On July 23, 2025 Crossbow Therapeutics, Inc., a biotechnology company developing T-Bolt therapies, a novel class of T-cell receptor (TCR)-mimetic antibody therapeutics, reported the nomination of its second development candidate, CBX-663, for the treatment of a broad range of solid tumor and hematologic malignancies (Press release, Crossbow Therapeutics, JUL 23, 2025, View Source [SID1234654494]). The next-generation T-cell engager targets telomerase reverse transcriptase (TERT), a protein that drives tumor growth and is expressed in up to 95% of cancers.1,2

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CBX-663, a bispecific antibody, binds to TERT-derived peptide human leukocyte antigen (pHLA) complexes on the surface of tumor cells and activates T-cells through a CD3-binding arm. The molecule includes two binding domains for TERT, which increase its ability to engage tumor cells and boost immune activation.

"CBX-663 illustrates how Crossbow’s TCR-mimetic platform can unlock new opportunities for antibody-based cancer therapies," said Briggs Morrison, MD, Chief Executive Officer of Crossbow. "With strong preclinical performance selectively targeting a pHLA expressed across a broad range of cancers, CBX-663 has the potential to offer a meaningful new treatment option for patients with limited therapeutic options."

In preclinical studies, CBX-663 drove potent, antigen-specific tumor killing across multiple TERT-positive cancer models, with minimal activity against TERT-negative or HLA-mismatched cells. The candidate also demonstrated a favorable safety profile and pharmacokinetics comparable to conventional antibody therapies. Crossbow presented data summarizing the initial characterization of CBX-663 at the 2025 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

Although TERT resides inside the cell, HLA molecules can present fragments of the protein, known as peptides, on the tumor surface. CBX-663 recognizes one of those peptides, the HLA-A*02:01-restricted TERT540 peptide, and redirects T-cells to attack tumor cells. CBX-663 demonstrated broad cytotoxic activity in vitro in both solid and hematologic cancer cell lines, as well as in primary patient samples ex vivo. In vivo studies further confirmed its anti-tumor efficacy and tolerability.

"CBX-663 reflects the depth of antibody discovery and protein engineering that underpins our T-Bolt platform and our ability to generate highly selective, potent molecules against difficult cancer targets," said Dmitri Wiederschain, PhD, Chief Scientific Officer of Crossbow. "Its performance in preclinical models reinforces the promise of TCR-mimetic therapeutics, and we’re excited to continue advancing this program."

Crossbow discovered and developed CBX-663 through its proprietary T-Bolt platform, which uses optimized antibody libraries and precision screening to find high-affinity, specific binders to intracellular tumor antigens displayed as pHLA complexes.

The nomination of CBX-663 underscores the platform’s potential to deliver a scalable pipeline of T-cell engagers for difficult-to-treat cancers.

On July 23, 2025 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical-stage oncology company leveraging its proprietary RADR artificial intelligence (AI) platform to systematically transform drug discovery paradigms, reported that a heavily pretreated patient with aggressive Grade 3 non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL) achieved a complete metabolic response in the ongoing Phase 1 clinical trial of LP-284 (Press release, Lantern Pharma, JUL 23, 2025, View Source [SID1234654493]). This represents the first complete response observed with LP-284 and displays profound clinical activity in one of the most therapeutically challenging hematologic cancers.

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The RADR-driven, AI approach enables Lantern to rapidly determine mechanisms of action of any cancer focused molecule, identify biomarker-driven subpopulations and optimize combination strategies for the clinical setting.

The 41-year-old patient had previously failed three aggressive treatment regimens over 18 months over the last 15 months. These included: standard R-CHOP/Pola-R-CHP chemotherapy, CAR-T cell therapy (liso-cel), and CD3xCD20 bispecific antibody therapy (glofitamab). Following enrollment in April 2025, the patient achieved complete metabolic response with non-avid lesions after completing just two 28-day cycles of LP-284 administered on days one, eight, and 15. This remarkable clinical outcome supports LP-284’s synthetic lethal mechanism and is an initial step towards a potential new paradigm for treating refractory aggressive lymphomas and B-cell malignancies.

Paradigm-Shifting Observation of Complete Response in Therapeutically Exhausted Patient

"This extraordinary clinical observation represents a transformative moment for our computationally guided, therapeutic development paradigm," said Panna Sharma, President and CEO of Lantern Pharma. "Our RADR platform’s systematic analysis of molecular vulnerabilities enabled us to rapidly advance LP-284 from computational concept to a clinical milestone in a patient in under three years at approximately $3 million — demonstrating how AI-driven precision has the promise to fundamentally reshape pharmaceutical innovation. This complete metabolic response in a patient who had exhausted all conventional therapeutic options strongly supports our strategic thesis that computational approaches can unlock previously inaccessible therapeutic opportunities."

LP-284, a computationally optimized next-generation acylfulvene, was systematically developed with guidance from Lantern’s RADR platform to exploit synthetic lethal interactions in cancer cells harboring specific DNA damage repair deficiencies. The compound represents a fundamentally different therapeutic strategy with the potential to preferentially target malignant cells while preserving healthy tissue function — a precision approach aimed at delivering transformative clinical benefit for patients who have failed multiple prior treatment modalities.

