Rina-S (rinatabart sesutecan) / Genmab - LARVOL DELTA

Rinatabart sesutecan (Rina-S) for patients with advanced endometrial cancer: First disclosure from dose expansion cohort B2 of the GTC1184-01 study. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05579366 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • Endometrial Cancer • Oncology • Solid Tumor

A phase 3, open-label, randomized study of rinatabart sesutecan (Rina-S) vs investigator's choice (IC) of chemotherapy in patients with platinum-resistant ovarian cancer (PROC). (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT06619236 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P3 data • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor

ENCORE: Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001) (clinicaltrials.gov) - P1/2 | N=529 | Recruiting | Sponsor: Genmab | N=404 ➔ 529 | Trial completion date: Oct 2026 ➔ Sep 2027 | Trial primary completion date: Apr 2026 ➔ Jun 2027

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Endometrial Cancer • Epithelial Ovarian Cancer • Fallopian Tube Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • Uterine Cancer • FOLR1 • HER-2

Rinatabart sesutecan (PRO1184) in combination with standard-of-care therapy exerted potentiated antitumor activity in preclinical cancer models (AACR 2025) - P1/2 | "Xenograft mouse models inoculated with OC (OVCAR-8 cells) or EC (HEC-1-A cells) received either phosphate-buffered saline (PBS) alone or Rina-S alone, with or without carboplatin (OC), bevacizumab (OC), or olaparib (EC). Syngeneic mouse models of lung cancer or colorectal cancer received either PBS alone or Rina-S alone, with or without an anti-PD1 agent nofazinilmab (CS1003)... These preclinical studies provide evidence for combination therapy with Rina-S and various SOC therapies and suggest that Rina-S may be investigated in different treatment settings in the clinic. A phase 1/2 study (NCT05579366) is currently ongoing to study the efficacy and safety of Rina-S in combination with carboplatin, bevacizumab, or pembrolizumab for the treatment of platinum-sensitive OC, PROC, and EC, respectively."

Combination therapy • IO biomarker • Preclinical • Colorectal Cancer • Endometrial Cancer • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • CALR • FOLR1 • HMGB1

Genmab to Vigorously Defend Alleged Claims of Trade Secret Misappropriation by AbbVie Inc. (GlobeNewswire) - "Genmab A/S...announced today that AbbVie Inc...has filed a complaint in the U.S. District Court for the Western District of Washington (Seattle) naming Genmab A/S; ProfoundBio US Co.; ProfoundBio (Suzhou) Co., Ltd.; and former AbbVie employees as defendants. AbbVie alleges that the defendants have misappropriated AbbVie’s alleged trade secrets relating to the use of disaccharides to improve the hydrophilicity of drug-linkers in antibody-drug conjugates (ADCs) in connection with rinatabart sesutecan (Rina-S™) and other ADC pipeline products of ProfoundBio. Genmab acquired ProfoundBio in May 2024."

Corporate lawsuit • Oncology

Investigational Rinatabart Sesutecan (Rina-S) Continues to Show Encouraging Antitumor Activity in Patients with Advanced Ovarian Cancer (GlobeNewswire) - P1/2 | N=404 | RAINFOL-01 (NCT05579366) | Sponsor: Genmab | "Genmab A/S...announced today updated data from cohort B1 of the Phase 1/2 RAINFOL-01 study of rinatabart sesutecan (Rina-S)...that showed Rina-S 120 mg/m2 every 3 weeks (Q3W) resulted in a confirmed objective response rate (ORR) of 55.6% (95% CI: 30.8-78.5) in heavily pre-treated ovarian cancer (OC) patients regardless of FRα expression levels. With a median on-study follow-up of 48 weeks, 1 out of 10 patients experienced disease progression and the median duration of response (mDOR) was not reached (95% CI: 40.14-NR). The data are from the dose expansion cohort of the multi-part study evaluating the safety and efficacy of Rina-S as a single agent in solid tumors that are known to express FRα and were presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO) in Seattle, Washington."

P2 data • Ovarian Cancer

(ENCORE) Rinatabart Sesutecan (Rina-S) for Patients With Advanced Ovarian Cancer: Results From Dose Expansion Cohort B1 of a Phase 1/2 Study (SGO 2025) - No abstract available

Clinical • Metastases • P1/2 data • Oncology • Ovarian Cancer • Solid Tumor

A Phase 3, Open-Label, Randomized Study of Rinatabart Sesutecan (Rina-S) Versus Investigator’s Choice of Chemotherapy in Patients With Platinum-Resistant Ovarian Cancer (PROC) (SGO 2025) - No abstract available

Clinical • P3 data • Oncology • Ovarian Cancer • Solid Tumor

Part C of a Phase 1/2 Study Evaluating Single-Agent Rinatabart Sesutecan (Rina-S) in Patients With Advanced and/or Metastatic Platinum-Resistant Ovarian Cancer (PROC) (SGO 2025) - No abstract available

Clinical • Metastases • P1/2 data • Oncology • Ovarian Cancer • Solid Tumor

Rinatabart Sesutecan For Patients With Heavily Pretreated Ovarian Or Endometrial Cancer: Results From The Dose Escalation Cohort Of A Phase 1/2 Study (ESGO 2025) - P1/2, P3 | "Median DOR was 35.3 weeks (95% CI 20.14, not evaluable), with ongoing responses in 2 patients receiving 120mg/m2 and 1 patient receiving 100mg/m2.Conclusion Single-agent Rina-S was well tolerated and showed encouraging antitumour activity in patients with heavily pretreated OC/EC. Further investigation of Rina-S is ongoing for platinum-resistant OC in a monotherapy cohort (part C) of this trial and a phase 3 study (NCT06619236), and for EC in the dose expansion cohort of this trial (cohort B2)."

Clinical • P1/2 data • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=530 | Recruiting | Sponsor: Genmab | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Ovarian Cancer • Solid Tumor

Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=530 | Not yet recruiting | Sponsor: Genmab | Trial completion date: Nov 2029 ➔ Apr 2028 | Trial primary completion date: Feb 2027 ➔ May 2027

Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

Rinatabart Sesutecan (Rina-S) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001) (clinicaltrials.gov) - P1/2 | N=404 | Recruiting | Sponsor: Genmab | Trial completion date: Apr 2026 ➔ Oct 2026 | Trial primary completion date: Oct 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Breast Cancer • Endometrial Cancer • Epithelial Ovarian Cancer • Fallopian Tube Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1 • HER-2

Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P3 | N=530 | Not yet recruiting | Sponsor: Genmab

New P3 trial • Oncology • Ovarian Cancer • Solid Tumor

A phase I/II study of rinatabart sesutecan (Rina-S) in patients with advanced ovarian or endometrial cancer (ESMO 2024) - P1/2 | "FRα expression is retrospectively tested. As of 02 April 2024, 53 pts were treated in Part A. Of 32 pts with OC, median number of prior therapies was 5 (1–14); 75% had received bevacizumab; 91% were platinum resistant. Rina-S was well tolerated at 100 and 120 mg/m2, with manageable TRAEs. Promising antitumor activity was observed across a wide range of FRα expression levels. Enrollment for Part B OC pts is complete; dose optimization analysis will be presented."

Clinical • IO biomarker • Metastases • P1/2 data • Endometrial Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Investigational Rinatabart Sesutecan (Rina-S) Shows Promising Anti-Tumor Activity as Single Agent in Heavily Pretreated Patients with Ovarian and Endometrial Cancers in Phase 1/2 Clinical Trial (GlobeNewswire) - P1/2 | N=354 | NCT05579366 | Sponsor: Genmab | "Genmab...announced today new data from the Phase 1/2 study of rinatabart sesutecan...demonstrated a confirmed objective response rate (ORR) of 50.0% (95% CI) in ovarian cancer patients treated with Rina-S 120 mg/m² once every 3 weeks (Q3W), regardless of FRα expression levels...These results, and additional findings from the study, were presented at the European Society of Medical Oncology Congress 2024...Results for 100 mg/m² and 120 mg/m² respectively also included: complete response: 0 (0%) and 1 (5.6%); partial response in 4 (18.2%) and 8 patients (44.4%); stable disease in 15 (68.2%) and 7 patients (38.9%)....Based on these results, Rina-S 120 mg/m² has been selected for further evaluation in a Phase 3 trial for patients with advanced ovarian cancer, which is expected to start in 2024."

New P3 trial • P1/2 data • Endometrial Cancer • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Genmab Completes Acquisition of ProfoundBio (Businesswire) - "Genmab A/S...announced today that it has completed its acquisition of ProfoundBio, Inc., a clinical-stage biotechnology company developing next-generation antibody-drug conjugates (ADC)s and ADC technologies for the treatment of cancers in an all-cash transaction of USD 1.8 billion (subject to adjustment for ProfoundBio’s closing net debt and transaction expenses)....The acquisition gives Genmab worldwide rights to ProfoundBio’s portfolio of next-generation ADCs, further broadening and strengthening its clinical pipeline. These programs include Rina-S, a potential best-in-class, clinical-stage, FRα-targeted, Topo1 ADC, currently in part 2 of a Phase 1/2 clinical trial, for the treatment of ovarian cancer and other FRα-expressing solid tumors."

M&A • Ovarian Cancer

PRO1184-001: PRO1184 for Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=374 | Recruiting | Sponsor: ProfoundBio US Co. | N=134 ➔ 374 | Trial completion date: Sep 2025 ➔ Apr 2026 | Trial primary completion date: Jan 2025 ➔ Oct 2025

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1 • HER-2

Preclinical characterization of PRO1106, a novel and promising SLITRK6-directed sesutecan ADC (AACR 2024) - "Sesutecan previously demonstrated promising characteristics in preclinical studies with multiple targets and conferred an encouraging benefit:risk profile in the clinic with a FRα-directed ADC (rinatabart sesutecan)...Target-binding was superior to sirtratumab (the parent antibody in AGS15E) and the binding epitope appeared to be distinct from that of sirtratumab in cross-block studies...In summary, PRO1106 is an ADC built on a clinically validated linker-drug directed at a clinically validated target, with promising data in preclinical pharmacology studies. As SLITRK6 expression in skin is negligible, PRO1106 may offer an exciting new option for patients with bladder cancer where the current standard-of-care ADC therapy (enfortumab vedotin) confers significant skin-related toxicity burden as well as for patients with additional cancer types."

