ixotatug vedotin (TORL-1-23) / TORL Biotherap - LARVOL DELTA

Claudin- 6 (CLDN6) is a therapeutic target in ovarian cancer (OC): Emerging results from the CATALINA 1 (CAT1) study (ESMO 2025) - P1 | "For all OC: median prior lines 3 (1-9); 73% received prior bevacizumab, 67% prior PARP inhibitors, and 11% prior mirvetuximab. OC pts received doses 3.0 mg/kg (11) with doses ≥3.0 mg/kg given with prophylactic pegfilgrastim (peg)...TORL-1-23 was generally well tolerated with an acceptable safety profile. These proof-of-concept data support further evaluation of TORL-1-23 in larger, registration studies that are now ongoing."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • CLDN6

CATALINA-2/ENGOT-ov83: A phase II study of TORL-1-23 monotherapy in advanced platinum-resistant epithelial ovarian cancer expressing Claudin 6 (ESMO 2025) - P1, P2 | "Stage 1, the dose-optimization stage, will randomize patients to TORL-1-23 at either 2.4, 3.0, or 3.4 mg/kg by IV every 3 Weeks in combination with prophylactic pegfilgrastim. Secondary endpoints include duration of response, progression free survival, and CA-125 response. The study is currently open with patients enrolling in stage 1."

Metastases • Monotherapy • P2 data • Platinum resistant • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer • CLDN6 • MUC16

A CATALINA-2 Trial-in-Progress poster will be presented at ESMO 2025 (#1225TiP). (PRNewswire)

Platinum resistant • Trial status • Endometrial Cancer • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Peritoneal Cancer

TORL BioTherapeutics…Presents Updated Phase 1 Results of Novel Claudin 6 Targeted Antibody-Drug Conjugate TORL-1-23 at the 2025 European Society of Medical Oncology Congress (PRNewswire)

P1 data • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Testicular Cancer

TORL BioTherapeutics LLC…announced closing of a $96 million Series C financing. (PRNewswire) - "Proceeds from this financing will advance CATALINA-2, the ongoing pivotal Phase 2 study of TORL-1-23 for CLDN6+ patients with platinum-resistant ovarian cancer (PROC) to pivotal data readout in 2027, and CATALINA-3, the confirmatory Phase 3 study of TORL-1-23 in CLDN6+ PROC initiating in 2026. In addition, funds will support registration-enabling Phase 2 and Phase 3 studies, as well as ongoing Phase 1 studies and IND-enabling work across TORL's pipeline of novel high-value targets in solid tumors and hematologic malignancies."

Financing • New P3 trial • P2 data • Platinum resistant • Endometrial Cancer • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Hematological Malignancies • Non Small Cell Lung Cancer • Peritoneal Cancer

Corneal pseudomicrocysts following claudin-6 antibody-drug conjugate infusion. (PubMed, Am J Ophthalmol Case Rep) - "Collagen and silicone punctal plugs were placed and the patient was started on preservative free artificial tears, topical loteprednol 0.5 %, later replaced with topical prednisolone acetate 1 % drops, and brimonidine 0.2 % in both eyes. Ocular symptoms and exam findings waxed and waned with continued infusions of the ADC. This case reports an incidence of corneal pseudomicrocysts associated with TORL-1-23 treatment, which should be recognized as a potential adverse effect of this novel therapy."

Journal • Oncology • Ophthalmology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pain • Solid Tumor • CLDN6

TRIO-049: First in Human Study of TORL-1-23 in Participants With Advanced Cancer (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: TORL Biotherapeutics, LLC | Trial primary completion date: Apr 2025 ➔ Aug 2026 | Trial completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

QLS5132, a highly selective anti-CLDN6 ADC with broader therapeutic window (AACR 2025) - "QLS5132 showed an expanded therapeutic window with superior efficacy and tolerability to TORL-1-23 in preclinical models. QLS5132 also demonstrated great potential to combine with PARPi in CLDN6 positive ovarian cancers. QLS5132 is expected to offer a novel and promising treatment option either as a single agent or combo with PARPi or other SoCs for patients with CLDN6 expressing tumors."

