TUB-040 / Tubulis - LARVOL DELTA

NAPISTAR 1-01: A phase I dose escalation study of TUB-040, a novel NaPi2b-targeting exatecan antibody-drug conjugate (ADC) in patients with platinum-resistant ovarian (PROC) high grade serous carcinoma (HGSC) (ESMO 2025) - P1/2 | "Pts had a median age of 62 y (range 34-81), ECOG PS 0 or 1, a median of 4 prior lines of therapy (range 1-7); prior treatment included bevacizumab (84%), PARP inhibitors (76%) and mirvetuximab soravtansine (13%). 1 Values reported with 95% CI. Conclusions TUB-040 was well tolerated with robust clinical activity even at low doses, offering a differentiated potential new option for treatment with a highly favorable benefit–risk profile."

Clinical • Late-breaking abstract • P1 data • Platinum resistant • Lung Cancer • Non Small Cell Lung Cancer • Oncology • MUC16 • SLC34A2

NAPISTAR 1-02: A Study Testing a New Targeted Drug (TUB-040) in combination with Standard Chemotherapy for Women with Ovarian Cancer (clinicaltrialsregister.eu) - P1/2 | N=42 | Recruiting | Sponsor: Tubulis GmbH | Not yet recruiting ➔ Recruiting

Enrollment open • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD • SLC34A2

NAPISTAR 1-01: A Phase 1 dose escalation study of TUB-040, a novel NaPi2b-targeting exatecan antibody-drug conjugate in patients with platinum-resistant high grade serous ovarian carcinoma. (ESGO 2026) - "Median age 62 years (34-81), median 4 prior lines (1-7), prior treatment included bevacizumab (84%), PARPi (76%), mirvetuximab soravtansine (13%). The cDCR was 96% [95% CI, 85-99]. Among CA-125 evaluable patients, GCIG CA-125 response occurred in 81% (34/42) and 96% (24/25) of RECIST responders achieved a CA-125 response.Conclusion TUB-040 was well tolerated with very promising clinical activity at low doses, offering a potential new option for treatment with a differentiated, highly favourable benefit–risk profile."

Clinical • P1 data • Platinum resistant • High Grade Serous Ovarian Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • MUC16 • SLC34A2

NAPISTAR1-01: FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: Tubulis GmbH | Trial completion date: Jan 2027 ➔ Dec 2027 | Trial primary completion date: Jan 2027 ➔ Dec 2027

First-in-human • Platinum resistant • Trial completion date • Trial primary completion date • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

NAPISTAR 1-02: A Study Testing a New Targeted Drug (TUB-040) in combination with Standard Chemotherapy for Women with Ovarian Cancer (clinicaltrialsregister.eu) - P1/2 | N=42 | Not yet recruiting | Sponsor: Tubulis GmbH

New P1/2 trial • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD • SLC34A2

NAPISTAR 1-01: A Phase 1 dose escalation study of TUB-040, a novel NaPi2b-targeting exatecan antibody-drug conjugate in patients with platinum-resistant high grade serous ovarian carcinoma. (ESGO 2026) - "Median age 62 years (34-81), median 4 prior lines (1-7), prior treatment included bevacizumab (84%), PARPi (76%), mirvetuximab soravtansine (13%). The cDCR was 96% [95% CI, 85-99]. Among CA-125 evaluable patients, GCIG CA-125 response occurred in 81% (34/42) and 96% (24/25) of RECIST responders achieved a CA-125 response.Conclusion TUB-040 was well tolerated with very promising clinical activity at low doses, offering a potential new option for treatment with a differentiated, highly favourable benefit–risk profile."

Clinical • P1 data • Platinum resistant • High Grade Serous Ovarian Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • MUC16 • SLC34A2

NAPISTAR1-01: FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Tubulis GmbH | N=100 ➔ 200

Enrollment change • First-in-human • Platinum resistant • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Tubulis Raises €308 Million Series C to Accelerate Clinical Development of Lead ADC Candidate TUB-040 and Expand Pipeline (Yahoo Finance) - "The proceeds from the Series C financing will be used to expand the clinical development of TUB-040, Tubulis’ lead antibody-drug conjugate (ADC) candidate, into earlier lines of therapy and additional tumor indications....The capital will also advance Tubulis’ pipeline, including the clinical-stage ADC candidate TUB-030, several preclinical programs, and expand its proprietary ADC platform technologies to bring ADCs into novel applications."

Financing • Platinum resistant • Non Small Cell Lung Cancer • Ovarian Cancer

Tubulis Presents First Clinical Data from Phase I/IIa Trial for TUB-040 in Platinum-Resistant Ovarian Cancer (PROC) at ESMO 2025 (Businesswire) - "Within the 1.67-3.3 mg/kg dose cohorts, an ORR of 59% (range of 50-67%), was achieved with a confirmed ORR of 50%; one complete response (CR) was observed at 2.5 mg/kg. Treatment is ongoing in 80% of patients within the 1.67 – 3.3 mg/kg cohorts and in 93% of all responding patients from this focus group; The confirmed disease control rate (DCR) at 1.67 – 3.3 mg/kg was 96% and a confirmed DCR of 91% was reached across all cohorts at the data-cut-off with efficacy data in the 3.3 mg/kg group still continuing to mature."

Late-breaking abstract • P1/2 data • Platinum resistant • Ovarian Cancer

NAPISTAR 1-01: An International Phase I/II Trial of the Novel ADC TUB-040 in Advanced/Metastatic NSCLC Adenocarcinoma (IASLC-WCLC 2025) - P1/2 | "The dose-escalation framework includes initial double-dosing steps with a 100% increment over the standard dose, transitioning to modified Fibonacci increments (67%, 50%, and 33% dose increments) with intra-patient escalation permissible at low exposure levels. Phase IIa involves the randomization of patients for dose optimization at two or more doses to further characterize the safety profile and identify the optimal therapeutic dose."

Metastases • P1/2 data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

Tubulis to Present First Phase I/IIa Trial Data for ADC Candidate TUB-040 in Platinum-Resistant Ovarian Cancer in Late-Breaking Oral Presentation at ESMO 2025 (Businesswire) - "The presentation by the principal investigator of the study, Dr. Antonio Gonzalez-Martin, will provide interim data from the dose escalation part of the ovarian cancer cohort in the first-in-human study with TUB-040."

Late-breaking abstract • P1/2 data • Platinum resistant • Ovarian Cancer

TUB-040, a homogenous and hydrophilic NaPi2b-targeting ADC with stably linked exatecan, exhibits long-lasting anti-tumor activity and a well-tolerated safety profile. (PubMed, Mol Cancer Ther) - "Repeated-dose toxicological assessment in rats indicates that TUB-040 is well-tolerated, with no evidence of lung toxicity or thrombocytopenia. Taken together, TUB-040 is designed to enable long-lasting, durable tumor responses and to optimize both efficacy and tolerability, supporting the advancement of TUB-040 into clinical trials."

Journal • Hematological Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • SLC34A2 • TOP1

NAPISTAR 1-01: An international phase I/II trial of the novel ADC TUB-040 in platinum-resistant ovarian cancer (PROC) and relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC). (ASCO 2025) - P1/2 | "Phase IIa involves randomized dose optimization at multiple dosing levels to identify the optimal therapeutic window. Enrollment of approximately 100 patients across the US, EU and UK is planned, with dose escalation currently underway."

P1/2 data • Platinum resistant • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

NAPISTAR 1-01 - An International Phase I/II Trial Of The Novel NaPi2b Targeting ADC TUB-040 In Platinum-Resistant Ovarian Cancer (PROC) And Relapsed/Refractory Non Small Cell Lung Cancer (NSCLC) (ESGO 2025) - P1/2 | "Safety monitoring is conducted by an independent Dose Escalation Board, which oversees recommendations based on Dose Limiting Toxicities and overall safety data. Results A randomized dose optimization phase IIa with at least two dose levels will follow.Conclusion The NAPISTAR 1-01 Phase I/IIa trial will establish the optimal dosing regimen for TUB-040, thus potentially offering a new therapeutic option for patients with PROC and advanced NSCLC who have exhausted available treatments."

