On June 15, 2023 Biostar Pharma, Inc. (hereinafter referred to as "Biostar"), the US subsidiary of Beijing Biostar Pharmaceuticals Co., Ltd. which is a synthetic biology driven biopharma company focusing on the discovery, development and commercialization of innovative oncology drugs, reported that, after having in-depth discussions with the FDA through pre-IND meetings, the FDA has approved the IND of a phase 2/3 clinical trial with seamless protocol design for the company’s core product utidelone injectable (UTD1) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, Biostar, JUN 15, 2023, View Source [SID1234632760]).

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Designated as BG01-2202, this trial is a multi-national, phase 2/3, open-label, randomized, controlled clinical study of utidelone injectable (UTD1) versus docetaxel. The study is going to be conducted at about 50 sites in about 10 countries and regions across US, Europe and Asia -Pacific. About 760 patients are planned to be enrolled, 90 for phase 2 with ORR (objective response rate) as the primary endpoint and 670 for phase 3 with OS (overall survival) as the primary endpoint and PFS (progression free survival), ORR, etc. as the secondary endpoints.

Dr. Li Tang, Chairman of Biostar Pharma commented: "This is an important milestone for global development of utidelone injectable — an innovative anti-cancer drug and new generation epothilone analogue. We are fully committed to advancing this pivotal multi-national study and also willing to partner with global pharmaceutical companies to bring this product to market around the world to benefit more patients".

This study was warranted by a previous open-label, multi-center phase 2 trial conducted in China (NCT03693547) of utidelone as single-agent to treat patients with advanced NSCLC who had received at least two prior systemic regimens including platinum-containing chemotherapy or targeted therapy, which demonstrated promising clinical efficacy and manageable safety profile with outcomes of 19.0% ORR, 81.0% DCR (disease control rate), 4.37 months of median PFS and 71% of 12-month OS rate. The median OS was not reached by the cut-off date. The results were selected by 2022 ELCC (European Lung Cancer Congress) as poster presentation. A phase 3 study to evaluate utidelone versus docetaxel in locally advanced or metastatic NSCLC patients that have failed chemotherapy with a platinum-containing regimen has also been initiated and being in progress now in China.

Unmet Medical Need

Lung cancer remains the leading cause of cancer death worldwide [1]. NSCLC accounts for about 85% of lung cancer cases [2,3] and more than 75% of patients with lung cancer are diagnosed with locally advanced or stage IV disease [4]. Although currently targeted therapies and/or immunotherapies are commonly used for advanced NSCLC, limitations are obvious. Many patients either do not have a targetable driver gene alteration or are not suitable for immunotherapy [5,6]. Besides, acquired resistance to targeted- and immune-therapy is a substantial problem. In this case, chemotherapy, such as platinum- and taxane-based regimens, remains the fundamental treatment. However, acquired resistance to standard chemotherapies still presents challenges, which may limit their efficacy [7,8]. There is a huge unmet clinical need for alternative chemotherapeutic agents that can overcome, or are less susceptible to, drug resistance and have clinical efficacy in heavily pretreated patients.

About Utidelone

Being derived from Biostar’s synthetic biology technology platform, utidelone is a genetically engineered best-in-class epothilone analog, which is a class of microtubule-targeting agent that has differential mechanisms of action from taxanes and is developed to overcome drug resistance. Utidelone injectable has been launched in China in 2021 for the treatment of metastatic breast cancer (MBC). It is the only approved new molecular of microtubule inhibitor in the past 10 years around the world. Among all single agent or combination regimen of non-taxane chemotherapies, utidelone injectable is the only one to achieve both PFS and OS benefits for heavily pretreated MBC patients. It demonstrated several advantageous features, such as overcoming taxane-resistant, low hematological toxicity suitable for longer term exposure, ability to cross the blood-brain barrier that is able to prevent and treat tumor brain metastasis. Relevant study results were twice selected for oral presentations at ASCO (Free ASCO Whitepaper) annual meetings and invited to publish in Lancet Oncology and Annals of Oncology.

