IMUNON to Present Phase 3 Ovarian Cancer Study of IMNN-001 at ESMO Congress

On October 14, 2025 IMUNON, Inc. (Nasdaq: IMNN), a clinical-stage company in Phase 3 development with its DNA-mediated immunotherapy, reported that a trials-in-progress abstract on the ongoing Phase 3 OVATION 3 clinical trial of IMNN-001, its investigational therapy for the treatment of women with newly diagnosed advanced ovarian cancer, was accepted for poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025, being held October 17-21, 2025 in Berlin, Germany.

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IMNN-001, based on IMUNON’s proprietary TheraPlas technology platform, is an interleukin-12 (IL-12) DNA plasmid vector incorporated in a nanoparticle delivery system, enabling cell transfection followed by persistent, local production and secretion of the IL-12 protein in the tumor microenvironment. IL-12 is a powerful pluripotent cytokine known for inducing strong anti-cancer immunity by promoting T-lymphocyte and natural killer cell proliferation while inhibiting tumor-mediated immune suppression. IMNN-001 is the first therapy to achieve a clinically effective response in advanced (stage IIIC/IV) ovarian cancer including benefits in both progression-free survival and overall survival in a first-line treatment setting when used with standard of care chemotherapy.

In July 2025, the Company announced treatment of the first patient in the pivotal Phase 3 OVATION 3 Study and is working with trial investigators to expand clinical sites and accelerate enrollment. Four sites have been activated to date and are open for patient enrollment, with up to 46 additional sites being considered for activation.

Details of the ESMO (Free ESMO Whitepaper) virtual poster presentation are as follows:

Abstract Title: OVATION-3: A randomized phase III trial evaluating the safety and efficacy of intraperitoneal IL-12 gene therapy administered in combination with standard neoadjuvant and adjuvant chemotherapy (N/ACT) in newly-diagnosed patients with advanced epithelial ovarian cancer (EOC)

Presenting Author: Premal H. Thaker, M.D., Chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, Study Chair of OVATION 2 and Phase 3 OVATION 3 trials

Poster Number: 1234eTiP

Following the conference, the poster presentation will be available on the "Scientific Presentations" page of the IMUNON website at View Source

About the OVATION 3 Study

OVATION 3 is IMUNON’s pivotal Phase 3 study of IMMN-001, an IL-12 gene-mediated immunotherapy, in women with advanced stage epithelial ovarian cancer. The study is supported with unprecedented overall survival (OS) data from a large, 112-patient, randomized Phase 2 OVATION 2 study showing the following:

Median 13-month increase in OS (HR 0.70) and median 3-month increase in PFS (HR 0.79) in IMNN-001 treatment arm compared to standard of care alone.
Better therapeutic effect observed with IMNN-001 treatment compared to the control arm (p=0.0375), as shown by mean 6.5-month extension of time free of progression or death (PFS + OS) captured in totality of treatment effect.
Use of poly ADP-ribose polymerase (PARP) inhibitors as part of maintenance therapy further enhanced outcomes, with median OS not yet reached in the IMNN-001 treatment arm as patients surpass 5 years since randomization in the trial compared to median OS of 37 months on standard of care (HR 0.42).

The results from the OVATION 2 Study have resulted in invitations to present data from the Phase 2 Study at both the ASCO (Free ASCO Whitepaper) and ESMO (Free ESMO Whitepaper) annual meetings and in the peer-reviewed journal Gynecologic Oncology.

The OVATION-3 trial is a robustly designed clinical study with at least 95% statistical power on the primary endpoint of overall survival. The trial design includes two planned interim analyses of the primary endpoint, designed to allow for an accelerated timeline for FDA submission of an IMNN-001 BLA if the primary endpoint reaches statistical significance. OVATION 3 is currently enrolling patients at four clinical sites with up to 46 additional sites being considered for activation.

