- Novel camptothecin-peptide conjugates are well tolerated and associated with significant tumor 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 tumors
“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
The SORT1+ Technology™ platform relies on the use of a novel, proprietary peptide called TH19P01, which can be conjugated (attached) to numerous well-characterized anticancer drugs.
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 anticancer 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 analog of camptothecin. Compared to 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 tumor 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-tumor effect at reduced doses, led to increased tumor growth inhibition and some complete responses in the HT-29 xenograft model, compared to either PDC administered alone. The combination also was well tolerated.
“The significant tumor 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
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 tumor cell-killing in SORT+1 cancers, can be found at the
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 granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial.
About
Forward-Looking Information
This press release contains forward-looking statements and forward-looking information (collectively, the “Forward-Looking Statements”) within the meaning of applicable securities laws, that are based on management’s beliefs and assumptions and on information currently available to it. You can identify forward-looking statements by terms such as “may”, “will”, “should”, “could”, “promising”, “would”, “outlook”, “believe”, “plan”, “envisage”, “anticipate”, “expect” and “estimate”, or the negatives of these terms, or variations of them. The Forward-Looking Statements contained in this press release include, but are not limited to, statements regarding the development of multiple PDCs, including, without limitation, camptothecin-peptide conjugates and sudocetaxel zendusortide, their use and the potential benefits to be derived from their use. Although the Forward-Looking Statements contained in this press release are based upon what the Company believes are reasonable assumptions in light of the information currently available, investors are cautioned against placing undue reliance on these statements since actual results may vary from the Forward-Looking Statements contained in this press release. These assumptions include, without limitation, that the Company’s Phase 1 clinical trial using sudocetaxel zendusortide will be successful, that signs of efficacy will be observed in such Phase 1 clinical trial and no untoward side effects will be reported, and that the findings observed from the preclinical work conducted on new PDCs will be replicated into human subjects. Forward-Looking Statements assumptions are subject to a number of risks and uncertainties, many of which are beyond the Company’s control, that could cause actual results to differ materially from those that are disclosed in or implied by such Forward-Looking Statements. These risks and uncertainties include, but are not limited to, the lack of observation of strong efficacy results from the Phase 1 clinical trial using sudocetaxel zendusortide, the reporting of adverse side effects from the use of sudocetaxel zendusortide leading to a halt of the clinical trial, and that the findings observed from preclinical work conducted on new PDCs are not observed when those are administered into human subjects. We refer current and potential investors to the “Risk Factors” section (Item 3.D) of our Form 20-F dated
We undertake no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise, except as may be required by applicable law.
Contacts:
Investor inquiries:
Senior Vice President and Chief Financial Officer
pdubuc@theratech.com
1-438-315-6608
Media inquiries:
Senior Director, Communications & Corporate Affairs
communications@theratech.com
1-514-336-7800
Source:
2024 GlobeNewswire, Inc., source