On September 16, 2025 On September 16, 2025 (the "Amendment Effective Date"), Carisma Therapeutics Inc. (the "Company") and ModernaTX, Inc. ("Moderna") reported to have entered into a First Amendment to the Collaboration and License Agreement (the "Amendment"), which amends that certain Collaboration and License Agreement, dated as of January 7, 2022, by and between the Company and Moderna (the "Moderna Agreement") (Filing, Carisma Therapeutics, SEP 16, 2025, View Source [SID1234656075]).

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Effective as of the Amendment Effective Date, in exchange for a one-time cash payment of $4.0 million payable to the Company within ten (10) business days following the Amendment Effective Date, Moderna has no further obligation to make any financial payments to the Company under or in connection with the Agreement, subject to certain specified exceptions. Specifically, Moderna is no longer required to pay to the Company any development target designation, development, regulatory and commercial milestone payments, any royalties on net sales of any products that are commercialized under the Moderna Agreement or any research costs, regardless of whether such applicable milestone event, sale of product or research cost occurs on or after the Amendment Effective Date. Effective as of the Amendment Effective Date, the royalty term for all products expired and the licenses granted to Moderna under the Agreement became fully paid-up, perpetual, irrevocable and royalty-free.

The foregoing description of the Amendment does not purport to be complete and is qualified in its entirety by reference to the complete text of such agreement, a copy of which is expected to be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ending September 30, 2025.

On September 16, 2025 Crossbow Therapeutics, Inc., a biotechnology company focused on advancing T-Bolt therapies, a novel class of antibody therapeutics, reported dosing of the first participant in its CROSSCHECK-001 Phase 1 clinical trial of CBX-250, a first-in-class, potent, and specific T-cell engager (TCE) for the treatment of myeloid malignancies (Press release, Crossbow Therapeutics, SEP 16, 2025, View Source [SID1234656014]).

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"Patients with relapsed or refractory myeloid malignancies urgently need new treatment options, and CBX-250 offers a novel approach," said Briggs Morrison, M.D., Chief Executive Officer of Crossbow. "The preclinical profile of CBX-250 and its novel targeting strategy bolster our confidence as we begin to bring the expansive potential of our T-Bolt platform to patients."

CBX-250 is the first candidate developed through Crossbow’s T-Bolt platform, a portfolio of novel TCE molecules that uniquely target peptide-loaded human leukocyte antigen (pHLA) complexes on tumor cells, using antibodies that mimic T-cell receptors (TCR-mimetics). Specifically, CBX-250 targets a cathepsin G pHLA complex, abundantly expressed on leukemic cells, but not normal cells. The Phase 1, open-label, dose-escalation CROSSCHECK-001 study is the first clinical trial for Crossbow and the T-Bolt platform. The study is evaluating the safety, tolerability, and preliminary clinical activity of CBX-250 in patients aged 12 years and older with relapsed or refractory acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (HR-MDS), and chronic myelomonocytic leukemia (CMML).

AML, one of the most common myeloid malignancies, is primarily a disease of older adults, with an average patient age of 68 years. In the United States, the estimated incidence of AML exceeds 22,000 new cases each year, and the five-year survival rate is approximately 33%.1 In AML patients, relapse is common within the first year of achieving complete remission, occurring in more than 50% of patients after induction chemotherapy, the current standard of care.2 Those with relapsed or refractory AML have an especially poor prognosis, underscoring the urgent need for potent therapies directed against novel tumor-selective therapeutic targets.

CBX-250 was developed through an ongoing strategic collaboration between Crossbow and The University of Texas MD Anderson Cancer Center. Crossbow designed and is conducting the CROSSCHECK‑001 clinical study, which is investigating CBX-250 on a fixed step-up dosing schedule. The company expects initial clinical data from CROSSCHECK-001 in 2026.

For additional trial details, visit the CROSSCHECK-001 study page on ClinicalTrials.gov.

On September 16, 2025 Tasca Therapeutics, ("Tasca" or the "Company") a clinical-stage biotechnology company focused on developing targeted therapies for genetically defined cancers, reported that the first patient has been dosed in Phase 1/2 clinical trial of its lead drug candidate CP-383 (Press release, Tasca Therapeutics, SEP 16, 2025, View Source [SID1234656013]).

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CP-383 is a first-in-class (FIC) small molecule designed to modulate a critical oncogenic signaling pathway. Preclinical studies have demonstrated robust anti-tumor activity across a range of tumor models, including those with limited response to existing therapies. Tasca developed CP-383 using its proprietary drug discovery auto-palmitoylation platform that integrates pathway biology, structure-based design, and precision oncology strategies to unlock previously intractable targets.

