On August 8, 2022: HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM, HKEX: 13) and AstraZeneca PLC ("AstraZeneca") (LON/STO/Nasdaq: AZN) reported that preliminary results from the SAVANNAH Phase II trial showed that TAGRISSO (osimertinib) plus savolitinib demonstrated an objective response rate ("ORR") of 49% (95% confidence interval ["CI"], 39-59%) in patients with epidermal growth factor receptor-mutated ("EGFRm") non-small cell lung cancer ("NSCLC") with high levels of mesenchymal epithelial transition ("MET") overexpression and/or amplification, defined as IHC90+ and/or FISH10+, whose disease progressed on treatment with TAGRISSO (Press release, Hutchison China MediTech, AUG 8, 2022, View Source [SID1234617739]).

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The highest ORR was observed in patients with high levels of MET who were not treated with prior chemotherapy (52% [95% CI, 41-63%]). In patients whose tumors did not show high levels of MET, the ORR was 9% (95% CI, 4-18%). These results are being shared at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC), taking place on August 6-9, 2022 in Vienna, Austria.

Savolitinib, marketed in China under the brand name ORPATHYS, is an oral, potent and highly selective MET tyrosine kinase inhibitor ("TKI") being jointly developed and commercialized by AstraZeneca and HUTCHMED.

While EGFR-targeted therapy can provide a durable survival benefit to patients with EGFRm NSCLC, most will eventually develop resistance to their treatment, with MET being the most common resistance biomarker.1 Among patients screened for enrolment in SAVANNAH, all of whom experienced disease progression on TAGRISSO, 62% had tumors with MET overexpression and/or amplification, and more than one-third (34%) met the defined high MET level cut-off.

Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and Principal Investigator in the SAVANNAH Phase II trial, said: "Acquired resistance to targeted therapy and disease progression are difficult realities for most patients with EGFR-mutated NSCLC. These preliminary SAVANNAH results potentially support a novel approach for identifying patients with MET overexpression and/or amplification who are most likely to benefit from a MET-directed therapy, like savolitinib. They also suggest that with the right biomarker testing strategy, MET may be a more prevalent target among resistant patients than previously understood, supporting further investigation of the osimertinib plus savolitinib regimen."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca said: "The current standard of care for patients with EGFR-mutated lung cancer who progress on targeted treatment is chemotherapy. The results from SAVANNAH suggest savolitinib added to TAGRISSO at the time of disease progression could possibly provide these biomarker-selected patients with a potentially less toxic, more effective treatment option. We look forward to better understanding the potential of the TAGRISSO plus savolitinib regimen in this trial and in the SAFFRON Phase III trial."

Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED, said: "It is encouraging to see the savolitinib and TAGRISSO combination regimen progress into a global Phase III study, SAFFRON, with a well-supported patient selection strategy that could benefit more patients than previously recognized. The preliminary results of the SAVANNAH study also affirm the role of molecular testing prior to initiating subsequent treatment for NSCLC patients who experience disease progression on an EGFR-targeted therapy. We are aligned in pursuing a selective, patient-centric approach in development efforts for savolitinib in this setting."

In this analysis, patients’ MET overexpression and/or amplification levels were determined by two tests: immunohistochemistry ("IHC"), which detects if cancer cells have a particular protein or marker on their surface, and fluorescence in situ hybridization ("FISH"), which detects a specific DNA sequence from cancer cells. All patients in this analysis (n=193) had at least IHC50+ and/or FISH5+, and were treated with savolitinib 300mg once daily added to TAGRISSO 80mg once daily following disease progression on TAGRISSO alone.

The safety profile of TAGRISSO plus savolitinib was consistent with the known profiles of the combination and each treatment alone. No new safety signals were identified. Less than half (45%) of patients in this analysis experienced Grade 3 or higher adverse events ("AEs"), with those most frequently reported including pulmonary embolism, dyspnea, decreased neutrophil count and pneumonia. AEs attributable to savolitinib and leading to discontinuation occurred in 13% of patients.

The global SAFFRON Phase III trial will further assess the TAGRISSO plus savolitinib combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.

About NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.3 The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease and approximately 10-15% of NSCLC patients in the U.S. and Europe and 30-40% of patients in Asia have EGFRm NSCLC.4,5,6,7

MET is a tyrosine kinase receptor that has an essential role in normal cell development.8 MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is the primary mechanism of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC. 8,9 The prevalence of MET depends on the sample type, detection method and assay cut-off used.10

About SAVANNAH
SAVANNAH is an ongoing global, randomized, single-arm Phase II trial studying the efficacy of savolitinib added to TAGRISSO in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification who progressed following treatment with TAGRISSO. Patients were treated with savolitinib 300 or 600 mg once-daily (QD) or 300 mg twice-daily, in combination with oral osimertinib 80 mg QD.

The trial has enrolled 294 patients to date in more than 80 centers globally, including centers in the U.S., Canada, Europe, South America and Asia. The primary endpoint is ORR. Key secondary endpoints include PFS, DoR and safety.

About TAGRISSO
TAGRISSO (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat approximately 575,000 patients across indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

In Phase III trials, TAGRISSO is being investigated in the neoadjuvant resectable setting (NeoADAURA), in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), in the Stage III locally advanced unresectable setting following chemoradiation therapy (LAURA), and in combination with chemotherapy in the advanced setting (FLAURA2). AstraZeneca is also researching ways to address tumor mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test TAGRISSO given concomitantly with savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.

About Savolitinib
Savolitinib is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

Savolitinib is marketed in China under the brand name ORPATHYS for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is currently under clinical development for multiple tumor types, including lung, kidney and gastric cancers, as a single treatment and in combination with other medicines.

About AstraZeneca and HUTCHMED collaboration
In 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration agreement to jointly develop and commercialize savolitinib. Joint development of savolitinib in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.

About AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and assessing innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations including TAGRISSO (osimertinib) and IRESSA (gefitinib); IMFINZI (durvalumab) and tremelimumab; ENHERTU (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; ORPATHYS (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

About AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On August 8, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the second quarter ended June 30, 2022 (Press release, CRISPR Therapeutics, AUG 8, 2022, View Source [SID1234617737]).

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"Strong progress continues across our broad portfolio of gene edited therapies and we remain on track to achieve important 2022 milestones," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "We and our partner Vertex presented new clinical data at EHA (Free EHA Whitepaper) highlighting the potentially transformative profile of exa-cel in patients with TDT or SCD. We also presented encouraging new clinical data for CTX130 for the treatment of both solid tumors and certain hematologic malignancies, and we expect to report data from our ongoing trial of CTX110 targeting CD19+ B-cell malignancies later this year. In addition, we and our partner ViaCyte continue to enroll and dose patients in the Phase 1 clinical trial of VCTX210 for T1D. We remain well positioned and well capitalized to bring transformative medicines for patients suffering from serious diseases."

Dr. Kulkarni further added, "During our Innovation Day in June, we presented the depth and breadth of our pipeline and highlighted our platform innovations to create the next generation of genomic medicines. We are poised to significantly expand our pipeline programs of potentially curative therapies with the addition of new development candidates as we continue to innovate our genome editing, delivery, and cell engineering capabilities."

Recent Highlights and Outlook

Hemoglobinopathies

In June, CRISPR Therapeutics and Vertex Pharmaceuticals presented new clinical data at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress on exagamglogene autotemcel (exa-cel), formerly known as CTX001, highlighting the potentially transformative profile of this investigational therapy for people with transfusion-dependent beta thalassemia (TDT) or severe sickle cell disease (SCD). Data from 75 patients (44 with TDT, 31 with SCD) from the CLIMB-111, CLIMB-121 and CLIMB-131 studies with follow-up ranging from 1.2 to 37.2 months after exa-cel infusion continued to demonstrate that exa-cel has the potential to be a durable, one-time functional cure. All 31 patients with severe SCD, characterized by recurrent vaso-occlusive crises (VOCs), were free of VOCs after exa-cel infusion through the duration of follow-up, with follow-up ranging from 2.0 to 32.3 months. Of the 44 patients with TDT, 42 were transfusion-free with follow-up ranging from 1.2 to 37.2 months. Two patients who were not yet transfusion-free had 75% and 89% reductions in transfusion volume, respectively. The safety profile was generally consistent with myeloablative conditioning with busulfan and autologous stem cell transplant. The CLIMB-111 and CLIMB-121 trials are in Phase 3 and fully enrolled.

