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Cellenkos® Announces Oral Presentation and Poster Presentation at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition

On November 6, 2023 Cellenkos Inc., a clinical stage biotechnology company focused on developing allogeneic, off-the-shelf, T regulatory (Treg) cell therapies for treatment of rare inflammatory diseases and autoimmune disorders, reported an oral presentation and poster presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is being held December 9-12, 2023, in San Diego, California (Press release, Cellenkos, NOV 6, 2023, View Source;exposition-301978056.html [SID1234637076]).

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The oral presentation will describe the differentiation and characterization of the CXCR4 enriched Treg cells and their preferential homing to bone marrow to resolve inflammation and decrease TGFβ1 and TGFβ2, in vivo, when compared to control Treg cells. This presentation has also been selected for ASH (Free ASH Whitepaper) Abstract Achievement Award.

The poster presentation will elaborate on the results of Company’s CK0804 Phase 1b trial. The study provides first-in-human safety of multiple infusions of CK0804 in myelofibrosis patients in the ambulatory setting as well as improvement in their blood transfusion requirements and symptom burden.

"We are very pleased with the breadth of our oral and poster presentations at this year’s ASH (Free ASH Whitepaper) meeting, which reflect the promising potential of CK0804 as the backbone for treating myelofibrosis," stated Tara Sadeghi, Chief Operating Officer of Cellenkos Inc. "Of particular note is the convergence of our CK0804 clinical data with the strong pre-clinical hypothesis and its mechanism of action. This marks dawn of a new era of differentiated Treg cell therapy that could be tailored to specific target tissue and can be investigated in combination with existing approved therapies, especially if there are complimentary mechanisms of action and favorable side effect profiles. The ability to administer CK0804 cells in ambulatory setting without requiring lymphodepletion or hospital admission, embarks the democratization of cellular therapies such that these potentially lifesaving treatments could be made available to patients in the community setting. In addition, the improvement in blood transfusions burden allows for CK0804 to be positioned as a potential novel therapy. We look forward to examining CK0804 in a larger trial."

Further details of the presentations are provided below.

Oral Presentation

Title: CXCR4 Enriched T Regulatory Cells Preferentially Home to Bone Marrow and Decrease Inflammation
Date: Saturday, December 9, 2023.
Time: 4:30 PM
Location: San Diego Convention Center, Room 6A

This oral presentation describes the CXCR4 enrichment of Treg cells using the CRANE technology platform and faster migration of CXCR4 enriched cells towards SDF1a as early as 15-minute time point. In vivo, the CXCR4 enriched Tregs preferentially trafficked to bone marrow and exhibit higher expression of CXCL12, CD62L, CD39, CD73 and CXCR5. A decrease in TGFα, TNFβ, IL-13 as well as TGFβ1 and TGFβ2 was also observed. These CXCR4 enriched Treg cells are being examined in phase 1b clinical trial (NCT05423691).

Poster presentation

Title: A Phase Ib, Open-Label Study of Add on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib Date: Saturday, December 9, 2023
Time: 5:30 PM
Location: San Diego Convention Center, Halls G-H

This presentation describes the safety and efficacy data from the ongoing phase 1b LIMBER-TREG108 study evaluating CK0804, CXCR4 enriched, T regulatory cells, as an add on therapy to ruxolitinib in patients with myelofibrosis who experience a suboptimal response to ruxolitinib. This is a single arm study where patients receive 6 infusions of CK0804 at a fixed dose at 100 million Treg cells every 28 days. Clinical data from 5 patients who have completed treatment show early promising results of improvement in blood transfusion as well as relief from symptom burden. Additionally, patients report improvement in their tolerance of anemia and daily activities of life.

Phase I Study Results for Qilu Pharmaceutical’s Iparomlimab (QL1604) Now Published

On November 6, 2023 Qilu Pharmaceutical Co., Ltd. reported that the results of the Phase I study for iparomlimab (R&D code: QL1604) were published online in the academic journal Frontiers in Immunology (2022 Impact Factor: 7.3) (Press release, Qilu Pharmaceutical, NOV 6, 2023, View Source [SID1234637075]). The title of the paper is "A first-in-human, open-label, dose-escalation and dose-expansion phase I study to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of QL1604, a humanized anti-PD-1 mAb, in patients with advanced or metastatic solid tumors". (https://www.frontiersin.org/articles/10.3389/fimmu.2023.1258573/full) The study, which is the first-in-human (FIH) study for iparomlimab, was conducted by a team led by Professor Yun Fan from Zhejiang Cancer Hospital.