About the Phase 2 OVATION 2 Study

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (N/ACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following N/ACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare N/ACT plus IMNN-001 versus standard-of-care N/ACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to N/ACT. As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response score.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel neoadjuvantly in patients with newly diagnosed ovarian cancer. IMUNON previously reported positive results from the recently completed Phase 2 OVATION 2 Study, which assessed IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (N/ACT) of paclitaxel and carboplatin compared to standard-of-care N/ACT alone in 112 patients with newly diagnosed advanced ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

(Press release, IMUNON, OCT 14, 2025, View Source [SID1234656641])

Mabwell’s CDH17-targeting ADC 7MW4911 Receives IND Clearance from NMPA

On October 14, 2025 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported that its self-developed CDH17-targeting ADC (R&D code: 7MW4911) received IND clearance from the National Medical Products Administration (NMPA) in China to initiate clinical study in patients with advanced solid tumors.

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7MW4911 is an investigational CDH17-targeting ADC developed using Mabwell’s proprietary IDDC platform. Its highly optimized structure integrates three key elements:

– Mab0727: A highly specific CDH17 monoclonal antibody with rapid internalization properties, cross-species (human/monkey) moderate affinity, and minimal off-target binding.

– Novel cleavable linker: Ensures precise payload release in tumor tissues.

– MF-6 payload: A proprietary DNA topoisomerase I inhibitor designed to overcome multidrug resistance (MDR), exhibiting superior plasma stability, controlled drug release, and potent bystander effects.

In July 2025, Mabwell published preclinical data in Cell Reports Medicine ("Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor"), demonstrating 7MW4911’s tumor-selective cytotoxicity via CDH17-mediated internalization. Key advantages include:

– Optimized molecular design: Homogeneous drug-to-antibody ratio (DAR=4, >95%) and stable linker confer exceptional plasma stability, while membrane-permeable MF-6 drives potent bystander killing.

– Broad Antitumor Efficacy: Demonstrates robust tumor regression in colorectal, gastric, and pancreatic cancer PDX/CDX models, including tumors with RAS/BRAF mutations and diverse Consensus Molecular Subtypes (CMS).

– MDR resistance: Outperforms MMAE/DXd-based ADCs in ABC transporter-mediated MDR models and reverses tumor progression post-ADC treatment.

– Target versatility: Active even in tumors with low-to-moderate CDH17 expression, expanding potential patient eligibility.

– Favorable safety profile: Limited tissue distribution in mice, controllable pharmacokinetics (moderate half-life, no accumulation), and a wide therapeutic window in cynomolgus monkeys, with no significant toxicity signals.

With this profile, 7MW4911 emerges as a promising therapeutic candidate for advanced gastrointestinal cancers. 7MW4911 has also received IND clearance from US FDA to initiate clinical study in patients with advanced colorectal cancer and other advanced gastrointestinal tumors.

About CDH17

CDH17 is a pan-cancer validated target with restricted expression in normal intestinal epithelium but marked overexpression in gastrointestinal cancers (e.g., colorectal, gastric, pancreatic). Its aberrant expression correlates with tumor metastasis and poor prognosis, positioning it as an ideal therapeutic target.

(Press release, Mabwell Biotech, OCT 14, 2025, View Source [SID1234656656])

Johnson & Johnson reports Q3 2025 results; raises 2025 sales outlook

On October 14, 2025 Johnson & Johnson (NYSE: JNJ) reported results for third-quarter 2025. "Johnson & Johnson delivered another strong performance in the third quarter fueled by the depth and strength of our portfolio and significant progress across our pipeline," said Joaquin Duato, Chairman and Chief Executive Officer, Johnson & Johnson. "With a sharpened focus on the six priority areas of Oncology, Immunology, Neuroscience, Cardiovascular, Surgery and Vision, Johnson & Johnson is in a new era of accelerated growth and innovation, with pioneering treatments that will continue to transform lives."

