On October 20, 2025 Upthera (CEO Si-Woo Choi), a company specializing in the development of innovative new drugs based on Targeted Protein Degradation (TPD) technology, reported that it has received approval from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for a Phase 1/2a clinical trial of its PLK1-targeted protein degradation-based (TPD) drug candidate ‘UP1002’ for small cell lung cancer (SCLC).

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This approval marks the first global entry into clinical trials for a new TPD-class drug targeting PLK1, and is considered an achievement that demonstrates Upthera’s proprietary protein degradation technology and global competitiveness. Next year, we plan to proceed with the IND approval process in Korea as well to expand the global clinical trials of ‘UP1002’ in earnest.

The clinical trial approved this time is a Phase 1/2a combined design that proceeds to confirm safety and tolerability through initial dose escalation, followed by evaluating efficacy indicators through an expansion cohort. Uptera aims to administer the drug to the first patient starting next year, involving 30 to 60 patients in the U.S., and plans to consider expanding to other solid tumor indications depending on future results.

Small cell lung cancer (SCLC) has been known for decades as a cancer where new drug development is significantly more difficult compared to other types of cancer, and even recently approved drugs have limited anticancer efficacy, such as extending survival.

In addition, it is an intractable cancer with a very low 5-year survival rate of less than 7% due to the rapid rate of tumor metastasis and high recurrence rate. While the development of numerous targeted anticancer drugs based on reliable biomarkers is underway for non-small cell lung cancer, the development of targeted anticancer drugs for small cell lung cancer is difficult due to the lack of accurate biomarkers.

To overcome these limitations, Upthera is developing ‘UP1002,’ a novel drug candidate that directly degrades PLK1 (Polo-like kinase 1), a key protein regulating cell division, by utilizing TPD technology. PLK1 is an essential protein (kinase) that regulates cell division during the cell cycle (G2/M phase) and is overexpressed in rapidly proliferating cells, such as cancer cells. While numerous global pharmaceutical companies, including Boehringer Ingelheim and Takeda, have developed PLK1 inhibitors (small molecule inhibitors), most have been discontinued during clinical trials due to dose-limiting toxicity (DLT). To date, there are no approved drugs with a mechanism that selectively inhibits or degrades PLK1.

UP1002 is characterized by inducing an anticancer effect even at lower concentrations than existing inhibitors by directly degrading the PLK1 protein, and by fundamentally overcoming the problem of dose-limiting toxicity (DLT). This mechanism is a novel approach that induces apoptosis by halting the cell cycle of cancer cells, and is expected to lead a paradigm shift in treatment for cancers with rapid cell proliferation, such as small cell lung cancer.

Upthera’s UP1002 (PLK1) was recognized for its innovation and technological capabilities and was selected as a project under the Korea Drug Development Fund (KDDF) ​​in 2022, receiving support. Based on the Global RA support program within the KDDF, Upthera has established a global clinical development strategy in collaboration with global clinical research institutions such as QubeST Bio and KCRN Research.

UP1002 is recognized as the first-in-class anticancer drug that degrades PLK1 and the first clinical pipeline in the TPD industry to target cell cycle-related proteins, which are difficult to develop. In addition, Upthera has filed 82 domestic and international patents related to UP1002, 19 of which have been registered. The company plans to continuously strengthen its patent portfolio and build patent barriers to effectively block the entry of latecomers in the PLK1 degradation field and solidify its position as a first mover.

"This FDA IND approval is an achievement that officially recognizes Upthera’s proprietary protein degradation technology and global development capabilities," said Choi Si-woo, CEO of Upthera. "We will present new treatment options to patients with small cell lung cancer through clinical results and strengthen our global competitiveness in the TPD field."

(Press release, Uppthera, OCT 20, 2025, View Source [SID1234664781])

On October 20, 2025 IMUNON, Inc. (Nasdaq: IMNN), a clinical-stage company in Phase 3 development with its DNA-mediated immunotherapy, reported that it will host an R&D Day for investors at the Harvard Club (35 West 44th Street) in New York City on November 10, 2025, beginning at 8:00 a.m. ET.