Endometrial Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer • CLDN6

TRIO-049: First in Human Study of TORL-1-23 in Participants with Advanced Cancer (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: TORL Biotherapeutics, LLC | Trial primary completion date: Nov 2024 ➔ Apr 2025

Trial primary completion date • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

TORL123-002: CATALINA-2: a Clinical Study of TORL-1-23 in Platinum-resistant Ovarian Cancer. (clinicaltrials.gov) - P2 | N=230 | Recruiting | Sponsor: TORL Biotherapeutics, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor • CLDN6 • PROC

TORL BioTherapeutics…Initiates TORL-1-23 Registration-Enabling Phase 2 Study in Platinum-Resistant Ovarian Cancer (PRNewswire) - "Additionally, TORL has initiated CATALINA-2, a global Phase 2 study of its novel Claudin 6 (CLDN6) targeted antibody-drug conjugate (ADC) TORL-1-23 in patients with CLDN6 positive (CLDN6+) platinum-resistant ovarian cancer (PROC)....In November, TORL initiated CATALINA-2, a global, multi-institutional randomized, open-label Phase 2 study of TORL-1-23 in women with CLDN6+ PROC who have received one to three prior lines of therapy. The study is designed to support accelerated registration in CLDN6+ PROC."

Trial status • Ovarian Cancer

CATALINA-2: a Phase 2 Study of TORL-1-23 in Advanced Ovarian Cancer. (clinicaltrials.gov) - P2 | N=230 | Not yet recruiting | Sponsor: TORL Biotherapeutics, LLC

Metastases • New P2 trial • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor • CLDN6 • PROC

PHASE I, TWO-PART, MUTLICENTER, FIRST-IN-HUMAN (FIH) STUDY OF TORL-1-23, A NOVEL CLAUDIN 6 (CLDN6) TARGETING ANTIBODY DRUG CONJUGATE (ADC) IN PATIENTS WITH ADVANCED SOLID TUMORS. (IGCS 2024) - P1 | "Clinical trial information: NCT05103683. Sponsor: TORL Biotherapeutics."

Clinical • Metastases • P1 data • Endometrial Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer • CLDN6

Phase I, Two-Part, Multicenter First-In-Human (FIH) study of TORL-1-23, a Novel Claudin 6 (CLDN6) targeting Antibody Drug Conjugate (ADC) in patients with advanced solid tumors (KSMO 2024) - No abstract available

Clinical • Metastases • P1 data • Oncology • Solid Tumor • CLDN6

Antibody-drug conjugate shows promise in treating ovarian and endometrial cancers (News-Medical) - P1 | N=90 | TRIO-049 (NCT05103683) | Sponsor: TORL Biotherapeutics, LLC | "A first-in-human phase I study of TORL-1-23, an antibody drug conjugate (ADC) targeting the protein claudin 6, showed good tolerability and antitumor activity in heavily pretreated patients with ovarian and endometrial cancers that expressed the protein...The researchers reported that the study...showed 'promising preliminary antitumor activity.'...the findings suggest potential efficacy in ovarian cancer...She considered that claudin 6 is of particular interest as a treatment target because its expression is very low in healthy cells. This means that targeting claudin 6 in cancer cells can reduce the risk of harming the healthy ones, thereby limiting the treatment's toxicity. 'The next step will be to confirm the response and the duration of response and assess the effect on progression free survival in a larger group of patients with ovarian cancer'...Ray-Coquard added."

