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Theratechnologies Announces Publication in Frontiers in Oncology Journal Highlighting SORT1+ Technology™ for Targeting SORT1-Mediated Vasculogenic Mimicry

On October 22, 2021 Theratechnologies Inc. (Theratechnologies, or Company) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported the publication of a peer-reviewed article demonstrating that the Company’s novel investigational peptide-drug conjugates (PDCs) TH1902 and TH1904, derived from its SORT1+ Technology, are effective in inhibiting vasculogenic mimicry (VM) in in vitro ovarian and triple negative breast cancer (TNBC) models (Press release, Theratechnologies, OCT 22, 2021, View Source [SID1234596236]).

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The article was published in the science journal Frontiers in Oncology and is titled "New Peptide-Drug Conjugates for Precise Targeting of SORT1-Mediated Vasculogenic Mimicry in the Tumor Microenvironment of TNBC-Derived MDA-MB-231 Breast and Ovarian ES-2 Clear Cell Carcinoma Cells."

"The results published in Frontiers in Oncology showcase for the first time that the sortilin receptor plays a role in the formation of VM, which is associated with cancer progression and resistance. By targeting SORT1, TH1902 and TH1904 have the potential to inhibit VM and cancer cell growth," said Dr. Christian Marsolais, Senior Vice President and Chief Medical Officer at Theratechnologies. "This recognition by our scientific peers highlights the great potential of our PDCs as a unique and effective vehicle for the potential treatment of many types of cancers in which SORT1 receptors are overexpressed and provides additional evidence that SORT1 plays a major role in the generation of VM, particularly in TNBC and ovarian cancer."

The article is the first to report that SORT1 plays a key role in VM formation and highlights the novel results from preclinical models evaluating the efficient inhibitory properties of TH1902 and TH1904 against VM in in vitro ovarian and TNBC cell models. These results further support the expectation that TH1902 and TH1904 may alter the VM process by bringing anticancer drugs, like docetaxel and doxorubicin, into SORT1-positive cancer cells.

The article can be accessed online here.

About Vasculogenic Mimicry
The formation of microvascular channels by deregulated cancer cells leads to aggressive, metastatic and resistant cancer cells and is known as vasculogenic mimicry. VM is believed to be associated with tumor growth, resistance and poor prognosis in many types of aggressive cancers including ovarian and TNBC.

About SORT1+ Technology
Theratechnologies is currently developing a platform of new proprietary peptides for cancer drug development targeting SORT1 receptors called SORT1+ TechnologyTM. SORT1 is a receptor that plays a significant role in protein internalization, sorting and trafficking. It is highly expressed in cancer cells compared to healthy tissue making it an attractive target for cancer drug development. Expression has been demonstrated in, but not limited to, ovarian, triple-negative breast, endometrial, skin, lung, colorectal and pancreatic cancers. Expression of SORT1 is associated with aggressive disease, poor prognosis and decreased survival. It is estimated that the SORT1 receptor is expressed in 40% to 90% of cases of endometrial, ovarian, colorectal, triple-negative breast and pancreatic cancers.

The Company’s innovative peptide-drug conjugates (PDCs) generated through its SORT1+ TechnologyTM demonstrate distinct pharmacodynamic and pharmacokinetic properties that differentiate them from traditional chemotherapy. In contrast to traditional chemotherapy, Theratechnologies’ proprietary PDCs are designed to enable selective delivery of certain anticancer drugs within the tumor microenvironment, and more importantly, directly inside SORT1 cancer cells. Commercially available anticancer drugs, like docetaxel, doxorubicin or tyrosine kinase inhibitors are conjugated to Theratechnologies’ PDC to specifically target SORT1 receptors. This could potentially improve the efficacy and safety of those agents.

In preclinical data, the Company’s SORT1+ TechnologyTM has shown to improve anti-tumor activity and reduce neutropenia and systemic toxicity compared to traditional chemotherapy. Additionally, in preclinical models, SORT1+ TechnologyTM has shown to bypass the multidrug resistance protein 1 (MDR1; also known as P-glycoprotein) and inhibit the formation of vasculogenic mimicry – two key resistance mechanisms of chemotherapy treatment.

About TH1902
TH1902 combines Theratechnologies’ proprietary peptide to the cytotoxic drug docetaxel. TH1902 is currently Theratechnologies’ lead investigational PDC candidate for the treatment of cancer derived from its SORT1+ Technology. The FDA granted fast track designation to TH1902 as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. TH1902 is currently being evaluated in a Phase 1 clinical trial for the treatment of cancers where the sortilin receptor is expressed.

