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 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.

On November 24, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that nearly 10 accepted clinical data of its novel oncology molecules, including an oral presentation of updated Phase 1 result of its novel TOPO1i CLDN18.2 ADC (IBI343) in previously-treated pancreatic cancer, will be released at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia (ESMO Asia) Congress 2024 from Dec 06-08, 2024, in Singapore (Press release, Innovent Biologics, NOV 24, 2024, View Source [SID1234648592]).

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Details on the abstracts are listed below:

Mini Oral

Abstract Title: Anti-claudin18.2 (CLDN18.2) antibody-drug conjugate (ADC) IBI343 in patients with advanced pancreatic ductal adenocarcinoma (PDAC): updated results from a Phase 1 study

Abstract No: 132MO

Session Type and Title: Mini Oral session: Gastrointestinal tumors

Presentation Time: 2024-12-07, 09:50-09:55

Presenter: Jian Zhang, Fudan University Shanghai Cancer Center, CN

Abstract Title: mFOLFOX6 + Bevacizumab + PD-1 Monoclonal Antibody in Locally Advanced MSS CRC (BASKETⅡ): A Prospective, Single-Arm, Open-Label, Phase 2 Study

Abstract No: 74MO

Session Type and Title: Mini Oral session: Gastrointestinal tumors

Presentation Time: 2024-12-07, 10:20-10:25

Presenter: Jun Huang, The Sixth Affiliated Hospital, Sun Yat-sen University, CN

Posters

Abstract Title: Anlotinib plus Sintilimab as First-line Treatment for Patients with Advanced Colorectal Cancer (APICAL-CRC): an Open-Label, Single-arm, Phase 2 study

Abstract No: 75P

Session Type and Title: Poster Display session

Presentation Time: 2024-12-07, 17:50-18:45

Presenter: Zhan Wang, Shanghai Changzheng Hospital, The Second Affiliated Hospital of Naval Medical University, CN

Abstract Title: A single-arm, multicenter, Phase 2 study of hepatic arterial infusion chemotherapy (HAIC) combined with donafenib and sintilimab as first-line treatment for unresectable intrahepatic cholangiocarcinoma (CHANCE 2203)

Abstract No: 137P

Session Type and Title: Poster Display session

Presentation Time: 2024-12-07, 17:50-18:45

Presenter: Gaojun Teng, Zhongda Hospital, Southeast University, CN

Abstract Title: FOLFOX-HAIC combined with sintilimab and bevacizumab for advanced hepatocellular carcinoma: a single-arm, Phase 2 study

Abstract No: 207P

Session Type and Title: Poster Display session

Presentation Time: 2024-12-07, 17:50-18:45

Presenter: Bin Liang/ Zizhuo Wang, Union Hospital Tongji Medical College Huazhong University of Science and Technology, CN

Abstract Title: Updated results from Phase 2 study of HAIC plus sintilimab and bevacizumab biosimilar in patients with advanced hepatocellular carcinoma (HCC)

Abstract No: 214P

Session Type and Title: Poster Display session

Presentation Time: 2024-12-07, 17:50-18:45

Presenter: Haibin Zhang, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, CN

Abstract Title: Anlotinib Combined with Sintilimab Versus Chemotherapy Combined with Immunotherapy in Perioperative NSCLC: A Phase 2 Study

Abstract No: 599P

Session Type and Title: Poster Display session

Presentation Time: 2024-12-07, 17:50-18:45

Presenter: Tianqing Chu, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, CN

Trial in Progress abstracts (TiP)

Abstract Title: A randomized, controlled, multicenter Phase 3 study of IBI310 (anti-CTLA-4 antibody) plus sintilimab (anti-PD-1 antibody) as neoadjuvant treatment for resectable microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colon cancer: Trial in Progress

Abstract No.: 119TiP

Session Type and Title: Poster Display session

Presentation Time: 2024-12-07, 17:50-18:45

Presenter: Ruihua Xu, Sun Yat-sen University Cancer Center, CN

Abstract Title: Efficacy and Safety of Combination Therapy of Sintilimab and Chemotherapy with Cryoablation in the First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Abstract No.: 722TiP

Session Type and Title: Poster Display session

Presentation Time: 2024-12-07, 17:50-18:45

Presenter: Zhiqiang Gao, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, CN

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are very pleased to present and share a robust set of clinical data at EAMO Asia 2024. Notably, we are highlighting the breakthrough potential for our TOPO1i CLDN18.2 ADC (IBI343) in pancreatic cancer, a global difficult-to-treat cancer. Consistent with the preliminary signal observed in small patient size, the data in dose expansion stage demonstrated encouraging efficacy and good safety, which reinforced our confidence in advancing its development. Given unique design of Fc-silent antibody, combined with stable linker and potent extecan payload, IBI343 pioneered in the exploration of CLDN18.2 ADC agents for PDAC treatment. As one of the few biopharmaceutical companies with both advanced technology platforms and a robust pipeline in "IO+ADC" areas, Innovent remains dedicated to transforming cancer treatment by delivering innovative, effective, and safe therapeutic options for doctors and patients."

On November 23, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a clinical-stage biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported the presentation of a poster featuring NOX-A12 data from preclinical studies performed at the U.S. National Cancer Institute (NCI) at the 2024 Society for Neuro-Oncology (SNO) Annual Meeting, taking place in Houston, Texas, USA, November 21-24, 2024 (Press release, TME Pharma, NOV 23, 2024, View Source [SID1234648583]).