On June 15, 2023 Avenge Bio, Inc. ("Avenge"), a clinical stage, oncology-focused biotechnology company developing the LOCOcyte Immunotherapy platform for the local administration of potent immune effector molecules to treat solid tumors, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to AVB-001 for the treatment of patients with mesothelioma (Press release, Avenge Bio, JUN 15, 2023, View Source [SID1234632759]).

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Mesothelioma is a highly symptomatic cancer that primarily affects adults. It occurs in the cells that make up the mesothelium of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. In 2022, there were approximately 3,000 new cases reported in the U.S. and approximately 2,500 people died from this cancer. Pleural mesothelioma accounts for approximately 85% of new mesothelioma cases, followed by peritoneal mesothelioma (approximately 15%), and pericardium or tunica vaginalis mesothelioma (<1% combined).

Avenge continues to enroll patients in an ongoing Phase 1/2 clinical trial evaluating AVB-001 for the treatment of refractory ovarian cancer. The Phase 1/2 clinical trial is a first-in-human, single-arm, open-label, dose-escalation and expansion study (NCT05538624) designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of AVB-001 delivered intraperitoneally (IP) to patients with high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube.

In March 2023, Avenge received positive feedback from the FDA on its preclinical and clinical development plans for pleural malignant mesothelioma. Avenge previously published preclinical data establishing the efficacy and safety of pleural administered AVB-001 for the treatment of pleural malignant mesothelioma. The manuscript, entitled "Activation of adaptive and innate immune cells via localized Interleukin-2 cytokine factories eradicates mesothelioma tumors," can be viewed on the Clinical Cancer Research website.

About LOCOcyte Platform

Our LOCOcyte allogeneic cell-based immunotherapy platform enables potent localized modulation of the immune system which also precipitates a systemic immune response, allowing us to treat previously intractable cancers. The technology leverages three unique advantages:

Potent immune effector molecules are generated by synthetically engineering allogeneic cells creating a ready-to-use therapy,
Therapy is localized in proximity to the primary tumor site and generates innate and adaptive immune response, and
The immunomodulator trains the patient’s immune system generating a robust immune response that seeks and eradicates distal metastasis without systemic toxicity.

On June 15, 2023 Recently, the preclinical study results of 9MW2821, the first domestically developed Nectin-4-targeting ADC by Mabwell, were reported in the renowned journal "Molecular Cancer Therapeutics" under the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Mabwell Biotech, JUN 15, 2023, View Source [SID1234632758]). The paper comprehensively elaborated on the development and preclinical study results of 9MW2821 as a new generation Nectin-4-targeting ADC, and systematically compared it with the only approved Nectin-4-targeting ADC on the market (PADCEV, EV).

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Nectin-4 is closely related to the progression and poor prognosis of malignant tumors. Enfortumab Vedotin (EV) is the first Nectin-4-targeting ADC approved by the US Food and Drug Administration (FDA) for the treatment of advanced urothelial carcinoma. However, inadequate efficacy has limited progress in the treatment of other solid tumors with EV. Ocular, pulmonary, and hematological toxic side effects are common in nectin-4-targeting therapy, which frequently results in dose reduction and/or treatment termination. These reasons may limit the wider use of Nectin-4-targeting therapy.

9MW2821 is a novel Nectin-4-targeting ADC based on inter-chain site specific conjugate technology, composed of specially designed linker, novel antibody molecule, and the cytotoxic drug MMAE. It not only has good tumor binding ability and target specificity, but also differs from existing Nectin-4-targeting ADC therapy (PADCEV, EV). It has more homogeneous composition, more stable structure, and superior tumor delivery ability.