P1 data • Endometrial Cancer • Ovarian Cancer

TORL BioTherapeutics Presents Updated Phase 1 Results of Novel Claudin 6 Targeted Antibody-Drug Conjugate TORL-1-23 at the 2024 European Society of Medical Oncology Congress (PRNewswire) - P1 | N=90 | TRIO-049 (NCT05103683) | Sponsor: TORL Biotherapeutics, LLC | "This mini-oral presentation (ESMO Presentation #721MO) included updated results from the TORL123-001 (TRIO-049) trial up to the 4.0 mg/kg dose level of TORL-1-23....In this ongoing Phase 1 study, 81 patients with CLND6 positive (CLDN6+), heavily pretreated ovarian, testicular, endometrial, non-small cell lung cancer (NSCLC), and other cancers were enrolled....At doses from 0.2 mg/kg to 2.4 mg/kg every 3 weeks, TORL-1-23 is generally well tolerated. The most common adverse events were grade 1 or 2 fatigue, peripheral neuropathy, and alopecia....Encouraging antitumor activity was observed in this heavily pretreated population during dose finding across all enrolled cancer histologies and dose levels. At doses of 2.4 mg/kg and 3.0 mg/kg every 3 weeks, there were deep and durable confirmed responses in 9/20 (45%) patients with CLDN6+ platinum-resistant/refractory ovarian cancer (PROC)."

P1 data • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Testicular Cancer

Phase I, two-part, multicenter first-in-human (FIH) study of TORL-1-23: A novel claudin 6 (CLDN6) targeting antibody drug conjugate (ADC) in patient with advanced solid tumors (ESMO 2024) - P1 | "Part 2 enrolled 20 pts with ovarian (n=11), endometrial (n=4), NSCLC (n=4), and testicular (n=1) cancers at 2.4 mg/kg (n=12) and 3.0 mg/kg (n=8) with pegfilgrastim. TORL-1-23 is well tolerated with promising preliminary antitumor activity in heavily-pretreated pts with CLDN6-expressing ovarian, endometrial, and testicular cancers. Dose expansion is ongoing at doses of 2.4mg/kg and 3.0mg/kg in CLDN6+ NSCLC and ovarian cancer, and CLDN6-low expressing tumors."

Clinical • Metastases • P1 data • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer • CLDN6

TORL BioTherapeutics Announces $158 Million Oversubscribed Series B-2 Financing to Advance the Clinical Development of its Novel Antibody-Drug Conjugate (ADC) Oncology Pipeline (PRNewswire) - "Proceeds from this Series B-2 financing will be used to continue the clinical development of TORL-1-23, the Company's first-in-class ADC to treat CLDN 6+ tumors, through Phase 1 and a pivotal Phase 2 trial that will start in the second half of 2024....Proceeds will also be used to fund the on-going Phase 1 studies for the TORL-2-307 program, both a monoclonal antibody (mAb) and an ADC, for the treatment of CLDN 18.2+ solid tumors, TORL-3-600, an ADC for the treatment of CDH17+ colorectal cancer, and TORL-4-500, an ADC for the treatment of Delta like non-canonical Notch Ligand 1 (DLK1) positive solid tumors."

Financing • New P1 trial • New P2 trial • Colorectal Cancer • Gastroesophageal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

TORL BioTherapeutics Announces Appointment of Mark J. Alles as Chairman and Chief Executive Officer; Highlights Significant Progress of its Oncology Clinical Programs (PRNewswire) - P1 | N=90 | NCT05103683 | Sponsor: TORL Biotherapeutics, LLC | "TORL-1-23 is generally well tolerated from 0.2 to 2.4 mg/kg IV every 21 days....Confirmed responses in 12/36 (33%) patients across all enrolled disease types and all nine dose levels without G-CSF (0.2 mg/kg to 3 mg/kg every 21 days); At the two highest dose levels without G-CSF (2.4 mg/kg and 3 mg/kg every 21 days) there were confirmed responses in 7/12 (58%) patients with CDLN6+ platinum resistant/refractory ovarian cancer....In preparation for a planned phase 2 study that could allow for regulatory approval, expansion cohorts of patients with pretreated ovarian, lung, and other CLDN6+ cancers have been initiated to further guide dose selection."

P1 data • Endometrial Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

First-in-human phase I study of a novel claudin 6 (CLDN6) targeted antibody drug conjugate (ADC) TORL-1-23 (ESMO 2023) - P1 | "Conclusions In participants with heavily-pretreated CLDN6-expressing ovarian cancer, the novel TORL-1-23 ADC has a favorable safety/tolerability profile and encouraging antitumor activity in a phase 1 dose finding study. Further evaluation in ovarian cancer and other CLDN6+ cancers is warranted."