CRISPR Therapeutics and Vertex have initiated two additional Phase 3 clinical trials, CLIMB-131 and CLIMB-141, for exa-cel in pediatric patients with TDT or SCD.

CRISPR Therapeutics and Vertex have completed discussions with the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) on the submission package for exa-cel and are on track to submit for regulatory approvals of exa-cel for SCD and TDT in Europe and the U.K. by the end of 2022. Discussions with the FDA are ongoing.

In June, CRISPR Therapeutics hosted an Innovation Day focused on research and development, during which it presented preclinical data on its anti-CD117 (c-Kit) antibody-drug conjugate (ADC). The Company plans to advance this internal targeted conditioning program towards clinical studies.

Immuno-Oncology

CRISPR Therapeutics continues to enroll and dose patients in the pivotal trial of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19+ B-cell malignancies. The Company expects to report additional data in 2022.

In June, CRISPR Therapeutics presented new T-cell lymphoma clinical data at the EHA (Free EHA Whitepaper) Congress from the Company’s ongoing Phase 1 COBALT-LYM trial evaluating the safety and efficacy of CTX130, its wholly-owned allogeneic CAR-T investigational therapy targeting CD70, for both solid tumors and certain hematologic malignancies. The preliminary data demonstrate that CTX130 has the potential to provide meaningful clinical benefit with a well-tolerated safety profile. The Company continues to enroll and dose patients in the dose expansion trial.

In June, at CRISPR Therapeutics’ Innovation Day, the Company provided the following updates regarding its wholly-owned oncology programs:
Presented new clinical data from the Company’s ongoing Phase 1 COBALT-RCC trial evaluating the safety and efficacy of CTX130 for the treatment of relapsed or refractory renal cell carcinoma (RCC). The preliminary data demonstrates the first signs of meaningful activity in solid tumors with an allogeneic cell therapy and a well-tolerated safety profile.
Announced plans to advance next-generation investigational therapies with additional gene edits that have the potential to improve upon first-generation programs. The Company expects to advance two next-generation constructs to IND by year end: CTX131 and CTX112 targeting CD70 and CD19, respectively.
Announced plans for a next-generation allogeneic CAR-T therapy targeting B-cell maturation antigen (BCMA) that incorporates proprietary edits to enhance the potency of the CAR-T cells.
Announced collaborations with top cancer centers on new targets. One with Moffitt Cancer Center will seek to advance a first-in-human trial for an autologous CAR-T investigational therapy targeting CD83 for the potential treatment of acute myeloid leukemia (AML) and other oncology and autoimmune indications. A second with Roswell Park Comprehensive Cancer Center will seek to advance an initial trial for an autologous, gene-edited CAR-T therapy targeting GPC3 for the potential treatment of solid tumors.

Regenerative Medicine

Enrollment and dosing are ongoing in the Phase 1 clinical trial of VCTX210 for the treatment of T1D. VCTX210 is an investigational, allogeneic, gene-edited, stem cell-derived product developed in collaboration with ViaCyte that applies CRISPR Therapeutics’ gene-editing technology to ViaCyte’s proprietary stem cell capabilities for the generation of pancreatic cells designed to evade recognition by the immune system. This immune-evasive cell replacement therapy is designed to enable patients to produce their own insulin.

In June, at CRISPR Therapeutics’ Innovation Day, the Company provided the following updates regarding its regenerative medicine programs:
Announced plans to expand its regenerative medicine pipeline with two next-generation approaches. The first, VCTX211, features novel edits to promote cell survival. The Company plans to file a CTA for VCTX211 in the second half of 2022. The second program, VCTX212, is in early-stage development for the treatment of Type 1 and Type 2 diabetes.
In Vivo
In June, at CRISPR Therapeutics’ Innovation Day, the Company provided the following updates regarding its in vivo programs:
Based upon ongoing progress with its in vivo approaches for liver gene editing utilizing both viral and non-viral delivery vehicles, CRISPR Therapeutics continues to expect to move multiple programs utilizing in vivo approaches into the clinic in the next 12 to 18 months, including programs in cardiovascular disease. The Company’s lead program, CTX310, targeting angiopoietin-related protein 3 (ANGPTL3) is currently in IND-enabling studies.
Announced the establishment of CRISPR-X, a dedicated group within CRISPR Therapeutics focused on emerging technologies, including those to allow HDR-independent and/or AAV-free whole gene correction and insertion.
Other Corporate Matters

In May, CRISPR Therapeutics announced the appointment of Phuong Khanh (P.K.) Morrow, M.D., FACP, as Chief Medical Officer. Dr. Morrow brings more than a decade of leadership experience in global drug development and joined CRISPR Therapeutics to lead the Company’s global clinical development and regulatory operations.
Second Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $2,073.7 million as of June 30, 2022, compared to $2,379.1 million as of December 31, 2021. The decrease in cash of $305.4 million was primarily driven by cash used in operating activities to support ongoing research and development of the Company’s clinical and pre-clinical programs.

