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Akeso Announces Completion of First Dosing in Phase III Clinical Trial of Ivonescimab (PD-1/VEGF) Combination Therapy for Immunotherapy-Resistant NSCLC

On July 30, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that the first patient has been dosed in its pivotal Phase III clinical study (AK112-305/HARMONi-8A) of ivonescimab (PD-1/VEGF bispecific antibody) in combination with docetaxel for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) that has progressed following PD-1/L1 inhibitors and platinum-based chemotherapy (Press release, Akeso Biopharma, JUL 30, 2025, View Source;therapy-for-immunotherapy-resistant-nsclc-302518092.html [SID1234654657]).

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Ivonescimab is the only bispecific immunotherapy antibody currently undergoing Phase III registration trials for IO-resistant lung cancer.

In recent years, immunotherapy has achieved significant progress in the treatment of NSCLC. PD-1/L1 inhibitors, whether used as monotherapy or in combination with platinum-based chemotherapy, have become the standard first-line treatment for advanced NSCLC in patients without driver mutations. However, despite these advances, 60%-70% of patients experience disease progression within the first year of treatment.

Currently, there are no approved standard treatment options for IO-resistant NSCLC. Docetaxel is recommended in both China’s and international treatment guidelines for immunotherapy-resistant (IO-resistant) NSCLC. However, docetaxel’s monotherapy efficacy in the IO-resistant NSCLC patients remains limited. Several Phase III clinical trials investigating IO-resistant lung cancer, including immunotherapy combination therapies studies and ADC therapy studies, have failed to demonstrate positive results.

Mechanistic studies suggest that PD-1 therapy can restore the immune system’s anti-tumor activity, while anti-VEGF therapy alleviates VEGF-mediated immune suppression and promotes T-cell infiltration. When combined, these two therapies may produce synergistic effects. Ivonescimab simultaneously targets both PD-1 and VEGF pathways, reversing the immune-suppressive tumor microenvironment and reactivating anti-tumor immune responses. These synergistic mechanisms provide a scientific rationale for using ivonescimab to treat IO-resistant tumors. Furthermore, the positive efficacy and safety data demonstrated in a Phase II study in this indication underscore the significant therapeutic potential of ivonescimab in this difficult to treat patient population.

The ivonescimab regimen has demonstrated remarkable efficacy and excellent safety across multiple tumor types. The ongoing AK112-305/HARMONi-8A Phase III study targeting IO-resistant NSCLC is expected to offer a novel and highly effective treatment option for patients with IO-resistant NSCLC, in line Akesos ‘ ‘Immuno-2.0’ strategy.

As the world’s leading PD-1/VEGF bispecific antibody, ivonescimab has achieved extensive population coverage for core indications in NSCLC and is positioned across multiple lines of treatment, with the potential to reshape the overall treatment landscape for advanced NSCLC.

Vivace Therapeutics Announces Receipt of Orphan Drug Designation for VT3989 for Treatment of Mesothelioma

On July 30, 2025 Vivace Therapeutics, Inc., a small molecule discovery and development company developing first-in-class cancer therapies targeting the Hippo pathway, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to VT3989 for the treatment of mesothelioma in the United States (Press release, Vivace Therapeutics, JUL 30, 2025, View Source [SID1234654656]). VT3989, the company’s first-in-class and best-in-class transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor, is a novel investigational small molecule cancer therapeutic that is designed to target the Hippo pathway by inhibiting palmitoylation of members of the TEAD protein family.

"The granting of Orphan Drug Designation to VT3989 underscores the critical need for new, effective therapies for mesothelioma, an aggressive cancer with limited treatment options. The benefits provided by this important designation will support our continued advancement of VT3989, which has already generated compelling clinical trial data, a first for this promising therapeutic class," said Sofie Qiao, Ph.D., president and chief executive officer of Vivace Therapeutics. "We are committed to continuing clinical development of VT3989 and discussing a move into a registrational Phase 3 study in mesothelioma with FDA by the end of 2025."

VT3989 has been evaluated in more than 200 patients to date in an ongoing, open-label Phase 1 clinical study and, to the company’s knowledge, is the first and only member of the TEAD autopalmitoylation inhibitor class for which compelling clinical efficacy data have been publicly reported. In addition to the promising data to date, VT3989 has demonstrated a positive safety profile in the Phase 1 trial, which supports its best-in-class potential.