In vitro cell experiments and animal studies have found that the unique structure of 9MW2821 brings the following significant characteristics:

9MW2821 enhances the antibody’s internalization activity, exhibiting similar tumor internalization activity as EV in Nectin-4 high-expressing tumors and superior tumor internalization activity compared to EV in low-abundance tumors.
9MW2821 improves the plasma stability of the drug and significantly improves its pharmacokinetic (PK) characteristics. In PK studies, it had a higher intra-tumoral concentration of MMAE (9MW2821, Cmax: 106 pmol/ml; EV, Cmax: 76 pmol/ml; p＜0.01) and intra-tumoral exposure (9MW2821, AUC0-t: 2452 pmol/mL*h; EV, AUC0-t: 2116 pmol/mL*h; p＜0.05).
In the CDX models, 9MW2821 exhibit comparable activity as EV in urothelial carcinoma, and has superior tumor suppression effects in non-small cell lung cancer and breast cancer. In addition, the PDX models show that it has excellent tumor suppression effects in different tumors, including cervical cancer and lung cancer models, and also has certain tumor therapeutic effects in low- to medium-abundance solid tumors and large volume solid tumors.
9MW2821 has good drug safety, and toxicology studies have shown that it has milder skin toxicity, eye toxicity and gastrointestinal toxicity at equivalent doses.
9MW2821 is an ideal ADC with homogeneous drug-to-antibody ratio, tumor-specific properties, bystander killing effect, ideal efficacy in multiple solid tumors, and an acceptable therapeutic window. Based on the above study results, the company is conducting phase I/II clinical studies for 9MW2821 in multiple solid tumors and validating the related study results.

About 9MW2821

The novel Nectin-4-targeting ADC, developed independently based on the Mabwell ADC Platform and High-throughput Screening Platform, has applied for multiple patents for its antibody molecule, linker, drug molecule, and platform-related site-specific conjugation technology.

Currently, multiple clinical studies covering more than 10 types of tumors are being conducted. Preliminary data shows that at the recommended phase 2 dose (RP2D), among 12 evaluable subjects with urothelial carcinoma, the objective response rate (ORR) reached 50%, and the disease control rate (DCR) reached 100%; among 6 evaluable subjects with cervical cancer, the ORR reached 50%, and the DCR reached 100%. The expansion of multiple cohorts, including urothelial carcinoma, cervical cancer, prostate cancer, HER-2 negative breast cancer, and non-small cell lung cancer, is actively being pursued.

On June 15, 2023 Takeda (TSE:4502/NYSE:TAK) and HUTCHMED (China) Limited (Nasdaq/AIM: HCM, HKEX: 13) ("HUTCHMED") reported that the European Medicines Agency ("EMA") has validated and accepted for regulatory review the marketing authorization application ("MAA") for fruquintinib, a highly selective and potent inhibitor of vascular endothelial growth factor receptors ("VEGFR") -1, -2 and -3 for the treatment of adult patients with previously treated metastatic colorectal cancer ("CRC") (Press release, Hutchison China MediTech, JUN 15, 2023, View Source [SID1234632743]). If approved, fruquintinib will be the first and only highly selective inhibitor of all three VEGF receptors approved in the E.U. for previously treated metastatic CRC.1,2

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"European patients with metastatic colorectal cancer have not benefitted from a treatment advancement in over a decade," said Awny Farajallah, M.D., head of Global Medical Affairs Oncology at Takeda. "We are thrilled to have submitted the marketing authorization application to the EMA, bringing us one step closer to potentially offering this innovative therapy to patients with advanced disease. We believe fruquintinib has the potential to address the longstanding unmet need for patients with previously treated metastatic colorectal cancer regardless of their biomarker status, and we look forward to working with the regulators throughout the process."

The MAA for fruquintinib includes results from the Phase III FRESCO-2 trial along with data from the Phase III FRESCO trial conducted in China. FRESCO-2 is a global Phase III multi-regional clinical trial (MRCT) conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus BSC vs. placebo plus BSC in patients with previously treated metastatic CRC. The FRESCO-2 trial met its primary and key secondary endpoints, showing a significant and clinically meaningful improvement in overall survival ("OS") and progression-free survival ("PFS"), respectively. Fruquintinib has been generally well tolerated in patients to date.

"Based on fruquintinib’s clinical profile to date, we are optimistic about its potential as a choice for patients and physicians in the E.U. who find treatment options to be limited for previously treated metastatic colorectal cancer," said Dr. Michael Shi, Head of R&D and Chief Medical Officer, HUTCHMED. "We believe the EMA validation of the marketing authorization application for fruquintinib represents an exciting initial step toward advancing treatment for patients in Europe and look forward to supporting Takeda as it pursues this goal."

The validation follows the acceptance by the U.S. Food and Drug Administration ("FDA") of a new drug application ("NDA"), announced on May 25, 2023, which was granted Priority Review and assigned Prescription Drug User Fee Act (PDUFA) goal date of November 30, 2023. Submission of an NDA to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) is also planned in 2023. Fruquintinib is currently approved in China under the brand name ELUNATE. Approval in China was based on the results of the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, published in The Journal of the American Medical Association, JAMA, in June 2018 (NCT02314819).3 In March 2023, HUTCHMED and Takeda closed an exclusive licensing agreement to further the global development, commercialization and manufacture of fruquintinib outside of China.

About Fruquintinib

Fruquintinib is a highly selective and potent oral inhibitor of VEGFR -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity with the intention of minimizing off-target toxicities, improving tolerability and providing more consistent target coverage. Fruquintinib has been generally well tolerated in patients to date and is being investigated in combinations with other anti-cancer therapies.

About FRESCO-2

The FRESCO-2 study is a multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus BSC vs placebo plus BSC in patients with previously treated metastatic CRC. As previously disclosed, the 691-patient study met its primary endpoint of OS in patients with metastatic CRC who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to OS, a statistically significant improvement in PFS, a key secondary endpoint, was observed. Fruquintinib has been generally well tolerated in patients to date. Summary results were initially presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September 2022.4 Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04322539.

About CRC

CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with more than 935,000 deaths in 2020.5 In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2023.6 In Europe, CRC was the second most common cancer in 2020 with approximately 520,000 new cases and 245,000 deaths. In Japan, CRC was the most common cancer with an estimated 148,000 new cases and 60,000 deaths in 2020.5 Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.

On June 15, 2023 Verastem Oncology, (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that it intends to offer and sell shares of its common stock and pre-funded warrants in an underwritten public offering (Press release, Verastem, JUN 15, 2023, View Source [SID1234632734]). In connection with the proposed offering, Verastem Oncology intends to grant the underwriters a 30-day option to purchase up to an additional 15% of the shares of its common stock offered in the public offering (including shares underlying the pre-funded warrants), at the public offering price, less underwriting discounts and commissions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering. All of the securities to be sold in the offering are to be sold by Verastem Oncology.

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RBC Capital Markets and Cantor are acting as joint book-running managers and representatives of the underwriters for the proposed offering.

Verastem Oncology intends to use the net proceeds from the proposed public offering for (i) continued research and development of its product candidates (ii) potential launch of avutometinib and defactinib in low-grade serous ovarian cancer, and (iii) working capital and other general corporate purposes.

A shelf registration statement on Form S-3 relating to the public offering of the securities described above was declared effective by the Securities and Exchange Commission (the "SEC") on April 6, 2022. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. Before you invest, you should read the preliminary prospectus supplement relating to and describing the terms of such public offering, the accompanying base prospectus, and the related registration statement and other documents that Verastem Oncology has filed with the SEC for more complete information about Verastem Oncology and the proposed offering. These documents, when available, are free and can be found by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the preliminary prospectus supplement and accompanying prospectus relating to the proposed offering may be obtained, when available, by contacting RBC Capital Markets, LLC, Attention: Equity Capital Markets, 200 Vesey Street, 8th Floor, New York, NY, 10281, or by telephone at (877) 822-4089 or by email at [email protected] or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 4th Floor, New York, NY, 10022, by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.