Potential to Address a Critical Therapeutic Void in Refractory DLBCL

This patient’s clinical journey exemplifies the devastating trajectory of aggressive DLBCL in the refractory setting. Despite achieving an initial complete metabolic response with CAR-T therapy (liso-cel) at day 30, the patient experienced disease progression by day 90. Subsequent treatment with the CD3xCD20 bispecific antibody glofitamab resulted in progressive disease with multifocal new lesions. At study entry on the LP-284-Phase 1 trial in April 2025, the patient presented with extensive multifocal bony lesions across thoracic and lumbar spine locations and hips — representing an extremely challenging clinical scenario.

The achievement of complete metabolic response with non-avid lesions following just two cycles of LP-284 therapy represents a potential future paradigm-shifting alternative for treating therapeutically exhausted DLBCL patients. This encouraging outcome underscores LP-284’s potential to address critical gaps in the therapeutic armamentarium for patients who have failed both conventional and cutting-edge immunotherapeutic approaches.

Advancing Strategic Clinical Development and Global Expansion

The complete metabolic response achievement positions LP-284 for accelerated development pathways and strengthens Lantern’s strategic position in the competitive hematologic oncology landscape. This clinical milestone provides important confirmation of the company’s systematic approach to therapeutic development and creates additional opportunities for international partnership expansion and collaborative research initiatives.

Lantern’s ongoing Phase 1 dose-escalation study (NCT06132503) is designed to evaluate LP-284’s safety profile, optimal dosing parameters, and preliminary efficacy signals across multiple aggressive lymphoma subtypes.

The trial’s systematic design enables precise evaluation of LP-284’s therapeutic potential across genetically defined patient populations, with a current focus on aggressive NHL subtypes including mantle cell lymphoma and high-grade B-cell lymphomas. LP-284’s multiple FDA Orphan Drug Designations position the compound for potential expedited regulatory pathways and enhanced market exclusivity frameworks.

Transforming Global Oncology Through Computational Precision

This clinical development provides important confirmation of the transformative potential of Lantern’s RADR platform, which leverages over 200 billion oncology-focused data points and 200+ machine learning algorithms to assist in systematically identifying and optimizing therapeutic opportunities. The platform’s computational efficiency enabled Lantern to rapidly advance the LP-284’s program into the clinic in under three years at a cost of approximately $3 million — representing striking development efficiency compared to traditional pharmaceutical paradigms.

The complete metabolic response achievement positions LP-284 to seek a future role within a global blood cancer market focused on B-cell cancer that is estimated at $4 billion annually, with DLBCL representing the largest aggressive lymphoma subtype affecting approximately 200,000 patients globally each year. The critical unmet need in refractory/relapsed settings represents a substantial commercial opportunity for innovative therapeutic approaches that can deliver meaningful clinical benefit to therapeutically exhausted patient populations.

Next Steps and Future Development

Lantern plans to continue enrollment in the Phase 1 trial while closely monitoring the responding patient and other potential future patients for durability of response and efficacy signals. The company anticipates providing additional clinical updates as the trial progresses and more patients reach evaluable timepoints.

The complete response achievement positions LP-284 for potential accelerated development pathways and creates opportunities for strategic partnerships as Lantern advances its synthetic lethal portfolio toward later-stage clinical trials.

About LP-284

LP-284 is an investigational next-generation acylfulvene designed to exploit synthetic lethal interactions in cancer cells with DNA damage repair deficiencies. Developed with guidance from Lantern’s AI platform RADR, LP-284 represents a novel therapeutic approach with potential to address critical gaps in the treatment of relapsed or refractory non-Hodgkin’s lymphoma and other hematologic malignancies. The compound is currently being evaluated in a Phase 1 clinical trial (NCT06132503) to determine its safety profile, optimal dosing, and potential activity in patients with aggressive NHL subtypes who have failed standard therapies.

LP-284 has received multiple Orphan Drug Designations from the U.S. Food and Drug Administration, including designations for mantle cell lymphoma and high-grade B-cell lymphomas, recognizing its potential to address significant unmet medical needs in rare cancer populations.

On July 23, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported it will host an in-person and virtual R&D Day on September 8, 2025 from 8:00am to 10:00am ET in New York City to present multiple clinical data updates across the pipeline and highlight the next key drivers of growth and upcoming milestones (Press release, Ideaya Biosciences, JUL 23, 2025, View Source [SID1234654492]).

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"This year marks IDEAYA’s ten-year anniversary since our founding, and we look forward to providing multiple clinical data updates across our potential first-in-class pipeline, and highlight our strategic vision, priority areas of scientific focus, and emerging clinical pipeline that will drive the next phase of our growth as a global leader in precision medicine oncology," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

Speakers will include members of IDEAYA’s senior leadership team and key opinion leader(s).