P1 data • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • CLDN6

FIRST-IN-HUMAN PHASE 1 STUDY OF TORL-1-23, A NOVEL CLAUDIN 6 (CLDN6) TARGETED ANTIBODY DRUG CONJUGATE (ADC) IN PATIENTS WITH OVARIAN CANCER (IGCS 2023) - P1 | "19 patients with platinum-resistant/refractory ovarian cancer were evaluated across 8 dose levels (0.2 to 2.4 mg/kg IV every 3 weeks, 21 day cycles) (data cutoff 01APR2023). Most pts had ≥ 3 prior treatment lines in the metastatic setting. The most common treatment-related adverse events were Gr1 peripheral neuropathy (n=3), Gr1/2 fatigue (n=2), and Gr1 nausea (n=2)."

Clinical • P1 data • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • CLDN6

Initial results of dose finding in a first-in-human phase 1 study of a novel Claudin 6 (CLDN6) targeted antibody drug conjugate (ADC) TORL-1-23 in patients with advanced solid tumors. (ASCO 2023) - P1 | "TORL-1-23 has a favorable safety/tolerability profile and PK characteristics with preliminary antitumor activity in pts with heavily-pretreated CLDN6-expressing ovarian and testicular cancers. Doses above the historic MTD for MMAE containing ADCs may be explored given the safety/tolerability and PK data observed up to 2.4 mg/kg. Dose finding is ongoing to identify the MTD and optimal doses for subsequent development."

Clinical • Metastases • P1 data • Endometrial Cancer • Fatigue • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pain • Solid Tumor • Testicular Cancer • CLDN6

TORL BioTherapeutics Announces Initial Results of Novel Claudin 6 (CLDN6) Targeted Antibody Drug Conjugate (ADC) TORL-1-23 Selected for Presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - P1 | N=90 | NCT05103683 | Sponsor: TORL Biotherapeutics, LLC | "TORL BioTherapeutics LLC...announces the initial results from an ongoing phase I study of their claudin 6 (CLDN6) targeted antibody drug conjugate (ADC), TORL-1-23, in patients with advanced cancer on the American Society of Oncology (ASCO)...TORL-1-23 is well tolerated with no dose limiting toxicities from 0.2 to 2.4 mg/kg IV every 21 days; Confirmed responses were observed in 7/25 (28%) patients across all dose levels and all patients treated with TORL-1-23; Confirmed responses were observed in 6/19 (32%) patients with platinum-resistant ovarian cancer across all dose levels, with 3/4 (75%) responses at the 2.4 mg/kg dose level; Pharmacokinetic data indicate sustained exposure of TORL-1-23 over the 21-day dosing period and low levels of free MMAE payload..."

P1 data • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Uterine Cancer

ASCO 2023 Spotlight: Claudin 6 Anticipated To Shine (Issuer Direct) - "At ASCO 2023, BioNTech and TORL will present Phase 1 clinical trial data on CLDN6-targeted programs, including BNT142, BNT211, and TORL-1-23....BioNTech will present multiple updates from its CLDN portfolio, most notably an update from their CLDN-6-targeting CAR-T cell therapy, BNT211, in combination with CLDN6- encoding mRNA vaccine (CARVac) in solid tumors (poster #2518)....BioNTech will also provide a trial-in-progress update for BNT142 (mRNA vaccine encoding a CD3 x CLDN-6 bispecific, poster abstract TPS2669)....TORL Biotherapeutics will present the first clinical data from its CLDN6 ADC TORL-1-23."

P1 data • Trial status • Oncology • Solid Tumor

TORL BioTherapeutics Launches with $158 Million Series B Financing to Advance Development of Novel Oncology Biologics (PRNewswire) - "TORL BioTherapeutics LLC...announced today its public launch and the closing of a $158 million Series B financing....The Company also expects to put 2-3 additional compounds into clinical trials over the next 12 months, with plans to advance 1-2 new compounds each year....'We believe TORL-1-23 and TORL-2-307 represent promising potential therapies for ovarian and gastric cancers, two indications with significant unmet patient need. We look forward to partnering with the TORL team to rapidly advance the lead programs toward late-stage clinical trials while progressing the broader portfolio of novel programs."

Financing • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor