On September 8, 2023 Haihe Biopharma K. K. (referred as "Company"), fully owned affiliate of Shanghai Haihe Biopharma Co., Ltd (China) reported that the New Drug Application ("NDA") of Gumarontinib (SCC244) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping mutation, has been filed to Ministry of Health, Labour and Welfare(厚生労働省) (Press release, Shanghai HaiHe Pharmaceutical, SEP 8, 2023, View Source [SID1234646872]).

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The indication application is based on the data from the SCC244-108 a pivotal Phase II study (GLORY study), a global multi-center, open-label, single-arm clinical trial to evaluate the efficacy and safety of Gumarontinib in locally advanced or metastatic NSCLC patients with METex14 skipping mutations. This indication has been approved by NMPA in China on March 7, 2023. The global leading principal investigator is Prof. Shun Lu at Shanghai Chest Hospital，China.

Dr. Ruiping Dong, Chief Executive Officer of Haihe Biopharma, stated,
"The file in Japan for Gumarontinib, demonstrates Haihe’s mission for the global development of the innovative drugs to bring more effective and much safer treatment options for cancer patients around the world, and marks a historic step of Haihe Biopharma’s innovative drug into the global market. We deeply appreciated the contribution from the patients and the efforts from the investigators, and the recognition of Gumarontinib. Haihe Biopharma will continue to file more global New Drug Applications to benefit cancer patients in the world."
Prof. Shun Lu, the global leading principal investigator of the GLORY study, from the Oncology Department of Shanghai Chest Hospital, commented,
"Gumarontinib is an oral, potent and highly selective MET inhibitor. The GLORY study data demonstrated that Gumarontinib has solid efficacy and good safetyin the treatment naive or previously treated NSCLC patients harboring METex14 skipping mutations, even those with brain metastases. We expect Gumarontinib with better efficacy and acceptable safety could address the unmet needs of patients in China and globally."
About NSCLC and METex14 Skipping Mutations
Primary lung cancer is the malignant tumor with the highest morbidity and mortality in China. NSCLC accounts for approximately 85% of all lung cancers1. The total incidence of METex14 skipping mutations in NSCLC is about 3%2, and the incidence in Chinese NSCLC population is about 1.3%3.
METex14 skipping mutations is a primary oncogenic driver gene, which usually does not coexist with other lung cancer mutations such as EGFR, KRAS and ALK4. Most patients were elderly, with a median age of 72.5 years5. METex14 skipping mutations predicted poor prognosis, with progression-free survival (PFS) of only 2.9 months, overall survival (OS) of 7.9 – 8.3 months, and objective response rate (ORR) of 8.8% — 9.1%6 in second-line chemotherapy. NSCLC patients with METex14 skipping mutations were insensitive to PD-1 therapy with ORR ranged from 16 to 17%, median PFS ranged from 1.9 to 3.4 months, and there was no increase in response rate among tumor patients with high PD-L1 expression7,8 In Japan, the number of new lung cancer patients is 120,000/year (2020) and the number of deaths is 70,000 /year 1. The proportion of non-small cell lung cancer among lung cancer patients in Japan is 88%, and the frequency of METex14 skipping mutation-positive expression is about 3%3. Thus, in Japan, the number of patients that may be eligible for treatment with this drug is estimated to be around 3,000/year.

About Gumarontinib (SCC244)
Gumarontinib (code: SCC244) is an oral, potent and highly selective small molecule MET inhibitor. Gumarontinib has shown excellent pharmacokinetic characteristics, highly effective and durable efficacy and favorable safety profile in NSCLC patients with MET alterations. As of today, compared with its competitors, Gumarontinib has long half-life to achieve sustained target inhibition, low DDI potential withless co-medication restrictions, convenient QD regimen. Gumarontinib has been approved by the NMPA in China with breakthrough designation for the treatment of non-small cell lung cancer (NSCLC) with MET genomic aberration.

On September 8, 2023 Biocept, Inc. (Nasdaq: BIOC), a leading provider of molecular diagnostic assays, products, and services, reported the signing of a non-exclusive licensing agreement for CNSide with Plus Therapeutics, Inc. (Nasdaq: PSTV) (Plus), which expands the comprehensive laboratory services agreement between the two companies that was announced in June 2022 (Press release, Biocept, SEP 8, 2023, View Source [SID1234635038]). Plus is using CNSide in a clinical trial with their targeted radiotherapeutic to treat patients with carcinomas and/or melanomas with suspected leptomeningeal metastases (LM), which is cancer in the membranes that surround the brain and spinal cord. CNSide is Biocept’s proprietary cerebrospinal fluid (CSF)-based tumor cell capture and enumeration platform used in detecting, quantifying, and monitoring tumor status in LM.

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This new agreement allows for Plus to perform CNSide testing during its clinical trials and commercially, subject to regulatory approval. Biocept will provide expertise, including consulting on equipment and materials sourcing, as well as providing the necessary technology and training to perform CNSide. Plus will pay Biocept an upfront fee of $150,000 in stock, plus $6,000 per CSF tumor cell enumeration analysis performed in Biocept’s CLIA-certified and CAP-accredited laboratory prior to the completion of the technology transfer. Once the technology transfer is complete, Plus will pay Biocept $300,000 plus fees on a sliding scale starting at $2,800 for each CNSide test they perform. The license agreement also gives Plus the option to negotiate for third-party exclusivity with a $1,000,000 payment to Biocept.

"We are gratified that Plus continues to recognize the value of CNSide in leptomeningeal metastases disease management. We share their commitment to improving the lives of patients suffering from cancer of the central nervous system (CNS)," said Antonino Morales, Biocept President and CEO. "We view this agreement as further validation of the clinical utility of CNSide and the important role it plays in diagnosing and monitoring patients with LM. It also sets the stage for future agreements with other companies developing treatments for cancer of the CNS and provides Biocept with non-dilutive funding to support our goal of establishing CNSide as standard of care under the National Comprehensive Cancer Network (NCCN) guidelines.

"Importantly, Plus will reimburse Biocept for CNSide testing performed prior to completion of the technology transfer at $6,000 per enumeration," he added. "This amount more than covers our costs and potentially sets the stage for reimbursement at a similar level in future arrangements."

Plus is using CNSide in its ReSPECT-LM Phase 1/2a dose-escalation clinical trial of Rhenium 186 Obisbemeda for the treatment of patients with LM. Plus recently announced completion of Phase 1/Part A of the trial and presented favorable preliminary safety and efficacy results. Plus has received U.S. Food and Drug Administration (FDA) approval to move to Phase 1/Part B of the ReSPECT-LM clinical trial. For more information on Plus, please visit www.plustherapeutics.com.

"The CNSide test is the emerging gold standard for the definitive diagnosis and follow up of patients with LM," said Marc H. Hedrick, M.D., President and CEO of Plus Therapeutics. "The CNSide technology may, in the near future, supplement or replace existing diagnostic technology for cerebrospinal fluid malignancies. We view CNSide as an important complement to our novel radiotherapeutic technology, Rhenium 186 Obisbemeda, now in clinical development for leptomeningeal metastases in our actively enrolling ReSPECT-LM trial."

About CNSide

CNSide is a laboratory developed test (LDT) based on Biocept’s proprietary quantitative tumor cell capture and detection method, paired with assays to identify actionable molecular treatment targets. Given the genetic changes that can occur as metastatic cancer spreads to the CNS, the evaluation of cerebrospinal fluid with CNSide provides a unique opportunity to identify biomarkers in patients with metastatic carcinoma or melanoma to help guide physicians in therapy selection. In addition, the quantitative tumor cell count assay can be used in a serial fashion to monitor the response to therapy more effectively than other current methods.

On September 8, 2023 Novocure (NASDAQ: NVCR) reported its participation in the upcoming International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC) from September 9 – 13, 2023 in Singapore (Press release, NovoCure, SEP 8, 2023, View Source [SID1234635037]). Novocure will take part in presentations and symposia throughout the event and will exhibit several posters exploring the use of Tumor Treating Fields (TTFields) therapy in the treatment of lung cancer, including a new post-hoc analysis of data from its LUNAR trial in metastatic non-small cell lung cancer.

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The LUNAR trial was designed to evaluate the use of TTFields therapy together with standard systemic therapies for the treatment of metastatic non-small cell lung cancer, following progression on or after platinum-based therapy. The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful extension in overall survival (OS) for patients treated with TTFields and standard systemic therapies, as well as a pronounced extension in OS for patients randomized to receive physician’s choice immune checkpoint inhibitor (ICI) together with TTFields.

In a new post-hoc analysis of data from the LUNAR trial, researchers reviewed survival patterns of patients with known Tumor Proportion Scores (TPS) randomized to receive ICI together with or without TTFields. Among patients with TPS >1%, median OS for patients treated with TTFields therapy and ICI (n=22) was 23.6 months compared to 10.5 months for patients treated with ICI alone (n=26; HR: 0.49, P=0.045).

Further analysis shows evidence of a relationship between increasing PD-L1 expression and improved survival outcomes. In patients with TPS 1–49%, median OS was 19.0 months for patients treated with TTFields therapy and ICI (n=17), compared to 9.7 months for patients treated with ICI alone (n=18; HR: 0.55, P=0.14). In patients with TPS >50%, median OS was not reached for patients treated with TTFields therapy and ICI (n=5) compared to 30.0 months for patients treated with ICI alone (n=8; HR: 0.17, P=0.07).

These data will be presented on September 12, 2023 at 2:30 p.m. UTC+8 by primary investigator Ticiana Leal, M.D., a researcher and medical oncologist at Winship Cancer Institute of Emory University and associate professor and director of the Thoracic Medical Oncology Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta.

"This analysis further elucidates the promising results from the LUNAR trial and the potential benefit of utilizing TTFields therapy for the treatment of metastatic non-small cell lung cancer," Dr. Leal said. "I look forward to sharing these data with the global thoracic oncology community and continuing to analyze the data from this impactful study."

Novocure’s presence at the 2023 WCLC will also include:

An Industry Sponsored Symposium: A Spotlight on Tumor Treating Fields in Thoracic Oncology, on September 10 at 6:30 p.m. UTC+8
A poster displayed in the Exhibit Hall on September 10 from 5:30-7:30 p.m. UTC+8: P1.12-10 – Sensitization of Cancer Cells to Tumor Treating Fields (TTFields) via Inhibition of the PI3K/AKT Signaling Pathway
Three ePosters on demand:
EP02.02-02 – Transcriptomic Response to Tumor Treating Fields (TTFields) Across Tumor Types
EP09.02-06 – Long-term Efficacy of Tumor Treating Fields (TTFields 150 kHz) in metastatic NSCLC: A Case Report
EP17.03-02 – Utilities Used in HTAs in mNSCLC Following Progression on or After Platinum-Based Chemotherapy
In addition, Novocure is partnering with the IASLC, host of the WCLC, to provide research opportunities to investigators worldwide who are conducting innovative research on TTFields in the treatment of non-small cell lung cancer and other thoracic malignancies. These grants offer $100,000 to fund projects to be completed in a two-year timeframe.

"We are honored to partner with the IASLC in their mission to study and eradicate lung cancer and other thoracic malignancies," said Moshe Giladi, Ph.D., Novocure’s Chief Science Officer. "We look forward to supporting researchers and together expanding understanding of how TTFields therapy can be beneficial in the treatment of these diseases."

To learn more about these grants, please visit View Source application deadline is noon MDT on October 9, 2023.

About LUNAR

LUNAR was a phase 3 trial testing the safety and effectiveness of TTFields therapy when used together with ICI or docetaxel versus ICI or docetaxel alone for patients with metastatic NSCLC who progressed during or after platinum-based therapy. The trial met its primary endpoint, exhibiting a statistically significant and clinically meaningful improvement in median OS when TTFields therapy was added to standard therapies. Patients randomized to receive TTFields therapy together with standard therapies (n=137) demonstrated median OS of 13.2 months compared to 9.9 months in patients treated with standard therapies alone (n=139; HR: 0.74, P=0.035).

The trial also demonstrated a statistically significant and clinically meaningful improvement in median OS when TTFields therapy was added to ICI. Patients randomized to receive TTFields therapy and physician’s choice ICI (n=66) demonstrated a median OS of 18.5 months versus a median OS of 10.8 months in patients treated with ICIs alone (n=68; HR=0.63; P=0.03). Patients randomized to receive TTFields therapy and docetaxel (n=71) had a positive survival trend with a median OS of 11.1 months vs 8.7 months in patients treated with docetaxel alone (n=71). TTFields therapy was well-tolerated with no added systemic toxicities and few grade 3 (no grade 4 or 5) device-related adverse events.

TTFields therapy is intended principally for use with other concomitant standard therapies, and LUNAR was designed to generate data that contemplates multiple outcomes, all of which Novocure believes will be clinically meaningful.

