On January 31, 2022 Tollys, a biopharmaceutical company developing the first anti-cancer immunotherapy based on a synthetic Toll-Like Receptor 3 (TLR3) specific agonist, reported that it has renewed and extended its research collaboration started in 2020 with a global pharmaceutical company, a leader in immuno-oncology (Press release, Tollys, JAN 31, 2022, View Source [SID1234607500]). The company also announces the acceleration and expansion of its R&D platform in the fields of TLR3 agonist candidates for intravenous administration and Antibody-Drug-Conjugates (ADC, or AOC for Antibody-Oligonucleotide-Conjugates).

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Based on the strong preclinical data collected to date with locally administered TL-532, Tollys is also accelerating and expanding its internal and collaborative R&D activities on TLR3 agonist candidates designed for intravenous administration and antibody-drug-conjugates. Tollys is thus running several parallel preclinical programs using different vectorization and targeting methods for its TLR3 agonist candidate(s). According to Tollys, TL-532 is the first chemically conjugable specific TLR3 agonist usable as a payload with antibodies and other carriers.

This acceleration in the development of candidates for intravenous administration is in line with the recommendations of the international board of the European oncology innovation acceleration program MATWIN which awarded Tollys TLR3 agonist the status of ‘best-in-class innovation of the year’ in May 2021.

"Our renewed and extended pharma collaboration is further confirmation of the potential of specific TLR3 agonists. We are also very excited to advance our R&D programs for the selection of candidates for intravenous administration; we estimate that a lot more patients could benefit from treatment with TLR3 agonists, if administered intravenously rather than locally," said Vincent Charlon, CEO of Tollys.

About TL-532
TL-532 is the first synthetic specific TLR3 agonist with a proprietary defined double-stranded RNA sequence. As such, TL-532 has the potential to be the best-in-class and first-to-market TLR3 agonist. TL-532 was shown to have a triple mechanism of action inducing 1) death by apoptosis selective to cancer cells-not in normal cells, leading to the in-situ release of tumor specific antigens, 2) activation of the myeloid dendritic cells of the immune system to mount a specific T-cell response against the tumor antigens and 3) switch of the tumor microenvironment, by producing cytokines and chemokines which prevent tumor development. The result is the immunogenic cell death of tumor cells, together with an autovaccination preventing the recurrence of cancer.

On January 31, 2022 NEC reported that Consolidated Financial Results for the Nine-month Period Ended
December 31, 2021 (April 1, 2021 – December 31, 2021) (Press release, NEC, JAN 31, 2022, View Source [SID1234607499])

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1. Consolidated Financial Results for the Nine-month Period Ended December 31, 2021

(1) Consolidated Operating Results
(2) Consolidated Financial Position

2. Dividends

3. Consolidated Financial Results Forecast for the Year Ending March 31, 2022 (April 1, 2021 – March 31, 2022)

This consolidated financial results falls outside the scope of quarterly review procedures to be performed by certified public accountants or an audit firm.

*Explanation concerning the appropriate use of the financial results forecast and other special matters
(Adjusted profit (loss))
"Adjusted operating profit (loss)" is an indicator for measuring underlying profitability in order to clarify the contribution of acquired companies to the NEC Group’s overall earnings. It is measured by deducting amortization of intangible assets recognized as a result of M&A and expenses for acquisition of companies (financial advisory fees and other fees) from operating profit (loss). Also, "Adjusted net profit (loss) attributable to owners of the parent" is an indicator for measuring underlying profitability attributable to owners of the parent. It is measured by deducting adjustment items of operating profit (loss) and corresponding amounts of tax and non-controlling interests from net profit (loss) attributable to owners of the parent.

On January 31, 2022 Patrys reported its Quarterly Activities Report and 4C Quarterly Cash Flow Report (Press release, Patrys, JAN 31, 2022, View Source [SID1234607498]).

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Standout achievements for this Quarter have included:

PAT-DX3 manufacturing development program significantly ahead of schedule;
Non-clinical studies further define biological and pharmaceutical profile of PAT-DX3 deoxymab and potential use for expanded clinical applications;
Business development momentum;
Rodent, non-GLP toxicology studies confirm an acceptable safety and tolerability profile for PAT-DX1; and,
Balance sheet capacity with closing cash balance of $10.76M at 31 Dec 2021, with an additional $2M in short-term investments.

On January 30, 2022 Akeso, Inc. (9926.HK) reported that the first patient was dosed in a Phase III registrational clinical trial of the Company’s novel immuno-oncology drug, Ivonescimab (PD-1/VEGF bi-specific antibody, AK112), combined with chemotherapy versus placebo combined with chemotherapy for the treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) with EGFR mutation failed after EGFR-TKI treatment (Press release, Akeso Biopharma, JAN 30, 2022, View Source [SID1234607496]).

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This clinical trial is the world’s first bi-specific antibody for the Phase III clinical trial of EGFR-TKI resistant NSCLC, and is also an important development of Ivonescimab in the field of lung cancer.

This clinical trial is a randomized, double-blind, multi-center Phase III clinical study with approximately 320 Chinese subjects planned to be enrolled. The purpose of the study is to evaluate the efficacy and safety of Ivonescimab combined with pemetrexed + carboplatin and placebo combined with pemetrexed + carboplatin in the treatment of patients with advanced nsq-NSCLC resistant to EGFR-TKI. The primary endpoint of the study is progression-free survival (PFS) assessed by IRRC.

Lung cancer is a common malignant tumor with high incidence and high mortality in the world, with the number of new lung cancer cases in the world exceeding 2,200,000 in 2020, and the number of new cases in China exceeding 810,000. By type, NSCLC accounts for about 85% of lung cancer, of which about 75% is non-squamous cell NSCLC, and about 70% of NSCLC patients are diagnosed at an advanced stage (Phase IIIB/IV).

For patients with EGFR mutation or ALK fusion mutation-positive NSCLC, although targeted therapy is a first-line standard therapy, issue of drug resistance has become increasingly prominent, and if resistant to targeted therapy, platinum-based chemotherapy remains the most important treatment method, and the existing treatment options cannot effectively meet clinical needs.

”Immunotherapy + anti-angiogenesis” has proven its combined advantages in several worldrenowned studies. As anti-angiogenic therapy can normalize tumor blood vessels and make the tumor microenvironment more suitable for immunotherapy, Immunosuppressants combined with anti-angiogenic drugs has a synergistic anti-tumor effect. This combination is widely appreciated. Lung cancer treatment is the main exploration direction of the above combination therapy; The ”immune + anti-angiogenesis” combination therapy under development in the world for first-line and later-line treatment of NSCLC has shown promising anti-tumor activity and clinical application prospects.

Ivonescimab also has the effect of stimulating antitumor immune responses and inhibiting tumor angiogenesis. Because of the immunosuppressive effect of the overexpressed VEGF in the tumor microenvironment, if a bi-specific antibody can be used to block both PD-1 and VEGF, theoretically the synergistic anti-tumor effect of anti-PD-1 antibody and anti-VEGF antibody can be realized. As a result, Ivonescimab with chemotherapy for the treatment of EGFR-TKI resistant NSCLC is expected to achieve better clinical efficacy and safety than other therapies.

In a number of early clinical studies in Australia and China, Ivonescimab has demonstrated good safety and tolerability in the treatment of various types of lung cancer, including NSCLC and small cell lung cancer (SCLC), with excellent anti-tumor effects. In addition to this study, Ivonescimab’s Phase III clinical trial for the first-line treatment of PD-L1positive NSCLC and Ivonescimab’s Phase III clinical trial for the first-line treatment of extensive SCLC will commence soon. The Phase Ib/II clinical study of Cadonilimab (PD-1/ CTLA-4 bi-specific antibody, AK104) plus Ivonescimab and/or in combination with chemotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) has also been carried out successively.

On January 30, 2022 Akeso, Inc. (9926.HK) reported that the Ligufalimab (CD47 monoclonal antibody, research and development code: AK117, the novel immuno-oncology drug independently developed by the Company) and Ivonescimab (PD-1/VEGF bi-specific antibody, research and development code: AK112) has obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the People’s Republic of China (”China”) to initiate a phase II clinical trial with chemotherapy as first-line therapy for unresectable locally advanced or metastatic triplenegative breast cancer (Press release, Akeso Biopharma, JAN 30, 2022, View Source [SID1234607495]).

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This clinical trial is an open and multi-center phase II clinical trial, which plans to include patients who have not received systemic anti-tumor therapy, are not suitable for radical surgical resection or local therapy, or subjects with locally advanced or metastatic triple-negative breast cancer whose disease progresses after surgical resection or local therapy.

Breast cancer is the most prevalent malignant tumor in women worldwide and in China, among which triple-negative breast cancer (that is, negative for progesterone receptor, estrogen receptor and human epidermal growth factor receptor 2) is highly aggressive and has a high recurrence rate, with a relatively poor prognosis. It is the subtype with the highest recurrence rate and mortality in breast cancer, accounting for approximately 15% of all breast cancers.

Related studies have shown that the mechanisms by which tumor cells evade the innate and adaptive immune systems play a key role in the occurrence and development of recurrent and/or metastatic tumors. An important mechanism of immune escape in triple-negative breast cancer is the expression of CD47. CD47 inhibits the phagocytosis of macrophages by releasing a ”don’t eat me” signal, and at the same time suppresses adaptive immunity by interacting with dendritic cells.

Under the tumor microenvironment, there is a strong correlation between VEGF and PD-1 expression. Therefore, the use of a bi-specific antibody to block PD-1 and VEGF simultaneously can provide a type of drug with more targets in the tumor microenvironment.

Related studies have also shown that the up-regulation of CD47 can inhibit the phagocytosis of macrophages and the anti-tumor effect of VEGF/VEGFR inhibitors. It can also induce the up-regulation of CD47 during anti-angiogenesis therapy. Therefore, blocking both VEGF and CD47 can effectively inhibit the immunosuppressive pathway induced by antiangiogenesis therapy (up-regulation of CD47) while enhancing the phagocytosis of macrophages to improve the anti-tumor efficacy.

Therefore, the combination therapy of Ivonescimab and Ligufalimab is expected to activate both innate and adaptive immune pathways and enhance the targeted recognition of tumors by the immune system, which can create a synergy effect of immunity, anti-angiogenesis and chemotherapy. It is expected to achieve better anti-tumor effects in subjects with advanced triple-negative breast cancer.