THE001 / Thermosome - LARVOL DELTA

CLINICAL DATA CONFIRM GALENIC PRINCIPLE AND DEMONSTRATE THERAPEUTIC POTENTIAL OF THE001 (DPPG2-TSL-DOX) PLUS REGIONAL HYPERTHERMIA IN SOFT TISSUE SARCOMA (CTOS 2025) - P1 | "Objective: Doxorubicin (DOX) remains standard therapy for soft tissue sarcoma (STS). THE001 + RHT demonstrates clinical activity, proof of galenic principle, and a favorable safety profile in STS. Exploration in the neoadjuvant setting aims to enhance pathological responses (e.g., pCR rate) and immune induction. Orphan Drug Designation by EMA and FDA were granted for THE001 + RHT, validating the potential in STS."

Clinical data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Initial clinical data confirm galenic principle and demonstrate therapeutic potential of THE001 (DPPG2-TSL-DOX) combined with regional hyperthermia (RHT) in soft tissue sarcoma (STS) (ESMO 2025) - P1 | "Background Doxorubicin (DOX) remains standard therapy for STS. Planned exploration in the neoadjuvant setting aims to enhance pathologic responses (such as pCR rate) and immune induction. Orphan Drug Designation by EMA and FDA were granted for THE001 + RHT, validating the potential in STS."

Clinical data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Study of DPPG2-TSL-DOX Combined With Hyperthermia in Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Thermosome GmbH | Active, not recruiting ➔ Completed | Trial primary completion date: May 2025 ➔ Jan 2025

Trial completion • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Local drug delivery of irinotecan with phosphatidyldiglycerol-based thermosensitive liposomes reduces systemic exposure and increases therapeutic efficacy compared to systemic drug and Onivyde®. (PubMed, Int J Pharm) - "DPPG2-TSL-DOX was the only formulation that led to a tumor size reduction. In vivo data indicated an advantage of the intravascular CPT-11 release over systemic drug application or passive tumor accumulation of liposomes."

Journal • Oncology • Solid Tumor

Thermosome Receives U.S. Orphan Drug Designation for Lead Compound THE001, Expands Patent Estate (GlobeNewswire) - "Thermosome...today announced that its lead compound, THE001, has been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of soft tissue sarcomas (STS)....This recognition, based on preclinical and early clinical data from our Phase 1 study, marks an important milestone and is a further step into the U.S. market – the world’s most important market for patent-protected drugs."

Orphan drug • Soft Tissue Sarcoma

Study of DPPG2-TSL-DOX Combined with Hyperthermia in Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Thermosome GmbH | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ May 2025 | Trial primary completion date: Dec 2024 ➔ May 2025

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Thermosome Initiates Final Dose Level in Phase I Trial of Lead Compound THE001 (PharmiWeb) - "Thermosome...announced its ongoing Phase I trial has progressed to dose level 3 (DL3) after the independent Data Safety Monitoring Board (DSMB) declared dose level 2 (DL2) as safe and recommended escalation to the final dose level (DL3). In the trial, the Company’s lead compound THE001 is tested in patients with heavily pre-treated, locally advanced unresectable or metastatic soft tissue sarcoma (STS) in combination with regional hyperthermia. To date, the safety profile remains favorable with no dose-limiting toxicities and no suspected unexpected serious adverse event (SUSAR) seen at DL1 and DL2, respectively."

DSMB • Trial status • Soft Tissue Sarcoma

Thermosome Presents Encouraging Initial Clinical Data from Phase I Trial of Lead Compound THE001 (PharmiWeb) - "With regards to anti-tumor activity, an overall 5 out of 6 efficacy-evaluable patients in DL1 and DL2 achieved local disease control and 4 out of 6 achieved stable disease (SD) per RECIST. In DL2, all 3 out of 3 patients were evaluated as stable disease (SD) per RECIST after the initial tumor restaging (3 cycles). While two patients have not yet reached the tumor staging after 6 cycles (end of the main study period), one patient remained in stable disease per RECIST for 9 cycles (representing a progression-free survival of 7 months) and showed evidence of a pathological response in MRI/PET-CT imaging at the end of the main study period, representing a partial response (PR) per Choi....Data presented at The Connective Tissue Oncology Society (CTOS) Annual Meeting 2024."