The Company is also evaluating TH1904 in preclinical research, a second PDC derived from its SORT1+ TechnologyTM TH1904 is conjugated to the cytotoxic drug doxorubicin.

The Canadian Cancer Society and the Government of Quebec, through the Consortium Québécois sur la découverte du médicament (CQDM), contributes a total of 1.4 million

Aadi Bioscience Announces Publication of its Phase 2 Registrational (AMPECT) Trial of nab-Sirolimus in Patients with Malignant Perivascular Epithelioid Cell Tumors in the Journal of Clinical Oncology

On October 22, 2021 Aadi Bioscience, Inc. ("Aadi") (Nasdaq: AADI), a clinical-stage biopharmaceutical company focusing on precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, reported the publication of "nab-Sirolimus for Patients with Malignant Perivascular Epithelioid Cell Tumors", detailing its AMPECT study of investigational ABI-009 in the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Journal of Clinical Oncology (Press release, Aadi Bioscience, OCT 22, 2021, View Source [SID1234592017]). The authors concluded that investigational nab-sirolimus (ABI-009, formerly known as nab-rapamycin), if approved, may represent an important new treatment option in malignant PEComa, a rare cancer and aggressive form of sarcoma, with no currently approved treatment.

The content of the publication included the primary analysis, which occurred 6 months after the last patient on the AMPECT study initiated treatment, as well as a 1.5-year follow-up after the primary analysis with a data cutoff of November 23, 2020. In the trial, 34 patients were treated with ABI-009. In the 31 evaluable patients, the overall independently assessed response rate was 39% (12 of 31; with a 95% confidence interval, 22% to 58%) with 1 complete and 11 partial responses. In addition, 52% (16 of 31) of patients had stable disease. The responses were durable and median duration of response was not reached after a median follow-up for response of 2.5 years, and 7 of 12 responders with treatment ongoing (range 5.6-47.2+ months). Responses were of rapid onset (67% by week 6). The safety profile was found to be acceptable with most treatment-related adverse events characterized as low grade and manageable for long-term treatment.

Andrew Wagner, M.D., Ph.D., a senior oncologist at the Dana-Farber Cancer Institute and Principal Investigator of the study, said, "We are excited to publish the data obtained from this trial. nab-Sirolimus delivered highly durable responses in patients with advanced PEComa. Most of the responding patients rapidly achieved a response by their first assessment at 6 weeks following initiation of therapy and these patients have stayed on therapy for extended periods with an acceptable safety profile. We are encouraged by the outcomes in this first-ever prospective clinical trial in patients with this extremely rare disease".

Neil Desai, Ph.D., co-author of the article and Founder, Chief Executive Officer and President of Aadi Bioscience, said, "The Aadi Bioscience team is extremely grateful to the patients, families, and clinical trial teams who help expand the boundaries of available care through their participation in clinical trials. The publication of these results is an important milestone not only for malignant PEComa patients but also for the ongoing development of nab-sirolimus across the planned investigation in TSC1 and TSC2 indications and other combination strategies."

A New Drug Application for investigational ABI-009 is under review by the U.S. Food and Drug Administration for treatment of patients with PEComa and has a Prescription Drug User Fee Action target date of November 26, 2021. If approved, ABI-009 will be known as FYARRO.

Privo Technologies, Inc. Announces Positive Results From Phase 1/2 Clinical Trial for PRV111 in Head and Neck Squamous Cell Carcinoma

On October 22, 2021 Privo Technologies, Inc. ("Privo"), reported the positive results of their Phase 1/2 clinical trial examining their lead asset PRV111 in subjects with early-stage Head and Neck Squamous Cell Carcinoma (HNSCC). PRV111 is an innovative transmucosal delivery system capable of delivering cisplatin topically and directly to the tumor site (Press release, Privo Technologies, OCT 22, 2021, View Source;utm_medium=rss&utm_campaign=privo-technologies-inc-announces-positive-results-from-phase-1-2-clinical-trial-for-prv111-in-head-and-neck-squamous-cell-carcinoma [SID1234591884]). The data from the trial supports the Company’s intended mission since its inception of optimizing state-of-the-art chemotherapeutic drugs to be "Tough on cancer, Easy on patients".