Registration for this event can be accessed here or at the investors section of the IDEAYA website at View Source

On July 23, 2025 Oncolytics Biotech Inc. (Nasdaq: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, reported a key opinion leader (KOL) webinar featuring leading physicians in the fields of oncology and immunotherapy discussing pelareorep’s robust clinical data and how it fits in the evolving treatment landscape for pancreatic and gastrointestinal (GI) cancers (Press release, Oncolytics Biotech, JUL 23, 2025, View Source [SID1234654491]). The KOLs provided individual presentations and then participated in a roundtable Q&A discussion. A replay of the full conversation can be found by clicking here.

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A selection of key takeaways includes:

The meaningful survival benefit demonstrated by pelareorep-based treatment combinations in first-line (1L) metastatic pancreatic ductal adenocarcinoma (mPDAC) patients across randomized and single-arm clinical studies necessitates evaluating pelareorep in a registration-enabling study in 1L mPDAC.
Immunotherapies have not yet been approved to treat mPDAC patients, illustrating an unmet need, which provides an opportunity for an immunologically active agent like pelareorep to deliver an impactful clinical benefit in this challenging indication.

The combination of pelareorep and chemotherapy would be an appealing treatment option for 1L mPDAC patients, even with the presence of RAS inhibitors in the treatment paradigm.
Translational data from multiple mPDAC and colorectal cancer clinical trials validate pelareorep’s mechanism of action, showing that it replicates in tumors, stimulates chemokine expression, and induces the expansion of tumor-infiltrating lymphocytes (TILs), which correlates with a reduction in tumor size.
"I want to thank our esteemed panel of oncologists for their meaningful contributions to our KOL event," said Jared Kelly, Chief Executive Officer of Oncolytics. "Their insights underscore a critical and timely message: pelareorep is a compelling immunotherapy platform that is well situated for combination strategies and a highly differentiated asset for pharma partners looking to expand or establish leadership in GI oncology. We are committed to moving forward aggressively toward registrational development while engaging with partners who share our vision of transforming outcomes in these difficult-to-treat cancers."

On July 23, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that the first patient has been enrolled in the pivotal/registration Phase III clinical trial (AK112-310/HARMONi-GI2) of ivonescimab, a first-in-class PD-1/VEGF bispecific antibody developed by the company (Press release, Akeso Biopharma, JUL 23, 2025, View Source [SID1234654490]). The trial is investigating ivonescimab in combination with chemotherapy, with or without ligufalimab (CD47 monoclonal antibody), for the first-line treatment of metastatic pancreatic cancer.

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Pancreatic cancer remains one of the most challenging types of tumors to find effective treatments for. While immunotherapies have demonstrated significant efficacy in different types of of solid tumors, pancreatic cancer’s unique immune evasion mechanisms and its highly immunosuppressive tumor microenvironment (TME) have rendered it resistant to current therapies. As a result, previous Phase III studies on using immunotherapies as first-line treatments for metastatic pancreatic cancer have mostly failed. To date, no immunotherapy has been approved for first line metastatic pancreatic cancer.

Ivonescimab, in combination with chemotherapy and/or ligufalimab, has the potential to address the current lack of effective options in first-line immunotherapy for metastatic pancreatic cancer. This randomized, controlled, multi-center Phase III trial is a key component of Akeso’s broader strategy to address the significant unmet clinical needs in global oncology.

Pancreatic cancer is an extremely aggressive form of malignancy that often result in poor patient prognosis. Its global incidence is on the rise, and the mortality rate closely mirrors the incidence, resulting in alarmingly low overall survival rates. In 2022, approximately 511,000 new cases of pancreatic cancer were diagnosed worldwide, and 467,000 deaths were recorded. Early diagnosis remains challenging, with around 80% of patients being diagnosed at an advanced stage. Even those diagnosed with early-stage or locally advanced disease may see progression to metastatic pancreatic cancer within a year following surgery or other treatments. Current first-line treatments are predominantly chemotherapies and have showed very limited success, with a median overall survival (OS) of less than one year.

PD-1 and VEGF are often co-expressed in the tumor microenvironment. As a PD-1/VEGF bispecific antibody, Ivonescimab can accumulate in the TME and effectively block both the PD-1 and the VEGF signaling pathways. While these pathways are independently active, they are also complementary. Inhibition of both PD-1 and VEGF enhances immune cells’ ability to target and destroy tumor cells. In addition, ligufalimab binds to CD47 on tumor cells, disrupting the interaction with signal regulatory protein alpha (SIRPα) on phagocytic cells. This process boosts phagocytosis and inhibits tumor growth. The combination of ivonescimab with ligufalimab is expected to synergistically enhance anti-tumor activity, offering a potential breakthrough in the first-line treatment for metastatic pancreatic cancer.

Professor Yu Xianjun, Director of Fudan University Shanghai Cancer Center, Professor Ying Jie’er from Zhejiang Cancer Hospital, and Professor Tai Sheng from Harbin Medical University Cancer Hospital are the co-principal investigators of HARMONi-GI2 study.