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 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a synthetic lethality focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a clinical data update for the Phase 1/2 trial evaluating darovasertib and crizotinib synthetic lethal combination in metastatic uveal melanoma (MUM) patients (Press release, Ideaya Biosciences, DEC 7, 2021, View Source [SID1234596581]).

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"The partial responses, percentage of patients with tumor shrinkage and disease control rate observed from the darovasertib and crizotinib synthetic lethal combination in heavily pre-treated MUM patients represents a new clinical efficacy benchmark and provides an opportunity to deliver meaningful patient impact in this high unmet medical need patient population," said Meredith McKean, M.D., Sarah Cannon Research Institute at Tennessee Oncology, Associate Director, Melanoma and Skin Cancer Research.

"These data provide clinical proof-of-concept for the PKC and cMET synthetic lethal combination, and further validate IDEAYA’s synthetic lethality platform. We look forward to exploratory evaluation of this novel PKC and cMET synthetic lethal combination in other potential tumor settings, including GNAQ/11 skin melanoma and MET-amplified and MET high expression tumors," said Yujiro S. Hata, President and Chief Executive Officer of IDEAYA Biosciences.

There are currently no FDA approved therapies for metastatic uveal melanoma or GNAQ/GNA11 solid tumors, highlighting the high unmet medical need. The historical overall response rate (ORR) in metastatic uveal melanoma has generally been reported with an ORR from approximately 0 to 5%, including: pembrolizumab and tebentafusp (each ~5%); MEK inhibitor selumetinib in combination with dacarbazine (3%); and cMET inhibitor cabozantinib monotherapy (~0%).

Darovasertib (IDE196) is a small molecule, potential first-in-class PKC inhibitor. IDEAYA is evaluating the synthetic lethal combination of darovasertib and crizotinib, a small molecule cMET inhibitor, pursuant to a clinical trial collaboration and drug supply agreement with Pfizer. The companies have agreed to support a target enrollment of approximately 40 patients into the ongoing Phase 1/2 clinical combination arm in MUM.

Clinical Data Update – Darovasertib and Crizotinib Combination

At the time of the data and analyses cutoff on November 25, 2021, twenty-two (22) heavily pre-treated (91% with prior therapies, and 59% with 2 or more prior therapies) MUM patients had enrolled in the darovasertib and crizotinib combination arm at the expansion dose, with sixteen (16) evaluable patients who have received one or more tumor scans and 6 patients who are awaiting their 1st tumor scan. Thirteen (13) patients have received two or more tumor scans for evaluation of potential responses. Reported data is preliminary and based on an unlocked database. Enrollment in the darovasertib and crizotinib combination arm of the clinical trial is ongoing.

The company observed encouraging clinical activity in Phase 1/2 clinical trial evaluating darovasertib and crizotinib synthetic lethal combination in metastatic uveal melanoma (MUM) patients in the expansion dose cohort.

The preliminary interim data includes:

100% Disease Control Rate (DCR): 16 of 16 evaluable patients with >1 post-baseline scan showed tumor shrinkage as determined by target lesion size reduction;
31% Overall Response Rate (ORR): 4 of 13 patients with > 2 post-baseline scans had a confirmed partial response (PR) as determined by RECIST 1.1 based on investigator or central review; and no patients have come off-treatment prior to the 2nd scan
46% of patients (6 of 13) with > 2 post-baseline scans observed >30% tumor reduction, including one patient with an unconfirmed PR as determined by RECIST 1.1 is awaiting follow-on tumor scan.
These data provide clinical proof-of-concept for the darovasertib and crizotinib synthetic lethal combination treatment. These data also validate the company’s translational research discovery that Phase 1 clinical response to darovasertib monotherapy associated with low cMETactivity, as measured by gene signature score.

The darovasertib and crizotinib combination therapy has a manageable side effect profile in MUM patients (n=22), with a low rate of drug-related serious adverse events (SAE’s); predominantly Grade 1 or 2 drug-related adverse events. Eighteen (18) patients experienced a drug-related AE, of which six (6) patients observed Grade 3, and no patients observed Grade 4 or Grade 5.

Upcoming Milestones

IDEAYA has selected a darovasertib and crizotinib combination expansion dose to support potential registrational studies. The company is targeting regulatory feedback for potential darovasertib and crizotinib combination registrational path in the first half of 2022.

IDEAYA is also targeting a further clinical data readout for the darovasertib and crizotinib combination, including median progression free survival (mPFS) in MUM patients, in the first half of 2022.

Darovasertib Expansion Opportunities

IDEAYA is also evaluating other indications as potential expansion opportunities, including GNAQ/11 mutant skin melanoma being evaluated in an ongoing arm of the current clinical trial, and adjuvant uveal melanoma (UM) that the company anticipates will be initiated through an investigator sponsor clinical trial (IST) in the first half of 2022. The company also has exploratory evaluation ongoing of the PKC-cMET synthetic lethal hypothesis in additional tumor settings with MET-amplification and MET high expression, such as hepatocellular carcinoma (HCC).

IDEAYA Investor Day – Webcast and Conference Call

IDEAYA will host an Investor Day webcast and conference call this morning, December 7, 2021 at 8:30 am ET, to present darovasertib and crizotinib Phase 1/2 clinical efficacy and tolerability data, as well as clinical landscape, potential registrational strategies and expansion opportunities. Presenters at the Investor Day will include Dr. Meredith McKean, M.D., Sarah Cannon Research Institute at Tennessee Oncology, Associate Director, Melanoma and Skin Cancer Research, a key opinion leader and clinical investigator. Yujiro S. Hata, President and Chief Executive Officer, and other members of the IDEAYA management team will also present.

Corporate Updates

IDEAYA’s Darovasertib Investor Day presentation, as well as an updated corporate presentation, will be available on the company’s website, at its Investor Relations portal (View Source) following the Investor Day event at approximately 10:30am ET.

IDEAYA had cash, cash equivalents and marketable securities of approximately $386 million as of September 30, 2021, which it believes will fund its planned operations into 2025.

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.