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CrossBridge Bio Awarded $15 Million CPRIT Grant to Advance CBB-120, Its Lead Dual-Payload ADC Targeting TROP-2, Into the Clinic

On November 20, 2025 CrossBridge Bio, a biotechnology company pioneering next-generation dual-payload antibody-drug conjugates (ADCs) that have the potential to deliver safer, more durable responses for patients, including those resistant to approved ADC therapies, reported it has been awarded a $15 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT). The award will support completion of IND-enabling activities and advancement of CBB-120, the company’s lead TROP-2 targeted TOP1i/ATRi dual-payload ADC, into first-in-human studies.

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CrossBridge Bio’s proprietary platform integrates branched tripeptide linkers (EGCit) with a dual-payload design that enables precise delivery of synergistic topoisomerase-1 inhibitor and ATR inhibitor payloads within a single ADC molecule. This architecture is engineered to deliver deeper, more durable responses and to overcome tumor resistance and heterogeneity – key limitations of earlier-generation ADCs.

CBB-120 has generated compelling preclinical data demonstrating potent and durable antitumor activity, including in models resistant to standard-of-care ADCs. The program was recently featured at the 2025 World ADC Conference, where it became the most attended non-plenary session in the event’s history, underscoring broad scientific interest in the platform and program.

The CPRIT award will enable CrossBridge Bio to complete GLP toxicology studies, scale up manufacturing, finalize analytical development, and prepare for an IND filing in 2026.

"We are honored to receive CPRIT’s support as we advance CBB-120 toward the clinic," said Michael Torres, Ph.D., Chief Executive Officer of CrossBridge Bio. "This grant is a strong validation of the innovation behind our dual-payload platform and reflects the importance of bringing new treatment options to patients facing difficult-to-treat cancers. CPRIT’s support allows us to accelerate development with the urgency this opportunity deserves."

"CBB-120 showcases the full strength of our scientific approach – dual-payload engineering, branched linker chemistry, and precision delivery," said Dan Pereira, Ph.D., Chief Scientific Officer of CrossBridge Bio. "We’re excited to build on the momentum from our World ADC recognition and move this program into clinical development, where we hope it will make a meaningful impact for patients with limited options."

(Press release, CrossBridge Bio, NOV 20, 2025, View Source [SID1234660859])

U.S. FDA Approves HYRNUO® (sevabertinib) for Previously Treated Patients with HER2-Mutated Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

On November 20, 2025 Bayer reported that the U.S. Food and Drug Administration (FDA) has approved HYRNUO (sevabertinib), an oral, reversible, tyrosine kinase inhibitor (TKI), for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.1

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1

Regulatory approval for HYRNUO is based on results from the ongoing Phase I/II SOHO-01 trial.1

In 2024, the U.S. FDA granted HYRNUO Breakthrough Therapy designation for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and who have received a prior systemic therapy.

HYRNUO is derived from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, MA, USA.

INDICATION

HYRNUO is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.

IMPORTANT SAFETY INFORMATION

Warnings & Precautions

Diarrhea

HYRNUO can cause severe diarrhea that can lead to dehydration and electrolyte imbalances.

In the pooled safety population, diarrhea was reported in 86% of patients who received HYRNUO including Grade 3 in 15%. The median time to first onset of any grade diarrhea was four days. Dosage interruptions occurred in 15% of patients, and dose reductions occurred in 12% of patients.

At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment (e.g., loperamide), and to increase their fluid and electrolyte intake. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity.

Hepatotoxicity

HYRNUO can cause severe hepatotoxicity characterized by elevations of liver function tests.

In the pooled safety population, based on adverse reaction data, hepatotoxicity occurred in 24% of patients treated with HYRNUO including 3% Grade 3.

Based on laboratory data, 35% of patients treated with HYRNUO experienced increased alanine aminotransferase (ALT), including 2.3% Grade 3. Increased aspartate aminotransferase (AST) occurred in 35% of patients treated with HYRNUO, including 2.3% Grade 3. Increased bilirubin occurred in 12% of patients treated with HYRNUO. The median time to first onset of AST or ALT elevation was 1.4 (range 0.2 to 14.5) months.

HYRNUO was interrupted for an adverse reaction of hepatotoxicity in 4.1% of patients, the dose was reduced in 4.1% and permanently discontinued in 0.4%.

Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to the first administration of HYRNUO, every 2 weeks for the first month and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose or permanently discontinue HYRNUO based on the severity of the adverse reaction.

Interstitial Lung Disease/Pneumonitis

HYRNUO can cause severe interstitial lung disease (ILD)/pneumonitis.

In the pooled safety population, ILD/pneumonitis occurred in two patients (0.7%) treated with HYRNUO, including 0.4% Grade 3. One patient required interruption of HYRNUO.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Discontinue HYRNUO upon confirmation of ILD/pneumonitis.

Ocular Toxicity

HYRNUO can cause ocular toxicity.

In the pooled safety population, ocular toxicity occurred in 14% of patients treated with HYRNUO, including 11% Grade 1, 2.6% Grade 2 and 0.4% Grade 3 (one case of corneal epithelial microcysts with temporary unilateral blindness).

Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity.

Pancreatic Enzyme Elevation

HYRNUO can cause elevations of amylase and lipase levels.

In the pooled safety population, based on laboratory data, increased amylase occurred in 32% of patients treated with HYRNUO, including 3.2% Grade 3 or 4. Increased lipase elevation occurred in 40% of patients treated with HYRNUO, including 10% Grade 3 or 4. Two patients (0.7%) required interruption of HYRNUO due to increased lipase and three (1.1%) required interruption of HYRNUO due to increased amylase. The median time to onset of increased amylase/lipase was 1.4 months (range: 0.2 to 17 months).

Monitor amylase and lipase regularly during treatment with HYRNUO. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity.

Embryo-fetal toxicity

Based on findings from animal studies and its mechanism of action, HYRNUO can cause fetal harm when administered to a pregnant woman. In embryo-fetal development studies, oral administration of sevabertinib to pregnant rats during the period of organogenesis resulted in alterations to growth at maternal exposures ≥0.18 times the human exposure based on area under the curve (AUC) at the clinical dose of 20 mg twice daily. Animal studies with disrupted or depleted HER2/EGFR and in vitro assays have demonstrated that inhibition of HER2 and/or EGFR results in structural abnormalities, alteration to growth, and embryo-fetal and infant mortality.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose.

Adverse Reactions

In SOHO-01 (Groups D and E), serious adverse reactions occurred in 31% of patients who received HYRNUO. Serious adverse reactions in ≥2% of patients were diarrhea (6%), pneumonia (3.7%), dyspnea (2.2%), and pleural effusion (2.2%). The most common adverse reactions (>20%) in patients who received HYRNUO were diarrhea (87%), rash (66%), paronychia (33%), stomatitis (29%), and nausea (21%). The most common Grade 3 and 4 laboratory abnormalities (≥2%) were potassium decreased (13%), lipase increased (12%), lymphocyte count decreased (6%), sodium decreased (4.4%), amylase increased (3.8%), aspartate aminotransferase (AST) increased (3%), and alanine aminotransferase (ALT) increased (3%). Laboratory abnormalities in <20% of patients who received HYRNUO include blood bilirubin increased (14%; all were Grades 1 or 2). Clinically relevant adverse reactions in <10% of patients who received HYRNUO included edema (8%), cardiac arrhythmia (6%; includes arrhythmia, atrioventricular block complete, electrocardiogram QT prolonged, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia) and alopecia (3.7%).

Drug Interactions

Effects of Other Drugs on HYRNUO – Sevabertinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor may increase sevabertinib plasma concentrations, which may increase the risk of HYRNUO adverse reactions. Monitor patients for increased HYRNUO-associated adverse reactions with moderate CYP3A inhibitors. Avoid concomitant use of HYRNUO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dose.

Concomitant use with a strong or moderate CYP3A inducer may decrease sevabertinib plasma concentrations, which may decrease the effectiveness of HYRNUO. Avoid concomitant use of HYRNUO with strong or moderate CYP3A inducers.

Effects of HYRNUO on Other Drugs – Sevabertinib is a weak to moderate CYP3A inhibitor. Sevabertinib increases exposure of CYP3A substrates, which may increase the risk of adverse reactions related to these substrates. Avoid concomitant use of HYRNUO with CYP3A substrates where minimal increases in the concentration may lead to serious adverse reactions unless otherwise recommended in the Prescribing Information of the CYP3A substrate.

Sevabertinib is a P-gp inhibitor. Sevabertinib increases exposure of P-gp substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information for P-gp substrates where minimal increases in the concentration may lead to serious adverse reactions.

Sevabertinib is an inhibitor of CYP1A1 in vitro. Sevabertinib may increase exposure of CYP1A1 substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information of CYP1A1 substrates.

(Press release, Bayer, NOV 20, 2025, View Source [SID1234660858])

Thermo Fisher Scientific’s Oncomine Dx Target Test Receives FDA Approval as a Companion Diagnostic to Identify Patients Eligible for Newest Targeted Therapy for Non-Small Cell Lung Cancer

On November 20, 2025 Thermo Fisher Scientific, the world leader in serving science, reported to have received approval from the U.S. Food and Drug Administration (FDA) for its Ion Torrent Oncomine Dx Target Test as a companion diagnostic (CDx) to identify patients who may be eligible for treatment with HYRNUO (sevabertinib), a new HER2-directed therapy developed and commercialized by Bayer. The test enables clinicians and pathologists to identify non-small cell lung cancer (NSCLC) tumors with certain HER2/ERBB2 tyrosine kinase domain (TKD) activating mutations, helping determine which patients may benefit from HYRNUO therapy.

The FDA also approved HYRNUO on November 19 for the treatment of adult patients with locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD activating mutations. The contemporaneous approval of Bayer’s therapy and Thermo Fisher’s companion diagnostic helps close access gaps, ensuring labs have access to essential companion testing as soon as the drug is available.

Lung cancer remains the leading cause of cancer death worldwide, with NSCLC representing approximately 87 percent of all lung cancer cases.1 For patients with NSCLC presenting with HER2 mutations, this approval represents an opportunity to provide more targeted treatment for a disease that has traditionally had limited therapeutic options as well as poor prognosis with a survival rate of less than 10% for metastatic disease.2 Historically, nearly 50% of eligible patients miss out on targeted therapies due to testing and report delays, access limitations or lab bottlenecks3, creating gaps that hinder precision medicine progress.

"We are committed to advancing innovation for patients with difficult-to-treat cancers, and this approval marks another step forward in ensuring all patients with cancer have access to optimal treatment options," said Emmanuelle Di Tomaso, VP, Global Head of Translational Sciences Oncology at Bayer. "Collaborating with Thermo Fisher to leverage the Oncomine Dx Target Test allows us to ensure clinical teams can identify patients who are most likely to benefit from sevabertinib, supporting timely and informed treatment decisions in real-world clinical settings."

The Oncomine Dx Target Test received its first approval by the FDA as a next-generation sequencing (NGS) CDx in 2017, followed by regulatory approvals in 20 countries for 11 biomarkers and over 20 targeted therapies (availability of these approvals vary per region).

"The power of precision medicine starts with accurate, timely genomic insights that help providers match patients to the right therapies," said Kathy Davy, president of clinical next-generation sequencing at Thermo Fisher Scientific. "Our experience as a companion diagnostics partner of choice for pharmaceutical companies allows us to support the development of new therapies, accelerate access and help clinicians make the best possible decisions for their patients."

Broad reimbursement coverage—including the U.S., Europe, Japan, South Korea, and Israel—makes the Oncomine Dx Target Test accessible to more than 550 million people worldwide. In the U.S., the Oncomine Dx Target Test is authorized for use alongside multiple therapies for NSCLC and a range of other tumor types, such as cholangiocarcinoma (CC), astrocytoma (AC) and oligodendroglioma (OG), anaplastic thyroid cancer (ATC), medullary thyroid cancer (MTC), and thyroid cancer (TC).

For more information on the Oncomine Dx Target Test and Thermo Fisher’s leadership in companion diagnostics, please visit thermofisher.com/cdx.

(Press release, Thermo Fisher Scientific, NOV 20, 2025, View Source [SID1234660857])

Mission Bio Announces Single-Cell Targeted DNA + RNA Assay at ASH 2025, Closing the Mutation-to-Expression Gap in Cancer Research

On November 20, 2025 Mission Bio, a leader in single-cell multi-omics solutions for precision medicine, reported its Tapestri Single-Cell Targeted DNA + RNA Assay, the first commercial platform to measure genotypic and transcriptional readouts within the same cell. The assay empowers oncology and translational researchers to directly link mutations to their functional consequences, uncovering the mechanisms that drive resistance, relapse, and therapeutic response– advancing precision medicine to enable more effective therapeutic innovation.

Advancements have been made in mapping clonal architecture in blood cancers via single-cell genotyping. However, linking these genetic mutations to gene expression, the driver of phenotype and treatment response, remains a major challenge. The Tapestri Targeted DNA + RNA Assay unifies both genotyping and gene expression in the same cell, eliminating multi-platform data integration and heavy computational alignment, enabling investigators to observe how mutations influence transcriptional states in acute myeloid leukemia, myelodysplastic syndromes, and engineered cell therapies.

Peer-reviewed work published in Nature Methods using the Tapestri platform showed that cells with higher mutational burden exhibit enhanced tumorigenic gene expression and B-cell-receptor signaling, evidence of the method’s sensitivity and relevance to hematology. Its debut at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2025 coincides with a broader shift toward functional, single-cell multi-omic profiling in translational hematology.

"The DNA+RNA assay provides powerful resolution into the mutational landscape and cell states within leukemia," says Bobby Bowman, PhD, Assistant Professor, University of Pennsylvania, Department of Cancer Biology. "With this assay, we were able to chart clonal evolution in response to therapy, and resolve not only which clones survived but the gene expression programs that emerged following therapy."

The assay unites targeted genotyping and transcript quantification in a single workflow, analyzing thousands of cells per run and quantifying expression of up to 200 transcripts to link genetic changes with their functional impact. The design preserves existing Tapestri chemistry and instrumentation, allowing current users to add RNA capability without re-validation of laboratory infrastructure or data pipelines.

"For translational and cell therapy researchers, combining DNA and RNA signals from the same cells reveals how variants act in real time," said Adam Sciambi, PhD, Mission Bio CTO and co-founder. "It turns inference into direct observation, an essential step toward mechanistic insights for next-generation therapies."

The assay is currently offered for research use only and will be featured in demonstrations at ASH (Free ASH Whitepaper) on Dec. 6-9, 2025, at Booth #2129, where Mission Bio will highlight use cases spanning therapy resistance, relapse modeling, and preclinical quality assessment.

This launch continues Mission Bio’s leadership in single-cell multi-omics. Adding RNA expression profiling to the established Tapestri platform used worldwide across cancer research, pharmaceutical development, and cell and gene therapy programs demonstrates Mission Bio’s focus in helping investigators truly understand the biological complexity of diseases at the single-cell level. By enabling the simultaneous analysis of genotype and gene expression within the same cells, Mission Bio has established a new analytical standard for translational hematology and engineered cell development.

For more information, you can visit View Source and View Source

(Press release, Mission Bio, NOV 20, 2025, View Source [SID1234660856])

Taiho Oncology, Taiho Pharmaceutical and Cullinan Therapeutics Initiate Rolling Submission of New Drug Application to U.S. Food and Drug Administration for Zipalertinib for Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

On November 20, 2025 Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) reported the companies have initiated the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval of zipalertinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations who have previously received platinum-based systemic chemotherapy.

Zipalertinib previously received Breakthrough Therapy Designation in 2021, which with FDA agreement, allows submission of portions of the application as they are completed. The companies anticipate completion of the NDA submission in the first quarter of 2026 with an associated request for priority review.

The NDA submission is based on the primary efficacy data from the REZILIENT1 trial, a Phase 1/2 clinical trial of zipalertinib (development code: CLN-081/TAS6417) monotherapy in patients with NSCLC harboring EGFR ex20ins mutations who have received prior therapy.

Positive results from the REZILIENT1 trial were presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and were simultaneously published in the Journal of Clinical Oncology.

About REZILIENT1
REZILIENT1 (Researching Zipalertinib In EGFR Non-Small Cell Lung Cancer Tumors) is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in adult patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations who have received prior therapy. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoints were objective response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (ICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Adverse events were characterized and graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE v5.0).

About Zipalertinib
Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA. Zipalertinib is investigational and has not been approved by any health authority.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

About EGFR Exon 20 Insertion Mutations
NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR exon 20 insertions, which makes them the third most common EGFR mutation subtype.1 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations,2 with insertions at exon 20 accounting for up to 12% of these mutations.

(Press release, Taiho, NOV 20, 2025, View Source [SID1234660855])