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Overall financial results
Q3
($ in Millions, except EPS)
2025
2024
% Change
Reported Sales

$23,993
$22,471
6.8%
Net Earnings
$5,152
$2,694
91.2%
EPS (diluted)
$2.12
$1.11
91.0%
Regional sales results
Q3

% Change

($ in Millions)
2025
2024
Reported
Operational1,2
Currency
Adjusted
Operational1,3
U.S.
$13,708
$12,909
6.2%
6.2

4.4
International
10,285
9,562
7.6
4.4
3.2
4.4
Worldwide
$23,993
$22,471
6.8%
5.4
1.4
4.4

1Non-GAAP financial measure; refer to reconciliations of non-GAAP financial measures included in accompanying schedules
2Excludes the impact of translational currency
3Excludes the net impact of acquisitions and divestitures and translational currency
Note: values may have been rounded

Segment sales results
Q3

% Change

($ in Millions)
2025
2024
Reported
Operational1,2
Currency
Adjusted
Operational1,3
Innovative Medicine
$15,563
$14,580
6.8%
5.3
1.5
3.7
MedTech
8,430
7,891
6.8
5.6
1.2
5.7
Worldwide
$23,993
$22,471
6.8%
5.4
1.4
4.4

1Non-GAAP financial measure; refer to reconciliations of non-GAAP financial measures included in accompanying schedules
2Excludes the impact of translational currency
3Excludes the net impact of acquisitions and divestitures and translational currency
Note: values may have been rounded

Third-Quarter 2025 segment commentary:
Operational sales* reflected below excludes the impact of translational currency.
Innovative Medicine
Innovative Medicine worldwide operational sales grew 5.3%*, with net acquisitions and divestitures positively impacting growth by 1.6% due to CAPLYTA. Growth was primarily driven by DARZALEX, CARVYKTI, ERLEADA and RYBREVANT/LAZCLUZE in Oncology, TREMFYA and SIMPONI/SIMPONI ARIA in Immunology, and SPRAVATO in Neuroscience. Growth was partially offset by an approximate (1,070) basis points impact from STELARA in Immunology, as well as IMBRUVICA in Oncology.
MedTech
MedTech worldwide operational sales grew 5.6%*, with net acquisitions and divestitures negatively impacting growth by 0.1%. Growth was primarily driven by electrophysiology products, Abiomed and Shockwave in Cardiovascular, wound closure products in General Surgery, as well as Surgical Vision.

Full-year 2025 guidance:
Johnson & Johnson does not provide GAAP financial measures on a forward-looking basis because the company is unable to predict with reasonable certainty the ultimate outcome of legal proceedings, unusual gains and losses, acquisition-related expenses, and purchase accounting fair value adjustments without unreasonable effort. These items are uncertain, depend on various factors, and could be material to Johnson & Johnson’s results computed in accordance with GAAP.
($ in Billions, except EPS)
October 2025
July 2025

Adjusted Operational Sales1,2,5
Change vs. Prior Year / Mid-point
3.5% – 4.0% / 3.8%
3.2% – 3.7% / 3.5%

Operational Sales2,5 / Mid-point
Change vs. Prior Year / Mid-point
$93.0B – $93.4B / $93.2B
4.8% – 5.3% / 5.1%
$92.7B – $93.1B / $92.9B
4.5% – 5.0% / 4.8%

Estimated Reported Sales3,5/ Mid-point
Change vs. Prior Year / Mid-point
$93.5B – $93.9B / $93.7B
5.4% – 5.9% / 5.7%
$93.2B – $93.6B / $93.4B
5.1% – 5.6% / 5.4%
Adjusted Operational EPS (Diluted)2,4 / Mid-point
Change vs. Prior Year / Mid-point
$10.63 – $10.73 / $10.68
6.5% – 7.5% / 7.0%
$10.63 – $10.73 / $10.68
6.5% – 7.5% / 7.0%

Adjusted EPS (Diluted)3,4 / Mid-point
Change vs. Prior Year / Mid-point
$10.80 – $10.90 / $10.85
8.2% – 9.2% / 8.7%
$10.80 – $10.90 / $10.85
8.2% – 9.2% / 8.7%

Other modeling considerations will be provided on the webcast
Notable announcements in the quarter:

Q3
Non-GAAP* ($ in Millions, except EPS)
2025
2024
% Change
Operational Sales1,2

5.4%
Adjusted Operational Sales1,3

4.4%
Adjusted Net Earnings1,4
$6,801
$5,876
15.7%
Adjusted EPS (diluted)1,4
$2.80
$2.42
15.7%
Free Cash Flow6,7
~$14,200
$14,471

