On February 4, 2024 Acepodia (6976:TT), a clinical stage biotechnology company developing first-in-class cell therapies with its unique Antibody-Cell Conjugation (ACC) and allogeneic gamma delta 2 (γδ2) T cell platforms to address gaps in cancer care, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s investigational new drug (IND) application for ACE2016, an allogeneic gamma delta 2 (γδ2) T cell therapy for the treatment of epidermal growth factor receptor (EGFR)-expressing malignancies in patients with solid tumors (Press release, Acepodia, FEB 4, 2024, View Source [SID1234639831]).

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This clearance enables Acepodia to initiate a Phase 1, first-in-human trial evaluating the safety, tolerability and pharmacodynamics of ACE2016 in adults with locally advanced or metastatic EGFR-expressing solid tumors. Acepodia expects to begin the trial in the coming months and treat the first patient in the second half of 2024.

"This milestone is a key step as we advance our pipeline of next generation cell therapies and explore the potential of our novel Antibody-Cell Conjugation (ACC) technology in solid tumors, which remain to be unmet medical needs in the cell therapy field," said Sonny Hsiao, Ph.D., chief executive officer of Acepodia. "The rapid progression of obtaining the third IND approval within 18 months highlights the team’s remarkable efficiency and dedication to advancing innovative programs swiftly. With our third program in the clinic, we are proud to continue progressing the field of cell therapy with the goal of delivering powerful, accessible treatments for patients through a first-of-its-kind approach."

About ACE2016

ACE2016 is an off-the-shelf γδ2 T cell therapy candidate developed from Acepodia’s proprietary ACC platform. ACE2016 targets EGFR-expressing solid tumors through antibody conjugated γδ2 T cells that target tumors driven by the cancer-causing EGFR gene. Leveraging the advantages of ACC technology and Acepodia’s proprietary γδ2 T cell platform, ACE2016 has shown promising cytotoxicity against several EGFR-expressing cancers in various pre-clinical study models. The Phase 1 trial will evaluate the safety, tolerability and pharmacodynamics of ACE2016 in patients with locally advanced or metastatic EGFR-expressing solid tumors. The trial is expected to dose its first patient in the second half of 2024.

On February 2, 2024 Hanmi reported its fourth quarter and full year 2023 financial results (Presentation, Hanmi, FEB 2, 2024, View Source [SID1234644665]).

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On February 2, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported that the final median overall survival (mOS)1 for newly diagnosed glioblastoma patients receiving NOX-A12, TME Pharma’s CXCL12 inhibitor, with the VEGF inhibitor bevacizumab and radiotherapy in the GLORIA expansion arm has reached 19.9 months (Press release, TME Pharma, FEB 2, 2024, View Source [SID1234639827]).

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The mOS achieved by NOX-A12 in combination with radiotherapy and bevacizumab compares very favorably to the matched standard of care reference cohort, which achieved an mOS of 10.5 months, and exceeds what TME Pharma believes to be all relevant competitor therapy trials in newly diagnosed glioblastoma patients resistant to standard chemotherapy.2 The NOX-A12-based therapy achieved this result despite having a more difficult population to treat since only patients with residual detectable tumor after surgery were included in the GLORIA trial, while competing trials also included patients with complete removal of the detectable tumor who have a better expected survival outcome.

Based on these data, TME Pharma has submitted an Investigational New Drug (IND)3 application and a Fast-Track Designation4 request to the US Food and Drug Administration (FDA) for the use of NOX-A12 in the treatment of aggressive adult brain cancer, glioblastoma. TME Pharma targets approval of the IND and a decision on the Fast-Track Designation by the FDA before the end of March 2024. The goal is to have an FDA-approved clinical trial protocol in glioblastoma with an expedited regulatory path in place in order to maximize chances of securing the necessary funding for the upcoming clinical trial via partnership, investment or other strategic transaction types.

"With the survival data from the GLORIA cohort receiving NOX-A12, bevacizumab and radiotherapy reaching an unprecedented median overall survival of 19.9 months for the population of patients recruited, we see here compelling evidence of the potential of this combination to provide significant survival benefit to patients suffering from aggressive brain cancer over both standard of care and other competing therapies being developed clinically," said Aram Mangasarian, CEO of TME Pharma. "The survival data formed a key part of our regulatory interactions, and following our recent constructive advice meeting with the FDA we are confident of being able to achieve our target of an approved IND and a decision on a Fast-Track Designation for NOX-A12 by the end of Q1 2024. We believe the strong clinical data produced by the GLORIA trial along with a clear regulatory roadmap will allow us to attract the right partner and financing for NOX-A12 to achieve its potential to become the best available therapy for glioblastoma patients."

On February 2, 2024 Rznomics Inc., a South Korea based biopharmaceutical company specialized in the development of RNA-based gene therapeutics, reported it has received an Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for RZ-001, for the treatment of patients with Hepatocellular carcinoma (HCC) (Press release, Rznomics, FEB 2, 2024, View Source [SID1234639826]).

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The ODD granted to RZ-001 in HCC may allow it to receive 7 years of marketing exclusivity upon product approval, exemption from user fee and tax credits. This also may provide access to specialized regulatory assistance from FDA’s Office of Orphan Products Development (OOPD).

The trans-splicing ribozyme is derived from the self-splicing Tetrahymena group I intron, which both recognizes and reprograms the target RNA into the therapeutic transcript of interest. Ribozyme-based RNA editing technology developed by Rznomics has unique features, differentiating it from other nucleic acid-based editing approaches, as follows: (1) A single RNA molecule is catalytically capable of both suppressing target RNA expression and simultaneously expressing a therapeutic RNA. Thus, this dual activity potentially requires no extra proteins or cofactors. (2) Safety can be improved by selectively inducing therapeutic RNA expression only in cells/tissues where the target gene is expressed. (3) Therapeutic gene expression can be regulated proportionally to endogenous cellular target RNA levels. (4) Editing occurs at the RNA level, not the genomic level, thus eliminating concerns about genomic toxicity and eternal genome changes. (5) Indications with multiple mutation sites scattered throughout a target RNA can be edited with a single RNA designed to react upstream of all mutations and by replacing and editing large stretches of RNA. (6) Additional safety can be conferred by building control mechanisms into the ribozyme itself, without the need to modulate intrinsic cellular mechanisms or external proteins.

More specifically, RZ-001 engenders effective anti-HCC activity by suppressing hTERT expression selectively in cancer cells, which over-express hTERT, and simultaneously inducing a cytotoxic effect by trans ligating an HSVtk-encoding sequence into the reprogrammed hTERT mRNA. Moreover, the result of such editing efficiently induces immune cell infiltrations into HCC tumors in preclinical animal models. (View Source).

"This FDA Orphan Drug Designation further underlines the potential of our pipeline to expeditiously address the current unmet medical needs of patients with Hepatocellular Carcinoma," said Seong-Wook Lee, CEO and founder of Rznomics.

Rznomics received Phase I/IIa IND approvals for RZ-001 in Hepatocellular Carcinoma (HCC) both from the FDA and the South Korean Ministry of Food and Drug Safety (MFDS), and this will be a dose escalation/expansion study to investigate the safety, tolerability, and efficacy of RZ-001 in HCC patients with no extrahepatic metastasis. In addition to HCC, Rznomics received Phase I/IIa IND approvals for RZ-001 GBM (Both in Korea and the U.S.) and Fast Track.

Most recently, Rznomics has entered into an HCC clinical collaboration agreement with F.Hoffmann-La Roche Ltd (Roche) to study RZ-001, in combination with Roche’s atezolizumab.

On February 2, 2024 Qilu Pharmaceutical reported that results of the phase II study on novel anticancer drug iparomlimab and tuvonralimab (QL1706) were published online in Signal Transduction and Targeted Therapy (Impact Factor=39.3) (Press release, Qilu Pharmaceutical, FEB 2, 2024, View Source [SID1234639825]). The study investigated the use of QL1706 in combination with chemotherapy, with or without bevacizumab, for the treatment of non-small cell lung cancer (NSCLC). The publication of the phase II study results signifies broader recognition of QL1706 in the international clinical research community and expands the drug’s impact within the global academia.

