On November 25, Hanmi reported that it presented the research and clinical progress of BH3120 in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) conference, held in Houston, USA, from November 6 to 10 (Press release, Hanmi, NOV 25, 2024, View Source [SID1234648591]).

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BH3120 is a novel anticancer drug based on Hanmi’s proprietary dual antibody platform, "Pentambody." This technology enables a single antibody to simultaneously bind to two distinct targets, allowing for a targeted anticancer action by specifically attacking cancer cells while activating immune cells to enhance immunotherapy effects.

BH3120 is designed to target PD-L1 on cancer cells and 4-1BB on immune cells, thereby acting as a "bridge" that facilitates immune cells’ recognition and killing of tumor cells.

While other 4-1BB-targeting antibody candidates have faced anticancer efficacy or safety challenges, BH3120’s preclinical studies reveal robust anticancer efficacy alongside a unique decoupling of immune activity between the tumor microenvironment (TME) and normal tissues. This distinct mechanism highlights BH3120’s potential as a breakthrough in developing an effective and safer anticancer therapy.

During the SITC (Free SITC Whitepaper) presentation, Hanmi outlined the background, design, and clinical progress of BH3120. Currently, a global Phase 1 clinical trial is underway in South Korea and the United States, assessing the safety and tolerability of BH3120 as a monotherapy in patients with advanced or metastatic solid tumors.

The Phase 1 clinical trial has progressed smoothly through cohort 3 (1 mg/kg) of the dose escalation phase, with no dose-limiting toxicities (DLT) or grade 3 or higher adverse drug reactions observed to date.

Dr. Dong-wan Kim, director of the Seoul National University Hospital Clinical Trials Center (Hemato-Oncology Department) and lead investigator for the phase 1 clinical trial of BH3120 remarked, "The phase 1 clinical trial of BH3120 is a critical step in verifying the potential of this next-generation immunotherapy. We are optimistic about achieving positive outcomes." He added, "We hope further research will establish BH3120 as an effective and safe treatment option for various cancer types, reducing the side effects often associated with current immunotherapies."

In parallel, Hanmi is also conducting a Phase 1 trial to assess the safety and efficacy of BH3120 in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with advanced or metastatic solid tumors.

In September, Hanmi obtained approval from both the Korean Ministry of Food and Drug Safety and the U.S. Food and Drug Administration (FDA) to modify the Phase 1 trial plan to evaluate BH3120 in combination with KEYTRUDA. Full-scale clinical development is expected to commence early next year. Hanmi will serve as the lead sponsor and conduct the clinical trial, while MSD will supply KEYTRUDA for the trial.

Young Su Noh, Director of Hanmi’s ONCO Clinical Team, emphasized, "The BH3120 trial represents a milestone as Hanmi’s first global clinical research project utilizing our proprietary Pentambody dual antibody platform in immuno-oncology, a field at the forefront of cancer treatment innovation." He continued, "We are committed to advancing a next-generation immunotherapy that overcomes the limitations of existing treatments and enhances therapeutic efficacy."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On November 25, 2024 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company in late-stage development with its DNA-mediated immunotherapy, reported the outcome of its recent End-of-Phase 2 in-person meeting with the U.S. Food and Drug Administration (FDA), supporting the advancement of its investigational interleukin-12 (IL-12) immunotherapy IMNN-001 for the treatment of advanced ovarian cancer into a Phase 3 pivotal study (Press release, IMUNON, NOV 25, 2024, View Source [SID1234648610]). IMUNON remains on track to initiate the 500-patient Phase 3 trial in the first quarter of 2025.

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"The collaborative End-of-Phase 2 meeting with the FDA represents another important milestone in our IMNN-001 clinical program, and we are very pleased that the Agency is aligned with the potential for IMNN-001 to address a significant unmet need in ovarian cancer treatment and our Phase 3 plans," said Stacy Lindborg, Ph.D., president and chief executive officer of IMUNON. "We are encouraged by the robust safety and efficacy data from our Phase 2 OVATION 2 Study, including the positive survival results recently presented in a late-breaking session at the SITC (Free SITC Whitepaper) Annual Meeting. IMNN-001 is the first immunotherapy to achieve a clinically effective response in ovarian cancer, including benefits in both progression-free and overall survival in frontline treatment."