Regulatory
U.S. FDA approves TREMFYA (guselkumab) for the treatment of pediatric plaque psoriasis and active psoriatic arthritis, marking a first and only approval for an IL-23 inhibitor1
Press Release
TREMFYA (guselkumab) achieves U.S. approval for subcutaneous induction in adults with ulcerative colitis, now the first and only IL-23 inhibitor with a fully subcutaneous regimen
Press Release
Johnson & Johnson receives positive CHMP opinion of nipocalimab to treat a broad population of antibody-positive patients living with generalised myasthenia gravis (gMG)
Press Release
Johnson & Johnson files with U.S. FDA to include new evidence in TREMFYA (guselkumab) label as the only IL-23 inhibitor to demonstrate significant inhibition of joint structural damage in active psoriatic arthritis
Press Release
European Commission approves DARZALEX (daratumumab) as the first licensed treatment for patients with high-risk smouldering multiple myeloma
Press Release

European Commission approves IMBRUVICA (ibrutinib) as the first targeted therapy for patients with previously untreated mantle cell lymphoma who would be eligible for autologous stem cell transplant
Press Release
Johnson & Johnson seeks first icotrokinra U.S. FDA approval aiming to revolutionize treatment paradigm for adults and adolescents with plaque psoriasis
Press Release
Data Releases
Johnson & Johnson to highlight breadth of its major depressive disorder portfolio at 2025 ECNP Congress1
Press Release
Icotrokinra data in ulcerative colitis show potential for a standout combination of therapeutic benefit and a favorable safety profile in once-daily pill1
Press Release
TREMFYA (guselkumab) is first and only IL-23 inhibitor to demonstrate sustained clinical and endoscopic outcomes with a fully subcutaneous regimen through 48 weeks in ulcerative colitis1
Press Release
Johnson & Johnson Unveils New Data Demonstrating Superior Clarity of Vision and Comfort of ACUVUE OASYS MAX 1-Day for ASTIGMATISM, and MULTIFOCAL for ASTIGMATISM Contact Lenses1
Press Release
Johnson & Johnson’s investigational seltorexant shows numerically higher response in patients with depression with insomnia symptoms, with fewer side effects compared to quetiapine XR
Press Release
TECVAYLI plus DARZALEX FASPRO treatment demonstrates 100 percent overall response rate in transplant-eligible patients newly diagnosed with multiple myeloma
Press Release
Icotrokinra shows superiority to deucravacitinib in first reported head-to-head trials reinforcing promise of novel targeted oral peptide for treatment of plaque psoriasis
Press Release
Johnson & Johnson to showcase industry-leading neuropsychiatry innovations at the 2025 Psych Congress Annual Meeting
Press Release
Data published in The New England Journal of Medicine demonstrate RYBREVANT (amivantamab-vmjw) plus LAZCLUZE (lazertinib) is re-setting survival expectations in first-line EGFR-mutated lung cancer
Press Release
RYBREVANT (amivantamab-vmjw) plus LAZCLUZE (lazertinib) prevents acquired resistance versus osimertinib in first-line EGFR-mutated non-small cell lung cancer
Press Release
New real-world data elevating patient perspectives highlight the need for scientific advancement in maternal fetal immunology at ISUOG 2025
Press Release
Johnson & Johnson Unveils Results from the VARIPURE Substudy of SECURE, a Real-World Study on VARIPULSE Platform, at 2025 European Society of Cardiology (ESC) Congress
Press Release
New Data from the DanGer Shock Randomized Control Trial, Published in The New England Journal of Medicine, Confirms the Long-Term Survival Benefit of the Impella CP Heart Pump
Press Release
Johnson & Johnson showcases latest advancements in Alzheimer’s research at AAIC 2025
Press Release

Product Launch
U.S. FDA approval of INLEXZO (gemcitabine intravesical system) set to transform how certain bladder cancers are treated
Press Release
Johnson & Johnson Launches VIRTUGUIDE AI-Powered Patient-Matched Lapidus System in U.S. to Reduce Complexity in Bunion Surgery for Millions
Press Release

Other
Johnson & Johnson Elects John Morikis, Retired Chairman, President and Chief Executive Officer of The Sherwin-Williams Company, to its Board of Directors

Webcast information:
Johnson & Johnson will conduct a conference call with investors to discuss this earnings release today at 8:30 a.m., Eastern Time. A simultaneous webcast of the call for investors and other interested parties may be accessed by visiting the Johnson & Johnson website. A replay and podcast will be available approximately two hours after the live webcast in the Investor Relations section of the company’s website at events-and-presentations.

