On July 14, 2022 Theratechnologies Inc. ("Theratechnologies" or "the Company") (TSX:TH) (NASDAQ:THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported an update on the dose escalation portion of the TH1902 Phase 1 clinical safety study (Press release, Theratechnologies, JUL 14, 2022, View Source [SID1234616671]). This is Theratechnologies’ first-in-human study of TH1902, its investigational lead peptide drug conjugate ("PDC") linked to docetaxel for the treatment of sortilin-expressing cancers. It has received Fast Track designation from the United States Food and Drug Administration ("FDA").

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"We are pleased to provide an update on TH1902’s safety profile and go forward dosage. The pharmacokinetics data observed in humans showed low levels of free docetaxel, consistent with what was observed in the prior animal studies, leading to a better safety profile than cytotoxics alone. We see this as a nod to TH1902’s safety profile," noted Dr. Christian Marsolais, Chief Medical Officer, Theratechnologies. "In addition, we are excited to see early efficacy signals in heavily pretreated patients in this dose escalation study."

"We are excited to be a part of the TH1902 Phase I study and to have had the opportunity to be the first in the world to enroll a patient," said Dr. Satish Shah, Pennsylvania Cancer Specialist and Research Institute. "Our research institute enrolled multiple patients in the dose escalation phase of the study (Part 1), and we are happy to report that two of our advanced prostate cancer patients, who had progressed on standard chemo/hormone therapies, showed signs of efficacy. The first patient achieved a confirmed partial response with the tumor mass reduction of 53%, and the other patient achieved a PSA response with stabilization of disease without any further progression. We also had an endometrial cancer patient with lung metastases achieve a reduction in lung mass. She achieved prolonged stabilization of disease, over a 33-week period, without further progression, and was able to receive 11 cycles of treatment with TH1902. This is a clinically meaningful result in late-stage disease with very limited treatment options."

A total of 18 heavily pre-treated patients, who received an average of 8 prior cancer treatments, were enrolled in the dose escalation portion of the study. Two of those patients remain on treatment. Following the safety observations at 420 mg/m2 including grade 3 neuropathy, grade 4 neutropenia, grade 3 ocular changes (visual acuity, keratitis and ocular surface dryness) and grade 2 skin toxicities (rash, pruritis and inflammation), the dose of TH1902 was decreased to 300 mg/m2 for the next dose level and was expanded to a total of 6 patients. No Dose Limiting Toxicities were observed during the first cycle, therefore, the dose of 300 mg/m2 was selected for continuation of the basket part of the study. In addition, the levels of free docetaxel are low, at only 11% of those observed at docetaxel treatment dosage of 75 mg/m2. Thus far 300 mg/m2 appears to be a well-tolerated dose level, which continues to be evaluated in the larger basket portion of the TH1902 study.

Signs of efficacy have been observed in three heavily pretreated patients in the dose escalation trial, and recorded results include:

Confirmed partial response in one prostate cancer patient with 53% overall reduction in target lesions after three cycles of TH1902 at 300 mg/m2, PSA continued to progress.
Stabilized disease observed in a prostate cancer patient with measurable reduction in target lesion sizes (single digit percentages), including one PSA response. The patient was treated with mixed cycles of TH1902 from 420 mg/m2 to 300 mg/m2.
Stabilized disease observed in an endometrial cancer patient with measurable reduction in target lesion sizes (single digit percentages). Notably, she received a total of 11 cycles. Her dose was escalated from 60 mg/m2 to 360 mg/m2.
In an effort to optimize and ensure success of this clinical research program, the Company has enrolled six active trial sites across the United States, including Cedars-Sinai in California, Karmanos Cancer Institute and START Midwest in Michigan, Pennsylvania Cancer Specialists Research Centre, Mary Crowley Cancer Research and University of Texas MD Anderson Cancer Center, both in Texas.

Based on the preclinical results obtained so far, Theratechnologies is optimistic for the continued development of a first-in-class and promising treatment for patients with Sortilin positive solid tumors. The Company continues to advance the development of its SORT1+ Technology platform by conjugating the proprietary peptide with other effective anti-cancer agents and by exploring other rational combinations with established anti-cancer drugs.

As noted earlier, the unique mechanism of entry of TH1902 in cancer cells is believed to be a key advantage to improving the therapeutic window of docetaxel. TH1902’s targeted delivery and rapid internationalization in cancer cells via the Sortilin receptor enables the potential to accumulate 7.5 to 10 times more docetaxel in cancer cells as compared to the administration of docetaxel alone. Additionally, as shown in preclinical models, this mechanism reduces the overall exposure of healthy tissue to docetaxel in the body.

About TH1902

TH1902 is Theratechnologies’ proprietary peptide drug conjugate ("PDC") linked to docetaxel, a well-established and well-characterized cytotoxic agent. TH1902 is being developed as a single agent for the treatment of all advanced solid tumors expressing sortilin that are refractory to standard therapy. TH1902 is the Company’s lead PDC drug candidate stemming from Theratechnologies’ SORT1+ Technology in oncology.

About SORT1+ Technology

Theratechnologies has developed a peptide which specifically targets sortilin (SORT1) receptors. SORT1 is expressed in ovarian, endometrial, HR+ and triple negative breast, skin, lung, prostate and thyroid, among other cancers. SORT1 plays a significant role in protein internalization, sorting and trafficking, making it an attractive target for drug development. Commercially available anticancer drugs, like free docetaxel, doxorubicin or tyrosine kinase inhibitors are conjugated to Theratechnologies’ investigational novel peptides to specifically target Sortilin receptors with the aim of improving the efficacy and safety of those agents. It has received Fast Track designation from the United States Food and Drug Administration ("FDA").

What is a basket trial? A type of clinical trial that tests how well a new drug or other substance works in patients who have different types of cancer that all have the same mutation or biomarker. In basket trials, patients all receive the same treatment that targets the specific mutation or biomarker found in their cancer. Basket trials may allow new drugs to be tested and approved more quickly than traditional clinical trials. Basket trials may also be useful for studying rare cancers and cancers with rare genetic changes.