Thermosome Initiates Final Dose Level in Phase I Trial of Lead Compound THE001

• Independent Data Safety Monitoring Board declared dose level 2 as safe and recommended escalation to final dose level 3

Munich, Germany – December 4, 2024 – Thermosome, a drug development company focused on targeted tumor therapies, today 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 THE001is 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. Most adverse events were low-grade (CTCAE ≤ grade 2), reversable, and were to be expected for the active pharmaceutical ingredient doxorubicin.

„After observing early signs of efficacy in our ongoing trial, this is another important milestone for our company, as it proves that THE001 can be administered safely,“ said Dr. Frank Hermann, CMO of Thermosome. „Of note, there were no signs of renal or cardiac impairment and no dedicated formulation-related adverse events such as infusion-related reactions due to the innovative liposomal formulation. No trial participant had to discontinue treatment due to adverse events. Together with the previously reported pharmacokinetic and anti-tumor activity data, the overall data from the trial look very encouraging as of now. They underline the great potential of THE001 plus regional hyperthermia in STS as a tolerable, innovative treatment modality that has significantly improved local clinical activity with non-inferior systemic exposure to doxorubicin, but with a favorable pharmacokinetic profile.“

„Overseeing various programs from the past, present and future of local treatment modalities, the initial clinical data of THE001 plus regional hyperthermia look very encouraging – not only from a clinical activity perspective in a heavily pre-treated patient population suffering from soft tissue sarcoma, but also from a pharmacokinetic and safety perspective,” said Prof. Alexander Eggermont, Professor of Clinical and Translational Immunotherapy at the University Medical Center Utrecht (The Netherlands) and a member of Thermosome’s Clinical Advisory Board. „For such innovative approaches, it is crucial to first demonstrate that there are no specific risks to patients, which the independent Data Safety Monitoring Board´s safety clearance indicates not only for DL1 but now also for DL2. I look forward to seeing the further development in DL3 and beyond. In my view, THE001 plus regional hyperthermia has great potential to be a promising tumor-targeted approach in STS and beyond.”

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About Thermosome

Thermosome is a clinical-stage drug development company focused on targeted tumor therapy combined with immune stimulation for improved cancer therapy. At its core is a novel, proprietary tumor targeting approach that allows for significantly increased local drug concentrations and improved tumor penetration to achieve improved clinical treatment efficacy.

The first clinical indication for its lead drug candidate THE001 is soft tissue sarcoma, where the Company aims to improve the current standard of care (free doxorubicin). Thermosome’s approach enables targeted tumor treatment independent of specific molecular targets and covers patient populations across all tumor subtypes. More information: www.thermosome.com

About THE001

Thermosome’s clinical-stage lead drug candidate THE001 is a thermosensitive liposomal formulation of the chemotherapeutic drug doxorubicin (DPPG₂-TSL-DOX). It has a different mode of action than conventional liposomes. Thermosome’s technology enables intravascular drug release initiated by a mild heat trigger using clinically established hyperthermia devices. This results in up to 15-fold higher local drug concentrations in the tumor and aims to improve clinical treatment efficacy by creating a local boost at the desired site of action. These high local concentrations, which also reach less well perfused areas, are intended to overcome drug resistance. This effect cannot be achieved by administration of conventional doxorubicin due to systemic toxicity. Thermosome intends to further enhance treatment efficacy through an additive immune response induced by regional hyperthermia. THE001 has potential for further development in other anthracycline-sensitive solid tumors, such as breast, bladder, and ovarian cancer.

About the Phase I Study

The Phase I, open-label, interventional dose-escalation trial enrolling patients with locally advanced unresectable or metastatic STS (NCT05858710) is being conducted at two German clinical sites testing THE001 at 3 different dose levels in initially up to 6 cycles every 3 weeks. The initial dose level of 20 mg/m² (DL1) was well tolerated and progressed to 40 mg/m² (DL2) in February 2024. At the last dose level, patients will receive 50 mg/m² (DL3). Primary endpoints of the study are the safety and tolerability of THE001 and the determination of the maximum tolerated dose. A secondary objective is the evaluation of anti-tumor activity. Initial clinical data were presented at the CTOS 2024 Annual Meeting (link).

About Soft Tissue Sarcomas (STS)

STS is an atypical tumor with a patient population that includes many young patients. Locally advanced STS (LA-STS) are large invasive tumors that are difficult or impossible to resect. Neoadjuvant therapy is used to shrink these tumors preoperatively to allow tumor surgery with curative intent. Free doxorubicin in combination with ifosfamide or dacarbazine has been the gold standard for neoadjuvant therapy of all chemo sensitive LA-STS for several decades. Guidelines also recommend combining DOX-based therapy with regional hyperthermia. However, with response rates of less than 30%, there is a significant unmet need for improved treatment options.

Soft tissue sarcomas occur in more than 50 different subtypes not having a common driver mutation, making biologic targeting more difficult than physically controlled targeting with the most active agent. THE001 has been granted European Orphan Drug Designation for STS.

Company Contact
Thermosome GmbH
Am Klopferspitz 19
82152 Planegg/Martinsried
phone +49 89 7167760 31
media@thermosome.com

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