P1/2 data • Epithelial Ovarian Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

Tubulis Receives FDA Fast Track Designation for Antibody-Drug Conjugate Candidate TUB-040 in Platinum-resistant Ovarian Cancer (Businesswire) - "Tubulis announced today that the U.S. Food and Drug Administration ('FDA') has granted Fast Track designation to its lead antibody-drug conjugate (ADC) TUB-040 for the treatment of patients with platinum-resistant ovarian cancer....The candidate is currently being evaluated in a multicenter Phase I/IIa study....in patients with platinum-resistant high-grade ovarian cancer (PROC) or relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC), who have exhausted other available treatment options."

Fast track • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Tubulis Doses First Patient in Phase I/IIa Trial Investigating ADC Candidate TUB-040 in Ovarian Cancer and Lung Adenocarcinoma (Businesswire) - "Tubulis announced today that the first patient has been treated in its first Phase I/IIa trial (NAPISTAR 1-01, NCT06303505). The study is evaluating Tubulis’ next-generation antibody-drug conjugate (ADC) TUB-040 in patients with platinum-resistant high-grade ovarian cancer (PROC) or relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC), who have exhausted other available treatment options....The multicenter, first-in-human, dose escalation and optimization Phase I/IIa study aims to investigate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy. The trial will be conducted in the US as well as the UK, Spain, Belgium, and Germany."

Trial status • Lung Adenocarcinoma • Non Small Cell Lung Cancer • Ovarian Cancer

NAPISTAR1-01: FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Tubulis GmbH | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

TUB-040, a novel Napi2b-targeting ADC built with ethynylphosphonamidate conjugation chemistry, demonstrates high and long-lasting anti-tumor efficacy via Topoisomerase-I inhibition and excellent tolerability predictive of a wide therapeutic window in humans (AACR 2024) - "Allometric scaling and PK/PD modelling predicts a human serum half-life greater 10 days and a therapeutic index in humans up to 55. Based on these results, TUB-040, designed with differentiating technology for optimal efficacy and tolerability, is ready for testing in clinical trials."

Clinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2 • TOP1

Tubulis Presents Preclinical Data for Solid Tumor Targeting ADC Candidates TUB-030 and TUB-040 Demonstrating Superior Efficacy Profile and a Wide Therapeutic Window at the AACR Annual Meeting 2024 (Businesswire) - "Tubulis today presented comprehensive preclinical data on its two lead antibody-drug conjugate (ADC) candidates TUB-030 and TUB-040 at this year’s Annual Meeting of the American Association for Cancer Research....TUB-040:...The ADC candidate is highly stable and highly inert in circulation, enabling powerful and continued on-tumor delivery of the payload, leading to complete eradication of tumors with a low dose single treatment in multiple ovarian cancer mouse models....In ovarian cancer and non-small-cell lung cancer (NSCLC) patient derived xenograft mouse models, treatment with TUB-040 led to robust long-lasting tumor regressions. Repeat-dose toxicology studies of TUB-040 in non-human primates demonstrated that TUB-040 was well tolerated with minor and reversible adverse effects."

Preclinical • Non Small Cell Lung Cancer • Ovarian Cancer

Tubulis Closes Upsized €128 Million Series B2 to Accelerate Clinical Development of Solid Tumor-Focused ADC Pipeline (Businesswire) - "The proceeds of the Series B2 will primarily support progress in Tubulis’ pipeline of next-generation ADCs toward clinical evaluation and help achieve clinical proof-of-concept for lead candidates, TUB-040 and TUB-030...The company expects to start its first Phase 1/2a clinical trial, including dose escalation and dose optimization cohorts in 2024."

Financing • New P1/2 trial • Lung Cancer • Ovarian Cancer

Tubulis to Present Preclinical Proof-of-Concept Data for Two Lead ADC Candidates Targeting Solid Tumors at the AACR Annual Meeting 2024 (Businesswire) - "The poster will provide a detailed overview of the preclinical proof-of-concept for TUB-040....TUB-040 induces DNA damage and cell death, without causing unspecific uptake and cytotoxicity in healthy, target-negative cells. Moreover, Pharmacokinetic analysis showed that TUB-040 is highly stable, thus efficiently delivering its payload to the tumor while reducing offsite toxicities."

Preclinical • Solid Tumor

NAPISTAR1-01: FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC (clinicaltrials.gov) - P1/2 | N=100 | Not yet recruiting | Sponsor: Tubulis GmbH

New P1/2 trial • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor