor specimens showed two developments: 1) an increased infiltration of CD8+ T cells, which are known to have anti-tumor cytotoxic effects, and 2) the expression of immune checkpoint proteins PD1 and PD-L1 that show evidence of turning "cold" tumors into "hot" tumors. Part B of the study—evaluating Immunopheresis therapy in combination with nivolumab—is currently ongoing. The SITC (Free SITC Whitepaper) 2021 Congress abstract is available on Immunicom’s Publications page.

"Our preliminary data, which show renewed immune modulation and intra-tumoral antitumor activity, support our hypothesis that Immunopheresis therapy has the potential to overcome immunotherapy resistance, which could be a significant breakthrough in refractory cancer patient care," said Professor Gal Markel, former Director of the Ella Lemelbaum Institute for Immuno-Oncology, and now Director of Davidoff Center & Deputy Director General, Rabin Medical Center at Clalit Health Services. "Immunicom’s innovative subtractive treatment approach to neutralize cancer’s ability to block the patient’s natural immune-defense mechanisms is especially attractive in these heavily pretreated patients, and it offers the potential for achieving much better clinical outcomes with fewer treatment side effects," added Dr. Ronnie Shapira, a melanoma expert, and Head of the Onco-Gynecological Cancer Unit at the Ella Lemelbaum Institute for Immuno-Oncology.

Speaking to the announcement, Amir Jafri, Immunicom’s Founder and CEO, added, "The clinical trial at Sheba Medical Center is one of three ongoing, groundbreaking clinical trials to assess Immunicom’s subtractive therapies. Right now, our other clinical trials are evaluating the LW-02 column for treating additional multiple cancers, including metastatic TNBC, non-small cell lung cancer, melanoma, and renal cell carcinoma."

Immunicom’s various clinical trials are being conducted in collaboration with world-renowned research organizations and thought leaders, including:

Poland – at Jagiellonian University of Krakow Hospital, under the direction of Principal Investigator, Professor Piotr Wysocki, MD, PhD

Turkey – at Acıbadem Altunizade Hospital (Istanbul), a member of the Acıbadem/IHH Healthcare Group, under the direction of Principal Investigator, Prof. Dr. Gokhan Demir, MD, PhD

Subtractive Therapy – Immunopheresis and the LW-02 Column

Immunicom’s innovative Immunopheresis approach uses the LW-02 column to extract specific immune-suppressive cytokine receptors produced by cancer tumors. Selective removal of these targeted cytokine receptors is intended to neutralize cancer’s ability to block a patient’s natural immune defense mechanisms—which are significantly compromised in late-stage, metastatic disease—thereby re-energizing the immune system to aggressively fight the cancer. Immunopheresis is a "subtractive therapy" in contrast to drugs that are "additive." Subtractive therapy is designed to avoid the side effects, toxicity, and negative impact on a patient’s quality of life that are typical of other cancer treatments.

Based on Immunicom’s clinical program, the LW-02 column could be used either in combination with other therapies, or as a stand-alone treatment. The LW-02 Immunopheresis column has already received Breakthrough Device Designation for stage IV metastatic cancers from the U.S. Food and Drug Administration (FDA) and European regulatory clearance (CE Mark certification) for use in adults with advanced, refractory TNBC. Immunicom has obtained ISO 13485 certification for its manufacturing and related quality systems.

For an overview of Immunopheresis and how this breakthrough technology works, watch Immunicom’s How it Works video.

Immunopheresis and the LW-02 column is considered an investigational therapy by the U.S. FDA and other regulatory authorities. The clinical efficacy of the LW-02 column has not yet been demonstrated. Clinical investigations evaluating the clinical efficacy of the LW-02 column for TNBC are ongoing.

On December 7, 2021 Tempus, a leader in artificial intelligence and precision medicine, reported six abstracts accepted for poster sessions at the 2021 San Antonio Breast Cancer Symposium (SABCS) taking place December 7 – 10 (Press release, Tempus, DEC 7, 2021, View Source [SID1234596576]). The presented findings highlight the unique insights that Tempus’ data and smart diagnostics generate to advance breast cancer research.

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"The research that Tempus is presenting at this year’s symposium underscores the impact that our comprehensive genomic profiling data has on enabling clinicians to make more informed treatment decisions while also powering research for future therapeutics," said Dr. Kimberly Blackwell, Chief Medical Officer at Tempus.

Tempus will present six posters that highlight research to support the use of more personalized treatments for breast cancer patients, conducted with researchers from institutions including Rush University Medical Center, Columbia University Irving Medical Center, and Washington University School of Medicine. Three abstracts selected for poster presentation at SABCS 2021 are highlighted below:

PD14-01: Comprehensive molecular characterization of patients with metastatic invasive lobular carcinoma (ILC): Using real-world data to describe this unique clinical entity
Overview: This study characterizes the genomic and transcriptomic landscape of advanced or metastatic ILC and co-mutational landscape of CDH1-mutant disease. Researchers retrospectively analyzed 201 de-identified patients with ILC or mixed lobular/ductal histology who were tested via Tempus xT, with abstracted pathology reports. CDH1 mutations were present in 65.3% of all metastatic ILC cases. PIK3CA mutations were more common in patients with CDH1-mutant disease than in patients with CDH1-wildtype disease, suggesting that therapies targeting PIK3CA may be further investigated for their actionability in CDH1-mutant metastatic ILC.
Session: Spotlight Poster Discussion 14
Date: Friday, December 10, 2021
Time: 7:00 am – 8:30 am CT
P3-08-04: The genomic and transcriptomic landscape of PIK3R1-mutated breast cancers
Overview: This study investigates the significance of PIK3R1 mutations in metastatic breast cancer. Researchers retrospectively analyzed a de-identified cohort of 4,296 patients with breast cancer who underwent Tempus xT testing. Patients with PIK3R1 mutations have more frequent mutations associated with poor outcomes and endocrine therapy resistance (PTEN and NF1) compared with patients who are PIK3R1 wild type.
Session: Poster Session 3
Date: Thursday, December 9, 2021
Time: 7:00 am – 8:30 am CT
P3-09-04: Genomic landscape of HER2-negative advanced or metastatic breast cancer with PIK3CA gain-of-function mutations
Overview: The study provides insight into possible mechanisms of therapeutic resistance to alpelisib/fulvestrant and identifies potential targeted pathways. Researchers retrospectively analyzed a cohort of 2,918 patients with HER2-negative advanced or metastatic breast cancer with PIK3CA gain-of-function mutations sequenced with Tempus xT, xO or xE. From this cohort, researchers found that there is substantial genomic heterogeneity among PIK3CA-mutated HER2- advanced/metastatic breast cancers, however future studies are needed to assess the prognostic and predictive role of the identified co-mutations and other candidate gene alterations.
Session: Poster Session 3
Date: Thursday, December 9, 2021
Time: 7:00 am – 8:30 am CT
Additional Tempus-affiliated abstracts accepted for poster presentation at SABCS 2021 include:

PD2-01: A platform of CDK4/6 inhibitor-resistant patient-derived breast cancer organoids illuminates mechanisms of resistance and therapeutic vulnerabilities
Session: Spotlight Poster Discussion 2
Date: Wednesday, December 8, 2021
Time: 7:00 am – 8:30 am CT
GS3-09: Loss of ASXL1 tumor suppressor promotes resistance to CDK4/6 inhibitors in ER+ breast cancer
Session: General Session 3
Date: Thursday, December 9, 2021
Time: 10:45 am CT
P5-08-05: Preclinical activity of KB-0742, an oral, highlight selective, CDK9 inhibitor, in cell lines and in MYC-high expressing, patient-derived models of multiple breast cancer subtypes
Session: Poster Session 5
Date: Friday, December 10, 2021
Time: 7:00 am – 8:30 am CT
The complete list of Tempus authored and affiliated abstracts can be found on the Tempus publications page.