"Our goal is to replicate these remarkable results in a Phase 3 trial, which would be transformative for the current standard of care, substantially improving overall survival and giving hope to thousands of women with advanced ovarian cancer who continue to experience disease progression," Dr. Lindborg added.

The interaction with the FDA included an extensive review of data generated to date, including positive results from the recently completed Phase 2 OVATION 2 Study, which assessed IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin compared to standard-of-care NACT alone in 112 patients with newly diagnosed advanced ovarian cancer. The OVATION 2 Study results demonstrated that IMNN-001 immunotherapy plus standard-of-care chemotherapy resulted in approximately a one-year (35%) improvement in overall survival compared to treatment with standard-of-care chemotherapy alone. Treatment was also generally well tolerated, with no reports of cytokine release syndrome or any other serious immune related adverse events.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

On November 25, 2024 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, reported results from the fully enrolled Phase 1 trial of INB-200 in a plenary oral presentation at the 29th Annual Meeting of the Society for Neuro-Oncology in Houston, TX (Press release, In8bio, NOV 25, 2024, View Source [SID1234648611]). The survival data along with histopathology and radiographic data are indicative of positive treatment effects, which highlight the potential of IN8bio’s genetically modified, chemotherapy-resistant gamma-delta T cells as a potential first-in-class therapy for patients with solid tumor cancers such as glioblastoma (GBM).

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"As the clinical trial data continues to mature, this novel immuno-cell therapy leveraging gamma-delta T cells is highly feasible with a well-tolerated safety profile and biological evidence of improved immune surveillance in glioblastoma patients," said Burt Nabors, M.D., Division Director, Neuro-Oncology at the Heersink School of Medicine at the University of Alabama at Birmingham.

"This novel treatment leverages the DNA damage induced by chemotherapy combined with genetically engineered gamma-delta T cells and we believe it represents a significant advancement in the treatment of solid tumor cancers such as GBM," said William Ho, co-founder and CEO of IN8bio. "Glioblastomas are often classified as cold, immune desert tumors due to their limited immune cell infiltration. For the first time, we have confirmed the infiltration of gamma-delta T cells into these tumors through paired tissue biopsies following treatment with INB-200. We are encouraged by the patient follow-up with repeat dose patients demonstrating a 79% increase in median PFS as compared to 6.9 months as reported by the Stupp regimen and an almost 50% increase in median PFS as compared to the 8.3 months in the three patients treated with only a single dose of INB-200 in Cohort 1. The addition of IN8bio’s DeltEx drug resistant immunotherapy (DRI) gamma-delta T cells show the potential for extending PFS in this difficult-to-treat patient population when INB-200 was administered in combination with the current standard-of-care used to treat newly diagnosed GBM patients."

The Phase 1 trial assessed the safety and preliminary efficacy of the addition of DeltEx DRI gamma-delta T cells to maintenance therapy with TMZ. The trial assessed the administration of 1×107 cells per dose across three different dosing regimens increasing from a single dose in Cohort 1, three doses in Cohort 2, and six doses in Cohort 3. A total of 13 patients have been enrolled and treated with INB-200, including three patients in Cohort 1, four patients in Cohort 2 and six patients in Cohort 3.

Key findings from the INB-200 Phase 1 trial:

92% of evaluable patients treated with INB-200 for GBM surpassed a median standard-of-care (Stupp regimen) PFS of 6.9 months, with a majority exceeding their expected PFS based on their age and the MGMT status of their tumors.
One patient with an IDH-mutant glioma remains alive and progression free at over 40.5 months; IDH-mutant patients in a recently published clinical trial demonstrated a median PFS of 11.1 months in the control arm and 27.7 months in the experimental arm.
No treatment-related serious adverse events, dose-limiting toxicities, cytokine release syndrome, infusion reactions, or immune effector cell-associated neurotoxicity syndrome have been reported in any cohort.
The most common treatment emergent adverse events were Grade 1-2 toxicities consisting of white blood cell and platelet count decreases related to standard-of-care TMZ.
Gamma-delta T cells and other immune subsets such as CD3+ and CD8+ T cells were found in relapsed tumor biopsies in two patients after treatment with INB-200, pointing to persistence of DRI gamma-delta T cells.
Gamma-delta T cells were within the normal range post-resection and remained stable with repeated doses (Cohorts 2 and 3), whereas the gamma-delta T cells in Cohort 1 continued to drop after the maintenance cycles with TMZ were initiated. This implies that repeat dosing of gamma-delta T cells may globally benefit the peripheral immune environment.
T cells were low prior to surgery, rose after resection and during the cell collection for the product, were below normal during chemotherapy, and in Cohorts 2 and 3 returned to the normal range following treatment.
Radiographic evaluation pre- and post-treatment included resolution of midline shift in one patient with evidence of changes in enhancement attributed to treatment effect in multiple patients. One subject was found to have a 36% decrease in a lesion attributed to positive treatment effect.