Preclinical • Bladder Cancer • Brain Cancer • Breast Cancer • CNS Tumor • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Genito-urinary Cancer • Glioblastoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • FOLR1 • SLITRK6

A Novel EGFR x cMET bispecific ADC PRO1286 demonstrated broad antitumor activity and promising tolerability in preclinical models (AACR 2024) - "Small molecule TKIs and amivantamab have been approved for non-small cell lung cancer with relevant actionable genomic alterations (AGA), and monoclonal antibodies offer treatment options for EGFR-expressing head and neck and colorectal cancers without AGA...Sesutecan previously demonstrated promising characteristics in preclinical studies with multiple targets and conferred an encouraging benefit:risk profile in the clinic with a FRα-directed ADC (rinatabart sesutecan)...It may also differentiate from existing EGFR- and/or cMET-targeting agents on broad coverage of EGFR and cMET-expressing tumors with or without the respective AGAs. Effort is under way to advance a DAR optimized molecule to the clinic for the treatment of many EGFR- or cMET-expressing solid tumors."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FOLR1

A tumor microenvironment-targeting CD98-directed ADC confers robust anti-tumor activity in multiple cancers with favorable pharmacokinetics and safety profiles in preclinical models (AACR 2024) - "Sesutecan previously demonstrated promising characteristics in preclinical studies with multiple targets and conferred an encouraging benefit:risk profile in the clinic with a FRα-directed ADC (rinatabart sesutecan). In summary, our studies demonstrate that the pH-dependent CD98-directed HH018- sesutecan exerts wide-ranging and potent anti-tumor efficacy, as well as favorable PK and safety profiles in preclinical models. HH018-sesutecan is a promising agent for further development in a broad range of CD98-expressing tumors."

Late-breaking abstract • PK/PD data • Preclinical • Tumor microenvironment • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Malignancies • Hypopharyngeal Cancer • Lymphoma • Oncology • Oral Cancer • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • FOLR1 • SLC3A2 • SLC7A5

Genmab to Broaden and Strengthen Oncology Portfolio with Acquisition of ProfoundBio (GlobeNewswire) - "Genmab A/S...and ProfoundBio, Inc. announced today that the companies have entered into a definitive agreement for Genmab to acquire ProfoundBio in an all-cash transaction....Genmab will acquire ProfoundBio for USD 1.8 billion in cash, payable at closing....Acquisition will give Genmab worldwide rights to three candidates in clinical development, including rinatabart sesutecan (Rina-S), plus ProfoundBio’s novel antibody-drug conjugate (ADC) technology platforms. Rina-S is a novel, next-generation, potential best-in-class Topo1 ADC targeting folate receptor alpha (FRα) in development for the treatment of ovarian cancer and other solid tumors."

M&A • Ovarian Cancer

ProfoundBio Raises $112 Million in Oversubscribed Series B Equity Financing to Advance its Clinical-Stage Antibody-Drug Conjugate (ADC) Pipeline (PRNewswire) - "ProfoundBio...announced an oversubscribed $112 million Series B financing supported by a syndicate of top healthcare dedicated and mutual fund institutional investors....The capital raised will support ProfoundBio's diverse array of clinical and preclinical ADC programs, primarily targeting solid tumor cancers. Key programs include: Rina-S, a folate receptor-alpha (FRα) targeted ADC, in Phase 2 trials for ovarian and endometrial cancers, with pivotal studies in ovarian cancer planned for later this year. PRO1160, a CD70 targeted ADC, in Phase 1 trials with initial results expected in 2024. PRO1107, a protein tyrosine kinase 7 (PTK7) targeted ADC, in Phase 1 trials with initial results anticipated in 2025. PRO1286, a bi-specific ADC, anticipated to enter the clinic in 2024."

Financing • New trial • P1 data • P2 data • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hematological Malignancies • Kidney Cancer • Lung Cancer • Lymphoma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

ProfoundBio Announces Rinatabart Sesutecan FDA Fast Track Designation for Patients with Advanced Ovarian Cancer (PRNewswire) - "ProfoundBio...today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for rinatabart sesutecan (Rina-S; PRO1184), a folate receptor alpha (FRα) targeted ADC, for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer."

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

A phase 1/2 study of rinatabart sesutecan (PRO1184), a novel folate receptor alpha-directed antibody-drug conjugate, in patients with locally advanced and/or metastatic solid tumors (SITC 2023) - P1/2 | "Antitumor activity has been observed at well tolerated dose levels. Dose escalation continues."

Clinical • Metastases • P1/2 data • Breast Cancer • Endometrial Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1