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The investor event will feature ovarian cancer thought leaders, principal investigators from the Company’s Phase 3 OVATION 3 Study and Phase 2 minimal residual disease (MRD) clinical trial, conducted in partnership with Break Through Cancer Foundation, statistical experts and members of IMUNON’s management team, delivering updates on new IMNN-001 data and discussing progress with the OVATION 3 Study and IMNN-001’s potential role in transforming the treatment landscape for women with advanced ovarian cancer. There will be a live Q&A session and networking opportunities with the speakers and IMUNON management team following the formal presentations.

Featured Presentations and Speakers:

Title: Advancing Ovarian Cancer Care: IMNN-001’s Potential to Transform the Microtumor Environment from Cold to Hot in Phase 3
Presenter: Premal H. Thaker, M.D., David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Chief of Gynecologic Oncology, Director of Gynecologic Oncology Clinical Research, Professor in Gynecologic Oncology, Washington University School of Medicine

Title: Unveiling Progress: Safety, Tolerability, and Translational Insights for IMNN-001
Presenter: Amir Jazaeri, M.D., Vice Chair for Clinical Research, Director, Gynecologic Cancer Immunotherapy Program, Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center
Title: OVATION 3 Probability of Success & the Statistical Properties of Phase 3 Trial Design
Presenter: Giorgio Paulon, Ph.D., Director & Senior Statistical Scientist, Berry Consultants, LLC
Title: Phase 3 OVATION 3 Trial Update
Presenter: Douglas V. Faller, M.D., Ph.D., Chief Medical Officer, IMUNON

(Press release, IMUNON, OCT 20, 2025, View Source [SID1234656816])

On October 20, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that the results from the Phase III registrational clinical study OptiTROP-Lung04—led by Professor Zhang Li’s team from Sun Yat-sen University Cancer Center—were published in the New England Journal of Medicine (Impact Factor = 78.5). The study evaluated the efficacy and safety of the TROP2 antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) monotherapy versus pemetrexed plus platinum chemotherapy for the treatment of patients with epidermal growth factor receptor (EGFR)-mutant locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed failed after treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy. The study was also selected as a Late-Breaking Abstract (LBA) at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and was presented as an oral report in the Presidential Symposium (Presentation # LBA5).

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OptiTROP-Lung04 is a randomized, open-label, multicenter Phase III study designed to evaluate the efficacy and safety of sac-TMT monotherapy versus pemetrexed plus platinum in patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on prior EGFR-TKI therapy. Eligible patients were those with histologically and/or cytologically confirmed disease. The primary endpoint was Progression-Free Survival (PFS) assessed by a Blinded Independent Review Committee (BIRC) per RECIST v1.1, and the key secondary endpoint was overall survival (OS). Results showed that compared with platinum-based doublet chemotherapy, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in both PFS and OS. Consistent PFS and OS benefits were observed across all prespecified subgroups, including prior EGFR-TKI therapy, presence of liver or brain metastases, and EGFR mutation subtype.

Based on the positive results of the OptiTROP-Lung04 study, sac-TMT has been approved by the National Medical Products Administration (NMPA) in China for the treatment of adult patients with EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC who have progressed after EGFR-TKI therapy. To date, sac-TMT monotherapy remains the only approved treatment option for advanced EGFR-mutant NSCLC patients who have progressed after prior TKI therapy, as well as those who have progressed after prior TKI and platinum-based chemotherapy (either concurrently or sequentially). This achievement provides comprehensive coverage for the entire population of TKI-resistant patients.

Dr. Michael Ge, Chief Executive Officer of Kelun-Biotech, commented: "OptiTROP-Lung04 is a key study that propels sac-TMT from late-line to an earlier-line treatment-setting in lung cancer, achieving a significant improvement in overall survival. We are thrilled that the results have been published in The New England Journal of Medicine, allowing this important finding to be shared widely among medical professionals and providing a reference for future lung cancer research. Together with our partner MSD, we will continue to advance sac-TMT’s clinical development and regulatory approvals, covering broader lung cancer and other indications, with the goal of making sac-TMT a cornerstone therapy for the benefit of patients."