"The dosing of the first patient with CP-383 is a major milestone for Tasca and a testament to the innovation and dedication of our team," said Milenko Cicmil, Ph.D., Co-Founder and Chief Executive Officer of Tasca Therapeutics. "CP-383 is a highly differentiated small molecule that targets a key pathway implicated in multiple difficult-to-treat cancers. We are looking forward to rapidly enrolling this study and beginning to define the clinical profile of this novel, targeted oncology candidate."

The Phase 1/2 trial is a multi-center, open-label study evaluating the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of CP-383 in patients with advanced or metastatic solid tumors. Future study stages will incorporate biomarker-enriched cohorts based on emerging clinical and translational data.

Tasca also reported a second closing of its $67 million Series A financing round driven by strong investor demand and with new participation from 8VC, a leading technology and life sciences venture firm. 8VC’s support provides deep domain expertise in biotech innovation and a track record of partnering with companies at the forefront of transformative science. As previously announced by the Company, the Series A financing was co-led by Regeneron Ventures and Cure Ventures, with participation by Invus Group.

"We are thrilled to support Tasca’s clinical development of CP-383," said Seth Lieblich, Principal at 8VC. "The discovery of a druggable auto-palmitoylation pocket represents a breakthrough in targeting previously intractable cancer drivers. We believe Tasca’s team, platform, and mechanistic insight into oncogenic signaling have the potential to reshape the treatment landscape for genetically defined cancers. We’re excited to join backing their vision to dramatically improve the lives of cancer patients."

On September 16, 2025 Senhwa Biosciences, Inc. (TPEx: 6492, "Senhwa") reported its official entry into the fast-growing global immuno-oncology market (Press release, Senhwa Biosciences, SEP 16, 2025, View Source [SID1234656010]). The Company’s novel investigational drug Pidnarulex (CX-5461) will be evaluated in combination with the approved PD-1 inhibitor Cemiplimab (Libtayo), provided by Sanofi and Regeneron Pharmaceuticals, in a Phase 1/2 clinical trial for patients with microsatellite-stable colorectal cancer (MSS CRC) who are refractory to immune checkpoint inhibitors.

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This strategic collaboration marks the third clinical trial under Senhwa’s NCI-sponsored five-year cancer research program with the U.S. National Cancer Institute (NCI). An Investigational New Drug (IND) application has been submitted to the U.S. FDA. The partnership underscores the unique mechanism of action of CX-5461 and the strong interest from leading global pharmaceutical companies in its potential to enhance the immunotherapy efficacy.

Dr. Pin-Yen Huang, Chief Medical Officer of Senhwa, stated:
"This is more than a clinical trial—it is a transformative opportunity to redefine the future of cancer therapy. The compelling synergy between CX-5461 and PD-1 inhibitors holds the promise of bringing renewed hope to countless patients, while also showcasing Taiwan’s spirit of innovation on the global stage."

Breaking Through Solid Tumor Immunotherapy Barriers

While immune checkpoint inhibitors have revolutionized cancer care, their response rates in solid tumors — other than melanoma — remain low at approximately 20–30%. The CX-5461 plus Cemiplimab combination aims to significantly improves these response rates, broaden the reach of PD-1 inhibitors, and potentially overcome treatment bottleneck in MSS CRC and other low-immunogenicity tumors.

Rising Momentum for Cross-Border Partnerships in Asia

According to recent data, cross-border licensing and M&A transactions in Asia’s pharmaceutical sector surged to US$66 billion in just the first seven months of 2025, already surpassing the total value for the entire previous year. Several blockbuster deals exceeding US$1 billion demonstrate how global pharma leaders are rapidly pivoting strategic investments toward Asia.

Amid this trend, Senhwa stands at the intersection of differentiated innovation, strong collaborations with the NCI, and partnerships with global pharmaceutical companies. As immunotherapy and precision medicine markets continue their robust expansion, Senhwa is well-positioned to become a pivotal partner for multinationals while emerging as a key innovator in Asia’s biotech landscape — creating a dual opportunity for growth and value for its stakeholders.

Unmet Need in MSS CRC and Young-Onset Colorectal Cancer

In metastatic CRC approximately 95% of metastatic colorectal cancer cases are MSS, for which effective immunotherapy options remain limited. Alarmingly, incidence among younger patients continues to rise, highlighting the urgent need for innovative approaches. Many patients either fail to respond or develop resistance to existing immunotherapies; and high treatment costs plus a lack of reliable biomarkers posing additional clinical challenges.

Through its innovative combination and precise design, this trial seeks to breakthrough current limitations, offering patients new hope by extending survival and improving quality of life.

Global Market Potential and Outlook for CX-5461

According to Coherent Market Insights, the global cancer immunotherapy market is projected to surpass US$150 billion by 2025, with sustained double-digit growth expected to push the market beyond US$300 billion by 2035. Combination therapies, in particular, have emerged as a central focus for industry R&D and investment.

