On November 6, 2023 Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeted therapies based on its proprietary Alluminox platform reported the presentation of two posters of AI-based analyses at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), held November 3-5, 2023, in San Diego, CA (SITC 2023) (Press release, Rakuten Medical, NOV 6, 2023, View Source [SID1234637072]). The posters present data that may be relevant to improved clinical outcomes with treatment based on Rakuten Medical’s Alluminox platform (photoimmunotherapy).

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The samples analyzed for these posters are from patients enrolled in an open-label Phase 1b/2 clinical trial (ASP-1929-181 study/ClinicalTrials.gov Identifier: NCT04305795) of ASP-1929 photoimmunotherapy in combination with anti-PD-1 for recurrent or metastatic head and neck squamous cell cancer or advanced or metastatic cutaneous squamous cell carcinoma. Promising early evaluation data from the ASP-1929-181 study* was presented at the American Head and Neck Society (AHNS) in July 2023 (Abstract #: S252). The studies presented at SITC (Free SITC Whitepaper) 2023 utilized AI technology developed by Rakuten Institute of Technology Bengaluru, a part of Rakuten India Enterprise Private Limited and a branch of the global R&D organization of Rakuten Group, Inc., to further interpret the response data presented at AHNS. Rakuten Medical and Rakuten Institute of Technology Bengaluru have collaborated on AI-based analyses of patient samples since 2020.

* These preliminary findings may change upon completion of follow up and final data analysis.

Key findings presented at SITC (Free SITC Whitepaper) 2023

Title: Development of an image-based tumor microenvironment analysis coupled with peripheral flow cytometry reveals a distinct immune cell phenotype in responder patients in the Phase 1b/2 study ASP-1929-181

Abstract #: 83

The first poster addresses immune characteristics between responders and non-responders who received ASP-1929 photoimmunotherapy. Potentially predictive immune biomarkers were identified using a combination of multiplex immunofluorescent imaging methods with AI-based quantification and flow cytometry analyses of peripheral blood. The study results suggest that lower frequencies of CD8+ T cells in the blood at screening correlate with treatment response. Interestingly, of CD8+ T cells in the blood, an increased frequency of PD-1 co-expression also correlates with treatment outcome. At the tumor, an increase in cytotoxic CD8+ T cells in all 22 analyzed patients was observed over the course of treatment, suggesting the induction of the immune response following photoimmunotherapy.

Title: Development of a novel, cellular-level drug uptake quantification pipeline for accurate quantification of fluorescence-conjugated therapeutics: Data from the Phase 1b/2 open-label study ASP-1929-181

Abstract #: 1307

The second poster describes the quantification of drug binding to target cells for ASP-1929 photoimmunotherapy. The preliminary data suggested that a modified drug quantification method using AI-based tumor detection and cell segmentation has the potential to accurately measure drug uptake in tumors at the cellular level. Using this method, high drug uptake (>50-100%) in tumors prior to light treatment was observed for the first time in the clinical samples. Understanding drug uptake levels could help support dose response analyses in future preclinical studies and clinical trials.

On November 6, 2023 XNK Therapeutics AB ("XNK") reported that it will participate in the SITC (Free SITC Whitepaper) meeting, which takes place in San Diego, USA, and present the latest research relating to the company’s leading natural killer (NK) cell therapies (Press release, XNK Therapeutics, NOV 6, 2023, View Source [SID1234637071]). Two abstracts have been accepted for presentation at the meeting.

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The first poster, titled Harnessing the Potential of Autologous NK Cells for Immune Therapy of Patients with Advanced Bladder Cancer, describes the successful expansion of autologous NK cells from peripheral blood mononuclear cells (PBMCs) from bladder cancer patients. Results demonstrate that NK cells from patients before and after first line platinum-based chemotherapy can be expanded and activated ex vivo to become cytotoxic against tumor cells.

The second poster, titled Feeder-free Expansion of Autologous Cytotoxic NK Cells for Acute Myeloid Leukemia Treatment, describes the successful expansion and activation of autologous NK cells from PBMCs of diverse cohorts of patients with Acute Myeloid Leukemia (AML).

XNK will be represented at the meeting by Chief Scientific Officer Dr. Anna-Karin Maltais.

The data have been generated in collaboration with XNK’s external partners, Dr. Anders Ullén and Dr. Fernanda Costa Svedman at the Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden, for the bladder cancer study, and Dr. Abhishek Maiti and Dr. Naval Daver at The University of Texas MD Anderson Cancer Center in Houston, Texas, USA, for the AML abstract.

On November 6, 2023 Biotheus Inc. ("Biotheus"), a clinical-stage biotech company dedicated to the discovery and development of biologics for oncology and inflammatory diseases, reported that the company has entered into an exclusive global license and collaboration agreement under which BioNTech will be developing, manufacturing and commercializing PM8002 globally ex-Greater China, whereas Biotheus retains the rights to exploit PM8002 in Greater China (Press release, Biotheus, NOV 6, 2023, View Source [SID1234637070]). PM8002 is currently being tested in Phase 2 studies in China to evaluate the efficacy and safety of the candidate as a monotherapy or in combination with chemotherapy in patients with advanced solid tumors.

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Under the terms of the agreement, Biotheus will receive an upfront payment of $55 million, and is eligible to receive additional development, regulatory and sales milestone payments potentially totalling over $1 billion as well as tiered royalties on potential future product sales. The transaction is expected to close in Q4 2023, subject to customary closing conditions, including clearance under the Hart-Scott-Rodino ("HSR") Antitrust Improvements Act, and regulatory clearances.