Professor Shengxiang Ren from the Department of Oncology at Shanghai Pulmonary Hospital, Tongji University, stated: "The application of third-generation EGFR-TKIs has significantly improved the overall prognosis for patients with advanced EGFR-mutant NSCLC. However, drug resistance is almost inevitable. Traditional treatment after resistance involves platinum-based doublet chemotherapy, which offers limited overall benefit. In recent years, regimens of chemotherapy plus immune checkpoint inhibitors+anti-angiogenic agents, or EGFR/c-Met bsAb, or PD-1/VEGF bsAb, have been successively approved for this indication. However, all these approaches are chemotherapy-based, highlighting an urgent need to explore novel treatment regimens. The OptiTROP-Lung04 study confirms sac-TMT as the first treatment option as a monotherapy to deliver clear dual benefits in both PFS and OS following EGFR-TKI progression. The sequential application of sac-TMT prior to chemotherapy demonstrates strong competence, establishing itself as a new standard of care for patients with advanced EGFR-mutant lung cancer after TKI resistance."

About Sac-TMT

Sac-TMT, a core product of the Company, is a novel human TROP2 ADC in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases the payload KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (includes Mainland China, Hong Kong, Macau, and Taiwan).

To date, three indications for sac-TMT have been approved and marketed in China for the treatment of adult patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting), EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC following progression on EGFR-TKI therapy and platinum-based chemotherapy and EGFR mutant-positive locally advanced or metastatic non-squamous NSCLC who progressed after treatment with EGFR-TKI therapy. Sac-TMT is the first TROP2 ADC drug approved for marketing in lung cancer globally. In addition, the new indication application for sac-TMT for the treatment of adult patients with unresectable locally advanced, metastatic hormone receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) BC who have received prior endocrine therapy and other systemic treatments in the advanced or metastatic setting was accepted by the Center for Drug Evaluation of the NMPA, and was included in the priority review and approval process.

As of today, the Company has initiated 9 registrational clinical studies in China. MSD has initiated 15 ongoing Phase Ⅲ global clinical studies of sac-TMT as a monotherapy or with pembrolizumab1 or other anti-cancer agents for several types of cancer. These studies are sponsored and led by MSD.

(Press release, Kelun, OCT 20, 2025, View Source [SID1234656832])

On October 20, 2025 SunRock Biopharma, a biotechnology company focused on developing next-generation therapeutic antibodies, and Chime Biologics, a global leading contract development and manufacturing organization (CDMO), reported a strategic collaboration for the development of SRB5, a novel anti-CCR9 monoclonal antibody targeting inflammatory bowel disease (IBD), with potential expansion into other immune-mediated inflammatory indications.

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SRB5 is a humanized monoclonal antibody with enhanced ADCC properties, designed to selectively deplete CCR9+ cells involved in chronic intestinal inflammation. It is the latest advancement in SunRock’s anti-CCR9 platform and represents a significant advance in a selective therapeutic approach for treating diseases such as Crohn’s disease and ulcerative colitis. Through this partnership, SunRock will benefit from Chime Biologics’ global-standard GMP manufacturing platform to scale production and accelerate preclinical and regulatory milestones.

"We are proud to collaborate with SunRock Biopharma on this promising anti-CCR9 antibody (SRB5) for inflammatory bowel disease, a condition that significantly impacts patients worldwide. This partnership reflects our commitment to applying our global-standard quality and comprehensive experiences in manufacturing biologics to accelerate the development of innovative therapies. We look forward to contributing to the long-term mission of SunRock Biopharma to develop innovative antibodies against highly invasive tumors with an urgent clinical need in oncology," said Dr. Jimmy Wei, President of Chime Biologics.

Dr. Laureano Simón, CEO of SunRock Biopharma, added "This collaboration with Chime Biologics reinforces our strategy of working with world-class partners across every stage of development. Chime’s technical expertise and industrial quality standards will help us scale SRB5 under optimal conditions. SRB5 has a distinctive biological profile that could transform the therapeutic landscape in IBD and potentially in highly aggressive CCR9-expressing tumors. This agreement is a critical step toward clinical validation."

(Press release, SunRock Biopharma, OCT 20, 2025, View Source [SID1234656848])

On October 20, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported final results from Part B of the DeFianCe study (NCT05480306), a Phase 2 study of sirexatamab (DKN-01), an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy (Sirexatamab Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease. The final clinical results were presented on behalf of the DeFianCe study investigators by Zev Wainberg, MD, Professor of Medicine and Co-Director of the GI Oncology Program at UCLA in a Mini Oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany.

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"Circulating DKK1 is a negative prognostic factor and elevated in patients with advanced, metastatic CRC. The data presented at ESMO (Free ESMO Whitepaper) demonstrate that sirexatamab, which binds to and removes free DKK1, has significant potential to provide a survival benefit for CRC patients who have high DKK1 levels and who are likely to have poor outcomes receiving the current standard of care alone," said Dr. Wainberg. "Sirexatamab has the potential to be a valuable addition to the CRC treatment paradigm as a targeted therapeutic for patients with high DKK1 and should move forward to be evaluated in a biomarker-focused registrational trial."

The DeFianCe study was a two part, open-label, multi-country study. Part A of the DeFianCe study enrolled 33 patients, including a significant number of patients who had early progression on first-line therapy, previous exposure to bevacizumab, tumors with RAS mutations, or liver and lung metastases. The study expanded into a 188 patient Part B randomized controlled trial. The primary objective of the study was progression-free survival PFS. Secondary objectives included objective response rate (ORR), duration of response, and overall survival (OS). A key pre-defined exploratory population was those patients who had high levels of circulating DKK1, as measured by a biomarker assay.

Key Part B DeFianCe Study Findings:

· Across the DKK1-high (upper median) patients (n=88):
o ORR was 38.0% in the Sirexatamab Arm compared to 23.7% ORR in the Control Arm.
o mPFS was 9.03 months in the Sirexatamab Arm compared to 7.06 months in the Control Arm, Hazard Ratio (HR) 0.61, p-value = 0.0255.
o mOS was not reached in the Sirexatamab Arm compared to 14.39 months in the Control Arm, HR 0.42, p-value = 0.0118.

· Across the DKK1-high (upper quartile) patients (n=44):
o ORR was 44.0% in the Sirexatamab Arm compared to 15.8% ORR in the Control Arm.
o mPFS was 9.36 months in the Sirexatamab Arm compared to 5.88 months in the Control Arm, HR 0.46, p-value = 0.0168.
o mOS was not reached in the Sirexatamab Arm compared to 9.66 months in the Control Arm, HR 0.17, p-value < 0.001.

· In the full intent-to-treat population (n=188):
o ORR was 35.1% in the Sirexatamab Arm compared to 26.6% ORR in the Control Arm.
o mPFS was 9.2 months in the Sirexatamab Arm compared to 8.3 months in the Control Arm, HR 0.84, p-value = 0.1712.
o Event-free rate favors Sirexatamab Arm beginning at month 9 (53 vs 47%) with further separation at month 12 (34 vs 23%).

· Sirexatamab, in combination with chemotherapy and bevacizumab, was safe and well tolerated
o Overall treatment-emergent adverse effects (TEAE) profile was similar between the Sirextamab and Control Arms, suggesting sirexatamab did not impact the safety profile when combined with the standard of care.

"The DeFianCe study results demonstrate the significant potential of sirexatamab in patients with advanced CRC. Patients with this aggressive cancer, particularly those with high DKK1 levels, have poor overall survival outcomes and few promising second-line or later options," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "Sirexatamab has repeatedly demonstrated its potential as a novel, first-in-class antibody targeting DKK1 that provides deep and durable benefit for patients in desperate need of new therapies. With support from a recently completed financing, Leap plans to engage with regulatory authorities over the registrational path for sirexatamab in CRC and to optimize the DKK1 biomarker diagnostic test that could be used to identify these CRC patients with poor prognosis."

(Press release, Leap Therapeutics, OCT 20, 2025, View Source [SID1234656817])