On July 15, 2025 GT Medical Technologies, Inc., a medical device company dedicated to improving the lives of patients with brain tumors, reported the company has completed the close of its oversubscribed $53 million Series D equity financing (Press release, GT Medical Technologies, JUL 15, 2025, View Source [SID1234654392]).

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The final close of the Series D comprised an additional $16 million from new investors including FemHealth Ventures, Warren Point Capital, an undisclosed strategic investor, and increased commitments from all existing institutional investors. Earlier this year, GT Medical Technologies announced the completion of a $37 million first close of the Series D equity financing led by Evidity Health Capital, alongside new investor Accelmed Partners and existing investors MVM Partners, Gilde Healthcare, and Medtech Venture Partners.

"Increasing the size of the Series D allows us to stay focused on driving results for patients into the foreseeable future," said Per Langoe, Chief Executive Officer at GT Medical Technologies. "We are thankful for our investors’ continued support as we expand our commercial footprint and clinical initiatives for GammaTile."

The company will use the funds to drive the expansion of its U.S. commercial activities for GammaTile. In addition, the financial resources will enable GT Medical Technologies to complete enrollment of its ROADS randomized controlled trial for newly diagnosed brain metastases and will fund an additional randomized control trial of GammaTile in newly diagnosed glioblastoma cases.

"FemHealth Ventures is excited to join GT Medical Technologies as an investor and support the commercial acceleration of GammaTile Therapy," stated Maneesha Ghiya, Managing Partner at FemHealth Ventures. "We are proud to back a company that is transforming the standard of care in oncology and shares our commitment to improving health outcomes, including meaningful applications in women’s health."

GammaTile is an innovative form of radiation therapy placed at the time of brain tumor removal surgery, delivering immediate, targeted radiation to the tumor site when cancer cells are at their lowest levels. Unlike conventional approaches, which often require a delay between surgery and radiation therapy to allow for wound healing, GammaTile eliminates this treatment gap. By delivering immediate, localized radiation directly at the tumor site, it is designed to maximize the treatment’s effectiveness against remaining cancer cells to reduce the risk of regrowth.1

"The completion of an oversubscribed Series D equity financing from premier medical device investors is a testament to the important work of our team and mission," added James Leech, Chief Financial & Strategy Officer of GT Medical Technologies.

Recent GT Medical Technologies Milestones

GT Medical Technologies recently celebrated important milestones, reflecting the growing adoption of GammaTile. To date, more than 1,900 patients have been treated with GammaTile Therapy, and over 800 patients have been enrolled in GammaTile clinical studies.

Looking Ahead

GT Medical Technologies anticipates completing enrollment in both the ROADS and GESTALT studies in Q3 2025.

On July 15, 2025 Pierre Fabre Pharmaceuticals, Inc. reported the transfer of the Investigational New Drug Application for tabelecleucel from its partner, Atara Biotherapeutics, Inc. (Nasdaq: ATRA) (Press release, Pierre Fabre, JUL 15, 2025, View Source [SID1234654391]). "This announcement marks an important milestone as Pierre Fabre Laboratories assumes global responsibility for clinical development of tabelecleucel following transfer of manufacturing responsibilities earlier in the year," said Adriana Herrera, Chief Executive Officer of Pierre Fabre Pharmaceuticals., the Pierre Fabre Laboratories pharmaceutical subsidiary in the United States. "Ongoing recruitment into the ALLELE study demonstrates our commitment to clinical research and development as we await regulatory action on the BLA resubmitted by our partner Atara."

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Atara Biotherapeutics resubmitted the tabelecleucel BLA on July 11, having rapidly addressed the third-party manufacturing facility observations outlined in the January 2025 Complete Response Letter in collaboration with Pierre Fabre Pharmaceuticals (PFP). On March 31, PFP assumed global responsibility for tabelecleucel manufacturing, including commercial product supply for European markets where the innovative cell therapy is already approved, as well as for global clinical trial supply. On July 14, 2025, Atara Biotherapeutics transferred the tabelecleucel IND to Pierre Fabre Medicament, a subsidiary of Pierre Fabre Laboratories.

The two studies currently open for tabelecleucel access in the US are:

NCT03394365: Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants with Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE)

The ALLELE study is investigating the effects of tabelecleucel, an off-the-shelf allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cell therapy, to treat relapsed/refractory EBV-associated post-transplant lymphoproliferative disease arising after SOT or HCT.

NCT04554914: A Study to Evaluate Tabelecleucel in Participants with Epstein-Barr Virus-associated Diseases

This study is a multicenter, multicohort, open-label, single-arm, Phase 2 study investigating the efficacy and safety of tabelecleucel for the treatment of EBV-associated diseases.

Tabelecleucel is an allogeneic, off-the-shelf, EBV-specific T-cell immunotherapy designed to selectively target and eliminate EBV-infected cells. Unlike autologous CAR-T therapies, allogeneic T-cells are derived from third party donors and are not genetically modified. Immune cells are collected from the blood of healthy donors and exposed to Epstein-Barr virus antigens to help enrich for T cells that recognize EBV. These EBV T cells are expanded, characterized, kept alive and stored for future use to treat patients.

Tabelecleucel was granted marketing authorization under the brand name EBVALLO in December 2022 by the European Commission (EC) as a monotherapy for the treatment of adult and pediatric patients two years of age and older with r/r EBV+ PTLD who have received at least one prior therapy.

In December 2023, Atara announced an expanded global partnership with Pierre Fabre Laboratories for the U.S. and remaining global commercial markets for tabelecleucel, building on an initial partnership covering Europe, Middle East, Africa, and other select emerging markets.

About EBV+PTLD

EBV+ PTLD is an ultra-rare, acute, and potentially deadly hematologic malignancy that occurs after transplantation when patent T-cell immune responses are compromised by immunosuppression. It can impact patients who have undergone solid organ transplant (SOT) or allogeneic HCT. Poor median survival of 3 weeks and 4.1 months for HCT and SOT, respectively, is reported in EBV+ PTLD patents for whom standard of care failed, underscoring the significant need for new therapeutic options.

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.

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 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.