The primary endpoint of the study, which was to determine a safe and efficacious dose of PRV111 based on the incidence of dose-limiting toxicities (DLTs) and tumor volume changes from baseline, was met. PRV111 was associated with an observable tumor volume reduction of 35-100% (mean 69%). The secondary endpoints were to evaluate tumor responses and evaluate systemic, tumor and lymph node platinum levels following administration of PRV111. The overall tumor response rate in evaluable subjects was 87.5% with an average time to response of 5.5 days. No loco-regional recurrence was observed in 100% of subjects who completed a six-month follow-up. An increase in tumor-infiltrating lymphocytes was present post-treatment.

PRV111 showed a favorable safety profile with no severe adverse events (SAEs). Reported treatment emergent adverse events (TEAEs) were mild or moderate in severity, and no dose-limiting toxicities (DLTs) were observed. PRV111 treatment resulted in cisplatin levels that were found to be >350 times higher in the tumor, >110 times higher in lymph nodes, and >700 times lower in the blood than standard of care cisplatin IV treatments. No reported cases of systemic toxicity were observed.

The clinical trial design was Open-Label, Single-Arm Safety, Tolerability, Anti-Tumor Effects, Systemic Exposure, and Device Technical Effects of PRV111 in subjects with Head and Neck Squamous Cell Carcinoma. This was a two-stage, adaptive, first-in-human pharmacokinetic (PK), safety, and efficacy study. In Stage 1 and Stage 2, a total of 10 enrolled subjects were analyzed for safety and PK; eight of the 10 enrolled subjects were analyzed for efficacy.

Following an End-of-Phase 2 Meeting with the U.S. Food & Drug Administration (FDA), Privo is working on establishing the key elements of a Phase 3 program to support a New Drug Application (NDA) for the treatment of early-stage head and neck squamous cell carcinoma (HNSCC) of the oral cavity.

These clinical trial results have clinically validated the Privo’s transmucosal delivery system, and Privo is now also working to further develop PRV111 platform in a range of mucosal cancers including anal, colorectal, genitourinary, nasal and skin cancers and to explore the use of PRV111 for the treatment of precancerous oral cavity lesions.

About SCC

Squamous cell carcinoma (SCC) is cancer of the squamous cells – thin and flat cells that line the epithelia. SCC is found for the most part as a part of skin cancer, but SCC also accounts for the majority of oral, cervical, vaginal/vulval, and colorectal cancers. SCC in body cavities historically is associated with low survival rates and disfiguring surgeries, demonstrating a clear need for a better treatment. Privo focuses on SCC of the oral cavity as it is on the rise globally and lacks a clear treatment option for such a rare disease. Privo was granted Orphan Drug Designation for Treatment of anatomically accessible oral cancers (lip, tongue, gum, floor of mouth, salivary gland, and other oral cavity) by the U.S. FDA.

Notice of Revisions to Financial Forecasts

On October 22, 2021 Chugai Pharmaceutical Co., Ltd. reported that has revised the full-year financial forecasts for the fiscal year ending December 2021 announced on February 4, 2021, considering the recent trend of business results, as follows (Press release, Chugai, OCT 22, 2021, View Source [SID1234591869]).

1. Revised consolidated financial forecasts for the full fiscal year ending December 2021 (January 1 to December 31, 2021)

2. Reasons for the revisions
Forecast of Revenues has been revised to ¥970.0 billion, an increase of ¥170.0 billion from the previous forecast. For domestic sales, forecasted sales amount attributable to the supply of Ronapreve to the government for the fiscal year has been included, and the progress and revised assumptions for each product including Avastin and Tecentriq, which have progressed better than the previous forecast have been reflected. For overseas sales, exports of Actemra and Hemlibra to Roche have been forecasted to be higher than the previous forecast. For royalties and other operating income, the forecast of income and one-time income for Actemra and Hemlibra has also been updated.

Core operating profit forecast has also been revised to ¥400.0 billion, an increase of ¥80.0 billion from the previous forecast. In addition to the above-mentioned revision of revenue forecast, higher cost to sales ratio due to a change in the product mix from the original assumption, etc., foreign exchange effects and increases in some expenses attributable to increased sales and profits have been included.

Core EPS is forecasted to be ¥178.00, an increase of ¥37.00 from the previous forecast. Year-end dividend forecast and the forecast for the Core dividend payout ratio have not been determined at this time.

The revised full-year consolidated forecasts are based on updated foreign exchange rate assumptions: 1CHF = 117 JPY, 1EUR = 130 JPY, 1USD = 107 JPY, and 1SGD = 81 JPY.

Chugai Announces 2021 3rd Quarter Results

On October 22, 2021 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported its financial results for the third quarter of fiscal year 2021 (Press release, Chugai, OCT 22, 2021, View Source [SID1234591824]).