QL1604 is an innovative monoclonal antibody drug developed by Qilu Pharmaceutical. The findings of the study demonstrated that QL1604 possessed favorable safety, tolerability, and pharmacokinetic (PK)/pharmacodynamic (PD) profiles and antitumor activity, providing valuable evidence for further clinical trials of QL1604.

I. Study Background and Objectives

This study was an open-label Phase I clinical trial of QL1604 in patients with advanced or metastatic solid tumors. The primary objective of the study was to evaluate the safety and tolerability of QL1604 and to determine the recommended dosage for future clinical trials.

II. Study Design and Patient Allocation

The study consisted of dose escalation and dose expansion phases. Between May 29, 2019 and July 24, 2020, a total of 35 patients were enrolled and treated with QL1604. As of the data cut-off date (July 14, 2022), four patients were still on treatment.

III. Safety, Tolerability and Efficacy Results

Out of the six patients in the iparomlimab 3 mg/kg once every two weeks (Q2W) group, one patient (16.7%) with thymic carcinoma experienced dose-limiting toxicity (DLT), grade 3 myasthenia gravis and immune-mediated myositis. No DLT occurred at the planned maximum dose level of 10 mg/kg for dose escalation. Thus, maximum tolerated dose (MTD) was not determined and QL1604 was well-tolerated.

Among all the patients, 94.3% (33 out of 35) experienced adverse events (AEs), with 82.9% (29 out of 35) being treatment-related adverse events (TRAEs). The safety profile was consistent with that of previously reported PD-1 monoclonal antibodies. The most common TRAEs (≥10%) included fatigue (37.1%), anemia (22.9%), increased blood thyroid-stimulating hormone (TSH) (17.1%), increased aspartate transaminase (AST) (17.1%), increased alanine transaminase (ALT) (14.3%), decreased white blood cell counts (11.4%), skin rashes (14.3%) and pruritus (14.3%). Most TRAEs were of grade 1 to 2. The incidence of grade 3 and higher TRAEs was 17.1% (6 out of 35). No grade 5 TRAEs occurred.

In total, 17 patients (48.6%) experienced immune-related adverse events (irAEs). The most common irAE was increased blood TSH (17.1%). Four patients (11.4%) experienced grade 3 or higher irAEs. Three (8.6%) experienced infusion-related reactions (all grade 1-2).

Safety data indicated that the safety profile of QL1604 was manageable. No new safety signals were observed.

Of all the patients, seven (20.0%) achieved partial response (PR) and five (14.3%) achieved stable disease (SD). The objective response rate (ORR) was 20.0% (7 out of 35), and the disease control rate (DCR) was 34.3% (12 out of 35). The median duration of response (DOR) was 26.64 months (95% CI, 2.79-not estimable).

IV. PK/PD Results

The half-life (T1/2) of QL1604 ranged from 3 to 11 days within the dose range of 0.3 mg/kg to 10 mg/kg. A linear relationship was observed between drug exposure and dosage.

PD results indicated that the mean PD-1 receptor occupancy (RO) exceeded 80% one cycle after administering fixed doses of QL1604 at 3 mg/kg every two weeks (Q2W), 3 mg/kg every three weeks (Q3W), 10 mg/kg Q2W, and 200 mg fixed dose Q3W.

V. Summary

The safety and PK profile of QL1604 monotherapy for advanced or metastatic solid tumors was favorable and clear signal of antitumor activity was showed. The recommended doses for future clinical studies were identified as 3 mg/kg Q3W and a fixed dose of 200 mg Q3W.

Currently, the clinical study of QL1604 in patients with unresectable or metastatic deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) advanced solid tumors who have failed standard treatment, has reached the primary endpoint. The Biologics License Application has been accepted by the Center for Drug Evaluation of China’s National Medical Products Administration on September 17, 2023.