On November 25, 2024 Flare Therapeutics Inc., a clinical-stage biotechnology company targeting transcription factors to discover precision medicines for oncology and other therapeutic areas, reported that the company will participate in two upcoming investor conferences in December (Press release, Flare Therapeutics, NOV 25, 2024, View Source [SID1234648627]):

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7th Annual Evercore ISI HealthCONx Conference: Douglas Manion, M.D., FRCP (C), Chief Executive Officer and Daphne Karydas, President and Chief Financial Officer will participate in a fireside chat on Wednesday, December 4, 2024 at 12:55 p.m. ET in Coral Gables, Florida.

Piper Sandler 36th Annual Healthcare Conference: Douglas Manion, M.D., FRCP (C), Chief Executive Officer, will present a company overview on Thursday, December 5, 2024 at 9:50 a.m. ET in New York, NY. Daphne Karydas, President and Chief Financial Officer will also be available for meetings with investors.

On November 24, 2024 Alpheus Medical, Inc., a private, clinical-stage oncology company pioneering sonodynamic therapy (SDT) for the treatment of solid body cancers, reported positive results from their Phase 1/2 clinical trial in patients with recurrent or refractory high-grade gliomas (Press release, Alpheus Medical, NOV 24, 2024, View Source [SID1234648593]). The company’s proprietary therapy demonstrated a strong safety profile and extended median overall survival (OS) and progression-free survival (PFS) compared to historical data. The data were presented by Michael Schulder, MD, at the 2024 Society of Neuro-Oncology (SNO) Annual Meeting.

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"Glioblastomas are the most common and aggressive primary brain cancer, presenting a devasting diagnosis for patients and their familes," said David Reardon, MD, Clinical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute, and member of the Alpheus Medical Scientific Advisory Board. "Current treatment options are limited and often ineffective due to the diffuse spread of the disease across the blood-brain barrier and often across the entire hemisphere, making it universally fatal with a rapid timeline. The early clinical results of Alpheus’s therapy are promising, offering hope for this new approach. I look forward to further exploring the potential benefits of their SDT therapy for this patient population who is in critical need of an effective solution."

Alpheus Medical’s non-invasive SDT treatment, which can be delivered in an outpatient setting, combines low-intensity diffuse ultrasound (LIDU) with oral 5-aminolevulinic acid (5-ALA) to target and kill cancer cells across the entire hemisphere without the need for imaging or sedation. Key findings from the study include:

Median overall survival (OS): 15.7 months vs. historical ~6-8 months
Median progression-free survival (PFS): 5.5 months vs. historical 1.8 month
Safety: No treatment-related deaths, serious adverse events (SAEs), or duration-limited toxicities (DuLTs) reported
"In addition to the strong safety data and early indications of efficacy, Alpheus’ non-invasive SDT therapy stands out for its ease of use – a significant improvement over the uncomfortable and often toxic treatments currently available for this rapidly fatal condition," stated Dr. Schulder, Director of the Brain Tumor Center at Northwell Health, and one of the trial’s primary investigators. "We look forward to expanding the ability for patients to receive this promising therapy."

The Phase 1/2 trial (NCT05362409) is an open-label, multicenter, duration-escalation study evaluating the safety, optimal dose, and efficacy of Alpheus Medical’s proprietary SDT platform. Twelve patients were enrolled across three cohorts, with treatment durations escalating to 60, 90, and 120 minutes per monthly session.

The company plans to initiate a randomized, controlled trial at multiple centers across the U.S. in 2025.