On August 24, 2022 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it obtained regulatory approval today from the Ministry of Health, Labour and Welfare for the anticancer agent/antimicrotubule binding anti-CD79b monoclonal antibody Polivy intravenous infusion 30 mg and 140 mg [generic name: polatuzumab vedotin (genetical recombination)] for an additional indication of treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, Chugai, AUG 24, 2022, View Source [SID1234618592]).

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"We are very pleased to be able to offer the first new treatment in 20 years to patients with previously untreated diffuse large B-cell lymphoma (DLBCL) through this line extension approval," said Chugai’s President and CEO Dr. Osamu Okuda. "Based on our long experience and expertise in hematological cancer, we will continue to provide information on the proper use of Polivy for the benefit of patients with untreated DLBCL, as well as those with relapsed or refractory DLBCL."

Polivy is an antibody-drug conjugate, which is a combination of an antibody and a small molecule compound. This approval is based on the global phase III clinical study (POLARIX study) in patients with previously untreated DLBCL. The study, which Japan participated in, is a phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy plus R-CHP versus R-CHOP. 879 patients were enrolled, and the primary endpoint was progression-free survival (PFS) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma.

As a leading company in the field of oncology in Japan, Chugai is committed to contribute to patients and medical professionals through offering innovative drugs to fulfill unmet medical needs in cancer treatment.

Approval Information *Changes are underlined.

Indication:
Diffuse large B-cell lymphoma

Dosage and administration:
The usual adult dosage is 1.8 mg/kg (body weight) polatuzumab vedotin (genetical recombination) administered by intravenous infusion every 3 weeks for 6 doses, in combination with the antineoplastic agents given below. Administer the first infusion over 90 minutes. If the first infusion is well tolerated, subsequent infusions may be administered over a shorter time of at least 30 minutes. Reduce the dose as necessary in accordance with the patient’s condition.

Administration in combination with rituximab (genetical recombination), cyclophosphamide hydrate, doxorubicin hydrochloride, and prednisolone or methylprednisolone
Administration in combination with bendamustine hydrochloride preparation and rituximab (genetical recombination)
[Reference Information]
Chugai Files for Additional Indication of Polivy for Previously Untreated Diffuse Large B-cell Lymphoma (Press release issued on December 10, 2021)
View Source

Roche’s Polivy combination reduced the risk of disease worsening or death by 27% in people with previously untreated aggressive form of lymphoma (Press release issued by Roche on December 14, 2021)
View Source

About Polivy (polatuzumab vedotin)
Polatuzumab vedotin was developed by Roche using Seagens’ ADC technology. It is a first-in-class anti-CD79b antibody-drug conjugate (ADC), comprising the anti-CD79b humanized monoclonal antibody and a tubulin polymerization inhibitor attached together using a linker. The CD79b protein is expressed specifically in the majority of B-cells, making it a promising target for the development of new therapies.1, 2) Polatuzumab vedotin binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to suppress the effects on normal cells.3, 4) Polatuzumab vedotin was granted accelerated approval in the US in June 2019 and conditional marketing authorization in the EU in January 2020, respectively.

About POLARIX study
POLARIX (NCT03274492) is an international phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy plus Rituxan (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). 879 patients were randomized 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of Rituxan.

The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma.
Data from the pivotal phase III POLARIX study showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP in patients with previously untreated DLBCL after a median follow-up of 28.2 months (hazard ratio [HR] 0.73; 95% CI: 0.57–0.95; P<0.02).The safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%), respectively.5)

POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

About the LYSA and the LYSARC
The Lymphoma Study Association, or LYSA, is the internationally leading cooperative group for lymphoma research in Europe, conducting clinical studies ranging from the first tests of new medicines in humans to the establishment of reference therapeutic strategies. LYSA includes in its network more than 120 care centers distributed throughout three countries (France, Belgium, Portugal), and collaborates with many scientific teams at the international level.
The Lymphoma Academic Research Organisation, or LYSARC, is the LYSA operational structure that conducts clinical research projects on lymphomas at the international level.

About diffuse large B-cell lymphoma (DLBCL)
DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.6) DLBCL is an aggressive type of NHL.7) While it is generally responsive to treatment in the frontline, as many as 40% of patients will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.7) Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.8)

Salvage therapy: Salvage chemotherapy or salvage therapy is used to treat patients with hematologic malignancy who experienced no therapeutic effects (refractory), or recurrence/relapse of the disease. Applicable treatment may vary depending on the type of cancer. Combination therapies of multiple drugs including anticancer agents9) are generally used.

Trademarks used or mentioned in this release are protected by law.

On August 24, 2022 Alaunos Therapeutics, Inc. ("Alaunos" or the "Company") (Nasdaq: TCRT), a clinical-stage oncology-focused cell therapy company, reported that it has been accepted to present a proffered talk at the CRI-ENCI-AACR Sixth International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) (CICON) being held in New York, NY from September 28 – October 1, 2022 (Press release, Alaunos Therapeutics, AUG 24, 2022, View Source [SID1234618608]).

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Details of the presentation are as follows:

Title: Objective clinical response by KRAS mutation-specific TCR-T cell therapy in previously treated advanced Non-small cell lung cancer

Presenter: Marcelo V. Negrao, MD, Department of Thoracic-Head & Neck Med Onc, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center

Date and Time: Friday, September 30, 2022, 8:30am ET

Session Title: Session 6: Cellular Therapies: Engineering T cells

On August 24, 2022 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 the 2022 Interim Results (Press release, Carsgen Therapeutics, AUG 24, 2022, View Source [SID1234618624]).

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Business Highlights

CARsgen’s pipeline
CARsgen’s pipeline
CT053: completed enrollment for pivotal Phase II trial in China, with plan to submit the NDA to the NMPA in the third quarter of 2022
CT041: initiated a confirmatory Phase II clinical trial in China
CT041: was granted RMAT by the FDA
CT041: data from a China Investigator-Initiated Trial was published in Nature Medicine
Continuous development of innovative CAR T technologies to empower the next generation pipeline products
U.S. CGMP manufacturing facility began operations, with plan to support clinical trials in North America from second half 2022
Appointed CARsgen CMO and CARsgen US President
Dr. Zonghai Li, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited, said that "In the first half of 2022, CARsgen has made significant progresses in advancing our technology innovations, product pipeline, and business operations in the U.S. and China, despite the impact of the COVID-19 pandemic. CT041 has become the world’s first and the only CAR T-cell candidate for the treatment of solid tumors entering a confirmatory Phase II clinical trial. For CT053, we plan to submit the NDA to the NMPA in the third quarter of 2022. Our U.S. CGMP manufacturing facility has also started operations. We continue to dedicate ourselves to advancing innovative CAR T technologies to address the major challenges of the industry. We have also established in-house, vertically integrated manufacturing capabilities. Driven by the vision of Making Cancer Curable, we expect to bring innovative and differentiated cell therapy to cancer patients around the world as soon as possible, creating value for investors and the public."

1. Steady development of product pipeline with leadership position in CAR T cell against solid tumors

CT053

CT053 is an upgraded fully human, autologous BCMA CAR T-cell product candidate for the treatment of R/R MM. It incorporates a CAR construct with a fully human BCMA-specific single-chain variable fragment (scFv) with lower immunogenicity and increased stability, which overcomes the challenge of T-cell exhaustion by reducing the self-activation of CAR T cells in the absence of tumor-associated targets.

CT053 received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations for the treatment of R/R MM from the U.S. FDA in 2019, PRIority Medicines (PRIME) eligibility in 2019 and Orphan Medicinal Product designation in 2020 for the treatment of R/R MM from the European Medicines Agency (EMA), and Breakthrough Therapy designation for the treatment of R/R MM from the NMPA in 2020.

CARsgen has completed the patient enrollment of the pivotal Phase II trial patients in China (LUMMICAR STUDY 1) and plans to submit the NDA to the NMPA in the third quarter of 2022. CARsgen is conducting the pivotal Phase 2 trial in North America (LUMMICAR STUDY 2), and the Company plans to submit the BLA to the U.S. FDA in the end of 2023. The Company also plans to conduct additional clinical trials to develop CT053 as an earlier line of treatment for multiple myeloma.

An update from the China investigator-initiated trials (IITs) was published in Haematologica in 2022.

CT041

CT041 is an autologous CAR T-cell product candidate against the protein Claudin18.2 (CLDN18.2) and has the potential to be first-in-class globally. CT041 targets the treatment of CLDN18.2-positive solid tumors with a primary focus on GC/GEJ and PC. CARsgen was the first in the world to successfully identify, validate and report CLDN18.2 as a solid tumor-associated antigen and viable target for CAR T-cell therapy for solid tumors in which CLDN18.2 is prevalently or highly expressed.

CT041 received Orphan Drug designation from the U.S. FDA in 2020 for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA in 2021 for the treatment of advanced gastric cancer. CT041 was granted PRIME eligibility by the EMA for the treatment of advanced gastric cancer in 2021 and was granted RMAT Designation for the treatment of advanced GC/GEJ with CLDN18.2-positive tumors in 2022.

As of the date of the announcement, CT041 is the world’s first and the only CAR T-cell candidate for the treatment of solid tumors entering a confirmatory Phase II clinical trial.

Active trials in CARsgen include a Phase 1b/2 clinical trial for advanced GC/GEJ and PC in North America (CT041-ST-02, NCT04404595), a Phase Ib clinical trial for advanced GC/GEJ and PC and a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), and IITs. CARsgen plans to submit an NDA to the NMPA in China in the first half of 2024. CT041 have now completed the dose escalation and initiated the dose expansion in U.S. CARsgen also plans to initiate a Phase 2 clinical trial in the second half of 2022 in North America and to submit the BLA to the U.S. FDA in 2024.

Updates from the Phase 1b study in the U.S. (NCT04404595) and the Phase Ib/II study in China (NCT04581473) were provided in poster presentations at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2022. An update from a China IIT was published in Nature Medicine in May 2022, which is the largest clinical trial for CAR T-cell therapy in solid tumors to date.

AB011

AB011 is a humanized monoclonal antibody product candidate against CLDN18.2 for the treatment of CLDN18.2-positive solid tumors. The company obtained the second investigational new drug (IND) clearance in the world for a mAb targeting CLDN18.2.

CARsgen has completed Phase I monotherapy cohort enrollment and initiated a trial for combination with chemotherapy.

2. Continuous discovery and technology development

CARsgen has established an integrated research and development platform covering the full CAR T development cycle including target discovery, antibody development, vector design, manufacturing, quality assurance, and quality control. CARsgen continues to dedicate itself to advancing innovative CAR T technologies to address the major challenges of the industry. The four strategic pillars include:

（1） Efficacy: To enhance efficacy against solid tumors, CARsgen continues to develop next generation CAR T technologies, such as CycloCAR. CycloCAR features the co-expression of cytokine IL-7 and chemokine CCL21 in CAR T cells to potentially improve clinical efficacy and reduce the requirement of lymphodepletion conditioning.

（2） Safety: To improve the applicability of adoptive cell therapies, CARsgen developed the sFv-ε-based T-cell therapy powered by a full T-cell receptor (TCR) complex comprising a GPC3-targeted scFv and a CD3ε subunit, which can form a functional TCR complex with other TCR subunits and redirect T cells to kill tumor cells in an MHC-independent manner.

（3） Patient accessibility: CARsgen is developing allogeneic CAR T-cell product candidates using THANK-uCAR technology, which it believes could potentially increase CAR T cell expansion, persistence, and efficacy. CARsgen believes the successful application of THANK-uCAR technology would significantly lower the cost of CAR T-cell therapy and increase patient accessibility.

（4） Target availability: CARsgen developed LADAR technology (local action driven by artificial receptor), in which an artificial receptor is triggered by a LADAR Ligand to induce the transcription of the gene(s) of interest. Through the LADAR artificial receptor, the antitumor CAR transcription is only triggered when the LADAR binds to a LADAR Ligand, making it possible to precisely control when and where immune cells act against cancer cells.

These technologies are currently being developed in-house with global rights and can be used alone or in combination to upgrade CARsgen’s existing product candidates and to generate future pipeline product candidates.

As of June 30, 2022, CARsgen had more than 300 patents of which 70 patents had been issued globally including China, the United States, Europe, and Japan. This is an increase of 7 issued patents and 21 patent applications from the end of 2021.

3. Vertically integrated manufacturing capabilities, supporting clinical trials globally

CARsgen has established in-house, vertically integrated manufacturing capabilities, including the production of plasmids, lentiviral vectors, and CAR T cells.

CARsgen has been expanding its global manufacturing capacity in China and the U.S. to support both clinical trials and the subsequent commercialization of pipeline products. With the clinical manufacturing facility in Xuhui, Shanghai and commercial GMP manufacturing facility in Jinshan, Shanghai, CARsgen manufactures CAR T-cell products in-house to support clinical trials in China and manufacture the lentiviral vectors in-house to support clinical trials globally.

In 2021, CARsgen has made significant progress in expanding CARsgen’s manufacturing capacity outside China by launching a state-of-the-art GMP Manufacturing Facility in Research Triangle Park, Durham, North Carolina. CARsgen successfully passed the official inspections and received the Certificate of Compliance from the City-County Inspections Department of Durham. CARsgen has commenced commissioning, qualification, and validation of RTP Manufacturing Facility through the RMAT consultation with the FDA. Concurrently, CARsgen has been executing the technology transfer to RTP Manufacturing Facility, advancing to the clinical manufacturing of CT041 and CT053 products.

4. Strengthened leadership team with rich experience

As of June 30, 2022, CARsgen had a total of 601 employees. The company has also strengthened the leadership team: CARsgen hired Dr. Raffaele Baffa as the Chief Medical Officer of the Company, and Mr. Richard Daly as the President of CARsgen Therapeutics Corporation. Biographical details of the senior management team are provided on the company’s website at www.CARsgen.com.

On August 24, 2022 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that the Janssen Biotech, Inc. (Janssen) received conditional marketing authorization (CMA) from the European Commission for TECVAYLI (teclistamab) as monotherapy for the treatment of patients with relapsed or refractory (R/R) multiple myeloma (Press release, Ligand, AUG 24, 2022, View Source [SID1234618609]). Teclistamab is a T-cell redirecting, bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3 that was discovered by Janssen scientists using OmniAb’s OmniRat antibody discovery technology.

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Under the terms of the licensing agreement with an affiliate of Janssen, OmniAb is eligible to receive a $10 million milestone payment upon the first commercial sale of teclistamab in the United Kingdom, Italy, Germany, France, or Spain.

"Approval of Janssen’s TECVAYLI by the European Commission adds another important medicine for the treatment of relapsed or refractory multiple myeloma. This marks the first European approval of an OmniAb-derived antibody, and the first approval of an OmniAb-derived bispecific antibody," said Matt Foehr, President and COO of Ligand. "We look forward to the continued advancement of therapies our collaborators have discovered using the OmniAb platform."

Ligand’s previously announced spin-off of OmniAb and merger (Business Combination) with Avista Public Acquisition Corp. II (APAC) (NASDAQ: AHPA), a publicly traded special purpose acquisition company (SPAC), remains on track to close in the fourth quarter of 2022. Under the terms of the separation and distribution agreement between Ligand and OmniAb, the milestone payments related to the first commercial sale of TECVAYLI will remain with the OmniAb business regardless of timing and achievement of the milestone and the timing of the merger closing. The license agreement between OmniAb and CNA Development LLC does not include royalty payments, and OmniAb will not receive royalties on sales of TECVAYLI.

About OmniAb

The OmniAb discovery platform provides Ligand’s pharmaceutical industry partners access to the diverse antibody repertoires and high-throughput screening technologies to enable discovery of next-generation therapeutics. At the heart of the OmniAb platform is the Biological Intelligence (BI) of our proprietary transgenic animals, including OmniRat, OmniChicken and OmniMouse that have been genetically modified to generate antibodies with human sequences to facilitate development of human therapeutic candidates. OmniFlic (transgenic rat) and OmniClic (transgenic chicken) address industry needs for bispecific antibody applications though a common light chain approach, and OmniTaur features unique structural attributes of cow antibodies for complex targets. We believe the OmniAb animals comprise the most diverse host systems available in the industry and they are optimally leveraged through computational antigen design and immunization methods, paired with high-throughput single B cell phenotypic screening and mining of next-generation sequencing datasets with custom algorithms to identify fully human antibodies with superior performance and developability characteristics. An established core competency focused on ion channels and transporters further differentiates our technology and creates opportunities in emerging target classes. OmniAb antibodies have been leveraged across modalities, including bispecific antibodies, antibody-drug conjugates and others. The OmniAb suite of technologies span from BI-powered repertoire generation to cutting edge antibody discovery and optimization offering a highly efficient and customizable end-to-end solution for the growing discovery needs of the global pharmaceutical industry.

On August 24, 2022 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported that the Japan Patent Office has granted Compugen a new composition of matter and use patent covering its potentially first-in-class anti-PVRIG, COM701 and backup anti-PVRIG antibodies (Press release, Compugen, AUG 24, 2022, View Source [SID1234618625]).

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Japanese patent No. 2017-562952, titled "Anti-PVRIG antibodies and Methods of Use" augments previously issued patents by expanding and protecting COM701 beyond Europe and the U.S. to include coverage in Japan.

"As part of our strategy to secure broad patent protection for our innovative pipeline, we are delighted to be granted protection to expand the coverage of COM701 to include Japan in addition to patents previously granted in the U.S. and Europe," said Anat Cohen-Dayag, Ph.D., President, and Chief Executive Officer of Compugen.

Japanese patent No. 2017-562952 is expected to expire no earlier than 2036.

About COM701

COM701 is a humanized antibody that binds with high affinity to PVRIG, a novel immune checkpoint discovered computationally by Compugen, blocking the interaction with its ligand, PVRL2. In pre-clinical studies, blockade of PVRIG by COM701 has demonstrated potent, reproducible enhancement of T cell activation, consistent with the desired mechanism of action of activating T cells in the tumor microenvironment to generate anti-tumor immune responses. Compugen has identified PVRIG and TIGIT as key parallel and complementary inhibitory pathways in the DNAM-1 axis, which also intersect with the well-established PD-1 pathway. Research from Compugen suggests that these three pathways have different dominance in different tumor types and patients, implying that to induce effective antitumor responses, certain patient populations may require the blockade of different combinations of these three pathways. To test this hypothesis, Compugen has established a science-driven, biomarker informed clinical program, which evaluates different combinations of these axis members across tumor types. Compugen is the only company with clinical assets targeting both PVRIG and TIGIT in its portfolio allowing it to explore the potential of blocking these parallel and complementary members of the DNAM axis comprehensively to drive robust immune responses.