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.

On January 30, 2022 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that LENVIMA (generic name: lenvatinib mesylate), the multiple receptor tyrosine kinase inhibitor discovered by Eisai, in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s KEYTRUDA (generic name: pembrolizumab) has been approved in Taiwan for the first-line treatment of patients with advanced renal cell carcinoma (RCC) (Press release, Eisai, JAN 30, 2022, View Source [SID1234607492]). This marks the first approval for LENVIMA which will be used in combination with KEYTRUDA for advanced RCC in Asia.

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The approval is based on results from the CLEAR (Study 307)/KEYNOTE-581 trial evaluating the combination for the first-line treatment of patients with advanced RCC. These results were presented at the 2021 Genitourinary Cancers Symposium (ASCO GU) and simultaneously published in the New England Journal of Medicine. 1 In this trial, LENVIMA plus KEYTRUDA demonstrated statistically significant improvements in the primary efficacy outcome measure of progression-free survival (PFS), as well as the key secondary efficacy outcome measures of overall survival (OS) and objective response rate (ORR) versus sunitinib. For PFS, LENVIMA plus KEYTRUDA reduced the risk of disease progression or death by 61% (HR=0.39 [95% CI: 0.32-0.49]; p<0.0001) with a median PFS of 23.9 months versus 9.2 months for sunitinib. For OS, LENVIMA plus KEYTRUDA reduced the risk of death by 34% (HR=0.66 [95% CI: 0.49-0.88]; p=0.0049) versus sunitinib. Additionally, the confirmed ORR was 71% (95% CI: 66-76) (n=252) for patients who received LENVIMA plus KEYTRUDA versus 36% with sunitinib (95% CI: 31-41) (n=129). LENVIMA plus KEYTRUDA achieved a complete response (CR) rate of 16% and partial response (PR) rate of 55% versus a CR rate of 4% and a PR rate of 32% for those who received sunitinib. 2 In this trial, the five most common adverse reactions (any grade) observed in the LENVIMA plus KEYTRUDA combination arm were fatigue, diarrhea, musculoskeletal disorders, hypothyroidism and hypertension. 2

Worldwide, it is estimated there were more than 430,000 new cases of kidney cancer diagnosed and more than 180,000 deaths from the disease in 2020. 3 In Taiwan, there were more than 1,400 new cases and more than 600 deaths in 2018. 4 Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCC. 5 Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. 6 Approximately 30% of patients with RCC will have metastatic disease at diagnosis, and as many as 40% will develop metastases after primary surgical treatment for localized RCC. 7,8　 The prognosis for these patients is poor as survival is highly dependent on the stage at diagnosis, and the five-year survival rate is 12% for patients diagnosed with metastatic disease. 8

Eisai positions oncology as a key therapeutic area and is aiming to discover innovative new medicines with the potential to cure cancer. Eisai is committed to expanding the potential clinical benefits of lenvatinib for cancer treatment, as it seeks to contribute to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families and healthcare professionals.

*In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with the anti-PD-1 therapy pembrolizumab from Merck & Co., Inc., Kenilworth, N.J., U.S.A.

On January 28, 2022, Shenzhen Aixindawei Pharmaceutical Technology Co., Ltd. (hereinafter referred to as: "Aixindawei" or "the Company") reported that the company’s independently developed small molecule targeted conjugate new drug (project number: AST-001) based on the AKR1C3 enzyme-activated prodrug platform has obtained NMPA’s implicit approval to enter clinical trials (acceptance number CXHL2101680) (Press release, Ascentawits Pharmaceuticals, JAN 28, 2022, View Source [SID1234650302]). The indication is malignant solid tumors. This is another major milestone in the company’s development after the company’s first project AST-3424 obtained NMPA’s implicit approval to enter clinical trials on June 13, 2019.

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Dr. Jianxin Duan, founder and chairman of Aixindawei Pharmaceuticals, said: "We are very pleased that the AST-001 project, another small molecule targeted conjugate new drug independently developed based on the AKR1C3 enzyme-activated prodrug platform, has obtained implicit approval for clinical trials from the NMPA. Multiple preclinical in vitro and in vivo studies have demonstrated that AST-001 has good safety and broad-spectrum anti-tumor activity. In addition, AST-001 has shown encouraging pharmacodynamic effects in multiple in vivo tumor models with high expression of AKR1C3 and KRAS G12D mutations. We are very much looking forward to the clinical performance of AST-001, which will bring more effective and more beneficial treatment options to patients with different tumor types and contribute to a healthy China."