On August 29, 2022 Veracyte, Inc. (Nasdaq: VCYT) reported that new data published in Nature Medicine provide the first evidence that the pre-treatment tumor microenvironment (TME) can impact response to chimeric-antigen-receptor (CAR) T-cell therapy among patients with large B-cell lymphoma (LBCL) (Press release, Veracyte, AUG 29, 2022, View Source [SID1234618726]). The study findings demonstrated for the first time the prognostic and predictive capabilities of Veracyte’s proprietary biomarkers among LBCL patients treated with CAR T-cell therapy.

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"CAR T-cell therapies are changing the standard of care in cancer treatment, and their expanded use increases the need for tools to help identify the patients most likely to benefit from them. The prognostic and predictive roles of the TME have been described for solid tumors, but the importance of TME for CAR T-cell therapy outcomes, and particularly in LBCL, has not previously been established," said Jérôme Galon, Ph.D., research director at Inserm in France and senior vice president and scientific executive director at Veracyte, as well as lead author on the published paper. "This study is the first to demonstrate this important clinical connection, and also confirms Immunoscore CR and Immunosign as one of the first pre-treatment TME biomarkers to be associated with prolonged survival following CAR T-cell therapy."

This study aimed to identify biomarkers associated with CAR T-cell therapy outcomes in patients treated with Kite’s axicabtagene ciloleucel (axi-cel), a first-in-class anti-CD19 CAR T-cell therapy. Study investigators conducted a retrospective analysis using Veracyte’s Immunoscore Clinical Research (CR) and Immunosign 21 (IS21) assays, along with three custom panels (Immunoscore T-cell Exhaustion, TCE+ panels and Immunoscore Suppressive Cells panel) to compare pre-treatment TME patterns that were associated with improved response in Kite’s ZUMA-1 study, the pivotal Phase 2 trial in adult patients with relapsed or refractory LBCL.

Results published today suggest that the pre-treatment tumor immune contexture was associated with, and potentially a major determinant of, clinical outcomes in ZUMA-1 patients. Improved clinical outcomes were more associated with high resolution pre-treatment immune contexture characterized by Immunoscore CR and Immunosign 21 rather than with general T-cell gene profiles and densities.

"These findings advance the understanding of the TME and its association with clinical responses to anti-CD19 CAR T-cell therapy in DLBCL and could therefore enhance clinical benefit and outcomes for patients," said Francesco Marincola, M.D., global head of Cell Therapy Research, Kite. "The availability of validated immuno-oncology biomarkers could support further clinical studies of these therapies, particularly in earlier lines of treatment, and help advance our ability to provide precision medicine for patients with hematologic malignancies."

In the study, researchers noted rapid and broad changes across post-treatment TME immune programs associated with improved response, with marked decrease in B-cell lineage gene expression in responders’ TME.

Researchers also suggest that immune-based therapies with curative potential such as axi-cel should be considered in earlier lines of therapy where a larger percentage of patients have more favorable TME features and lower tumor burden, to potentially maximize clinical benefit.

"These findings suggest that our offerings can help provide key insights into the mechanism of action for immuno-therapies such as CAR T-cell treatment," said Corinne Danan, general manager for Veracyte’s Biopharma business unit. "We believe our extensive capabilities and expertise in immuno-oncology position us well to serve biopharma companies that are developing cutting-edge treatments such as CAR T-cell therapies, immune checkpoint inhibitors and others."

About Veracyte’s Immuno-Oncology Biopharma Offerings

Veracyte offers its biopharma partners unique, multi-omic capabilities, expertise and tools designed to optimize biomarkers, companion diagnostics and therapeutic clinical trials through robust analysis of patient oncology samples. These offerings include a comprehensive platform of immuno-oncology expertise and technologies focused on analyzing the tumor immune response. Assays currently available within this platform include Immunoscore, which measures patient immune response at the tumor site; Immunosign immune gene signature, which provides powerful pan-cancer immune gene signature analysis; and Brightplex multiplex spatial profiling, which provides quantitative immune phenotyping using digital pathology and image analysis software. For more information, please visit View Source

On August 29 Novo Nordisk reported that initiated a share repurchase programme in accordance with Article 5 of Regulation No 596/2014 of the European Parliament and Council of 16 April 2014 (MAR) and the Commission Delegated Regulation (EU) 2016/1052 of 8 March 2016 (the "Safe Harbour Rules") (Press release, Novo Nordisk, AUG 29, 2022, View Source [SID1234618725]). This programme is part of the overall share repurchase programme of up to DKK 24 billion to be executed during a 12-month period beginning 2 February 2022.