About NSCLC

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. Physicians use different combinations of surgery, radiation and pharmacological therapies to treat NSCLC, depending on the stage of the disease. Surgery, which may be curative in a subset of patients, is usually used in early stages of the disease. Since 1991, radiation with a combination of platinum-based chemotherapy drugs has been the first-line standard of care for locally advanced or metastatic NSCLC. Certain immune checkpoint inhibitors have been approved for the first-line treatment of NSCLC and the standard of care in this setting appears to be evolving rapidly. The standard of care for second-line treatment is also evolving and may include platinum-based chemotherapy for patients who received immune checkpoint inhibitors as their first-line regimen, docetaxel, immune checkpoint inhibitors or pemetrexed. It is estimated that approximately 46,000 patients receive second-line treatment for metastatic NSCLC each year in the U.S.

On September 8, 2023 Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR) reported that the Company has received additional guidance from the U.S. Food and Drug Administration (FDA) regarding the planned resubmission of the Company’s Biologics License Application (BLA) for LYMPHIR (denileukin diftitox), an engineered IL-2-diphtheria toxin fusion protein for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy (Press release, Citius Pharmaceuticals, SEP 8, 2023, View Source [SID1234635036]).

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The FDA has agreed with the Company’s plans to address the requirements outlined in the complete response letter (CRL) received July 28, 2023. The guidance from the FDA provides Citius with a path for completing the necessary activities to support the resubmission of the Company’s Biologics License Application (BLA) for denileukin diftitox. No additional clinical efficacy or safety trials have been requested by FDA for the resubmission.

"We are encouraged by the constructive engagement with the FDA," stated Leonard Mazur, Chairman and CEO of Citius. "Based on the clear feedback from the FDA, Citius plans to complete the CRL remediation activities by the end of the year and file the resubmission in early 2024. We do not expect these efforts will impact our cash runway."

About LYMPHIR (denileukin diftitox-cxdl)

LYMPHIR is a recombinant fusion protein that combines the interleukin-2 (IL-2) receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. In 2011 and 2013, the FDA granted orphan drug designation to LYMPHIR for the treatment of PTCL and CTCL, respectively. In 2021, denileukin diftitox received regulatory approval in Japan for the treatment of CTCL and peripheral T-cell lymphoma (PTCL). Subsequently in 2021, Citius acquired an exclusive license with rights to develop and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia.

About Cutaneous T-cell Lymphoma

Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and Sézary Syndrome (SS) comprise the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle through multiple agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients qualify, there is currently no curative therapy for advanced CTCL.

On September 8, 2023 Grit Biotechnology reported the completion of a Series B financing round, raising over 60 million USD (Press release, Grit Bio, SEP 8, 2023, View Source [SID1234635035]). The investment was led by CICC with participation from Qianhai Ark, Liando Group, Yuanhe Capital, HeFangTian Venture Partnership and existing investors Sherpa Healthcare Partners, Decheng Capital and Matrix Partners China.

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The financing will support Grit Biotechnology’s Tumor-Infiltrating Lymphocyte (TIL) pipeline development, including the pivotal Phase II trial for GT101 and the advancement of next-gen gene-edited TIL products. Founded in 2019, Grit Biotechnology is a pioneering cell therapy company focused on delivering transformative cancer treatments. GT101 is currently the fastest-developing TIL therapy in China and will enter a Phase II trial by the end of 2023.

Grit Bio has four core technology platforms central to its TIL development: StemTexp, StaViral, KOReTIL and ImmuT Finder, a genome-wide CRISPR/Cas9 screening platform. These platforms have enabled the development of next-generation gene-edited TIL products.

GT201, a genetically engineered TIL product by Grit Biotechnology, boosts T cell survival and function by expressing a vital membrane-bound cytokine. It surpasses traditional TIL therapies in proliferation, tumor-killing and persistence with reduced reliance on IL-2. GT201 IND is approved by CFDA and entered Phase I clinical trials.

GT316, Grit Biotechnology’s next-gen TIL product, enhances TIL performance through knock-out of immunoregulatory targets identified via ImmuT Finder CRISPR/Cas9 screening. In PDX mouse models, GT316 effectively eliminates tumors supported by low-dose IL-2 support with minimal toxicity. It offers substantial clinical benefits compared to conventional TIL products and is currently in IIT clinical trials in China.

With 100+ experienced professionals and a 10,000 sqm GMP-level cell therapy manufacturing facility in Suzhou, China, Grit Bio is a leading player in cell therapy field in China aimed at expediting the development of GT101 and next-generation TIL pipelines and addressing the unmet medical needs of solid tumor patients.