On September 20, 2024 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, reported the publication of the Phase 3 SIERRA results of Iomab-B in the peer-reviewed Journal of Clinical Oncology (JCO) (Press release, Actinium Pharmaceuticals, SEP 20, 2024, View Source [SID1234646772]). The article, titled, "Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation vs Conventional Care for Relapsed/Refractory Acute Myeloid Leukemia" and is available online on the ASCO (Free ASCO Whitepaper) Journal of Clinical Oncology website HERE.

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The Phase 3 SIERRA (Study of Iomab-B in Elderly Relapsed Refractory AML) trial was a randomized, multi-center, controlled trial that enrolled 153 patients aged 55 and above with active relapsed or refractory Acute Myeloid Leukemia (r/r AML), including heavily pre-treated patients and those with high-risk characteristics such as a TP53 mutation. The SIERRA trial compared outcomes of patients receiving Iomab-B (Iodine-131-apamistamab) and a bone marrow transplant (BMT) to physician’s choice of salvage chemotherapy and standard allogeneic BMT in the control arm.

The SIERRA trial met the primary endpoint of durable Complete Remission (dCR) of 6-months following initial complete remission after BMT with high statistical significance (p-value of <0.0001) with 22% of patients (13/76) achieving dCR in the Iomab-B arm compared to 0% of patients (0/77) in the control arm. A significant improvement in Event Free Survival (EFS), a secondary endpoint of the SIERRA trial with a Hazard Ratio = 0.22 (p-value <0.0001) was also achieved. SIERRA did not meet the secondary endpoint of overall survival (OS) on an intent to treat basis analysis due to the high crossover rate with nearly 60% of control arm patients receiving Iomab-B followed by a BMT.

The Phase 3 SIERRA results were first presented in a late-breaker presentation at the Transplantation & Cellular Therapy (TCT) Tandem Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR) in February 2023. Since TCT, the results of the SIERRA trial have been presented in several oral presentations at leading BMT, hematology, nuclear medicine and nursing meetings and congresses in the U.S. and EU. Supplemental analyses of the SIERRA results have shown improved survival outcomes in patients with a TP53 mutation, which is associated with poor outcomes, as well as increased 1-and 2-year overall survival in patients aged 65 and above.

Dr. Sergio Giralt, Deputy Division Head, Division of Hematological Malignancies and Attending Physician, Adult BMT Service at the Memorial Sloan Kettering Cancer Center, and leading SIERRA Trial investigator and corresponding author, said, "The SIERRA trial was important for the field of transplant and demonstrated for the first time in a randomized study that the CD45 antibody-radioconjugate Iomab-B can provide patients with improved access to a potentially curative hematopoietic stem cell transplant, and improved outcomes compared to current chemotherapy-based regimens. Importantly, Iomab-B demonstrated a statistically significant improvement in key efficacy endpoints including durable Complete Remission and event-free survival. The SIERRA trial was conducted as multiple new therapies gained approval and was designed to address the nuances and difficulty of treating this patient population including allowing physician’s choice of care in the control arm given the heterogeneity of treatment across institutions and the crossover design to provide best patient care. Despite multiple drug approvals for patients with AML, there remains no curative options for older patients with relapsed or refractory disease and outcomes for these patients also remain dismal. My fellow investigators and I are disappointed that the SIERRA trial will not support the approval of Iomab-B despite the positive results and significant unmet medical need of this patient population. However, there is continued significant interest from the transplant community to participate in the upcoming phase 3 study with Iomab-B to provide patients access to this important drug candidate."

On August 05, 2024, Actinium announced that after concluding both its clinical and Chemistry, Manufacturing and Controls ("CMC") interactions with the FDA regarding the BLA pathway for Iomab-B, the FDA determined that demonstrating an overall survival benefit in a randomized head-to-head trial is required for a BLA filing, and the SIERRA trial alone will not be adequate for BLA filing.

Sandesh Seth, Actinium’s Chairman and CEO, stated, "We are excited that the SIERRA results have been published in the peer-reviewed Journal of Clinical Oncology. We believe the SIERRA trial was a major advancement for the field of BMT and targeted radiotherapeutics but most importantly for patients with relapsed and refractory AML. We look forward to completing our interactions with the FDA to finalize the specifics of the additional Phase 3 randomized trial and working to secure a U.S. partner for Iomab-B. In doing so, we hope to accelerate Iomab-B reaching patients with high unmet need that can benefit from a bone marrow transplant."

On September 20, 2024 Biosyngen, an innovative biotechnology company specializing in immune cell therapies, reported its groundbreaking technology on gene-modified, functionally enhanced tumor-infiltrating lymphocytes (TILs) derived from liver cancer biopsy samples (Press release, BioSyngen, SEP 20, 2024, View Source [SID1234646771]).

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BioSyngen has secured ten clinical trial approvals in China and the U.S. for its innovative fourth-generation oncology therapies. Currently, our leading pipeline product, BRG01, is in the pivotal Phase II clinical trial stage for solid tumors. Additionally, the first patients have been enrolled in the Phase I trials for our other groundbreaking therapies, BST02 and BRL03, with completion of Phase I trials anticipated later this year.

Abstract Title

Pre-clinical Development of Genetically Modified Tumor-infiltrating Lymphocytes using Biopsy Samples from Liver Cancer Patients

Abstract No.

1034P

Tumor-infiltrating lymphocytes (TILs) are heterogeneous lymphocyte populations within the tumor microenvironment that contains T cells capable of recognizing tumor- or virus-associated antigens. In February of this year, the FDA approved the first TIL-based therapy used with IL-2 for advanced metastatic/recurrent melanoma. However, due to the variability in T cell infiltration between hot and cold tumors, differential abundance of antigen-specific T cells with robust immune response functionality, and the dependence of TIL anti-tumor efficacy on concomitant use of high-dose IL-2 combination therapy, the therapeutic applications of non-edited TILs are quite limited outside of melanoma.

To address these challenges, Biosyngen has developed a proprietary platform for expanding TILs from biopsy samples, achieving production of 1011 cells within four weeks. Additionally, the company has established a stable gene modification platform that reprograms TIL metabolism, enhances TIL activity and sustained antitumor efficacy by expressing membrane anchor proteins. Anti-tumor efficacy has significantly enhanced (without IL-2 co-injection) and no obvious toxicity observed.

Biosyngen houses best-in-class proprietary TIL platform aiming to expand the clinical applications of TIL technology with following features:

Efficient Automated TILs Manufacturing System: Pioneering the use of tumor biopsy samples for TIL preparation with the ability to cryopreserve both tumor tissue and final products, overcoming logistical constraints.
Effective In Vitro Gene-engineering System: Employs viral vector technology for stable gene modification, maintaining high gene expression efficiency in TILs.
Enhanced In Vivo Expansion and Persistence: Increased proportion of central memory T cells (TCM) in the final product, leading to prolonged persistence.
Powerful Antitumor Efficacy: Demonstrates strong tumor-killing effects without the need for concomitant use of IL-2.

On September 20, 2024 BioVaxys Technology Corp. (CSE: BIOV) (FRA: 5LB) ("BioVaxys" or the "Company") reported an increase to its previously announced non-brokered private placement offering of units of the Company ("Units") at a price of $0.05 per Unit (the "Private Placement") (Press release, BioVaxys Technology, SEP 20, 2024, View Source [SID1234646770]). Each Unit consists of one common share (a "Common Share") and one whole Common Share purchase warrant (a "Warrant"), whereby each Warrant is exercisable for one additional Common Share at an exercise price of $0.15 for a period of 24 months from the date of issue. The Private Placement initially comprised a maximum of 10,000,000 Units (see news release dated July 23, 2024) for total gross proceeds of $500,000 and was later upsized to a maximum of 20,000,000 Units (see news release dated July 26, 2024) for total gross proceeds of $1,000,000. The Company has now further increased the size of the Private Placement to up to 30,000,000 Units for total gross proceeds of up to $1,500,000.

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To date, the Company has issued an aggregate of 17,312,340 Units in connection with the Private Placement.

Closing of the Private Placement is subject to receipt of all necessary regulatory and other approvals. All securities to be issued pursuant to the Private Placement will be subject to a statutory hold period of four months from the date of issuance in accordance with applicable securities legislation.

The Company intends to use the net proceeds of the Private Placement for general working capital purposes, including enabling the Company to fund and advance its business plans in regard to its successful recent acquisition of the entire portfolio of discovery, preclinical, and clinical development stage assets in oncology, infectious disease, antigen desensitization, and other immunological fields based on the DPX immune educating platform technology, developed by the former Canadian biotechnology company, IMV Inc., Immunovaccine Technologies Inc., which was purchased from IMV USA ("IMV") on February 16, 2024. The Company may pay finder’s fees in connection with the Private Placement.

In addition, the Company announces that it has entered into a debt settlement agreement with a consultant of the Company, to settle an aggregate of $76,625 in debt owed to the consultant by issuing 1,532,500 Common Shares at a deemed price of $0.05 per Common Share (the "Debt Settlement"). The board of directors of the Company has determined that it is in the best interests of the Company to settle the outstanding debt through the issuance of Common Shares in order to preserve the Company’s cash for working capital purposes.

All securities proposed to be issued in connection with the Debt Settlement will also be subject to a statutory hold period of four months from the date of issuance in accordance with applicable securities legislation. Closing of the Debt Settlement is conditional upon a number of conditions, including receipt of all applicable regulatory approvals.

The securities described herein have not been, and will not be, registered under the United States Securities Act of 1933, as amended (the "U.S. Securities Act"), or any state securities laws, and may not be offered or sold within the United States except in compliance with the registration requirements of the U.S. Securities Act and applicable state securities laws or pursuant to available exemptions therefrom. This release does not constitute an offer to sell or a solicitation of an offer to buy of any securities in the United States.

On September 20, 2024 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending approval of HANSIZHUANG (serplulimab), Henlius’ independently developed anti-PD-1 monoclonal antibody (mAb), as a first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) (Press release, Henlius Biopharmaceuticals, SEP 20, 2024, View Source [SID1234646769]). In 2023, Henlius entered into an exclusive license agreement with Intas Pharmaceuticals Limited ("Intas") for the development and commercialisation a total of more than 50 countries in Europe and India. This positive opinion from CHMP marks another step closer for both companies to providing serplulimab for patients in Europe. If approved, serplulimab will be marketed by Intas’ subsidiary, Accord Healthcare Ltd, in Europe.

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Dr. Jason Zhu, Executive Director and Chief Executive Officer of Henlius, stated: "The positive opinion from CHMP signifies a major milestone in our efforts to accelerate the global reach of our products, and further validates Henlius’ patient-centred R&D approach and commitment to global strategy. We look forward to the formal approval of this treatment in Europe, bringing more treatment options and hope to patients there and worldwide."

Paul Tredwell, Executive Vice President of EMENA at Accord, said, "I am thrilled with the CHMP’s positive opinion. This not only strengthens our current partnership with Henlius but also means serplulimab is on track to become part of the treatment landscape for extensive stage small cell lung cancer patients who currently have limited options and face a poor prognosis."

Innovative Approach to Address Clinical Needs of SCLC

According to GLOBOCAN 2022, lung cancer is the most diagnosed and the first mortality cancer around the world. There were more than 2.48 million new cases of lung cancer worldwide in 2022, accounting for 12.4% of all new cancer cases.[1] Small cell lung cancer (SCLC) accounts for 15%–20% of the total number of lung cancer, which is featured by high malignancy, early metastasis, and rapid disease progression, with extremely poor prognosis. SCLC is divided into limited-stage and extensive-stage, with approximately 30%-40% of patients diagnosed at the limited stage and the rest at the extensive stage. With a prevalence of 1-5 per 10,000 people in the European community, SCLC has an orphan disease designation.[2] In December 2022, HANSIZHUANG was granted orphan drug designation by the European Commission (EC) for the treatment of SCLC, and in March 2023, EMA validated the marketing authorisation application (MAA) of HANSIZHUANG for ES-SCLC.

The positive opinion from CHMP is primarily based on ASTRUM-005, a randomized, double-blind, placebo-controlled international multi-centre clinical study, which evaluated the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with ES-SCLC. The study has set up a total of 128 sites in various countries including China, Poland, Turkey, and Georgia, and enrolled 585 subjects, among whom 31.5% were Caucasians. The ASTRUM-005 clinical trial results were firstly presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and published in the Journal of the American Medical Association (JAMA), making it the first study published on JAMA in SCLC immunotherapy. Based on the ASTRUM-005 study, HANSIZHUANG has been approved in China and Southeast Asian countries for first-line treatment of ES-SCLC, making it the world’s first anti-PD-1 mAb approved for first-line treatment of SCLC.

Global Strategy to Fuel Innovation-driven Expansion

HANSIZHUANG, Henlius’ first innovative mAb developed in-house, focuses on high-incidence cancers such as lung cancer and gastrointestinal tumours. In China, it has been approved by the NMPA for the treatment of microsatellite instability-high (MSI-H) solid tumours, squamous non-small cell lung cancer (sqNSCLC), ES-SCLC, and esophageal squamous cell carcinoma (ESCC). The company is also conducting more than 10 clinical studies on immuno-oncology combination therapies worldwide.

Notably, Henlius covers the full range of first-line treatment of lung cancer. In addition to sqNSCLC and ES-SCLC, HANSIZHUANG’s marketing application for first-line treatment of non-squamous NSCLC (nsNSCLC) has been accepted by the National Medical Products Administration (NMPA). Additionally, the company is conducting a phase 3 international multi-centre clinical trial of HANSIZHUANG combined with chemotherapy and radiotherapy for limited-stage SCLC (LS-SCLC). Henlius is also running a bridging head-to-head trial in the U.S. to compare HANSIZHUANG with standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC, which is expected to propel the product towards U.S. market approval further.

The global expansion of HANSIZHUANG is accelerating. It has already been approved in several countries, including China, Indonesia, Cambodia, and Thailand, and has been licensed to over 70 countries and regions, including the US, Europe, Southeast Asia, the Middle East, and North Africa. On December 2023, Henlius received the European Union (EU) GMP Certificates for the production lines of HANSIZHUANG, marking that the company’s Xuhui Facility and Songjiang First Plant have successfully passed the EU GMP on-site inspection for HANSIZHUANG and meet the EU GMP standards. The first overseas shipment of HANSIZHUANG was completed in Q1 2024, making it the first Chinese anti-PD-1 mAb to enter Southeast Asian, offering new treatment options for more global patients.

Looking ahead, Henlius will continue to prioritize patient needs, address unmet clinical demands, and accelerate efforts to deliver high-quality biologics from China to patients worldwide.

On September 19, 2024, Veru Inc. (the "Company") reported to have entered into an Amended and Restated Forbearance Agreement and Amendment to September 2024 Note (the "Amended Forbearance Agreement") with Onconetix, Inc. f/k/a Blue Water Vaccines Inc. (the "Borrower"). The Amended Forbearance Agreement amends and restates the entirety of the Forbearance Agreement, dated as of April 24, 2024 (the "Original Forbearance Agreement"), which related to certain defaults by the Borrower under a Promissory Note in the principal amount of $5,000,000 due on April 19, 2024 (the "April 2024 Promissory Note") and a Promissory Note in the principal amount of $5,000,000 due on September 30, 2024 (as amended, the "September 2024 Promissory Note" and together with the April 2024 Promissory Note, the "Promissory Notes") that were issued by the Borrower to the Company to reflect payment obligations pursuant to the Asset Purchase Agreement, dated as of April 19, 2023 (the "Asset Purchase Agreement"), between the Company and the Borrower (Filing, 8-K, Veru, SEP 20, 2024, View Source [SID1234646768]).

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Pursuant to the Amended Forbearance Agreement, the forbearance period relating to the Company’s agreement to forbear from exercising its rights and remedies on account of the failure by the Borrower to pay the amounts due under the April 2024 Promissory Note on the due date of April 19, 2024 continues to end on the earlier of (a) March 31, 2025 and (b) the occurrence of an Event of Default (as defined in the Amended Forbearance Agreement) (such period, the "April 2024 Forbearance Period"). The Amended Forbearance Agreement extends the due date for the September Promissory Note until the earlier to occur of: (i) June 30, 2025 or (ii) the occurrence of any Event of Default under the Amended Forbearance Agreement. The Amended Forbearance Agreement also effected certain modifications to the payment terms in the Original Forbearance Agreement and amended certain terms of the September 2024 Promissory Note as summarized below.

The Borrower agreed in the Amended Forbearance Agreement to make the following required payments (the "Required Payments") during the April 2024 Forbearance Period first to accrued and unpaid interest under the April 2024 Promissory Note and then any remainder to the outstanding principal amount of the April 2024 Promissory Note:

•
monthly payments equal to 25% (increased from 15% in the Original Forbearance Agreement) of cash receipts of the Borrower or its subsidiaries from certain sale or licensing revenues or payments, which increased amount shall begin on October 20, 2024 for cash receipts in September 2024; and

•
payment of 20% (increased from 10% in the Original Forbearance Agreement) of the net proceeds from certain financing or other transactions outside the ordinary course of business completed by the Borrower or any of its subsidiaries during the April 2024 Forbearance Period, which increased amount will begin for any net proceeds received after September 19, 2024.

The remaining balance of the April 2024 Promissory Note will be due at the end of the April 2024 Forbearance Period.

The Borrower and the Company also agreed to the following amendments to the September 2024 Promissory Note in the Amended Forbearance Agreement:

•
As noted above, an extension of the maturity date to June 30, 2025;

•
The accrual of interest at the rate of 10% per annum on any unpaid principal balance of the September 2024 Promissory Note commencing on October 1, 2024 through the date that the outstanding principal balance under the September 2024 Promissory Note is paid in full.

•
Any amounts owed on the September 2024 Promissory Note, including but not limited to unpaid principal and accrued interest, will be paid in cash or, upon the mutual written consent of the Borrower and the Company, in shares of the Borrower’s common stock or a combination of cash and the Borrower’s common stock.

•
Following full repayment of all principal and interest under the April 2024 Promissory Note, the Borrower will make the Required Payments first towards accrued and unpaid interest under the September 2024 Promissory Note and then towards the remaining principal balance payable under the September 2024 Promissory Note.

•
If the aggregate unpaid principal outstanding under the April 2024 Promissory Note and the September 2024 Promissory Note and all accrued and unpaid interest thereon is repaid in cash on or before December 31, 2024, then the total principal balance under the September 2024 Promissory Note that will be payable by the Borrower in satisfaction of its obligations under the September 2024 Promissory Note will be reduced from $5,000,000 to $3,500,000.