As a first-in-class small molecule with a novel mechanism, preclinical data has shown CX-5461to have the ability to reprogram the tumor microenvironment, increase tumor mutational burden, and induce neoantigen presentation. Preclinical data also suggests the drug to enhance dendritic and cytotoxic T-cell infiltration while reducing immunosuppressive macrophages, thereby boosting sensitivity and efficacy of immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 therapies.

Crucially, CX-5461 has not shown marked bone‑marrow suppression at evaluated doses, in contrast to levels commonly seen with conventional chemotherapy. This advantage not only preserves cytotoxic immune cells but also creates a tumor microenvironment more favorable to immunotherapy and even cell-based therapies.

On September 16, 2025 Researchers at Children’s Hospital of Philadelphia (CHOP) reported a novel antibody-drug conjugate (ADC) that shows striking efficacy against cancers that express the anaplastic lymphoma kinase (ALK) protein on the cancer cell surface (Press release, CHOP, SEP 16, 2025, View Source [SID1234656009]). The therapy, named CDX0239-PBD, achieved complete and lasting tumor responses in preclinical models of neuroblastoma, rhabdomyosarcoma and colorectal carcinoma, according to findings published in Nature Communications. The breakthrough could unlock a new class of precision medicine treatments for both childhood and adult cancers, potentially improving short- and long-term patient outcomes and minimizing the harmful side effects of many current treatments.

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Yael P. Mossé, MD, Professor of Pediatrics and leader of the Neuroblastoma Developmental Therapeutics Program at CHOP’s Cancer Center, and her team are renowned for the groundbreaking discovery of gain-of-function mutations in the ALK gene, which are the primary cause of hereditary neuroblastoma and the most common mutations in its sporadic forms. This discovery was pivotal as it identifies ALK as the only mutated oncogene in neuroblastoma that can be targeted for therapy, reducing the likelihood of toxic side effects. The new research, an outgrowth of Mossé’s work, was led by Alberto D. Guerra, MD, PhD, a fellow within the Division of Oncology at CHOP.

In the study, researchers combined CDX0239, a humanized antibody targeting ALK, with a potent chemotherapy agent called pyrrolobenzodiazepine (PBD) dimer. This innovative approach directs the antibody to cancer cells, delivering the chemotherapy inside to kill cancerous cells while mostly sparing healthy ones that do not express ALK. The ADC remained stable in the bloodstream, an essential step for moving the research into human trials.

"Our findings represent an important advance in the field of antibody-drug conjugates for pediatric solid tumors, an area where progress has lagged," said Guerra. "By combining tumor selectivity with potent drug delivery, CDX0239-PBD offers a potential blueprint for future pediatric solid tumor therapies."

The therapy’s effectiveness is closely linked to ALK levels on the surface of cancer cells. Those with a range of ALK surface expression responded well, even when expression was modest. This is particularly exciting as these findings credential the opportunity to leverage an ADC approach for a broad population of patients. In preclinical studies with human tumor models, three total weekly doses of CDX0239-PBD successfully eliminated tumors, resulting in 100% survival across several highly drug-resistant preclinical models. The effects were seen not only in pediatric cancers like neuroblastoma and rhabdomyosarcoma but also in colorectal carcinoma, underscoring the treatment’s potential versatility.

The therapy also achieved success where others did not. For example, in models resistant to lorlatinib, an FDA-approved ALK inhibitor, and those with TP53 mutations and MYCN amplification, treatment with CDX0239-PBD led to lasting positive effects and complete survival. Molecular analyses confirmed that the treatment caused DNA damage and activated cell-death pathways inside tumors, validating its mechanism of action to be selective delivery of a potent chemotherapy drug to cancer cells expressing ALK, and likely also to neighboring tumor cells which may not necessarily express ALK, a phenomenon referred to as the "bystander effect."

Moving forward, the research team is working on refining the technology to meet strict regulatory requirements for developing a first-in-class ALK-directed ADC, aiming for first-in-human/first-in-children early phase clinical trial testing within the next two years. The team is also exploring alternative antibodies with features that would allow for better penetration into the solid tumor microenvironment.

"Precision medicine is transforming our approach to cancer treatment by moving beyond one-size-fits-all therapies," said Mossé. "By tailoring treatments to the unique characteristics of each tumor, we can specifically target cancer cells, thereby increasing the potency and reducing harmful side effects on healthy cells. Our hope is to significantly boost survival rates for patients fighting aggressive cancers while also enhancing their quality-of-life post-treatment."

This work was supported in part by the National Cancer Institute grants (R01CA140198-11-1, R37CA282041 and K08CA230223), Patricia Brophy Endowed Chair in Neuroblastoma Research, DOD Award (W81XWH-12-1-0486), the National Institutes of Health grant (R013208130624), the National Institutes of Health grant (DP2HD108775), funding from Braden’s Hope Foundation, the Margaret Q Landenberger Foundation, NIH Grant (2T32CA009615) and the Howard Hughes Medical Institute (HHMI).