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Under the programme initiated 3 August 2022, Novo Nordisk will repurchase B shares for an amount up to DKK 4.4 billion in the period from 4 August 2022 to 31 October 2022.

Since the announcement 22 August 2022, the following transactions have been made:

With the transactions stated above, Novo Nordisk owns a total of 19,133,211 B shares of DKK 0.20 as treasury shares, corresponding to 0.8% of the share capital. The total amount of A and B shares in the company is 2,280,000,000 including treasury shares.

Novo Nordisk expects to repurchase B shares for an amount up to DKK 24 billion during a 12-month period beginning 2 February 2022. As of 26 August 2022, Novo Nordisk has since 2 February 2022 repurchased a total of 17,422,432 B shares at an average share price of DKK 768.20 per B share equal to a transaction value of DKK 13,383,917,995

On August 29, 2022 Yumanity Therapeutics, Inc. ("Yumanity") (Nasdaq: YMTX), a clinical-stage biopharmaceutical company focused on the discovery and development of innovative, disease-modifying therapies for neurodegenerative diseases, reported the filing of a registration statement on Form S-4 (the "Registration Statement") with the U.S. Securities and Exchange Commission (the "SEC") (Press release, Kineta, AUG 29, 2022, View Source;utm_medium=rss&utm_campaign=kineta-announces-the-filing-of-a-registration-statement-on-form-s-4-with-the-u-s-sec-related-to-the-reverse-merger-with-yumanity-therapeutics-ymtx [SID1234618724]).

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The Registration Statement contains a preliminary proxy statement and prospectus in connection with Yumanity’s previously announced proposed asset sale to Janssen Pharmaceutica NV ("Janssen") and merger with Kineta, Inc. ("Kineta"). Although the Registration Statement has not yet become effective and the information contained therein is subject to change, it provides important information about Yumanity and the proposed transactions.

Both definitive transaction agreements were announced on June 6, 2022.

The two transactions are expected to close during the fourth fiscal quarter of 2022, subject to customary closing conditions, including approval of both transactions by the stockholders of Yumanity.

On August 29, 2022 TRACON Pharmaceuticals, Inc. (Nasdaq: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent product development platform to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application for the initiation of a Phase 1/2 clinical trial of YH001 in combination with envafolimab and doxorubicin for the treatment of sarcoma patients, including patients who have not received prior therapy (Press release, Tracon Pharmaceuticals, AUG 29, 2022, View Source [SID1234618723]).

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The Phase 1/2 trial will assess the safety and efficacy of YH001 and envafolimab in patients with the rare sarcoma subtypes of alveolar soft part sarcoma and chondrosarcoma. Additionally, the safety and efficacy of the combination of YH001, envafolimab and doxorubicin will be assessed in the more prevalent sarcoma subtypes of leiomyosarcoma and dedifferentiated liposarcoma.

"We are pleased to receive approval from the FDA to initiate our triplet combination therapy trial in sarcoma, which includes our potentially best-in-class CTLA-4 antibody YH001 and the only subcutaneous checkpoint inhibitor approved anywhere in the world, envafolimab," said Charles Theuer, M.D., Ph.D., TRACON’s Chief Executive Officer. "We look forward to enrolling patients in this trial and giving patients additional options for their sarcoma treatment."

About YH001

YH001, an IgG1 antibody against CTLA-4 invented by Biocytogen, the parent company of Eucure Biopharma, and licensed by TRACON, has shown enhanced antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) in vitro. In preclinical studies YH001 demonstrated superior T cell activation and superior tumor growth inhibition activity compared to ipilimumab. YH001 also demonstrated superior activity compared to ipilimumab in human transgenic mouse tumor models when combined with a PD-(L)1 antibody. In these models, single agent YH001 depleted regulatory T cells and increased CD8+ T cells in tumor tissue. YH001 has been dosed as a single agent in a Phase 1 trial in China (NCT04699929) and in combination with the PD-1 antibody toripalimab in a Phase 1 trial in Australia (NCT04357756).

About the Phase 1/2 Clinical Trial of YH001, envafolimab and doxorubicin (NCT05448820)

The Phase 1/2 clinical trial is a multicenter, open label study of YH001 initially given in combination with envafolimab, and then given in combination with envafolimab plus doxorubicin in patients with advanced or metastatic sarcoma, followed by Phase 2 cohorts of patients with select histologies of advanced or metastatic sarcoma, including treatment naive patients. The primary objective of the Phase 1 portion of the trial is to determine the recommended phase 2 dose of YH001 in combination with envafolimab and in combination with envafolimab with doxorubicin. The primary objective of the Phase 2 portion is to determine the objective response rate (ORR) of the combination of YH001 and envafolimab in patients with alveolar soft part sarcoma and chondrosarcoma and the ORR of the combination of YH001, envafolimab and doxorubicin in patients with leiomyosarcoma and dedifferentiated liposarcoma.

About Envafolimab

Envafolimab (KN035), a single-domain antibody against PD-L1 invented by Alphamab Oncology and licensed by TRACON, is the first approved subcutaneously injected PD-(L)1 inhibitor. Envafolimab was approved by the Chinese NMPA in November 2021 in adult patients with MSI-H/dMMR advanced solid tumors who failed systemic treatment and have no satisfactory alternative treatment options. In December 2019, Alphamab Oncology, 3D Medicines and TRACON entered into a collaboration whereby TRACON has the right to develop and commercialize envafolimab in soft tissue sarcoma in North America. Envafolimab is currently being studied in the pivotal ENVASARC Phase 2 trial in the United States sponsored by TRACON and a Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China sponsored by TRACON’s corporate partners, Alphamab Oncology and 3D Medicines.

On August 29, 2022 ONK Therapeutics, an innovative company dedicated to developing optimally engineered natural killer (NK) cell therapies to cure patients with cancer, reported the first in-vivo data for ONKT102, a fully human, optimized affinity CD38 CAR-NK cell therapy (Press release, ONK Therapeutics, AUG 29, 2022, View Source [SID1234618722]).

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The positive data, presented in a poster at the International Myeloma Society late on Friday 26 August by ONK Therapeutics CSO Prof. Michael O’Dwyer showed potent anti-tumor activity for ONKT102 in-vitro and in-vivo in a CD38 positive MM.1S-LUC tumor model of multiple myeloma.

ONK Therapeutics is developing a pipeline of off-the-shelf, optimally engineered natural killer (NK) cell therapies expressing a chimeric antigen receptor (CAR), further modified to enhance tumor homing, persistence and metabolism, and to overcome exhaustion in the tumor microenvironment. Currently it has four programs in pre-clinical development across hematological malignancies and solid tumors. ONKT102 is the company’s most advanced program, and is being advanced towards clinical development as a potential treatment for patients with relapsed or refractory multiple myeloma (MM).

CD38 is an established immunotherapeutic target in MM. In this study, expanded cord blood (CB) derived NK cells first underwent CRISPR gene editing to knock out CD38 to prevent fratricide, following which they were genetically modified to express the optimized affinity CD38 CAR, using Tc Buster, a non-viral transposon approach developed by BioTechne. The anti-tumor efficacy of the optimized CD38 CAR-NK cells was then evaluated in NOD scid gamma (NSG) mice inoculated with MM.1S-LUC cells. Mice underwent weekly bioluminescient imaging to monitor tumor burden. The results showed that CD38 CAR-NK cells significantly reduced tumor burden and improved survival versus control CB NK cells and vehicle control.

Prof. Michael O’Dwyer, founder and CSO at ONK Therapeutics said, "These results suggest that non-virally engineered, optimized affinity CD38 CAR-NK CD38 KO cells have potent anti-tumor activity in-vitro and in-vivo in a CD38 positive tumor model.

"We are encouraged by these data and future work at ONK Therapeutics aims to optimize the dose and schedule, confirm the favorable safety profile and potential beneficial immune modulatory effects of our approach, as well as the added benefit of gene-editing with CRISPR/Cas9 to knock out CISH to enhance persistence."