Clinical findings for VT3989 have been particularly notable in patients with mesothelioma who have failed chemotherapy and immuno-oncology combination regimens, which represent the only approved therapies in this indication. These results will be presented at a major medical conference in the second half of 2025.

Orphan Drug Designation is granted by FDA and is intended to support the development and evaluation of treatments for rare diseases affecting fewer than 200,000 people in the U.S. The designation provides drug developers with potential benefits including tax credits for qualified clinical trials, exemptions from certain FDA fees for clinical trials, and the potential for seven years of market exclusivity following drug approval.

About Phase 1 study of VT3989
The Phase 1 study of VT3989 (View Source) is a multi-center, open label trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and biological activity of VT3989 in patients with refractory metastatic solid tumors, including refractory pleural and non-pleural malignant mesothelioma.

Espervita’s EVT0185 Shows Dramatic Tumor Reduction and Immune Activation in Preclinical MASH-Driven Hepatocellular Carcinoma

On July 30, 2025 Espervita Therapeutics, a biotechnology company developing targeted metabolic reprogramming therapies, reported the publication in Nature featuring groundbreaking preclinical data for the treatment of hepatocellular carcinoma (HCC) with its lead drug candidate, EVT0185, a first-in-class liver and kidney targeted inhibitor of acetyl-CoA metabolic enzymes (ACLY, ACSS2, ACC) (Press release, Espervita Therapeutics, JUL 30, 2025, View Source [SID1234654654]). Over 80% of people with advanced HCC do not respond to immunotherapies due to a "cold" immune deficient tumor microenvironment. EVT0185 reverses this effect, making tumors "hot" and harnessing the body’s immune system to attack and kill tumors more effectively than current standards of care.

Unmet Need

Liver cancer is the third leading cause of cancer death globally. HCC, the most common form of liver cancer, is increasingly caused by the global rise in metabolic dysfunction-associated steatohepatitis (MASH). With current treatment options, five-year survival for advanced HCC is < 5% and the five-year recurrence rate for earlier-stage HCC following surgical resection or ablation is > 75%, with HCC being the only common cancer in the world with no approved adjuvant therapy. HCC is thus one of the highest priority unmet needs in oncology.

Preclinical Efficacy in HCC

Espervita Therapeutics evaluated the therapeutic potential of acetyl-CoA metabolic enzyme inhibition in MASH-HCC using EVT0185 across three preclinical models.

Key findings from the studies:

EVT0185 significantly reduced tumor burden in multiple preclinical models of MASH-HCC prevention and treatment, both as a monotherapy and in enhancing the effects of existing treatments, including tyrosine kinase inhibitors and immunotherapies.

EVT0185 enhanced immune recognition of tumors by reprogramming the tumor microenvironment, increasing CXCL13 expression and B cell infiltration, and triggering strong anti-tumor responses.

Through tissue-selective activation, EVT0185 minimized off-target effects and avoided immune cell suppression.
"These findings illustrate how targeted metabolic reprogramming can counter the immunosuppressive tumor microenvironment and significantly reduce tumor burden in MASH-HCC," said Spencer Heaton M.D., CEO at Espervita Therapeutics. "They also highlight the potential of EVT0185 to redefine how we approach oncology immunotherapies."

Sumitomo Pharma America Announces that the European Medicines Agency Has Granted Orphan Drug Designation to Nuvisertib (TP-3654) for the Treatment of Myelofibrosis

On July 30, 2025 Sumitomo Pharma America, Inc. (SMPA) reported that the European Medicines Agency (EMA) granted Orphan Drug Designation to nuvisertib (TP-3654), an oral investigational highly selective inhibitor of PIM1 kinase, for the treatment of patients with myelofibrosis (MF) (Press release, Sumitomo Pharmaceuticals, JUL 30, 2025, View Source [SID1234654653]).

Orphan Drug Designation is granted by the EMA to investigational therapies addressing rare diseases or conditions that affect not more than 5 in 10,000 people in the European Union, and for which there is no satisfactory method of diagnosis, prevention or treatment of the condition. This designation comes on the heels of the recent U.S. Food and Drug Administration (FDA) Fast Track Designation granted to nuvisertib, and following the oral presentation of updated preliminary Phase 1/2 data at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress in Milan, Italy.

"Following the recent FDA Fast Track Designation, being granted Orphan Drug Designation from European regulators emphasizes the potential of nuvisertib as a future option for patients living with myelofibrosis," said Tsutomu Nakagawa, Ph.D, President and Chief Executive Officer of SMPA. "As we pursue our mission of addressing unique and unmet patient needs, we look forward to working with the EMA to advance the clinical development of nuvisertib."

MF, a rare type of blood cancer, is characterized by the buildup of fibrous tissues in the bone marrow, which is caused by dysregulation in the Janus-associated kinase (JAK) signaling pathway. The clinical manifestations of MF include an enlarged spleen, debilitating symptoms and reduction in hemoglobin and/or platelets. MF affects 1 in 500,000 people worldwide.1

"Patients living with incurable blood cancers like myelofibrosis continue to face limited treatment options, particularly in the relapsed or refractory setting," said Professor Francesco Passamonti, M.D., Head of Department of Oncology and Hematology-Oncology, University of Milan, Italy. "The orphan drug designation for nuvisertib underscores its potential and the urgent need for new therapeutic approaches to a difficult to treat disease."

About Nuvisertib (TP-3654)
Nuvisertib (TP-3654) is an oral investigational selective inhibitor of PIM1 kinase, which has shown potential antitumor and antifibrotic activity through multiple pathways, including induction of apoptosis in preclinical models.2,3 Nuvisertib was observed to inhibit proliferation and increase apoptosis in murine and human hematopoietic cells expressing the clinically relevant JAK2 V617F mutation.3 Nuvisertib alone and in combination with ruxolitinib showed white blood cell and neutrophil count normalization, and also reduced spleen size and bone marrow fibrosis in JAK2 V617F and MPLW515L murine models of myelofibrosis.2 The safety and efficacy of nuvisertib is currently being clinically evaluated in a Phase 1/2 study in patients with intermediate and high-risk myelofibrosis (NCT04176198). The FDA granted Orphan Drug Designation to nuvisertib for the indication of myelofibrosis in May 2022. The Japan Ministry of Health, Labour and Welfare (MHLW) granted Orphan Drug Designation to nuvisertib for the treatment of myelofibrosis in November 2024. The FDA granted Fast Track Designation to nuvisertib for the indication of myelofibrosis in June 2025.

Pancreatic Cancer Phase 2a Study with Can-Fite’s Namodenoson Achieved Over 50% Enrollment Milestone

On July 30, 2025 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a clinical-stage biotechnology company developing a pipeline of proprietary small molecule drugs for the treatment of cancer and inflammatory diseases, reported that it achieved the over 50% enrollment milestone in its Phase 2a trial of Namodenoson for pancreatic cancer (Press release, Can-Fite BioPharma, JUL 30, 2025, View Source [SID1234654651]).

The Phase 2a study is a multicenter, open-label trial enrolling patients with advanced pancreatic adenocarcinoma whose disease has progressed following at least one line of prior therapy. The study is evaluating the safety (primary endpoint), clinical activity, and pharmacokinetics (PK) of Namodenoson in this patient population. Participants receive oral Namodenoson at a dose of 25 mg, administered twice daily in continuous 28-day cycles. Patients are regularly monitored for safety, and to date, Namodenoson has demonstrated a favorable safety profile. The study is led by Prof. Salomon Stemmer, a renowned oncologist and key opinion leader at the Davidoff Center, Rabin Medical Center, Israel.

"This milestone reflects the strong interest among both investigators and patients in exploring Namodenoson as a potential treatment for one of the deadliest and most aggressive cancers," stated Pnina Fishman, Ph.D., Chief Scientific Officer of Can-Fite BioPharma. "We are encouraged by the pace of enrollment and remain committed to advancing Namodenoson as a much-needed therapeutic option for patients with pancreatic cancer."

Namodenoson is a highly selective A3 adenosine receptor (A3AR) agonist, which has shown a compelling safety profile and demonstrated anti-tumor activity in preclinical pancreatic cancer models. The drug is also being evaluated in clinical trials for advanced liver cancer.

Namodenoson has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer.