On December 9, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), an early commercial-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported an oral presentation and three poster presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, being held from December 7-10, 2024, in San Diego (Press release, Autolus, DEC 9, 2024, View Source [SID1234648932]).

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"Our oral presentation at ASH (Free ASH Whitepaper) this year with data from the FELIX trial demonstrates that obe-cel treatment produces a high incidence of deep molecular remission in r/r adult ALL patients, which correlates with better outcomes and is associated with longer event free survival (EFS) and overall survival (OS)," said Dr. Christian Itin, Chief Executive Officer of Autolus. "We’re also presenting three posters that aim to further our understanding of the use of obe-cel in a real-world context, suggesting the positive clinical outcomes of obe-cel even after effective bridging therapy; the reduced healthcare resource utilization costs associated with lower severity of ICANS and CRS; and how hematotoxicity scores could help identify patients who are at higher risk for hematotoxicity from treatment with obe-cel."

Abstract 194508 – Oral presentation:
Title: Obecabtagene autoleucel (obe-cel) for Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL): Deep Molecular Remission May Predict Better Outcomes
Session Name: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Risk Stratification and CAR-T Therapies
Session date and time: Monday, December 9, 2024. 4:30 PM – 6:00 PM PT
Presentation Time: 5:00 PM
Session room: Marriott Marquis San Diego Marina, Marriott Grand Ballroom 5-6
Publication Number: 963
Presenting Author: Dr. Elias Jabbour, Professor, Department of Leukemia, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX

Summary: Obe-cel treatment produces a high incidence of deep remission, which is predictive of better clinical outcomes. The majority of responders to obe-cel achieved deep remission to MRD <10–6 level (84%, 57/68), measured by clonoSEQ NGS assay. Deep MRD remission correlates with better outcomes and is associated with longer event free survival (EFS) and overall survival (OS). The largest EFS and OS benefit was seen with lower tumor burden at lymphodepletion.

Abstract 201514 – Poster presentation:
Title: Obecabtagene autoleucel (obe-cel) for Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) in the Open-Label, Multi-Center, Global, Single-Arm, Phase Ib/II FELIX study: The Impact of Bridging Therapies on CAR T-Cell Expansion and Persistence
Session Name: 704. Cellular Immunotherapies: Early Phase Clinical Trials & Toxicities: Poster II
Session date and time: Sunday December 8, 2024; 6:00 PM – 8:00 PM PT
Session room: San Diego Convention Center, Halls G-H
Publication Number: 3458
Presenting Author: Dr. Jae H Park, Leukemia Specialist & Cellular Therapist, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Summary: Comparable expansion and long-term persistence of obe-cel was observed with all the bridging therapies evaluated, suggesting that long-term persistence of obe-cel is possible irrespective of the bridging therapy and independent of disease burden at lymphodepletion. Bridging therapy with inotuzumab ozogamicin was effective in reducing disease burden prior to lymphodepletion and obe-cel infusion. Reduction in disease burden at lymphodepletion through bridging therapy led to improved event-free survival and overall survival compared to bridging therapy without INO and maintained a tolerable safety profile.

Abstract 205694 – Poster presentation:
Title: Healthcare Resource Utilization and Costs Associated with Managing CRS and ICANS in Patients with Relapsed/Refractory Adult B-Cell Acute Lymphoblastic Leukemia Receiving Obecabtagene autoleucel (obe-cel)
Session Title: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster III
Session date and time: Monday December 9, 2024; 6:00 PM – 8:00 PM PT
Session room: San Diego Convention Center, Halls G-H
Publication Number: 4837
Presenting Author: Dr. Bijal D Shah, Associate Member in the Department of Malignant Hematology Moffitt Cancer Center, Tampa, FL, USA

Summary: Grade ≥3 cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) are associated with increased healthcare resource utilization (HCRU) and costs, but these events were rare in the FELIX study. Costs for adverse events generally increase with event severity. Medication usage and intensive care unit costs were key drivers of CRS and/or ICANS management costs. Obe-cel has the potential to optimize utilization of resources and reduce costs associated with CAR T-cell therapy for patients with R/R B-ALL as a result of the low incidence of Grade ≥3 CRS and/or ICANS.