Galvanize Therapeutics Announces Promising Data on the Aliya™ Pulsed Electric Field (PEF) System in Early-Stage Non-Small Cell Lung Cancer

On November 6, 2023 Galvanize Therapeutics, Inc., a leader in developing pulsed electric field therapies, reported compelling data from the INCITE-ES clinical study at the recent Society for Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) conference (Press release, Galvanize Therapeutics, NOV 6, 2023, View Source [SID1234637074]). The study evaluated the ability of the Aliya Pulsed Electric Field (PEF) system to induce adaptive anti-tumor immunity in patients with Non-Small Cell Lung Cancer (NSCLC).

The Aliya PEF System delivers high voltage, short duration electrical energy locally to alter the transmembrane potential of a cell, which results in loss of homeostasis, inducing non-thermal programmed cell death without denaturing cellular proteins and extracellular matrix. In addition to focal ablation, preclinical studies suggest this process may release damage associated molecular patterns (DAMPs) and antigens from the dying tumor cells that may stimulate an immune response for a potential systemic effect beyond focal ablation.

The INCITE-ES clinical study is a treat and resect study conducted outside of the U.S., designed to assess safety and examine immune activation in patients with early stage IA2‐IB NSCLC (NCT04732520). The two-arm study enrolled 34 patients in the PEF treatment group and 8 in the control group. Blood, bronchoalveolar lavage, and tumor tissue samples were collected from treated and untreated patients. Single‐cell RNA sequencing (scRNA‐Seq) from pre‐PEF and post‐PEF tumor samples was performed to examine PEF‐induced changes in the cell frequency and gene expression of tumor immune cells. Flow cytometry and serum cytokine profiling were used to evaluate systemic changes in the immune cell populations and cytokines after PEF treatment. Data presented previously demonstrated safety and feasibility to deliver PEF with no device or procedure-related adverse events, a significant reduction in malignant tissue, and an increase in formation of tertiary lymphoid structures (TLS) in PEF-treated patients.

Initial results from the INCITE-ES study highlight the potential for the Aliya PEF system to enhance the body’s natural defenses against tumors. The data suggest that Aliya PEF may facilitate and stimulate the migration of immune cells into the tumor, as well as the activity of the immune cells against tumor cells. This could lead to a stronger immune response, allowing the body to better target and fight the tumors.

Single-cell RNA sequencing in PEF-treated samples revealed a shift in gene expression in cell types that are instrumental in supporting a local inflammatory response.
Single-cell RNA sequencing showed that PEF‐treated tumors had a significant increase in plasma B cells and cytotoxic CD8 T cells (p < 0.05), which are key cells that target cancer cells.
Ingenuity Pathway Analysis (IPA) of serum cytokines in PEF-treated samples demonstrated that PEF induces immunogenic cell death, a type of cell death that triggers the stimulation of the immune system.
Flow cytometry showed higher levels of circulating B cells and effector memory T cells, and lower Tregs in PEF-treated samples, further suggesting activation of multiple aspects of the patients’ immune system.
Jonathan Waldstreicher, M.D., Founder and CEO of Galvanize Therapeutics, commented on the significance of the findings, stating, "The data from the INCITE-ES study underscores the potential of Aliya PEF as a transformative approach in the fight against cancer. By harnessing the body’s own immune system, we are moving closer to offering patients a personalized and potentially more effective treatment option. Our team has been dedicated to investigating the biologic mechanism of action and the data presented at SITC (Free SITC Whitepaper) reflects our ongoing efforts to establish Aliya in the treatment of solid tumors."

The Aliya System is 510(k) cleared in the United States for the surgical ablation of soft tissue. It is not currently commercially available in any other geography.

Aadi Bioscience to Participate in Jefferies London Healthcare Conference

On November 6, 2023 Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage biopharmaceutical company focused on developing and commercializing precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, reported its participation in the Jefferies London Healthcare Conference, taking place November 14-16, 2023, in London (Press release, Aadi Bioscience, NOV 6, 2023, View Source [SID1234637073]). Dave Lennon, Ph.D., President and CEO, will participate in a fireside chat on Tuesday, November 14, 2023, at 8:30 am GMT.

The fireside chat will be webcast live on the IR pages of the Aadi Bioscience website and will be available for replay for approximately 30 days following each investor event.

Rakuten Medical Presents AI-based Study in Two Posters on Immune Characteristics in Responders and Cellular Level Drug Quantification of Alluminox Treatment (Photoimmunotherapy) at SITC 2023

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).

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.