Mr. Philippe Dubuc reports

THERATECHNOLOGIES' SUDOCETAXEL ZENDUSORTIDE ASCO 2024 PRESENTATION DEMONSTRATES SIGNS OF LONG-TERM EFFICACY AND MANAGEABLE SAFETY PROFILE IN PATIENTS WITH SOLID TUMORS

Phase 1 data have demonstrated signs of long-term efficacy and a manageable safety profile of Theratechnologies Inc.'s lead investigational peptide drug conjugate candidate, sudocetaxel zendusortide (TH1902), in patients with solid tumours. The data will be presented in a poster session on June 1, at 9 a.m. to 12 p.m. CDT (abstract No. 3081 and poster board No. 226) at the 2024 American Society of Clinical Oncology annual meeting, which is taking place May 31 to June 4, 2024, in Chicago, Ill.

In an updated analysis from parts 1 and 2 of a continuing phase 1 clinical trial, sudocetaxel zendusortide induced durable disease stabilization (up to 45 weeks) lasting beyond treatment completion. The results suggest a unique, multimodal mechanism of action distinct from other cancer therapeutics, including induction of immune cell infiltration even in cold tumour models, inhibition of vasculogenic mimicry, targeting of chemotherapy-resistant cancer stem cells and activation of the cGAS/Sting immune pathway, among other actions. Additionally, investigators observed an early efficacy signal primarily in female cancers (ovarian cancer, endometrial cancer and triple-negative breast cancer), with seven of 16 participants (44 per cent) achieving a clinical benefit rate (complete response plus partial response plus stable disease), as confirmed by response evaluation criteria in solid tumours (recist), Version 1.1. The poster presentation, which constitutes the first report of long-term efficacy, safety and pharmacokinetic data from the phase 1 study, also suggests that sudocetaxel zendusortide has a manageable safety profile when dosed at 300 milligrams per square metre, with few Grade 3 adverse events.

"The initial long-term phase 1 data further validate and expand upon the preliminary evidence of anti-tumour activity with sudocetaxel zendusortide in individuals with solid tumours," said Dr. Ira Winer, MD, PhD, FACOG, a member of the gynecologic oncology and phase 1 clinical trial multidisciplinary teams at Karmanos Cancer Center, and associate professor of oncology at Wayne State University. "It is highly unusual to see such long-lasting disease stabilization even after treatment cessation in patients with advanced disease. These updated data provide an informative baseline as we seek to optimize the dose of this novel peptide-drug conjugate in patients with platinum-resistant ovarian cancer in the next stage of the phase 1 trial."

Study details

Dr. Winer and colleagues conducted an analysis of the long-term efficacy, safety and PK of sudocetaxel zendusortide from parts 1 and 2 of the phase 1 trial, which seeks primarily to characterize the agent's safety and tolerability. Part 1 (modified intrapatient dose escalation, n equals 18) included patients with recurrent/refractory advanced tumours (all comers) with no limit on the number of previous therapies, including taxanes. Part 2 (dose expansion, n equals 18) included patients with cancers with known high expression of the sortilin (Sort1) receptor, including ovarian cancer, endometrial cancer, TNBC and melanoma. Part 3 (dose optimization) of the phase 1 trial, in patients with advanced ovarian cancer that is no longer platinum sensitive, is continuing.

In a subanalysis of efficacy in 16 patients with TNBC, ovarian and endometrial cancers, seven patients exhibited recist-1.1-confirmed clinical benefit, with six patients achieving long-term stabilization of disease (up to a maximum of 45 weeks in duration) even after drug discontinuation in some patients. One patient with ovarian cancer had an overall partial response, with a recist-1.1-confirmed complete response in target lesions, and stabilization of disease in non-target lesions, lasting up to 24 weeks from initiation of treatment. In addition, one patient with endometrial cancer, whose dose was escalated from 60 milligrams per square metre to 360 milligrams per square metre in Part 1, completed a total of 11 treatment cycles. This patient's disease remained stable throughout eight months of treatment, up to the time of consent withdrawal. All 16 patients had prior exposure to taxane-containing regimens (range: one to six). The investigators characterized the prolonged stabilization of disease as clinically significant in this heavily pretreated patient population, which typically experiences recurrence during or shortly after treatment discontinuation.

Sudocetaxel zendusortide has a manageable safety profile, with most treatment-related AEs rated as mild to moderate in severity and managed with standard supportive care or dose reductions. Investigators noted that the low number of Grade 3 AEs compares favourably with the published literature for unconjugated docetaxel.

PK measures showed that exposure to free docetaxel was much lower than that for sudocetaxel zendusortide, a finding that may explain the lower incidence and severity of AEs seen with sudocetaxel zendusortide versus docetaxel alone. The maximum concentration of sudocetaxel zendusortide was 30.4 micromolar, compared with 0.58 micromolar for free docetaxel. The 24-hour area under the curve for sudocetaxel zendusortide was 74.8 nanomoles per hour per litre versus 3.1 nanomoles per hour per litre for free docetaxel. The free docetaxel/sudocetaxel zendusortide AUC ratio was less than 1 per cent up to 300 milligrams per square metre, suggesting that most docetaxel remains associated with the peptide over the period of analysis.

"One year after our presentation of preliminary evidence of anti-tumour activity at the 2023 ASCO annual meeting, the phase 1 sudocetaxel zendusortide trial continues to yield important information about long-term efficacy, safety and pharmacokinetics of this promising peptide-drug conjugate," commented Christian Marsolais, PhD, senior vice-president and chief medical officer at Theratechnologies. "These latest data leave us well positioned for Part 3 of the study, in which we aim to optimize the dose to see further signs of efficacy while limiting toxicity. We look forward to sharing more data from this ongoing trial in the future."

About sudocetaxel zendusortide (TH1902) and Sort1+ technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin-receptor-(Sort1)-targeting PDC, and the first compound to emerge from the company's broader licensed oncology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The Food and Drug Administration granted fast-track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumours that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a phase 1 clinical trial.

Theratechnologies has established the Sort1+ technology platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumour types. Sort1 is a scavenger receptor that plays a significant role in protein internalization, sorting and trafficking. Expression of Sort1 is associated with aggressive disease, poor prognosis and decreased survival. It is estimated that Sort1 is expressed in 40 per cent to 90 per cent of endometrial, ovarian, colorectal, triple-negative breast and pancreatic cancers, making this receptor an attractive target for anti-cancer drug development.

About Theratechnologies Inc.

Theratechnologies is a biopharmaceutical company focused on the development and commercialization of innovative therapies addressing unmet medical needs.

We seek Safe Harbor.