On July 15, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that the first patient has been successfully enrolled in the registration Phase III clinical trial (AK112-312/HARMONi-GI6) of ivonescimab in first-line treatment for advanced metastatic colorectal cancer (mCRC) (Press release, Akeso Biopharma, JUL 15, 2025, View Source [SID1234654388]).

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This randomized, controlled, multi-center Phase III clinical trial for first-line treatment of mCRC is one of the company’s key initiatives to address the significant unmet clinical need worldwide with ivonescimab.

Colorectal cancer remains the third most common cancer globally and the second leading cause of cancer-related deaths. In 2022, over 1.9 million new cases were reported, with approximately 904,000 deaths. Of these, about 95% of mCRC cases are classified as microsatellite stable (MSS) or proficient mismatch repair (pMMR), which traditionally show poor responses to immunotherapy and the tumors are often referred to as an "immune desert."

For first-line treatment of MSS/pMMR-type mCRC, which represents up to 95% of cases, several PD-1/L1 inhibitors have been explored in multiple international studies. However, the efficacy has been limited, and as of now, no first-line immunotherapy has been approved globally for patients with pMMR/MSS-type mCRC.

Chemotherapy combined with targeted therapies (such as bevacizumab, cetuximab, etc.) remains the standard first-line treatment for mCRC, though its overall efficacy is limited, with a five-year survival rate for advanced patients of less than 20%. Bevacizumab is the most well-established and clinically impactful treatment in the mCRC space. It is also one of the core indications of bevacizumab.

At the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, Professor Yanhong Deng from the Sixth Affiliated Hospital of Sun Yat-sen University, presented promising Phase II efficacy data of ivonescimab in combination with chemotherapy for first-line treatment of MSS/pMMR-type mCRC.

The combination of ivonescimab with FOLFOXIRI demonstrated compelling anti-tumor activity in this hard to treat patient population, with an overall response rate (ORR) of 81.8% and a disease control rate (DCR) of 100%. After a median follow-up of 9 months, the median progression-free survival (mPFS) was not reached, with a 9-month PFS rate of 81.4%. Regardless of KRAS/BRAF mutation status, patients can benefit from ivonescimab combination therapy.

The results published at the 2024 ESMO (Free ESMO Whitepaper) suggest that ivonescimab may offer a significant improvement over existing treatment options for MSS/pMMR mCRC patients. The Phase III trial AK112-312/HARMONi-GI6 can potentially further validate the clinical benefits of ivonescimab in this setting, offering a novel first-line immunotherapy treatment option for patients with advanced mCRC.

On July 15, 2025 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW, BCTXZ) (TSX: BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company developing novel immunotherapies to transform cancer care, reported the addition of a key clinical site, Mayo Clinic, to its ongoing pivotal Phase 3 clinical study (ClinicalTrials.gov as NCT06072612 ) in metastatic breast cancer (Press release, BriaCell Therapeutics, JUL 15, 2025, View Source [SID1234654405]).

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BriaCell’s Phase 3 study now has 69 active clinical sites across 15 states, including Mayo Clinic, DHR Health Oncology Institute, Hematology Oncology Associates of Fredericksburg, Los Angeles Cancer Network, Manhattan Hematology/Oncology Associates, New York Cancer & Blood Specialists, Northwestern University, Smilow Cancer Hospital at Yale New Haven, Sylvester Comprehensive Cancer Center, Texas Oncology-Baylor Charles A. Sammons Cancer Center, and University of Arizona.

"We are very excited to be working with renowned clinical experts at a leading cancer center like Mayo Clinic, who also participated in BriaCell’s Phase 2 study," stated Dr. Giuseppe Del Priore, BriaCell’s Chief Medical Officer. "We strongly believe that our novel immunotherapy has the potential to transform cancer care for patients and their families."

BriaCell’s pivotal Phase 3 clinical study is evaluating BriaCell’s lead clinical candidate, Bria-IMT, plus immune check point inhibitor (CPI) versus physician’s choice in advanced metastatic breast cancer (Bria-ABC).

Interim data will be analyzed once 144 patient events (deaths) occur, comparing the overall survival (OS) in patients treated with the Bria-IMT combination regimen versus those treated with physician’s choice as the primary endpoint. BriaCell recently (ASCO 2025) announced positive Phase 2 survival data in a similar MBC patient population treated with the same Bria-IMT combination regimen . The Bria-IMT combination regimen has received FDA Fast Track designation.

For additional information on BriaCell’s pivotal Phase 3 study of Bria-IMT and an immune check point inhibitor in metastatic breast cancer, please visit ClinicalTrials.gov NCT06072612.

On July 15, 2025 Researchers at Korea University reported the protein kinase WEE1 as a key driver of this resistance (Press release, Korea University, JUL 15, 2025, View Source [SID1234654389]). They discovered that, outside its traditional role in the cell nucleus as tumor suppressor, cytoplasmic WEE1 fosters tumor growth and immune evasion by enhancing AKT hyperactivation. Targeting WEE1 with clinically available inhibitors may re-sensitize tumors to immunotherapy, offering new hope for treatment-resistant cancer patients.

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Immune checkpoints are regulatory proteins that prevent the immune system from attacking healthy tissues. Some cancer cells exploit these checkpoints to avoid immune detection. Immune checkpoint blockade (ICB)—a therapy that uses antibodies to block these deceptive signals—can unleash the immune system to destroy cancer.

However, a major challenge in oncology remains: why do some tumors resist ICB?

In a landmark study, researchers from Korea University have discovered a surprising answer: the protein WEE1, traditionally known as a cell cycle regulator and tumor suppressor, can paradoxically drive immune resistance when located in the cytoplasm of cancer cells.

Highlighting the significance of this achievement, Professor Tae Woo Kim from the Department of Biochemistry and Molecular Biology at Korea University College of Medicine, Seoul, Republic of Korea reveals, "Our findings uncover a non-canonical oncogenic mechanism of cytoplasmic WEE1 and provide a proof of principle that targeting WEE1 is an appealing combinational strategy to overcome refractory tumor to ICB therapy." This study was published in Volume 13, Issue 6 of Cancer Immunology Research journal on June 04, 2025.

RNA samples were obtained from patients with metastatic melanoma and non–small cell lung cancer who were undergoing ICB treatment. These patients were categorized as responders and non-responders, and their transcriptomic signatures were analyzed to understand WEE1 expression levels. The team found that WEE1 expression was significantly elevated in non-responders, correlating with poor prognosis, high tumor proliferation, and cancer stem cell (CSC)-like features.

Mechanistically, the transcription factor NANOG upregulates WEE1. Once phosphorylated by AKT, WEE1 relocates from the nucleus to the cytoplasm, where it activates the HSP90A–TCL1A–AKT loop, sustaining AKT hyperactivation.

Elucidating the molecular mechanism, Dr. Hyo-Jung Lee, the first author of the study, explains, "WEE1 is phosphorylated by AKT and then translocated in the cytosol, in which it phosphorylates HSP90A, consequently enhancing chaperon activity of HSP90A toward TCL1A, an AKT coactivator. Subsequently, stabilization of TCL1A results in an increase of its proteins levels, leading to amplification of the WEE1/HSP90A1/TCL1A/AKT auto-loop that promotes immune-refractory phenotypes and CSC-like properties of tumor cells."

Importantly, this study reveals the paradoxical role of cytoplasmic WEE1. While its canonical function involves DNA repair and tumor suppression in the nucleus, its non-canonical cytoplasmic role promotes tumor progression and immune resistance. These findings underscore the potential of WEE1 expression levels as predictive biomarkers for selecting patients who may benefit from ICB combination therapies.

Discussing the therapeutic implications of WEEI inhibitors, Prof. Kim comments, "Importantly, inhibiting WEE1 with a clinically relevant drug, adavosertib (AZD1775), sensitizes NANOG+ immune-refractory tumors to ICB and reinvigorates antitumor immunity via abrogating the autoamplifying loop triggered by AKT-dependent cytoplasmic WEE1."

This proof-of-concept study may also extend to other cell cycle regulators with similar dual functions, such as p21, p27, and CHK1, thereby broadening the landscape of therapeutic targets and paving the way for the development of novel treatment strategies.

Reference

Title of original paper:

Cytoplasmic WEE1 Promotes Resistance to PD-1 Blockade

Through Hyperactivation of the HSP90A/TCL1/AKT Signaling Axis in NANOGhigh Tumors

Journal:

Cancer Immunology Research

DOI:

10.1158/2326-6066.CIR-24-0379

On July 15, 2025 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW, BCTXZ) (TSX: BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, reported the pricing of a best-efforts public offering of 12,000,000 units (Press release, BriaCell Therapeutics, JUL 15, 2025, View Source [SID1234654406]). Each unit consists of one common share (or pre-funded warrant ("Pre-Funded Warrant") in lieu thereof) and one warrant (the "Warrants"). Each unit is being sold to the public at a price of $1.25 per unit (inclusive of the Pre-Funded Warrant exercise price) for gross proceeds of $15 million, before deducting placement agent fees and offering expenses. Each Warrant is immediately exercisable, and entitles the holder to purchase one common share at an exercise price of $1.50 per share and will expire five years from the date of issuance. The common shares (or Pre-Funded Warrants) and Warrants can only be purchased together in the offering but will be issued separately.

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The offering is expected to close on July 16, 2025, subject to satisfaction of customary closing conditions. No Canadian prospectus has been or will be filed in a province or territory of Canada to qualify the securities in connection with the offering. The Company is relying upon the exemption set forth in Section 602.1 of the TSX Company Manual, which provides that the TSX will not apply its standards to certain transactions involving eligible interlisted issuers on a recognized exchange, such as Nasdaq.

The Company intends to use the net proceeds from the offering for working capital requirements, general corporate purposes, and the advancement of business objectives.

ThinkEquity is acting as the sole placement agent for the offering.

A registration statement on Form S-1 (File No. 333-288562) relating to the securities was filed with the Securities and Exchange Commission ("SEC") and became effective on July 15, 2025. This offering is being made only by means of a prospectus. Copies of the final prospectus, when available, may be obtained from ThinkEquity, 17 State Street, 41 st Floor, New York, New York 10004. The final prospectus will be filed with the SEC and will be available on the SEC’s website located at View Source

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On July 15, 2025 Aethlon Medical, Inc. (Nasdaq: AEMD), a clinical-stage biotechnology company developing the investigational Aethlon Hemopurifier, an extracorporeal device for Oncology and other indications, reported that the independent Data Safety Monitoring Board (DSMB) overseeing its ongoing clinical trial AEMD-2022-06 has completed its scheduled safety review and recommended advancing to the next patient cohort without modification (Press release, Aethlon Medical, JUL 15, 2025, View Source [SID1234654390]).

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The trial, titled "Safety, Feasibility, and Dose-Finding Study of Aethlon Hemopurifier in Patients with Solid Tumors Who Have Stable or Progressive Disease While on a Treatment That Includes Pembrolizumab or Nivolumab", is being conducted to assess the Hemopurifier’s safety, feasibility, and optimal dosing.

The DSMB- comprising independent medical experts in nephrology and oncology- reviewed data from the initial cohort of three participants, each of whom received a single 4-hour Hemopurifier treatment. Based on their evaluation, the board found no safety concerns and confirmed that the Hemopurifier continues to demonstrate a favorable safety and tolerability profile. To date, no serious adverse events (SAEs) or Dose-Limiting Toxicities (DLTs) related to the Hemopurifier have been reported.

"The DSMB’s positive recommendation is encouraging and underscores the favorable safety profile observed to date in patients with cancer," according to Steven LaRosa, M.D, Chief Medical Officer of Aethlon Medical. "This marks a significant step forward in the clinical development program for the Hemopurifier in Oncology and brings the company closer to potentially addressing the significant unmet medical need for the approximately 60-70% of patients with cancer who do not experience a lasting clinical response to anti-PD-1 immunotherapy."

Enrollment for Cohort 2 is now open. In this phase, participants will receive two Hemopurifier treatments over a one-week period at the study’s three active clinical sites in Australia. This trial, which aims to enroll approximately 9 to 18-patients, is designed to evaluate the safety, feasibility of administering the Hemopurifier at varying dosing intervals in patients with solid tumors who have stable or progressive disease, while receiving treatment that includes Pembrolizumab (Keytruda) or Nivolumab (Opdivo).

The primary endpoint of this trial is the incidence of adverse events and clinically significant changes in safety laboratory tests of Hemopurifier- treated patients. In addition to safety monitoring, the study is designed to examine the number of Hemopurifier treatments needed to decrease the concentration of EVs and if these changes in EV concentrations improve the body’s own natural ability to attack tumor cells. These findings are expected to inform the design of a future efficacy and safety, Premarket Approval (PMA), study required by regulatory authorities.

Aethlon Medical, Inc. remains committed to advancing the Hemopurifier for use in oncology and will continue to provide updates as the clinical trial progresses.

About the Hemopurifier

The Aethlon Hemopurifier is an investigational medical device designed to remove enveloped viruses and tumor-derived extracellular vesicles (EVs) from circulation. It is used extracorporeally with a blood pump and combines plasma separation, size exclusion, and affinity binding using a plant lectin resin that targets mannose-rich surfaces found on EVs and viruses. EVs released by solid tumors are believed to play a role in metastasis and the resistance to immunotherapies and chemotherapy. Removal of enveloped viruses and extracellular vesicles has been demonstrated in both vitro studies and human subjects.

The Hemopurifier holds a U.S. Food and Drug Breakthrough Device for:

The treatment of individuals with advanced or metastatic cancer unresponsive to or intolerant of standard-of-care therapy; and
The treatment of life-threatening viruses not addressed with approved therapies.
The Hemopurifier is being developed under an open Investigational Device Exemption (IDE) for both indications.