Abstract 208028 – Poster presentation:
Title: Risk Factors Associated with Sub-Optimal Outcomes Following Obecabtagene autoleucel (obe-cel) for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL): What We Have Learned from the FELIX Trial
Session Name: 704. Cellular Immunotherapies: Early Phase Clinical Trials & Toxicities: Poster III
Session date and time: Monday, December 9, 2024; 6:00 PM – 8:00 PM PT
Session room: San Diego Convention Center, Halls G-H
Publication Number: 4845
Presenting Author: Dr. Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London (UCL)

Summary: The CAR-HEMATOTOX risk score correlated with disease burden in this patient population – patients with high-risk CAR-HEMATOTOX scores had consistently worse outcomes than patients with low-risk CAR-HEMATOTOX scores. Risk-stratification, using pre-lymphodepletion clinical parameters together with disease burden, has the potential to be a useful tool for identifying patients at a high risk for hematotoxicity who may benefit from obe-cel treatment.

On December 9, 2024 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for hematologic malignancies and solid tumors, reported that it presented the latest data from two clinical studies of selinexor in two posters at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH 2024) (Press release, Antengene, DEC 9, 2024, View Source [SID1234648948]).

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Details on the Posters:

Title: Weekly Selinexor, Bortizomib and Dexamethasone (SVd) Versus Twice Weekly Bortizomib and Dexamethasone (Vd) in Chinese Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Primary Analysis of Phase III Bench Study
Publication Number: 4748
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Poster III
Date: Monday, December 9, 2024
Time: 6:00 PM – 8:00 PM (Pacific time)
10:00 AM – 12:00 PM, December 10, 2024 (Beijing time)

The BENCH study is a Phase III randomized, open-label, multicenter clinical trial, aiming to evaluate the efficacy and safety of selinexor, bortezomib and dexamethasone (SVd) regimen against bortezomib and dexamethasone (Vd) regimen in Chinese adult patients with R/R MM who have received one to three prior lines of therapy. At present, a New Drug Application (NDA) based this study has already been submitted to and accepted by China’s National Medical Products Administration (NMPA).
As of May 9, 2024, a total of 154 Chinese R/R MM patients were randomized to SVd group (n=101) or Vd group (n=53) and 152 patients received at least one dose of study drug (safety population).
Efficacy results showed that the median progression-free survival (mPFS) was 8.1 months with SVd group and 6.3 months with Vd group. The overall response rate (ORR) was higher in SVd group than in Vd group. SVd group had a significantly higher proportion of patients with a very good partial response (VGPR) or better responses. The median time to response and the median duration of response were 0.8 vs 1.4 months and 9.7 vs 7.2 months (SVd vs Vd), respectively.
During the study, some subjects experienced treatment emergent adverse events (TEAEs). The most frequent Grade 3-4 adverse events (AEs) for SVd and Vd (≥10%) included thrombocytopenia, lymphocytopenia, and anemia. The incidence of Grade≥2 peripheral neuropathy (PN) was significantly lower in SVd than in Vd group.
The BENCH study has met its primary and key secondary endpoints, with results consistent with the BOSTON study. These results showed that the SVd regimen decreased the risk of progression and obtained much more profound responses compared to standard Vd regimen in Chinese patients with R/R MM. The incidence of Grade ≥2 PN were significantly reduced.
Title: Selinexor Combined with Tislelizumab in Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma (R/R ENKTL): Preliminary Results of Arm C, from a Multicenter, Single-Arm, Phase I/II Study, Touch
Publication Number: 4448
Session: 625. T Cell, NK Cell, or NK/T Cell Lymphomas: Clinical and Epidemiological: Poster III
Date: Monday, December 9, 2024
Time: 6:00 PM – 8:00 PM (Pacific time)
10:00 AM – 12:00 PM, December 10, 2024 (Beijing time)