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The presentation showed that combining CXCL12 inhibition with anti-PD-1/CTLA4 immune checkpoint inhibition increases the presence of anti-cancer immune cells in tumor tissues both inside and outside the brain, including activated cytotoxic ("killer") T cells. Importantly, improved long-term survival and immunological protection from tumor recurrence were seen in models of tumors growing outside but not inside the brain. This suggests that while the combination with anti-PD-1/CTLA4 immune checkpoint inhibitors is a promising therapy for tumors outside the brain, it may not be an optimal approach for treating brain tumors.

These results support the different combination strategies pursued by TME Pharma in both brain and pancreas cancer. In pancreas cancer, a tumor originating outside the brain, NOX-A12 is combined with an anti-PD-1 immune checkpoint inhibitor and chemotherapy. In brain cancer (glioblastoma), TME Pharma pursues a different strategy combining NOX-A12 with anti-VEGF therapy and radiotherapy, which has already shown exceptional efficacy in animal models (100% complete response1) and in the GLORIA clinical trial where a statistically significant survival benefit over a matched standard of care cohort was shown with a doubling of median overall survival from 9.5 to 19.9 months2.

"The presented results confirm the activity of NOX-A12 on the tumor microenvironment and support TME Pharma’s strategy to focus on combination with the VEGF inhibitor bevacizumab in brain cancer that has yielded excellent results in newly diagnosed chemotherapy-resistant patients with residual tumor remaining after surgery," said Aram Mangasarian, CEO of TME Pharma. "The survival benefit shown at the SNO conference for the NOX-A12 combination with anti-PD1/CTLA4 immune checkpoint inhibitors suggests potential to treat multiple tumor types outside the central nervous system and supports our plans to combine NOX-A12 with the anti-PD-1 immune checkpoint inhibitor pembrolizumab and chemotherapy in the OPTIMUS pancreatic cancer study."

The research was conducted at the NCI, part of the National Institutes of Health, under the material transfer agreement established with TME Pharma in June 2022 to explore the effects of TME Pharma’s CXCL12 inhibitor NOX-A12 in brain tumors.3

Details of the poster presentation at the 2024 SNO Annual Meeting are as follows:

Title: Potentiating the efficacy of immune check-point inhibitors in glioblastoma by inhibition of CXCL12
Presenter: Dr. Chen Cam-El Makranz, Neuro-Oncology Research Fellow, National Cancer Institute, National Institutes of Health
Session: Poster Session, Poster number EXTH12
Time and Date: 7.30-9.30 p.m. CST, Friday, November 22, 2024

The abstract and poster presentation are available on the TME Pharma website.

On November 22, 2024, BioXcel Therapeutics, Inc. (the "Company") reported to have entered into an underwriting agreement (the "Underwriting Agreement") with Canaccord Genuity LLC, as underwriter (the "Underwriter"), in connection with the issuance and sale by the Company in a public offering of (i) 5,600,000 shares of the Company’s common stock, par value $0.001 per share ("Common Stock"), and accompanying warrants to purchase 5,600,000 shares of Common Stock, at a combined public offering price of $0.48 per share, and, in lieu thereof to certain investors, (ii) pre-funded warrants to purchase 9,000,000 shares of Common Stock, and accompanying warrants to purchase 9,000,000 shares of Common Stock, at a combined public offering price of $0.479 per pre-funded warrant, which equals the public offering price per share of Common Stock and accompanying warrant less the $0.001 exercise price per share of the pre-funded warrants, less underwriting discounts and commissions, pursuant to an effective shelf registration statement on Form S-3 (Registration No. 333-275261) and a related prospectus supplement filed with the Securities and Exchange Commission (the "SEC") (Filing, 8-K, BioXcel Therapeutics, NOV 22, 2024, View Source [SID1234648604]).

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Each of the warrants in the offering is subject to customary beneficial ownership limitations on exercisability, is exercisable at any time after the date of issuance of such warrant and, in the case of the accompanying warrants, will expire on the fifth anniversary of the date of issuance. Each of the accompanying warrants will have an exercise price of $0.48 per underlying share of Common Stock.

The Company received net proceeds from the offering of approximately $6.2 million, after deducting underwriting discounts and commissions and estimated offering expenses, excluding the proceeds, if any, from exercise of any of the warrants. The Company intends to use the net proceeds of the offering to fund the SERENITY At-Home trial, prepare for the initiation of the TRANQUILITY In-Care trial, working capital and general corporate purposes. The Company expects the net proceeds from this offering combined with existing cash and cash equivalents will be sufficient to fund operations and service debt obligations into the first quarter of 2025. Our expectations regarding our anticipated cash runway into the first quarter of 2025 will be affected by many factors, our ability to execute our current business plan, the progress of our clinical trials and regulatory interactions. These expectations are based on estimates and the judgment of management. The Company’s cash runway may not extend as far as forecasted and anticipated cash needs could be greater than expected.

The Underwriting Agreement contains customary representations, warranties and agreements by the Company, customary conditions to closing, indemnification obligations of the Company and the Underwriters, including for liabilities under the Securities Act of 1933, as amended, other obligations of the parties and termination provisions.

The foregoing description of the Underwriting Agreement, the pre-funded warrants and the accompanying warrants are not complete and is qualified in its entirety by reference to the full text of the Underwriting Agreement, the Form of Pre-funded Warrant and the Form of Warrant, copies of which are filed as Exhibit 1.1, 4.1 and 4.2, respectively, to this Current Report on Form 8-K and is incorporated by reference herein. An opinion of Honigman LLP regarding the validity of the shares to be issued and sold in the offering by the Company is filed as Exhibits 5.1 to this Current Report on Form 8-K and is incorporated by reference herein.

On November 21, 2024, the exercise price of warrants to purchase 8,545,398 shares of common stock previously issued in March 2024 was reduced to $0.571 per share.