"We achieved robust double-digit growth in both revenues and profits in the nine months under review. This was due to significant increases in both domestic and overseas sales, driven by new products and mainstay products, as well as continued growth in royalty income. As a result, we raised our full year forecast for FY2021. In terms of R&D, I am very pleased that our first mid-size molecule project, LUNA18, has entered the clinical development phase. Mid-size molecule drugs are expected to become the third modality to drive our future growth. Concerning COVID-19, we have filed Ronapreve for subcutaneous administration and the additional indications of treatment for asymptomatic patients and prophylaxis. In order to satisfy unmet medical needs through innovation, we will continue pursuing world-leading science and technology to contribute to patients awaiting treatments." said Dr. Osamu Okuda, Chugai’s President and CEO.

[Third quarter results for 2021]

Revenues and Core operating profit increased by approximately 17% and 25%, respectively, for the third quarter (nine months, Core-basis), mainly due to increases in sales and royalty and profit-sharing income.

Revenues increased by approximately 20% in total since sales, which recorded flat year-on-year growth for the first half, turned to double-digit growth. Domestic sales increased by double digits as the strong oncology field grew further with a mainstay product Tecentriq maintaining high growth despite the NHI price revision in August this year, and the contribution of a new product Polivy. In the primary field, sales increased approximately 30% after reporting a decrease by roughly 10% in the first half. The growth was driven by new products, with the supply of Ronapreve to the government and the market penetration of Enspryng, and double-digit growth of mainstay products, Actemra and Hemlibra. Overseas sales recovered growth and increased by approximately 10% as the further growth of Hemlibra outweighed the decrease in the sales of Actemra. Royalties and other operating income increased by approximately 20% mainly due to increases in royalty and profit-sharing income related to Hemlibra, despite a continued decrease in other operating income resulting from one-time income.

Cost to sales ratio improved by 1.2% points year-on-year to 41.9%, mainly due to an increase in the proportion of in-house products including Hemlibra. Operating expenses increased approximately by 10% as research and development, marketing and distribution, and general and administration expenses all increased. Research and development expenses increased by double digits, continued from the first half, associated with the progress of projects. The increases in marketing and distribution expenses were affected by last year’s decrease in activities due to the spread of the COVID-19. General and administration expenses increased owing to the enterprise tax and various expenses. As a result, core operating profit increased by approximately 25%.
The Company also made good progress in research and development. Its first mid-size molecule project, LUNA18, has entered the clinical development phase. Chugai has been focusing on mid-size molecule drugs as a new modality to constitute the mainstay for driving its medium-to long-term growth. LUNA18 is an oral cyclic peptide RAS inhibitor, and a Phase I clinical trial has been initiated for solid tumors. As for other in-house projects, Chugai has started development of Enspryng in generalized Myasthenia Gravis (gMG), initiating a Phase III clinical trial.

In the efforts to develop treatments for COVID-19, Chugai filed an application for the antibody cocktail Ronapreve, which had received Special Approval in July. The filing is to obtain approval for additional indications for prophylaxis of COVID-19 and treatment of asymptomatic COVID-19, and additional subcutaneous administration. In addition, an application for approval was filed in Europe for Actemra for an additional indication of COVID-19 pneumonia.

[Revision of Full-Year Forecast for 2021]

Chugai raised forecasts (Core-basis) for FY2021 following the strong nine-month results. Regarding domestic sales, the sales forecast attributable to the supply of Ronapreve to the government, which was not expected at the beginning of the fiscal year, has been included, and the progress and revised assumptions have been reflected for each product including Avastin and Tecentriq, which are progressing ahead of the initial forecast. The forecast for overseas sales has been revised upward reflecting that sales of Actemra and Hemlibra should exceed the original forecast. Royalties and other operating income have been also revised upward. As a result, the revenues have been raised to ¥970 billion, an increase of ¥170 billion from the initial forecast. Operating profit forecast has been revised to ¥400 billion, up ¥80 billion from the initial forecast, taking into account a higher cost to sales ratio due to a change in the product mix, and increases in some expenses including the foreign exchange effects.

In accordance with the revision of the financial forecast, year-end dividends forecast was also revised to an undecided value. Reflecting the significant changes in the profit structures, year-end dividends will be decided based on the Company’s dividend policy* after the fiscal year ends.

*Regarding income distribution, taking into account the strategic funding needs and earning prospects, Chugai aims for a consolidated dividend payout ratio of 45% on average in comparison with Core EPS to provide a stable allocation of profit to all shareholders.