Dr. Christian Marsolais reports

THERATECHNOLOGIES TO PRESENT PRELIMINARY SAFETY AND EFFICACY DATA FROM PHASE 1 TRIAL OF SUDOCETAXEL ZENDUSORTIDE IN HEAVILY PRETREATED CANCER PATIENTS AT ASCO 2023

Theratechnologies Inc. today released preliminary efficacy data from a phase 1 study of its lead investigational peptide-drug conjugate (PDC) candidate, sudocetaxel zendusortide (formerly TH1902), in patients with advanced solid tumours. In a June 3 poster session at the 2023 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, researchers will present early results from part 1 (dose escalation) and part 2 (dose expansion) of the multicentre, open-label trial of sudocetaxel zendusortide, in which 36 per cent of heavily pretreated participants experienced a clinical benefit, including two patients with partial responses (PR) and seven achieving prolonged stable disease (SD).

• Preliminary signs of antitumour activity noted in 36 per cent of patients, with two partial responses (PR) and seven patients with prolonged stable disease (SD);
• Efficacy and tolerability data from dose escalation and expansion results inform protocol amendment designed to improve therapeutic window of sudocetaxel zendusortide.

Based on the results presented at ASCO, Theratechnologies is engaged with the United States Food and Drug Administration (FDA) to amend the protocol of the phase 1 clinical trial of sudocetaxel zendusortide. The amendments are designed to improve the therapeutic window and allow for more prolonged therapy with sudocetaxel zendusortide, reflecting changes in patient selection and evaluation of alternative dosing regimens.

"The early efficacy data for our lead peptide-drug conjugate, sudocetaxel zendusortide, confirm that it rapidly internalizes and hyper-targets delivery of cytotoxic payload directly into cancer cells," said Christian Marsolais, PhD, senior vice-president and chief medical officer at Theratechnologies. "We look forward to reinitiating our trial with a revised protocol that increases the likelihood of showing the full therapeutic potential of sudocetaxel zendusortide."

"These preliminary data on safety and antitumour activity have informed the proposed changes to the protocol, with the intention of improving the risk-benefit profile of sudocetaxel zendusortide in the next stage of the trial," commented lead investigator Funda Meric-Bernstam, MD, chair of the department of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center.

Study details and results

Part 1 of the study enrolled 18 adults with a confirmed diagnosis of a metastatic or advanced-stage solid tumour that is refractory to standard therapies (average of eight prior lines of therapies). The starting dose of 30 milligrams per square metre every three weeks (Q3W) was selected based on sudocetaxel zendusortide preclinical data. Among participants in part 1, one patient with endometrial cancer experienced SD for 233 days (33 weeks), a second patient with prostate cancer had SD that lasted for 119 days (17 weeks) and a third patient with ovarian cancer experienced SD for 295 days (42 weeks).

Eighteen additional patients were enrolled into the 300 mg/square metre Q3W dose expansion cohort (part 2). In an interim efficacy and safety analysis of the 300 mg/square metre dose cohort from parts 1 and 2 (n equals 25), five of six patients (83 per cent) with ovarian cancer had a best overall response (BOR) of either PR (n equals one) or SD (n equals four). In the triple-negative breast cancer (TNBC) population, three of four patients (75 per cent) had a BOR of SD, with one patient experiencing SD for at least four cycles and continued clinical benefit up to at least 24 weeks. In the two patients with prostate cancer, one experienced a PR.

Sudocetaxel zendusortide doses below 300 mg/square metre were well tolerated in part 1 of the trial, which established the maximum tolerated dose (MTD) and dose-limiting toxicities at 360 mg/squar emetre and 420 mg/square metre, respectively. Based on those results, investigators selected a 300 mg/square metre dose for part 2 (dose expansion) of the basket trial, to determine the safety and efficacy of sudocetaxel zendusortide in patients with multiple tumour types with high expression of the sortilin (SORT1) receptor. At 300 mg/square metre, the most common treatment-related adverse events (greater than 20 per cent) were ocular changes, neuropathy, gastrointestinal disturbances and musculoskeletal complaints, with grade 3 or greater toxicities at a frequency of less than or equal to 12 per cent.

Poster presentation details:

Title:  "Sudocetaxel zendusortide (TH1902), a novel sortilin-receptor (SORT1)-targeting peptide-drug-conjugate (PDC) in patients (pts) with advanced solid tumors: Results from part 1 (dose-escalation) of a phase 1, open-label study"

Lead author:  Funda Meric-Bernstam, MD, chair of the department of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center

Abstract No.:  3089

Session date and time:  Saturday, June 3, 2023, developmental therapeutics -- molecularly targeted agents and tumour biology, 8 a.m. to 11 a.m. CT

About SORT1+ technology and sudocetaxel zendusortide (TH1902)

Theratechnologies has established its SORT1+ Technology platform as an engine for the development of proprietary peptide-drug conjugates (PDCs) that target the sortilin (SORT1) receptor, 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 (TNBC) and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

Sudocetaxel zendusortide is the first-of-its-kind SORT1-targeting PDC, and the first to emerge from the SORT1+ technology 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 FDA 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. Patient recruitment was voluntarily paused on Dec. 1, 2022, and in alignment with this decision, the FDA placed the trial on partial clinical hold. In May. 2023, the company submitted a proposed protocol amendment to the FDA that is currently under review.

About Theratechnologies Inc.

Theratechnologies (TSX: TH) (Nasdaq: THTX) is a biopharmaceutical company focused on the development and commercialization of innovative therapies addressing unmet medical needs.

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