The Phase I/II TOUCH study is investigating selinexor combined with different drugs in R/R ENKTL. Arm C of the study aims to evaluate the safety, tolerability and preliminary efficacy of selinexor in combination with anti-PD-1 antibody tislelizumab.
As of 18 May 2024, 17 R/R ENKTL patients were enrolled in Arm C [Sel 40mg (n=3); Sel 60mg (n=14)]. Sixteen patients previously exposed to both L-asparaginase (L-Asp) and checkpoint inhibitors (CPIs) including 8 patients who had received prior Tislelizumab (Tis); eleven (64.7%) patients were refractory to their last-line therapy.
Efficacy results showed that, of 16 CPIs exposed patients (one patient was efficacy non-evaluable), the ORR was 75% (12/16), including 7 CRs and 5 PRs; and the median PFS was 6.7 months (95% CI 1.5, NE).
During the study, all patients experienced TEAEs. The most common TEAEs included anemia, neutropenia, asthenia, decreased appetite, weight loss, and thrombocytopenia. Ten patients (58.8%) experienced Grade≥3 TEAEs. Treatment emergent serious adverse events (TESAEs) occurred in 4 patients (23.5%), of which two were considered treatment related. No patient discontinued due to TEAEs. Most of toxicities were manageable by dose modification and supportive care.
In the study, the chemo-free regimen, Sel plus Tis, showed a favorable response rate and manageable safety profile in R/R ENKTL. This approach may probably reverse drug resistance in ENKTL that has progressed after prior CPI treatment.

On December 9, 2024 GenScript Biotech, a global biotechnology leader in the life science, biologics manufacturing, synthetic biology, and cell therapies, and its partner, Base Therapeutics, reported the FDA approval of its NK510 program’s IND (Press release, GenScript, DEC 9, 2024, View Source [SID1234648964]). The NK510 cell program is an NK cell therapy for the clinical treatment of advanced solid tumors, and uses GenScript’s cGMP sgRNA to perform base editing, with CytoSinct Cell Isolation Nanobeads (GMP) and CytoSinct 1000 instruments to perform cell isolation. This is the first FDA IND approval of a base-edited NK cell program and follows NK510’s clinical trial approval by China’s NMPA in October 2024.

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"I am honored that Base Therapeutics has partnered with GenScript to advance the AccuBase Edited NK Cell Therapy project, NK510, which has successfully received IND approval in both the United States and China," remarked Dr. Tianhong Xu, founder of Base Therapeutics. "We are grateful to GenScript for providing services and products (sgRNA & instruments) that meet the regulatory requirements of both countries. This achievement not only marks a significant breakthrough in base editing technology, but also underscores our unwavering commitment to innovation, safety, and efficacy."

"GenScript congratulates Base Therapeutics on their remarkable achievements. We are proud to be the sole provider of their RUO to cGMP sgRNA material and cell isolation platform, essential for reliably generating accurately base-edited cells throughout the product development process," said Dr. Ray Chen, President of the Life Science Group at GenScript. "This collaboration underscores GenScript’s capabilities in supporting gene and cell therapy clients in achieving global IND approvals in an expedited timeline, ultimately helping them make innovative therapies more accessible worldwide."

NK510 is a universal "off-the-shelf" allogeneic NK cell program independently developed by Base Therapeutics. It leverages AccuBase, a proprietary zero off-target base editor with global freedom to operate (FTO) protection, to precisely modify key genes in NK cells, achieving over 90% editing efficiency.

GenScript’s GMP Guide RNA: Enabling Diversified Cell Therapies

With 22 years of expertise in nucleic acid synthesis, GenScript has built a comprehensive gene editing portfolio with RUO to cGMP grade materials, including chemically synthesized guide RNA (gRNA) and HDR knock-in templates. "We can produce cGMP gRNA up to 140 nucleotides long at gram-scale quantities, enabling a wide range of editing technologies, including Cas9, Cas12a, base editing, and prime editing," said Dr. Jianpeng Wang, Senior Director of GenScript’s GMP Production Department. "We also support the preparation of submission materials for regulatory agencies in the US, EU, and APAC markets. This combination of superior product quality and extensive regulatory experience makes GenScript an ideal partner for accelerating cell therapy development."

As of May 2024, GenScript has successfully delivered over 120 batches of cGMP gRNA and HDR knock-in templates, supported more than 40 regulatory submissions, passed over 30 audits, and helped global clients obtain 13 IND approvals.

GenScript’s CytoSinct Platform: Enabling Precise Nanobead-Based Cell Isolation

The CytoSinct Cell Isolation Nanobeads leverage advanced nanoparticle-empowered immuno-magnetic isolation technology to enrich specific cell populations of interest. Its expertise in antibody development and magnetic bead production ensures high precision and reliability. The CytoSinct 1000 Instrument complements the nanobead technology with automation for large scale processing and is designed with 21 CFR Part 11 compliance, adhering to FDA regulations for electronic records and e-signatures to safeguard data integrity throughout the cell isolation process. With customizable programming and alert functions streamline the operation, the system streamlines operations and ensures efficient and reliable automated cell isolation. The CytoSinct platform has also completed FDA DMF filing, underscoring its readiness for clinical applications.

On December 9, 2024 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for OP-3136, a novel small molecule that potently and selectively inhibits KAT6, a validated epigenetic target that is dysregulated in breast and other cancers (Press release, Olema Oncology, DEC 9, 2024, View Source [SID1234649036]).

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"We are very pleased to have received notification from the FDA that OP-3136 may proceed into the clinic," said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. "The compelling activity demonstrated by OP-3136 in preclinical models both as a single agent and in combination with palazestrant has generated strong investigator interest in OP-3136. We expect to initiate the Phase 1 clinical trial early next year and are excited by OP-3136’s potential in breast cancer and beyond."

On December 9, 2024 GSK plc (LSE/NYSE: GSK) reported that the National Medical Products Administration (NMPA) of China has accepted for review a new drug application (NDA) for Blenrep (belantamab mafodotin) in combination with bortezomib plus dexamethasone (BVd) as a treatment for relapsed or refractory multiple myeloma (Press release, GlaxoSmithKline, DEC 9, 2024, View Source [SID1234648901]). Earlier this year, the NMPA granted priority review for this application as well as Breakthrough Therapy Designation1 for the BVd combination, which is intended to expedite development of investigational drugs with potential for substantial improvement over available therapies.

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Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "Today’s regulatory filing acceptance, with a priority review, is a meaningful step forward in our efforts to bring the benefits of Blenrep in combination to patients in China. Multiple myeloma patients need new options that may improve outcomes, particularly at first relapse. The DREAMM-7 trial shows statistically significant efficacy, including overall survival and could redefine treatment in this patient population."

This is the seventh major regulatory filing acceptance this year for belantamab mafodotin in combination for the treatment of relapsed or refractory multiple myeloma based on the results of the DREAMM-7 and DREAMM-8 trials. In 2024, belantamab mafodotin combinations have been accepted for review in the US3, European Union4, Japan5 (with priority review), United Kingdom, Canada and Switzerland (with priority review for DREAMM-8).

The application is based on the interim results of the phase III head-to-head DREAMM-7 trial, which met its primary endpoint, showing statistically significant and clinically meaningful improvement in progression-free survival (PFS) for BVd compared to daratumumab plus bortezomib and dexamethasone (DVd) in relapsed or refractory multiple myeloma. In a subsequent planned interim analysis, the DREAMM-7 trial met the key secondary endpoint of overall survival (OS), showing that BVd significantly reduced the risk of death versus standard of care DVd.

About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.6,7 There are approximately more than 180,000 new cases of multiple myeloma diagnosed globally each year.8 In China, multiple myeloma is a growing health concern with approximately 30,000 new cases each year.9 The incidence of multiple myeloma in China has doubled and mortality has increased 1.5-fold in the past three decades.10 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.11

About DREAMM-7
The DREAMM-7 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with bortezomib plus dexamethasone (BVd) compared to a combination of daratumumab and bortezomib plus dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy.

A total of 494 participants were randomised at a 1:1 ratio to receive either BVd or DVd. Belantamab mafodotin was scheduled to be dosed at 2.5mg/kg intravenously every three weeks.

The primary endpoint is PFS as per an independent review committee. The key secondary endpoints include OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient reported and quality of life outcomes.

Results from DREAMM-7 were first presented12 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series in February 2024, shared in an encore presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, and published in the New England Journal of Medicine.

About Blenrep
Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Blenrep is approved as monotherapy in Hong Kong. Refer to the local Summary of Product Characteristics for a full list of adverse events and complete important safety information.