P1 data • Soft Tissue Sarcoma

PHASE I STUDY OF THE001 DPPG2-TSL-DOX) COMBINED WITH REGIONAL HYPERTHERMIA IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOFT TISSUE SARCOMA (CTOS 2024) - P1 | "Objective: Doxorubicin (DOX) is the most relevant chemotherapy (CTx) for treatment of soft tissue sarcomas (STS). THE001 is well-tolerated as monotherapy and in combination with RHT in the ongoing phase 1 study and confirms the feasibility of this innovative combined modality. Signs of clinical activity in heavily pretreated STS participants, together with the PK profile, indicate the potential of THE001+RHT as a promising tumor-targeted therapy with heat-triggered release of high peak concentrations of DOX in the heated tumor area together with systemic exposure non-inferior to non-liposomal DOX as a potential future treatment option for DOX-sensitive tumors such as STS. Recruitment is ongoing and further updates will be reported at upcoming conferences."

Clinical • Metastases • P1 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Study of DPPG2-TSL-DOX Combined With Hyperthermia in Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Thermosome GmbH | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Metastases • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Thermosome Announces Participation in IMAGIO Consortium to Improve Cancer Treatment (GlobeNewswire) - "Thermosome...today announced its participation in the IMAGIO consortium set out to develop innovations in interventional oncology focused on lung cancer, liver cancer and soft tissue sarcomas (STS)....Thermosome will receive EUR 1.3 million of funding and will participate in the work package...which will be carried out by a group of partners coordinated by Prof. Dr. Holger Grüll, Chair of Experimental Imaging and Image-Guided Therapy at the University Hospital of Cologne, Germany. Further participants in the work package are Profound Medical, Philips, Turku University Hospital, and Gremse IT....The objectives of the trial in soft tissue sarcoma patients will be the evaluation of the novel hyperthermia feature with respect to safety and performance, and tumor targeting following THE001 treatment in combination with the MR-HIFU technology. The trial will be conducted in the second half of the 4-year program, following animal studies of THE001 in combination with..."

Financing • New trial • Oncology • Soft Tissue Sarcoma • Solid Tumor

Thermosome Announces First Patient Dosed in Phase I Trial with Lead Program THE001 (GlobeNewswire) - "Thermosome...announced that the first patient has been dosed in April 2023 in the ongoing Phase 1 trial of its lead program THE001. Additional patients will be enrolled following a 6-week monitoring period that includes two treatment cycles. The trial will enroll patients with locally advanced unresectable or metastatic soft tissue sarcoma at two clinical sites in Germany: Helios Klinikum Berlin-Buch and LMU Klinikum, Munich. THE001 will be administered at three dose levels, with three to six patients treated at each dose level (3+3 design). The primary endpoints of the Phase 1, open-label, interventional, dose-escalation study are the safety and tolerability of THE001 and the determination of the maximum tolerated dose. A secondary objective is to evaluate anti-tumor activity."

Trial status • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Study of DPPG2-TSL-DOX Combined With Hyperthermia in Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Thermosome GmbH

Metastases • New P1 trial • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Thermosome Receives Regulatory Approval for First-In-Human Trial with its Lead Program THE001 (GlobeNewswire) - "Thermosome...announced that it has received approval from the German Federal Institute for Drugs and Medical Devices (BfArM) and the responsible Ethics Committee to conduct a Phase 1 trial with its lead program THE001 in Germany. Patient enrollment is expected to start in Q2, 2023....Patients will be recruited at two clinical sites in Germany specialized in the treatment of soft tissue sarcoma patients: Helios Klinikum Berlin-Buch and LMU Klinikum, Munich."

New P1 trial • Oncology • Sarcoma • Soft Tissue Sarcoma