On April 13, 2023 Bold Therapeutics, a clinical-stage biopharmaceutical company developing first-in-class oncology therapeutics, reported that it will present two posters – a clinical poster (#CT149) and a translational research poster (#2259) – at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 on April 14 – 19, 2023 in Orlando, Florida (Press release, Bold Therapeutics, APR 13, 2023, View Source [SID1234630060]).

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The clinical poster (#CT149) is entitled "BOLD-100-001 (TRIO039): a Phase 1b/2a Dose-Escalation Study of BOLD-100 in Combination with FOLFOX Chemotherapy in Patients with Pre-treated Advanced Colorectal Cancer: Interim Efficacy, Safety and Tolerability Analysis," and will be presented April 17, 2023 at 1:30PM.

The translational research poster (#2259) is entitled "Novel Metallotherapeutic BOLD-100 Induces Circulating Cytokine Changes When Administered in Combination with FOLFOX in Advanced Gastrointestinal Cancer Patients," and will be presented April 17, 2023 at 9:00AM.

"We are thrilled to share these posters, showcasing the profound progress we’ve made with BOLD-100 over the last year," said Jim Pankovich, EVP Clinical Development. "This robustly positive interim clinical data is a testament to the hard work and dedication of our team, collaborators, clinical sites, investigators and patients. We look forward to continuing development of this innovative therapeutic."

Bold Therapeutics’ BOLD-100 is a first-in-class ruthenium-based small molecule therapeutic that (1) alters the unfolded protein response (UPR) through selective GRP78 inhibition; and (2) induces reactive oxygen species (ROS) which causes DNA damage and cell cycle arrest. Collectively, these effects result in cell death in both sensitive and resistant cancers, giving BOLD-100 the potential to significantly improve outcomes in a wide range of both solid and liquid tumors in combination with other anticancer therapies ranging from traditional chemotherapies to targeted therapies and immuno-oncology agents. Earlier preclinical data showed that BOLD-100 has potential immune modulating capabilities, including the induction of immunogenic cell death pathways. The translational data to be presented at AACR (Free AACR Whitepaper) shows that BOLD-100 in combination with FOLFOX induced short-term plasma level changes in multiple cytokines, including IL-10 and IL-27.

BOLD-100 is currently being studied in a global Phase 1b/2 trial for the treatment of advanced gastrointestinal cancers, with more than 100 patients successfully treated to date. Previous Phase 1b trial results, presented at ASCO (Free ASCO Whitepaper) 2022, demonstrated that BOLD-100 in combination with FOLFOX was generally safe and well-tolerated. This data release expands on the prior data with a much larger sample size and includes progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) data that positions BOLD-100 as a potentially best-in-class therapy for mCRC.

Additional Phase 2 safety and efficacy results in advanced gastric and bile duct cancer have been accepted for presentation at ASCO (Free ASCO Whitepaper) 2023 in June.

On April 13, 2023 Menarini Silicon Biosystems (MSB), a pioneer of liquid biopsy and single cell technologies, reported the data from two posters to be presented at the April 14-19, 2023 annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Menarini Silicon Biosystems, APR 13, 2023, View Source [SID1234630059]). Among them, one demonstrated the benefit of an AI algorithm for automated, reliable, and reproducible CELLSEARCH CTC identification, while the other focused on the additional information available through the parallel immunomagnetic enrichment of tumor derived extracellular vesicles and CTCs from a single blood sample.

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According to Ralf Schoenbrunner, Ph.D., Chief Global R&D Officer at MSB "these two posters underline the multiple opportunities that our technologies can provide for the retrieval of enhanced qualitative and quantitative information in liquid biopsies." Findings were made possible thanks to the use of the company’s gold standard CELLSEARCH technology for CTC capture and enumeration, and the use of CellMag for manual immunomagnetic enrichment of CTCs and tumor derived extracellular vesicles (tdEVs).

The posters are scheduled for Monday the 17th of April between 1:30 and 5:00 PM in Session PO.CL01.16 – Liquid Biopsies: Circulating Nucleic Acids and Circulating Tumor Cells 3.

● 3373 /16 – Deep learning for circulating tumor cell (CTC) identification with the CELLSEARCH system: achieving top human-level performance

● 3364 / 7 – Combined enrichment of plasma EpCAM-positive extracellular vesicles (EVs) and circulating tumor cells (CTCs) from a single tube of cancer patient blood samples, for subsequent molecular analysis

The first poster shows the benefit of an AI-based tool (for research use) that removes human subjectivity and automates the process of CTC identification with CELLSEARCH. The AI was trained to identify CTCs using anonymized CELLTRACKS ANALYZER II images acquired over several years, for a total of 13.469 CTCs and 35.792 non-CTC examples from cancer patients’ samples. The performance of the AI-based tool on a separate set of 55 patient samples was compared to that of experienced human reviewers. The results overwhelmingly support the use of AI for which performance surpassed 4 out of 5 expert reviewers.

The second poster opens the door to the clinical utility of a simultaneous assessment of multiple analytes from the same blood sample. The parallel enrichment of tumor-derived Extracellular Vesicles (tdEVs) and CTCs from the same blood sample, by means of CellMag EpCAM-based immunomagnetic capture, enabled additional molecular analyses and led to the identification of oncogenic miRNAs (microRNAs) in cancer patients’ blood samples resulting in additional insight into the molecular mechanism of cancer.

Additional posters will be presented during the AACR (Free AACR Whitepaper) 2023 annual meeting using the CellSearch and DEPArray technologies.

3385 / 28 – A pipeline for mRNA analysis on circulating tumor cells (CTCs) collected and stored in preservative tubes
2463 / 3 – Protein folding chaperonin as biological indicator for cancer progression and metastasis
1031 / 8 – Specific gene alterations of HER2 positive single circulating tumor cell (CTC) compared to autologous leukocytes in metastatic breast cancer (MBC)
5595 / 19 – Serial monitoring of circulating tumor cells and circulating tumor DNA in metastatic lobular breast cancer identifies intra-tumor heterogeneity and precision and immuno-oncology biomarkers of therapeutic importance
3370/ 13 – Liquid Biopsy approaches to determine tumor cell heterogeneity in advanced prostate cancer
For Fabio Piazzalunga President and CEO of MSB "both our posters and those presented by our partners highlight our never-ending efforts to gather clinically relevant information from blood to develop needed assays for both clinical research as well as improved patient prognosis and care". Indeed, over time, MSB’s liquid biopsy assays aim to improve cancer care with respect to early detection, identification of residual disease, assessment of treatment response and monitoring of tumor evolution with the ultimate goal to support clinicians in treatment decisions.

More information on the unique and comprehensive MSB offering is available at the company’s commercial booth, #100, within the AACR (Free AACR Whitepaper) exhibit center. During your visit, you will be able to discover new tests available, and those under development, for user defined biomarker assays for CTCs through the MSB biopharma global laboratory service. Most importantly, two new biomarkers, ARV7 and DLL3, coupled to CTC enumeration, will be available, for research use, in May 2023.

On April 13, 2023 Pyramid Biosciences, Inc., a privately-held, clinical-stage biotechnology company focused on developing transformative medicines for patients with cancer, reported that it has entered into an exclusive license agreement with GeneQuantum Healthcare (Suzhou) Co. Ltd, a privately-held biotechnology company based in China, to develop and commercialize GQ1010, a potential best-in-class antibody drug conjugate (ADC) targeting TROP2, worldwide except for Greater China (mainland China, Hong Kong, Macau, and Taiwan) (Press release, Pyramid Biosciences, APR 13, 2023, View Source [SID1234630058]). GQ1010 has shown a highly differentiated preclinical profile, and is anticipated to enter a first-in-human trial within the next 12 months.

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"We are thrilled to be partnering with GeneQuantum in bringing this exciting asset, GQ1010, into the clinic," said Brian Lestini, M.D., Ph.D., Chief Executive Officer of Pyramid Biosciences. "By leveraging the unique features of the GeneQuantum bioconjugation platform and Pyramid’s deep expertise in oncology drug development, this partnership significantly expands our growing oncology portfolio. This highly differentiated program has the potential to address substantial limitations of current ADCs and unmet needs for patients with TROP2-expressing tumors, a clinically validated target in oncology."

"GeneQuantum was founded with the goal of addressing critical unmet needs in global healthcare through the development of innovative technologies. GQ1010 highlights its best-in-class potential through GeneQuantum’s cutting-edge technology in the development of differentiated bioconjugate drugs such as GQ1001, an anti-HER2 ADC, which has demonstrated a differentiated profile in Phase 1 data. We believe this agreement between GeneQuantum and Pyramid Biosciences represents the ideal partnership to rapidly advance the worldwide development of GQ1010, and to help patients overcome their cancer," said Qin Gang, Ph.D., Chief Executive Officer of GeneQuantum. "Our collaboration with Pyramid for global development of the GQ1010 program brings together the best of GeneQuantum’s proprietary technology and Pyramid’s extensive capabilities and track record of success in delivering transformative medicines to patients with cancer."

GQ1010 utilizes a unique site-specific conjugation technology and incorporates a novel linker-payload which may lead to improved stability, safety and potency of the ADC. Preclinical data suggests GQ1010 has a broader therapeutic margin compared to more advanced TROP2 ADCs, that may translate to an improved efficacy and safety profile for GQ1010. TROP2 is a cell surface glycoprotein that is highly expressed in a variety of tumors including breast, lung, pancreatic, ovarian, and prostate cancer, and plays a role in tumor cell proliferation.

Under the terms of the agreement, Pyramid Biosciences will develop and commercialize GQ1010 in exchange for an upfront payment of $20 million and up to an additional $1 billion of milestone payments. GeneQuantum would also be eligible to receive tiered royalties ranging from mid-single digit to low double digits on net sales.

On April 13, 2023 Adcendo ApS ("Adcendo"), a biotech company focused on the development of breakthrough antibody-drug conjugates (ADCs) for the treatment of cancers with a high unmet medical need, reported that it will be presenting novel data evaluated in co-operation with the Laboratory of Experimental Oncology at KU Leuven/Leuven Cancer Institute on the expression of the novel ADC target uPARAP in Soft Tissue Sarcoma (STS) and Bone Sarcoma at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held in Orlando, Florida on the 14-19 April, 2023 (Press release, ADCendo, APR 13, 2023, View Source [SID1234630057]).

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Details of the conference and presented poster are as follow:

Presentation title: 1457 / 27 The urokinase plasminogen activator receptor-associated protein (uPARAP) is an attractive target for the development of antibody-drug conjugates (ADCs) for treatment of mesenchymal malignancies

Session: Experimental and Molecular Therapeutics, Chemistry

Session Title: Antibody Drug Conjugates

Authors: Pernille Barkholt (1), Agnieszka Wozniak (2), Chao-Chi Wang (2), Che-Jui Lee (2), Lore De Cock (2, 3), Lars Henning Engelholm (1), Carmel Lynch (1), Dominik Mumberg (1), and Patrick Schöffski (2, 3)

Date & Time: 17 April at 09:00am – 12.30pm CDT

Abstracts will be published on 04 April, and can be accessed at View Source

uPARAP is a novel ADC target overexpressed by mesenchymal cancer cells including soft tissue and bone sarcomas and may play an important role in shaping the tumor microenvironment.

The presentation entitled "The urokinase plasminogen activator receptor-associated protein (uPARAP) is an attractive target for the development of antibody-drug conjugates (ADCs) for treatment of mesenchymal malignancies" demonstrates that uPARAP is strongly over-expressed by cancer cells in multiple soft-tissue & bone sarcoma subtypes, with limited expression in healthy tissues.

Based on its differentiated expression profile, uPARAP is an attractive novel target for development of uPARAP-targeting ADCs in a broad range of sarcoma subtypes. Additionally, uPARAP receptor levels may serve as a potential biomarker for patient enrichment in clinical studies of such uPARAP-targeting ADCs.

Dominik Mumberg, Chief Scientific Officer of Adcendo, said: "We are excited to share data on the expression of uPARAP in soft tissue and bone sarcoma. In addition to its differentiated expression profile in multiple sarcoma subtypes uPARAP is a constitutively recycling endocytic receptor with unique internalization properties, making it a highly attractive ADC target."