Revenue: Total collaboration revenue was $0.2 million for the second quarter of 2022, compared to $900.2 million for the second quarter of 2021. Revenue for the second quarter of 2021 was primarily associated with the $900.0 million upfront payment from Vertex in connection with the Amended and Restated Joint Development and Commercialization Agreement.

R&D Expenses: R&D expenses were $123.2 million for the second quarter of 2022, compared to $82.3 million for the second quarter of 2021. The increase in expense was driven by development activities supporting the advancement of our wholly-owned immuno-oncology programs, as well as expenses related to our new U.S. research and development headquarters.

G&A Expenses: General and administrative expenses of $26.3 million for the second quarter of 2022 were consistent with general and administration expenses of $28.8 million for the second quarter of 2021.

Collaboration Expense: Collaboration expense, net, was $33.9 million for the second quarter of 2022, compared to $26.9 million for the second quarter of 2021. The increase in collaboration expense, net, was primarily driven by increased pre-commercial and manufacturing scale-up costs associated with our hemoglobinopathies programs under our collaboration with Vertex.

Net Loss: Net loss was $185.8 million for the second quarter of 2022, compared to net income of $759.2 million for the second quarter of 2021.
About exagamglogene autotemcel (exa-cel)

Exa-cel, formerly known as CTX001, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with TDT or SCD characterized by recurrent VOCs, in which a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. The elevation of HbF by exa-cel has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, exa-cel has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA for both TDT and SCD. Exa-cel has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among gene-editing approaches being evaluated for TDT and SCD, exa-cel is the furthest advanced in clinical development.

About CLIMB-111 and CLIMB-121
The ongoing Phase 1/2/3 open-label trials, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after exa-cel infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial.

About CLIMB-131
This is a long-term, open-label trial to evaluate the safety and efficacy of exa-cel in patients who received exa-cel in CLIMB-111, CLIMB-121, CLIMB-141 or CLIMB-151. The trial is designed to follow participants for up to 15 years after exa-cel infusion.

About CLIMB-141 and CLIMB-151
The ongoing Phase 3 open-label trials, CLIMB-141 and CLIMB-151, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 2 to 11 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years of age and will plan to extend to patients 2 to less than 5 years of age at a later date. Each trial will enroll approximately 12 patients. Patients will be followed for approximately two years after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up- trial.

About the CRISPR-Vertex Collaboration
CRISPR Therapeutics and Vertex Pharmaceuticals entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. Exa-cel represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development, manufacturing and commercialization of exa-cel and split program costs and profits worldwide 60/40 with CRISPR Therapeutics.

About CTX110 and CARBON Trial
CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial, a Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies. CTX110 has been granted Regenerative Medicine Advanced Therapy designation from the FDA.

About CTX130 and COBALT Trials
CTX130, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being developed for the treatment of both solid tumors, such as renal cell carcinoma (COBALT-RCC), and T-cell and B-cell hematologic malignancies (COBALT-LYM). CTX130 is being investigated in two ongoing independent Phase 1, single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 for the treatment of relapsed or refractory renal cell carcinoma and various subtypes of lymphoma, respectively. CTX130 has been granted Orphan Drug designation for the treatment of T-cell lymphoma from the FDA.

About VCTX210
VCTX210 is an investigational, allogeneic, gene-edited, immune-evasive, stem cell-derived therapy for the treatment of T1D. VCTX210 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and ViaCyte, Inc.

On August 8, 2022 Modulus Discovery, Inc., a computation-driven drug discovery company, reported the signing of a research collaboration with Fujitsu Limited and the unveiling of its proprietary computational technology platform, ModBind (Press release, Modulus Discovery, AUG 8, 2022, View Source [SID1234617733]). The collaboration will accelerate the large-scale deployment of Modulus discovery tools across world-leading supercomputers, including the supercomputer "Fugaku"(*1), and AI Bridging Cloud Infrastructure (ABCI, *2).

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ModBind is a complementary addition to Modulus’ cutting-edge drug discovery platform that includes large-scale GPU-accelerated physics-based simulations, large-scale virtual screening algorithms, and specialized machine learning models. ModBind is a dynamic molecular simulation-based predictor of ligand efficacy, based on a theoretical approach that is fundamentally different from other simulation-based technologies on the market. This allows for up to 100-fold higher speed / throughput, the ability to predict efficacy for highly diverse / unrelated compound sets, higher reliability and repeatability of predictions, and accuracy comparable to the leading available technologies.

ModBind was originally developed by the Modulus team and is now being actively deployed to drive a number of the discovery programs in the company’s portfolio. Its accuracy has been demonstrated through internal validation studies that showed high levels of correlation with experimental measurements on publicly available diverse datasets for multiple relevant drug targets. The validation on these targets gave a correlation coefficient R2 = 0.67 and an average error = 0.51 log units. Because the technology is able to predict efficacy of ligand sets with highly diverse and unrelated chemical structures, this level of accuracy makes the technology suitable for use in higher accuracy medium-throughput virtual screening (VS) or post-VS filtering, as well as lead optimization of drug candidate molecules.

Modulus is working with Fujitsu to further optimize the performance, scalability, and deployment across multiple supercomputing environments for use in large scale virtual screening, compound library predictions, and in combination with generative methods to accelerate lead optimization. Fujitsu has already applied its HPC acceleration technologies to the MD simulation component of ModBind, implementing the method on a number of computing environments and has reproduced the original validation studies.

On August 8, 2022 JSR Corporation (Headquarters: Minato-ku, Tokyo, CEO: Eric Johnson, "JSR") reported that it has been selected for the first time as a member of the MSCI Japan ESG Select Leaders Index (Press release, JSR, AUG 8, 2022, View Source [SID1234617732]).

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The MSCI Japan ESG Select Leaders Index is an index created by MSCI Inc., a major U.S. financial services company. It uses its proprietary ratings to select stocks from among listed Japanese stocks that comprehensively capture ESG-related risks within each industry and have relatively superior ESG ratings. As of June 2022, 305 companies were included in the MSCI Japan ESG Select Leaders Index.

JSR has also been included in all five ESG indices for japanese equities adopted by the Government Pension Investment Fund (GPIF), the world’s largest pension fund.

Based on its corporate mission, the JSR Group aims to contribute to the realization of a sustainable global environment and society by creating value through its corporate activities.

On August 8, 2022 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM, HKEX: 13) reported that the pivotal global Phase 3 FRESCO-2 trial evaluating the investigational use of fruquintinib met its primary endpoint of overall survival ("OS") in patients with advanced, refractory metastatic colorectal cancer ("CRC") (Press release, Hutchison China MediTech, AUG 8, 2022, View Source [SID1234617731]).

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The FRESCO-2 study was a multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia that investigated fruquintinib plus best supportive care ("BSC") vs placebo plus BSC in patients with metastatic CRC who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to OS, a statistically-significant improvement in progression-free survival ("PFS"), a key secondary endpoint, was observed. The safety profile of fruquintinib in FRESCO-2 was consistent with previously reported studies. Full results will be submitted for presentation at an upcoming medical meeting.

HUTCHMED has been in communication with regulatory agencies globally regarding the FRESCO-2 trial design and conduct and will discuss these data with the agencies in the U.S., Europe and Japan with the intent to submit marketing authorization applications as soon as possible. The U.S. FDA granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in June 2020.

"We are very happy to see the positive outcomes of the FRESCO-2 study which offers a potential new treatment for patients with advanced metastatic colorectal cancer, where the unmet need is very high and patients have limited treatment options," said Dr Marek Kania, Executive Vice President, Managing Director and Chief Medical Officer of HUTCHMED International. "Results from the global FRESCO-2 study supplement findings from the original FRESCO study that led to the marketing approval and commercialization of fruquintinib in China. We would like to thank the patients, their families, and the healthcare professionals who participated in this study and helped achieve this important milestone."

Professor Cathy Eng, MD, FACP, FASCO, David H. Johnson Endowed Chair in Surgical and Medical Oncology and Co-Leader, Gastrointestinal Cancer Research Program, at the Vanderbilt-Ingram Cancer Center, who served as the FRESCO2 co-PI and Steering Committee member said: "Completion of the international FRESCO-2 phase III trial in a timely fashion during the era of COVID-19 isolation demonstrates the unmet need for new therapeutic agents in metastatic colorectal cancer. By meeting the primary endpoint of OS with a secondary endpoint of PFS, fruquintinib provides a significant potential new option for our refractory colorectal cancer patients. As an oral agent, fruquintinib also provides added convenience for our patients. Based on fruquintinib’s profile, we will likely see further exploration in future clinical trials in different settings. This is extremely encouraging, and I look forward to seeing the final results."

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: "We are pleased to have successfully completed our first multi-regional clinical trial, FRESCO-2, to support the global registration of fruquintinib. It has already benefited patients with advanced CRC in China since its launch in 2018. It is also being evaluated alone and in combination with other agents in various tumor types in ongoing studies around the world."

HUTCHMED retains all commercial rights to fruquintinib outside of China. In China, where fruquintinib is marketed under the brand name ELUNATE, HUTCHMED is partnered with Eli Lilly and Company and is responsible for development and execution of all on-the-ground medical detailing, promotion and local and regional marketing. Fruquintinib is not approved for use outside of China.

About CRC
CRC is a cancer that starts in either the colon or rectum. CRC is the third most common cancer worldwide, estimated to have caused more than 915,000 deaths in 2020.[i] In the U.S., an estimated 151,000 people will have been diagnosed with CRC and 53,000 people will have died from CRC in 2022.[ii] In Europe, CRC is the second most common cancer, with an estimated 507,000 new cases and 240,000 deaths in 2020.1 In Japan, CRC is the most common cancer, with an estimated 147,000 new cases and 59,000 deaths in 2020.1

About Fruquintinib
Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.

About Fruquintinib Approval in China
Metastatic CRC in China: Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and commercially launched in China in late November 2018 under the brand name ELUNATE. It has been included in the China National Reimbursement Drug List (NRDL) since January 2020. ELUNATE is indicated for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study[iii], a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).

About Fruquintinib Development Beyond CRC Monotherapy
The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:

Gastric Cancer ("GC") in China: The FRUTIGA study is a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for the treatment of patients with advanced gastric or esophagogastric junction ("GEJ") adenocarcinoma who did not respond to first-line standard chemotherapy. Approximately 700 patients have received either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. The co-primary efficacy endpoints are OS and PFS (clinicaltrials.gov identifier: NCT03223376).

Immunotherapy combinations: HUTCHMED has entered into collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd) and sintilimab (IBI308, developed by Innovent Biologics, Inc. and marketed as TYVYT in China).

Metastatic breast, endometrial, and colorectal cancers in the U.S.: HUTCHMED initiated this open-label, multi-center, non-randomized, Phase Ib/II study in the U.S. to investigate if the addition of fruquintinib can potentially induce activity to immune checkpoint inhibitor therapy in advanced, refractory triple negative breast cancer ("TNBC"), endometrial cancer, and CRC. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04577963. Safety and preliminary efficacy of fruquintinib as a single agent were demonstrated in advanced solid tumors, including TNBC, in a Phase I study conducted in China (NCT01645215) and a Phase I/Ib study is ongoing in the U.S. (NCT03251378).
Gastric, colorectal and non-small cell lung cancers in China & Korea: BeiGene, Ltd. initiated this open-label, multi-center, Phase II study to assess the safety and efficacy of fruquintinib in combination with tislelizumab in patients with advanced or metastatic, unresectable GC, CRC or non-small cell lung cancer ("NSCLC"). Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04716634.
Endometrial cancer and other solid tumors in China: HUTCHMED initiated this open-label, multi-center, non-randomized, Phase II study to assess the safety and efficacy of fruquintinib in combination with sintilimab in patients with advanced cervical cancer, endometrial cancer, GC, hepatocellular carcinoma (HCC), NSCLC or renal cell carcinoma (RCC). Preliminary results of certain cohorts were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) and the Chinese Society of Clinical Oncology Annual Meeting (CSCO). Following encouraging data in the advanced endometrial cancer cohort, it has been expanded into a single-arm registrational Phase II study of over 130 patients. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT03903705.