On August 22, 2023 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported its 2023 Interim Results (Press release, Carsgen Therapeutics, AUG 22, 2023, View Source [SID1234634637]).

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Business Highlights

Collaboration agreement for zevor-cel commercialization in mainland China with Huadong Medicine.
CT041 has achieved IND clearance from the NMPA for the postoperative adjuvant therapy of Claudin18.2 positive pancreatic cancer (PC).
CT041 Phase 2 clinical trial has been initiated in the U.S. for the treatment of Claudin18.2 positive advanced gastric cancer/gastroesophageal junction cancer (GC/GEJ) in patients who have failed at least 2 prior lines of systemic therapies.
CARsgen and Moderna have initiated a collaboration agreement to investigate CT041 in combination with Moderna’s investigational Claudin18.2 mRNA cancer vaccine.
Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited, said, "In the past six months, we have made significant progress in driving technological innovation, product development, and business operations. Our team has achieved remarkable accomplishments not only in the United States but also in China, continuously expanding the horizons of our scientific exploration and commercial boundaries. Looking ahead, we will persist in our commitment to innovation and strengthen international collaborations, aiming to rapidly translate cutting-edge scientific achievements into feasible treatment solutions. Our goal is to expedite the global availability of the innovative CAR T-cell therapy, benefiting cancer patients worldwide."

Zevorcabtagene Autoleucel (Zevor-cel, R&D code: CT053) is an autologous fully human CAR T-cell product candidate against B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma (R/R MM). In October 2022, China National Medical Products Administration (NMPA) accepted the New Drug Application (NDA) and has granted the priority review for zevor-cel. Zevor-cel is expected to be approved by the NMPA for the treatment of R/R MM at the end of 2023 or the beginning of 2024. The enrollment in the Phase 2 clinical trial in the United States and Canada is underway. In January 2023, CARsgen and Huadong Medicine (Hangzhou) Co., Ltd., a wholly-owned subsidiary of Huadong Medicine Co., Ltd. (Stock Code: SZ.000963) ("Huadong Medicine") entered into a collaboration agreement for the commercialization of CARsgen’s lead drug candidate, zevor-cel, in mainland China. Since reaching the agreement, teams from CARsgen and Huadong Medicine have been working together closely to implement this collaboration and prepare for the approval and commercialization of zevor-cel in China.

CT041 is an autologous humanized CAR T-cell product candidate against Claudin18.2. Based on our information, CT041 is the world’s first CAR T-cell candidate for the treatment of solid tumors that has entered a confirmatory Phase II clinical trial. In April 2023, CT041 has achieved IND clearance from the NMPA for the postoperative adjuvant therapy of Claudin18.2 positive pancreatic cancer (PC) (CT041-ST-05, NCT05911217). In May 2023, a Phase 2 clinical trial of CT041 in the U.S. has been initiated for the treatment of Claudin18.2 positive advanced gastric cancer/gastroesophageal junction cancer (GC/GEJ) in patients who have failed at least 2 prior lines of systemic therapies. Active CT041 trials include a Phase 1b/2 clinical trial for advanced gastric cancer (GC) and PC in the United States and Canada (CT041-ST-02, NCT04404595), a Phase Ib clinical trial for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJ) and PC (CT041-ST-01, NCT04581473), a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), and an investigator-initiated trial (NCT03874897). On August 21, 2023, CARsgen announced that CARsgen and Moderna, Inc. (Nasdaq: MRNA) have initiated a collaboration agreement to investigate CT041 in combination with Moderna’s investigational Claudin18.2 mRNA cancer vaccine.

On top of these existing clinical programs, CARsgen will actively explore the treatment with innovative CAR T-cell products for the earlier lines of therapies. CARsgen has also been taking efforts to develop innovative technologies and product candidates that will better address the challenges with existing cell therapy products. As of June 30, 2023, we had more than 300 patents of which 101 patents had been issued globally including China, the United States, Europe, and Japan. This status is an increase of 9 issued patents and 24 patent applications from the end of 2022. Our R&D activities would continue to generate substantial intellectual property in our areas of expertise.

We have established in-house, vertically integrated manufacturing capabilities for the three key stages of CAR T manufacturing, including the production of plasmids, lentiviral vectors, and CAR T cells. We have been expanding our global manufacturing capacity in China and the U.S. to support both clinical trials and the subsequent commercialization of our pipeline products. With the clinical manufacturing facility in Xuhui, Shanghai and commercial GMP manufacturing facility in Jinshan, Shanghai, we manufacture CAR T-cell products in-house to support clinical trials in China and manufacture the lentiviral vectors in-house to support clinical trials globally. Our Research Triangle Park (RTP) CGMP manufacturing facility in Durham, North Carolina, has commenced operations of GMP production of autologous CAR T-cell products. The RTP Manufacturing Facility will provide CARsgen additional manufacturing capacity of autologous CAR T-cell products for 700 patients annually to support clinical studies and early commercial launch in the United States, Canada, and Europe.

On August 22, 2023 Geneos Therapeutics, a clinical stage biotherapeutics company focused on the development of personalized therapeutic cancer vaccines (PTCV), reported updated data from GT-30, an ongoing single-arm open-label multi-center Phase 1b/2a study in second-line advanced hepatocellular carcinoma (HCC) (Press release, Geneos Therapeutics, AUG 22, 2023, View Source [SID1234634636]). Previously, Geneos reported three patients to have achieved a complete response (CR) and a fourth patient to be cancer-free, whose liver and lung lesions shrank to become fully responsive to surgery and radiation (secondary resectability).

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Geneos reports today that four additional patients have achieved a complete molecular response (CMR) by ultrasensitive, third-generation, circulating tumor DNA (ctDNA) analysis. The ctDNA dropped below the limit of detection in all four patients. By RECIST1.1, three of these four patients are durable partial responses (PR) and one a durable stable disease (SD). Applying mRECIST criteria as additional evaluation, each of the three PR patients is a CR and the SD patient is a PR.

Among all CR and PR patients for whom ctDNA data is available, the reductions in ctDNA level (molecular response) have preceded improvement by MRI.

To date, among 32 evaluable patients from the first 34 enrolled, by RECIST1.1 the study has achieved 3 complete responses, 7 partial responses, 9 stable disease and 13 progressive disease.

By either RECIST1.1 or by ctDNA response, 11 of 32 evaluable have achieved either a complete response, partial response, or complete molecular response.

There have been no vaccination-related serious adverse events (SAEs). Vaccination-related AEs, mostly injection site reactions, have been transient, mild, and all Grades 1 and 2.

GT-30 is evaluating the safety, immunogenicity, and efficacy of PTCV (GNOS-PV02 plus plasmid-encoded IL-12) administered in combination with the immune checkpoint inhibitor pembrolizumab, in 36 patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progress on, or are intolerant to, first-line tyrosine kinase inhibitors (sorafenib or lenvatinib). HCC is characterized by a low tumor mutational burden and is resistant to immune checkpoint monotherapy in the majority of patients due to the immune-excluded tumor microenvironment. The study is fully enrolled. View Source

"As hepatologists and oncologists treating patients with HCC, we’re increasingly using ctDNA to monitor tumour response to therapy. In this study, the ctDNA improvements all preceded the MRI improvements, which shows ctDNA’s prognostic importance, especially since HCC lesions sometimes never fully resolve on MRI despite patients having no clinical evidence of residual viable cancer," said Dr Ed Gane, professor of medicine at the University of Auckland, New Zealand, hepatologist and deputy director of the New Zealand Liver Unit at Auckland City Hospital. "Historically, CRs in advanced HCC from checkpoint inhibitor treatment alone are virtually unheard of. The numerous CRs and CMRs seen here are remarkable and emphasize the role Geneos’ vaccines may have to treat seriously ill patients with late-stage HCC. I’m excited for what these vaccines may mean for these patients, who may now be able to hope, realistically, for a complete response to treatment," Dr Gane added.

"While we welcome the advances currently observed with mRNA-based cancer vaccines, they are being deployed almost exclusively in the adjuvant setting, to prevent cancer recurrence in patients who have had surgery to remove their tumor. As a result, some are even suggesting that personalized therapeutic vaccines may only be effective in the adjuvant setting and ineffective at reducing advanced, unresectable, and metastatic tumors." stated Niranjan Sardesai, PhD, president and chief executive officer of Geneos. "We feel these latest data should set the record straight. Cancer vaccines based on our DNA vaccine platform are showing complete responses in patients with late-stage, advanced cancer. We look forward to continuing to develop in the advanced setting with the goal to offer this profoundly important treatment option to patients with advanced cancer, one with a side effect profile, as seen to date, as benign as that for the typical seasonal flu shot," added Dr. Sardesai.

GT-30 Trial of Geneos’ Personalized Therapeutic Cancer Vaccines
In the GT-30 trial, DNA plasmid-encoded personalized therapeutic cancer vaccine (PTCV) together with plasmid-encoded interleukin-12 (pIL12, a T cell-stimulating cytokine) adjuvant are administered via intradermal injection followed by electroporation (EP) in combination with pembrolizumab. The potential utility of this combination was suggested by preclinical studies which demonstrate Geneos’ PTCV to rescue PD-1 in murine tumor therapeutic challenge models. Geneos’ PTCVs have been engineered to drive a strong CD8+ T cell response against the tumor. CD8 cells are the killing machines of the immune system, seeking out and destroying cancer cells, but have been difficult to induce using prior vaccine approaches. Adjuvant pIL12 and EP serve to optimize the effectiveness of peripheral vaccination, and their utility is seen by the effective CD4+/CD8+ T cell responses observed to the delivered neoantigens in the GT-30 patients. Each patient’s PTCV is designed based on their unique tumor neoantigens (abnormal mutations and genomic variations produced by cancer cells), and unlike other personalized platforms, in almost every case, Geneos’ PTCVs include all of a patient’s specific neoantigens. This removes any requirement to try to pre-select the "high value" neoantigens accurately and, instead, leaves it to nature to decide which ones will matter for triggering the desired immune response. PTCV manufacturing "needle to needle" time, i.e., from biopsy to treatment, is six to eight weeks and is in the process of being reduced to three to four weeks.

Circulating tumor DNA (ctDNA) has enabled non-invasive detection and monitoring of potentially actionable mutations and can identify therapeutic response/resistance prior to confirmation by MRI imaging. For the data announced here, the NeXT Personal platform (Personalis, Inc.) was used to longitudinally monitor molecular residual disease (MRD). NeXT Personal platform is an ultra-sensitive tumor-informed ctDNA assay that leverages whole genome sequencing of tumor/normal samples to generate personalized liquid biopsy panels. Each panel includes up to 1,800 selected variants of the highest value specific to each patient, enabling detection of ultra-low traces of residual cancer, as low as 1 – 3 parts per million (PPM).

On August 22, 2023 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that additional clinical data of bemcentinib in combination with chemotherapy and with immunotherapy in Non-Small Cell Lung Cancer (NSCLC) have been recently published and accepted for presentation at two upcoming international oncology conferences (Press release, BerGenBio, AUG 22, 2023, View Source [SID1234634635]):

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Comprehensive results from the investigator led trial of bemcentininb + docetaxel in previously treated NSCLC patients (Study BGBIL005) were published in the August 2023 issue of Lung Cancer. "Phase 1 trial of bemcentinib (BGB324), a first-in-class, selective AXL inhibitor, with docetaxel in patients with previously treated advanced non-small cell lung cancer." Lung Cancer 182 (2023) The trial was led by David Gerber, MD., Professor at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center.

The abstract "Bemcentinib + Pembrolizumab show promising efficacy in metastatic NSCLC harbouring mutations associated with poor prognosis: Exploratory sub-analysis from the BGBC008 trial (NCT03184571)" has been accepted for poster presentation at the SITC (Free SITC Whitepaper) 38th Annual Meeting, to be held November 3-5, 2023, in San Diego, CA (Abstract #598).

The abstract "Final top-line results of the BGBC008 phase 2, multicenter study of bemcentinib and pembrolizumab (bem+pembro) in 2nd line (2L) advanced non-squamous (NS) non-small cell lung cancer (NSCLC) (NCT03184571)" has been accepted for poster presentation at the ESMO (Free ESMO Whitepaper) Congress 2023, to be held October 20-24, 2023, in Madrid, Spain (Abstract #5343)

"The accumulating evidence supporting the potential role of bemcentinib in NSCLC aligns with our strategic focus on this disease where a large portion of patients still have very poor clinical outcome from existing therapies" said Martin Olin, Chief Executive Officer of BerGenBio. "The publication of data in a prestigious peer reviewed publication and at ESMO (Free ESMO Whitepaper) and SITC (Free SITC Whitepaper) provides us with the opportunity to share our data with a broad audience of oncologists and key opinion leaders in the field of NSCLC and the pharmaceutical industry."

On August 22, 2023 Sanyou Biopharmaceuticals (Shanghai) Co., Ltd. (referred to as "Sanyou" hereafter) and Sinorda Biomedicine (referred to as " Sinorda " hereafter) reported to have officially signed a strategic cooperation agreement to advance the innovative bispecific antibody drug project (Press release, Jiangsu Sinorda Biomedicine, AUG 22, 2023, View Source [SID1234634634]).

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According to the cooperation agreement, leveraging Sanyou’s world-leading core technology platform for integrated R&D and preclinical development of innovative biological drugs, along with a world-class "super-trillion innovative biologics discovery platform", a strong collaboration will be formed with Sinorda’s rich experience in preclinical and clinical oncology immunotherapy. This collaboration aims to jointly advance the R&D of the product pipeline through cooperative efforts.

Pingsheng Hu, CEO of Sinorda, stated, "Sinorda focuses on the research and development of innovative drug and industrialization of oncology immunotherapy. Our partnership with Sanyou merges our strengths, accelerating the drug development process and transforming innovative achievements into reality faster. This collaboration improves treatment choices for patients. With this shared vision, we can work together to advance innovative drug products and contribute to human health."

Guojun Lang, CEO of Sanyou, commented, "We’re truely honored to establish a strategic cooperation with Sinorda. Their strong scientific and medical expertise, robust clinical capabilities, and extensive experience in industrial collaboration perfectly align with Sanyou. Both Sanyou and Sinorda share the common goal of using biopharmaceutical technology to enhance human health. Our combined strengths and robust collaboration will open new opportunities and forge a pioneering model of cooperation between innovative drug research and development services and pharmaceutical enterprises. Together, we are committed to delivering positive outcomes for patients worldwide."

On August 22, 2023 Verismo Therapeutics, a clinical-stage CAR T company, Penn spinout, and pioneer of the novel KIR-CAR platform technology, reported that it had entered into a licensing agreement with the University of Pennsylvania for worldwide exclusive rights for two newly discovered anti-CD19 binders (Press release, Verismo Therapeutics, AUG 22, 2023, View Source [SID1234634633]).

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The newly discovered binders are a result of the sponsored research agreement between Verismo and the University of Pennsylvania that was executed in 2022. Donald Siegel, MD, PhD’s lab utilized his state-of-the-art phage display technique to discover two anti-CD19 binders with high activity. Verismo will utilize one of these binders, DS191, as the basis for its SynKIR-310 product, a KIR-CAR T cell immunotherapy therapeutic for blood cancer, while reserving both binders for potential future partnering.

"Our team at Verismo is thrilled to announce the discovery of these two groundbreaking anti-CD19 binders," said Dr. Laura Johnson, Chief Scientific Officer at Verismo. "These findings have the potential to significantly impact the field of immunotherapy, allowing us to develop more precise and effective treatments for patients in need."

With its pioneering capabilities in binder discovery for cell therapy, Verismo is at the forefront of driving innovation and success in this transformative field. Their commitment to excellence, research-driven approach, and dedication to supporting client needs position them as an invaluable partner for companies and institutions involved in advancing cell-based therapies.

Verismo plans to submit an IND for its SynKIR-310 product, which utilizes the DS191 binder, by the end of 2023 and to seek collaborations with key industry partners. Moving forward, Verismo also plans to initiate discovery of binders towards additional immune-oncology targets.

"We are thrilled to unveil the groundbreaking discovery of two novel CD19 binders," said Dr. Bryan Kim, CEO of Verismo. "As we move forward, we are eager to forge strategic partnerships with like-minded organizations who share our vision for advancing precision medicine. Together, we can harness the potential of these CD19 binders to develop transformative therapies that provide targeted and personalized solutions to patients in need. We welcome collaboration opportunities and look forward to shaping the future of cancer treatment through innovative partnerships."

For additional information on Verismo, its recent discoveries, or partnership opportunities, please visit www.verismotherapeutics.com

About the KIR-CAR Platform
The KIR-CAR platform is a dual-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging solid tumor environments. DAP12 acting as a novel costimulatory molecule for T cells, aids additional T cell stimulating pathways, further sustaining chimeric receptor expression and improving KIR-CAR T cell persistence. This continued T cell function and persistence can lead to ongoing regression of solid tumors in preclinical models, including those refractory to traditional CAR T cell therapies. Furthermore, the KIR-CAR platform can be combined with many additional emerging technologies, such as in vivo gene engineering, advanced cell manufacturing and reprogramming, combinational therapies, and even allogeneic cellular therapies to provide the next-generation multimodal targeted immunotherapy for patients in need."