Patrick Schöffski, Head of the Department of General Medical Oncology at the University Hospitals and the Laboratory of Experimental Oncology at the Catholic University in Leuven, commented: "Due to its significant morphological and biological heterogeneity, treatment progress and therapeutic options in soft tissue and bone sarcoma have so far been quite limited. We are extremely encouraged by the data highlighted in this study, which provides further evidence on the potential utility of uPARAP as a novel target for drug development across multiple sarcoma subtypes. We are looking forward to continuing to explore the molecular epidemiology of uPARAP in various types of sarcoma and to investigate uPARAP-directed ADCs in patient-derived xenograft models of sarcoma.

On April 13, 2023 The Wisconsin Alumni Research Foundation (WARF), which has a mission of supporting research at the University of Wisconsin-Madison, and Ginkgo Bioworks (NYSE: DNA), which is building the leading platform for cell programming and biosecurity, reported a partnership to leverage Ginkgo’s proprietary high-throughput combinatorial CAR discovery and screening platform with the aim of discovering next generation GD2 CAR T-cell therapies with improved persistence, proliferation, fitness, and other functional properties to improve efficacy for the treatment of solid tumors (Press release, Ginkgo Bioworks, APR 13, 2023, View Source [SID1234630056]).

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Through this partnership, Ginkgo will collaborate with the University of Wisconsin-Madison researchers Professor Krishanu Saha, Ph.D., as principal investigator (PI) and Dr. Christian Capitini, M.D. as co-PI. Professor Saha’s lab focuses on developing the next-generation cell engineering techniques to advance human therapeutics, and Dr. Capitini is a pediatric oncologist who has extensive clinical experience with CAR T-cell therapies, including serving as a site PI for the clinical trial that led to the first FDA approval of a CAR T-cell therapy. The two have collaborated on the development of a GD2 CAR T-cell therapeutic candidate for the treatment of neuroblastoma, a type of cancer generally affecting young children, using a non-viral, site-specific integration method developed by Professor Saha and published in the Journal for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper): Production and characterization of virus-free, CRISPR-CAR T cells capable of inducing solid tumor regression.

Under this collaboration, Ginkgo will use its pooled CAR screening platform to design and characterize novel intracellular signaling domains that prevent the exhaustion of T-cells in the GD2 solid tumor context. Any novel designs will be validated in high throughput in vitro screens and in in vivo murine models. In addition, Ginkgo and WARF plan to collaborate on the development of a pooled in vivo screening platform to advance novel CAR discovery further.

"Ginkgo’s high throughput screening method has proven successful in enabling massively parallel testing of CAR designs, and has already led to the discovery of new intracellular domains (ICD) combinations," said Krishanu Saha, a professor at the University of Wisconsin-Madison. "By partnering with Ginkgo, we aim to unlock the potential to transform patient outcomes and reimagine the future of solid tumor cancer treatment."

CAR T-cell therapies show tremendous promise for the treatment of cancer. However, their use has thus far largely been limited to targeting blood cancers because they have failed to show consistent efficacy in treating solid tumors, which represent approximately 90% of adult human cancers. Part of the challenge when applying CAR T-cell therapies to solid tumors is T-cell exhaustion, a state of dysfunction arising from excessive antigen stimulation in the immunosuppressive environment of a solid tumor.

WARF and Ginkgo hope to work towards solving this challenge by utilizing Ginkgo’s high-throughput combinatorial CAR discovery platform. As a platform technology company, Ginkgo can leverage its full stack of mammalian cell engineering expertise and capabilities to enable the high throughput screening of CAR T-cells to help discover and optimize future next-generation therapeutic candidates for its partners.

"WARF is delighted to see this important collaboration," says Erik Iverson, WARF CEO. "We know these alliances between our university researchers and leading biotech industry partners have the potential to result in benefits that positively impact human health."

"This collaboration represents a fantastic opportunity to demonstrate the potential value of pooled CAR screening approaches directly in the context of devastating diseases like early childhood cancers," said Narendra Maheshri, Head of Mammalian Engineering at Ginkgo. "It’s especially exciting to work with pioneers like Professors Saha and Capitini, who have pushed R&D boundaries in the laboratory and whose approach is thoroughly grounded in the translation of their findings for clinical impact."