Mr. Philippe Dubuc reports

THERATECHNOLOGIES PRECLINICAL DATA PRESENTATION AT AACR 2024 HIGHLIGHTS VERSATILITY AND FLEXIBILITY OF SORT1+ TECHNOLOGY™ ONCOLOGY PLATFORM

Theratechnologies Inc. today presented preclinical data that highlight the versatility and flexibility of the company's SORT1+ Technology platform. In a poster session at the 2024 annual meeting of the American Association for Cancer Research (AACR) in San Diego, Calif., researchers reported that Theratechnologies' investigational camptothecin-peptide conjugates are well tolerated and associated with significant tumour regression in colorectal cancer (CRC) and triple-negative breast cancer (TNBC) xenograft models. The study also demonstrated synergistic anti-tumour efficacy and good tolerability with the combination of two peptide drug conjugates with different payloads.

• Novel camptothecin-peptide conjugates are well tolerated and associated with significant tumour regression in colorectal cancer and triple-negative breast cancer xenograft models.
• SORT1 gene-silencing results in drastic decrease in peptide-drug conjugate uptake which supports a SORT1-mediated internalization process.
• Poster presentation broadens evidence supporting potential utility of platform-derived peptide-drug conjugates alone or in combination in numerous SORT1-positive tumours.

"The preclinical data presented at AACR add to the sizeable body of evidence supporting the potential utility of the SORT1+ Technology platform as an engine for the development of novel peptide-drug conjugates to treat various types of cancer," said Christian Marsolais, PhD, senior vice-president and chief medical officer at Theratechnologies. "In addition to our lead peptide-drug conjugate, sudocetaxel zendusortide, these latest data highlight the promising tolerability and anti-tumour effects of our investigational camptothecin-peptide conjugates, further demonstrating the versatility and flexibility of the platform. We welcome discussions with potential partners who are interested in the further development of these innovative therapies."

The SORT1+ Technology platform relies on the use of a novel, proprietary peptide called TH19P01, which can be conjugated (attached) to numerous well-characterized anti-cancer drugs. Theratechnologies designed TH19P01 to interact with and be transported by the scavenger receptor sortilin (SORT1), which is involved in protein internalization, sorting and trafficking, and is expressed in multiple tumour types. Targeting SORT1 with platform-derived peptide-drug conjugates (PDCs) leads to receptor-mediated internalization (endocytosis) of anti-cancer agents. Once inside cancer cells, active drug is released from the peptide and exerts its cytotoxic effect directly on the cancer cell.

In the poster presented at AACR, the investigators noted that SORT1 gene-silencing inhibits camptothecin-conjugate uptake in human HT-29 colorectal adenocarcinoma cells. This observation suggests that these PDCs enter cancer cells via a SORT1-mediated internalization process.

The investigators also described the preclinical effects of three PDCs -- TH2101, TH2205 and TH2310 -- that have a cytotoxic payload of SN-38, the active metabolite of irinotecan, an anti-cancer agent that is derived from the Chinese tree Camptotheca acuminate. In addition, the poster summarized the activity of another PDC, TH2303, which carries an exatecan payload, a structural analogue of camptothecin. Compared with unconjugated irinotecan, the exatecan- and SN-38-conjugates exerted greater anti-proliferative activities against CRC cells in mice. In two different CRC xenograft models, as well as in the TNBC xenograft model, TH2303 was associated with increased tumour growth inhibition and greater tolerability compared to unconjugated exatecan or irinotecan.

In another experiment described in the poster, the combination of two SORT1-targeting PDCs -- sudocetaxel zendusortide (TH1902) and TH2101, which have a synergistic anti-tumour effect at reduced doses, led to increased tumour growth inhibition and some complete responses in the HT-29 xenograft model, compared with either PDC administered alone. The combination also was well tolerated.

"The significant tumour regression following combination therapy is notable because the HT-29 xenograft model is known for its resistance to multiple cytotoxic drugs," commented Prof. Borhane Annabi, chair in cancer prevention and treatment in the chemistry department at the Universite du Quebec a Montreal. "That observation, along with the impressive anti-cancer efficacy of the camptothecin-peptide conjugates when administered alone, underscores the potential feasibility of this approach in treating various tumour types."

A copy of the AACR poster, as well as a second poster presented at the conference, which reinforces existing data for the company's lead investigational PDC sudocetaxel zendusortide (TH1902) in activating anti-PD-L1 immunotherapy tumour cell-killing in SORT+1 cancers, can be found at the Theratechnologies website.

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 FDA (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 (TNBC) 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.