(Press release, Johnson & Johnson, OCT 14, 2025, View Source [SID1234656642])

Great Novel Therapeutics Biotech & Medicals Corporation (GNTbm) Presented Preclinical Data on GNTbm-TKI, a Novel Multi-tyrosine Kinase Inhibitor with Potent Immune Activation, at the 2025 ESMO Annual Meeting

On October 14, 2025 GNTbm (stock code: 7427, Taiwan) reported the preclinical data on GNTbm-TKI, a novel multi-receptor tyrosine kinase inhibitor for cancer immunotherapy. GNTbm-TKI will be presented as posters at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting, which is held in Berlin, Germany, from Oct 17 to 21, 2025.

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Abstract: 2242
Title:Preclinical development of GNTbm-TKI, a novel multi-receptor tyrosine kinase inhibitor, while combined with GNTbm-38 showing potent induced tumor microenvironment remodeling activity in cancer immunotherapy
Session Date/Time: 10/19/2025, 12:00-12:45 CEST
Poster Board Number: 1577P

Currently, although there are many options for cancer immunotherapy, they still cannot meet the needs of clinical treatment, especially for advanced solid tumors defined as ‘cold tumors’. Genetic alterations of certain receptor tyrosine kinases (TKs), including TAM (TYRO3, AXL, and c-MER), are critical in creating environment conducive to tumor development in several cancers such as HNSCC, CRC, HCC, and RCC. GNTbm-TKI is a novel multi-targeted TKI, showing induction of immune activation in the tumor microenvironment (TME), that indicates the potential application in cancer immunotherapy for unmet medical needs.

The results of the study show that GNTbm-TKI strongly inhibited the activities of TYRO3, AXL, c-MER, BTK, ROS1, NTRK2, MET, and VEGFR2 at nanomolar level. GNTbm-TKI showed anti-proliferation activity in NCI-60 human cancer cell lines with low GI50 values. GNTbm-TKI showed a superior in vivo efficacy in WT mice compared to immune-deficient mice in CT-26 model, indicating anti-cancer immune activation induced by the treatment. Furthermore, treatment with GNTbm TKI + GNTbm-38 (an immune activator of class ⅠHDACi) combined with ICI significantly improved tumor response rate and boosted survival rate through synergistic effect by normalizing tumor vessels, increasing activated CD8+ T cell infiltration into tumors, inducing memory T cell persistence, and strongly inhibiting mobilization of immunosuppressive cells into tumors. On the other hand, GNTbm-TKI + GNTbm-38 combined with anti-PD-1/VEGF bispecific antibodies in a humanized B-PD-1/PD-L1/VEGFA mouse model also greatly improved anti-cancer with a strong synergistic effect.

GNTbm-TKI is a potent immune-activating multi-tyrosine kinase inhibitor, and it is surprisingly found capable of significantly reshaping the tumor microenvironment when combined with GNTbm-38. When further combined with ICI or anti-PD-1/VEGF bispecific antibodies, it can greatly enhance anti-cancer efficacy, providing a scientific basis for future clinical trials.

About GNTbm-TKI
GNTbm-TKI is a new chemical entity independently developed by GNTbm. It is a drug candidate selected by an immuno-competent tumor-bearing animal testing platform, and has undergone many preclinical research studies to be demonstrated that it has very outstanding anti-cancer activity in tumor microenvironment. GNTbm-TKI is an oral drug with dual effects of strong immune activation and multi-tyrosine kinase, which is unique when compared to the mechanism of other TKI drugs. GNTbm-TKI can remodel the tumor microenvironment (TME) through a unique multiple regulatory mechanism based on its kinase targets which it selectively inhibits. GNTbm-TKI strongly inhibits tumor growth and development, suppresses tumor invasion and metastasis, inhibits tumor angiogenesis, and most importantly, possesses potent tumor immune regulatory activity. When GNTbm-TKI is combined with GNTbm-38, based on their respective unique mechanisms, they have a complementary and powerful tumor microenvironment remodeling function, capable of converting ‘cold tumors’ into ‘hot tumors.’ When further combined with ICI or anti-PD-1/VEGF bispecific antibodies, they exhibit exceptionally superior anti-tumor immuno-oncology activity, which can attract CTL to infiltrate into the TME, and activate CTLs and reduce CTL exhaustion. At the same time, it can also reduce the attraction of immunosuppressive cells (such as: TAM, Treg, and MDSCs) into the TME, so as to achieve the remodeling of the TME, which is more conducive to obtaining the therapeutic benefits of cancer immunotherapy. GNTbm-TKI monotherapy can be used in the treatment of advanced neuroendocrine tumor, and GNTbm-TKI can also be combined with GNTbm-38 or/and ICI/anti-PD-1/VEGF bispecific antibodies for treatment of a variety of solid tumors, mainly through a unique anti-cancer immune-regulating and multiple-tyrosine kinase inhibition mechanism to achieve anti-cancer treatment goals.

(Press release, GNT Biotech & Medicals, OCT 14, 2025, View Source;medicals-corporation-gntbm-presented-preclinical-data-on-gntbm-tki-a-novel-multi-tyrosine-kinase-inhibitor-with-potent-immune-activation-at-the-2025-esmo-annual-meeting-302583015.html [SID1234656657])

NuCana Announces Encouraging Data for NUC-3373 in Combination with Anti-PD-1 Therapy

On October 14, 2025 NuCana plc (NASDAQ: NCNA) ("NuCana" or the "Company") reported the publication of new data on NUC-3373. The update includes results from the NuTide:303 clinical study, published on medRxiv, the preprint server for health sciences, together with complementary preclinical findings published in the peer-reviewed journal Public Library of Science ONE (PLOS ONE).

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NUC-3373, a potent thymidylate synthase inhibitor that induces DNA damage in cancer cells, has previously shown encouraging activity in combination with the PD-1 inhibitor pembrolizumab in the Phase 1/2b modular study, NuTide:303. In Module 1 of this study, 12 patients with advanced solid tumors who had exhausted all standard treatment options and had previously received PD-1 inhibitors were treated with NUC-3373 plus pembrolizumab.

Encouraging signals of durable activity were observed, including:

A 100% reduction in tumor lesion size (classified as a partial response due to the presence of non-target lesions) in a patient with urothelial carcinoma of the bladder who remained on treatment for over 15 months; and

An 81% reduction in target lesions in a patient with metastatic melanoma resistant to prior pembrolizumab therapy, who continues to remain progression-free at 23 months.

These promising clinical findings are further supported by preclinical data. The published results demonstrate that NUC-3373 in a model in vitro system:

Promotes the release of immunogenic damage-associated molecular patterns (DAMPs);

Enhances activation of first-line defense immune cells, including natural killer (NK) cells; and

In combination with a PD-1 inhibitor, enhances tumor cell death by activating lymphocytes, regardless of the tumor’s genomic stability status.

"It is becoming increasingly clear that the majority of future standards of care for advanced cancers will rely on combination regimens incorporating novel immuno-oncology backbones," said Professor David Harrison, Head of Translational Medicine at NuCana. "The combination of NUC-3373 with pembrolizumab has demonstrated both a favorable safety profile and evidence of efficacy and durable disease control in this patient cohort."

Andrew Kay, NuCana’s Executive Chairman, added: "The complementary mechanisms of action of NUC-3373 and PD-1 inhibition provide a strong rationale for synergy. We are currently evaluating optimal combinations and indications for further clinical studies of NUC-3373, while continuing to maintain our anticipated cash runway into 2029. We are committed to advancing these assets and working toward our vision of delivering significantly improved treatment outcomes for patients with cancer."

(Press release, Nucana, OCT 14, 2025, View Source [SID1234656643])