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The study, led by Prof. Li Zhang from the Sun Yat-sen University Cancer Center, focused on using QL1706 in combination with chemotherapy, with or without bevacizumab, as a first-line treatment for advanced NSCLC. The research also examined the efficacy of QL1706 in combination with chemotherapy and bevacizumab in patients with epidermal growth factor receptor (EGFR)-mutant NSCLC that progressed after tyrosine kinase inhibitor (TKI) therapy. The findings indicated that QL1706, when used with chemotherapy, with or without bevacizumab, exhibited improved tolerability and promising anti-tumor activity in first-line treatment of patients with EGFR wild-type NSCLC. The combination of QL1706 with chemotherapy and bevacizumab showed notable anti-tumor effects in patients with EGFR-mutant NSCLC who did not respond to TKI therapy, presenting a potential new treatment option.

NSCLC is the predominant pathological type of lung cancer. The systemic management of advanced NSCLC has been revolutionized through advances in chemotherapy, targeted therapy, and immunotherapy, leading to extended overall survival for patients. Among immunotherapies, PD-1/PD-L1 and CTLA-4 inhibitors have become crucial in the first-line treatment of NSCLC, showing remarkable effects on survival outcomes. Despite their efficacy, these treatments can often present safety concerns. Currently, EGFR-TKIs are the standard therapy for EGFR-mutant advanced NSCLC. Despite the high initial objective response rate (ORR), tumors inevitably become resistant to first- and second-generation EGFR-TKIs. The secondary EGFR mutations are considered one possible resistance mechanism. For instance, the T790M mutation impairs binding between first-/second-generation EGFR-TKIs and mutated EGFR. Osimertinib, a third-generation EGFR-TKI, is used for treating NSCLC with EGFR T790M mutation, but its benefits in terms of overall survival are limited.

This trial was designed based on current evidence, to investigate whether dual immunotherapy plus chemotherapy (2 or 4 cycles), with or without bevacizumab, followed by maintenance therapy, could provide durable response and survival benefits. QL1706, targeting both PD-1 IgG4 and CTLA-4 IgG1, blocks both pathways. In a phase I study, QL1706 demonstrated robust anti-tumor effects in patients with advanced solid tumors, including those with NSCLC. Building on these findings, the multi-cohort phase II study assessed the effectiveness of QL1706 in combination with chemotherapy, with or without bevacizumab, in treating both EGFR wild-type and mutant advanced NSCLC. Out of the 112 patients screened in the trial, 91 were enrolled and divided into five distinct cohorts based on genotype: cohorts 1-4 comprised EGFR wild-type individuals, while cohort 5 included EGFR-mutant patients who had experienced disease progression on EGFR-TKI therapy.

The study’s findings revealed that the combination of QL1706 with chemotherapy, with or without the addition of bevacizumab, demonstrated promising efficacy in the treatment of advanced NSCLC. For patients with EGFR wild-type NSCLC, the ORR was 45%, and the median progression-free survival (mPFS) was 6.8 months. Notably, the median duration of response (mDOR) was not reached, and for those who responded to the treatment, the median immune duration of response (iDOR) was 11.5 months. These outcomes provide strong support for the efficacy of QL1706. Regarding safety, grade 3 or higher treatment-related adverse events (TRAEs) were reported in 31.7% of the patients, but no grade 4 or 5 TRAEs occurred.

In patients with EGFR-mutant NSCLC that progressed after EGFR-TKI therapy, the combination of QL1706 with bevacizumab and chemotherapy resulted in an impressive ORR (54.8%) and mPFS (8.5 months). This suggests the potential advantage of the combination therapy over the use of PD-1 inhibitor combined with chemotherapy and bevacizumab. In the study, 18 (58.1%) of the EGFR-mutant patients experienced immune-related adverse events (irAEs), the most common being hypothyroidism (29%), increased aspartate transaminase (AST) level (25.8%), and increased alanine transaminase (ALT) level (22.6%). Despite the irAEs, the combination therapy was deemed safe and effective, providing a valuable treatment option for patients with EGFR-mutant NSCLC.