PM8002 is a bispecific antibody candidate with humanized anti-PD-L1 single heavy-chain variable (VHH) domains fused to an anti-VEGF-A IgG1 antibody containing Fc-silencing mutations. PM8002 has demonstrated a positive safety profile and encouraging antitumor activity presumably through reduced systemic toxicity by enriching anti-VEGF activity into the tumor microenvironment at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting and ESMO (Free ESMO Whitepaper) Congress 2023.

"Biotheus’ innovative platform has the capability to expedite preclinical research, bolstering our impressive innovative pipeline of products with encouraging efficacy and safety including PM8002. Collaborating with industry trailblazer BioNTech, we hope to advance PM8002 through multi-regional clinical trials with the aim to be able to provide it to patients worldwide," stated Xiaolin Liu, Co-founder, Chairman, and CEO of Biotheus.

On November 6, 2023 Landmark Bio, a collective endeavor bringing together leaders in industry, academia, and research hospitals to accelerate development and industrialization of next-generation genomic medicines, reported that it has signed a multi-year strategic manufacturing agreement with Galapagos NV (Euronext & NASDAQ: GLPG), an innovative biotech company with operations in Europe and the U.S (Press release, Landmark Bio, NOV 6, 2023, View Source [SID1234637069]).

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Under the terms of the agreement, Landmark Bio will perform GMP manufacturing of clinical trial batches of Galapagos’ development programs of chimeric antigen receptor (CAR) T-cell therapies in hematology-oncology in the Boston metropolitan area.

The manufacturing agreement aims at implementing Galapagos’ novel decentralized CAR-T manufacturing model, designed to enable clinicians to administer CAR T-cells within a median of seven days of leukapheresis, thereby aiming to address important limitations of current CAR-T treatments.

"We are excited to partner with Galapagos to support their CAR-T clinical development programs in the U.S.," said Ran Zheng, CEO of Landmark Bio. "This strategic manufacturing collaboration is a testament to our expertise in cell and gene therapy manufacturing and underscores our commitment to bring more life-saving therapies to patients faster."

Landmark Bio’s 44,000 square-foot fully integrated development and manufacturing facility includes laboratory space for translational research and early development, process and analytical development, and technology innovation. The biomanufacturing area is comprised of nine cleanrooms for cell therapies, genome editing, viral vector, mRNA, and lipid nanoparticle production as well as fill and finish and in-house Quality Control (QC) testing. In addition, Landmark Bio provides wraparound services such as drug development and regulatory consulting, program management and other support services.

Financial terms of the agreement were not disclosed.

On November 6, 2023 Verastem Oncology (Nasdaq: VSTM) (the "Company"), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported results of the efficacy and safety of avutometinib and defactinib in recurrent low-grade serous ovarian cancer (LGSOC) following prior systemic therapy (Press release, Verastem, NOV 6, 2023, View Source [SID1234637068]). The results of this planned subgroup analysis of Part A of the Phase 2 RAMP 201 (ENGOT-ov60/GOG-3052) trial were presented as a late-breaking abstract in an oral presentation during a plenary session at the Annual Global Meeting of the International Gynecologic Cancer Society (IGCS 2023) November 5-7, 2023, in Seoul, Korea.

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"Patients with recurrent LGSOC currently have no medicines approved by the U.S. Food and Drug Administration and limited treatment options for their disease," said Rachel Grisham, M.D., Section Head, Ovarian Cancer and Director, Westchester Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center N.Y., and the lead U.S. investigator of RAMP 201. "The results from this analysis are encouraging as the combination of avutometinib and defactinib demonstrates robust efficacy in recurrent LGSOC irrespective of the number of prior therapies, and for most of which, response to previous therapy was poor."

This planned subgroup analysis was performed to assess efficacy (confirmed objective response rate (ORR) via blinded independent central review per RECIST v1.1) and safety in prior lines of therapy (LoT) (1-3 LoT, ≥4 LoT). The analysis also evaluated efficacy in the context of best response to most recent prior treatment in the metastatic/recurrent setting.

In the combination arm, the observed ORRs were consistent across patients who received 1-3 (45.5%, 5/11, 95% CI 17-77) and ≥4 lines of therapy (44.4%, 8/18, 95% CI 22-69). Prior to enrollment in RAMP 201, only 2/23 (8.7%) patients responded to their last prior treatment in the metastatic/recurrent setting, whereas the combination of avutometinib and defactinib yielded an ORR of 43.5% (10/23) in this subgroup. The safety profiles of avutometinib and defactinib were similar in the less and more heavily pretreated subgroups and both analyses were consistent with previously reported safety data. The majority of treatment-emergent adverse events were mild to moderate.

Initial results of RAMP 201 Part A, presented at the American Society for Clinical Oncology Annual Meeting in May 2023, demonstrated an ORR of 45% (13/29) and tumor shrinkage in 86% (25/29) of evaluable patients that were treated with the combination of avutometinib and defactinib. Safety and tolerability were favorable and consistent with previously reported data. As previously announced, Verastem Oncology intends to file for accelerated approval with the FDA for the combination of avutometinib and defactinib based on mature data from the RAMP 201 trial, together with the results of the investigator-initiated FRAME trial. The Company plans to initiate its Phase 3 confirmatory trial (RAMP 301) of avutometinib and defactinib in LGSOC versus standard of care (SOC) chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole) before the end of the year.

Dr. Grisham is a paid consultant for Verastem Oncology.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its (Raf And Mek Program). RAMP 301 is a Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and has completed enrollment in the dose optimization and expansion phases and is enrolling for low-dose evaluation. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.