Dr. Christian Marsolais reports

THERATECHNOLOGIES RECEIVES FDA AGREEMENT TO AMENDED TRIAL PROTOCOL FOR ITS LEAD PDC CANDIDATE SUDOCETAXEL ZENDUSORTIDE

The United States Food and Drug Administration (FDA) has agreed to Theratechnologies Inc.'s amended protocol for the phase 1 clinical trial of sudocetaxel zendusortide, an investigational, first-in-class peptide-drug conjugate (PDC) that targets the sortilin (SORT1) receptor, and expedites the internalization and delivery of a cytotoxic payload directly into cancer cells. Today's announcement also marks the lifting of the FDA's partial clinical hold on the phase 1 trial, following the company's voluntary pause of patient recruitment in December, 2022.

In May, 2023, Theratechnologies filed the amended trial protocol, which is designed to improve the therapeutic window of sudocetaxel zendusortide and extend its duration of therapy. The updates include a change in the frequency of administration to weekly dosing and a narrowing of the patient population to focus on those with high-grade serous ovarian cancer, including high-grade peritoneal or fallopian tube cancer, or high-grade endometrioid cancer -- a population in which preliminary efficacy has been observed thus far. Patient selection has also been refined to focus on those who are less heavily pretreated, with no more than one taxane failure and a maximum of eight prior cancer treatment regimens.

"We are very pleased that the FDA has agreed to our plans to optimize the dosing regimen for sudocetaxel zendusortide, and to other proposed changes to the protocol so that we can now restart this important phase 1 clinical trial," said Christian Marsolais, PhD, senior vice-president and chief medical officer at Theratechnologies. "We have been working closely with our scientific advisory committee and the FDA to align on this updated protocol, which we believe will expedite development of this novel peptide-drug conjugate and ultimately deliver effective targeted therapy to people with advanced cancers, while minimizing toxicity."

The amended study will be a modified six-plus-six design with two different dosing regimens that are within the efficacious range for sudocetaxel zendusortide: 1.75 milligrams per kilogram (mg/kg) on days 1, 8 and 15 of a 28-day cycle (similar to 210 mg/square metre every three weeks); and 2.5 mg/kg on the same schedule (similar to 300 mg/square metre every three weeks). A minimum of six patients will be enrolled at the 1.75 mg/kg dose followed, by an observational period of three months to assess dose-limiting toxicity (DLT). If deemed safe (zero or one DLT), the trial will enroll an additional six patients at the 2.5 mg/kg dose. Following a second three-month observational period, four more patients will be enrolled at the higher dose, for a total of 16 patients in part 3 of the trial. The amendments also include an option for a basket expansion stage that will comprise patients with selected, difficult-to-treat tumour types in which sudocetaxel zendusortide has shown activity.

"Based on our pharmacokinetic and pharmacodynamic analyses, we decided to switch from body-surface-area dosing to an equivalent weight-based dosing so we could provide a more precise dose and minimize toxicity for each trial participant," added Dr. Marsolais.

"By exploring lower doses administered more frequently, the company has put sudocetaxel zendusortide in the best position to characterize its full therapeutic potential and tolerability," said Mace Rothenberg, MD, scientific adviser to Theratechnologies. "The early stages of the trial have already yielded preliminary data on safety and antitumour activity, and the protocol amendment should build upon that encouraging start. Given the limited treatment options for patients affected by high-grade serous ovarian cancer, I look forward to further results from this trial."

Researchers are presenting early results from part 1 (dose escalation) and part 2 (dose expansion) of the multicentre, open-label, phase 1 trial of sudocetaxel zendusortide at a poster session at the 2023 annual meeting of the American Society of Clinical Oncology (ASCO) on Saturday, June 3, in Chicago. Those preliminary safety and efficacy data, which can be found at the company's website, informed the FDA-approved amended protocol.

On June 13, the company will host a video conference call for investors and analysts at 10 a.m. ET, during which investigators from the sudocetaxel zendusortide phase 1 trial will provide insights on the data presented at ASCO 2023 and the amended trial protocol. Registration information can be found on-line.

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 anti-cancer drug development.

Sudocetaxel zendusortide is a first-of-its-kind SORT1-targeting PDC, and the first compound 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.

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.