On October 23, 2023 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported the latest clinical progress of 2 novel drugs including Nectin-4 ADC 9MW2821, as well as the clinical study data to be reported on ESMO (Free ESMO Whitepaper) 2023 (Press release, Mabwell Biotech, OCT 23, 2023, View Source [SID1234636280]).

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Latest progress & phase I/II study data to report on ESMO (Free ESMO Whitepaper) 2023 of 9MW2821

Up to now, 195 patients with advanced solid tumor have been enrolled in the phase I/II study of Nectin-4 ADC 9MW2821. Among 115 patients with solid tumor treated with 9MW2821 at 1.25mg/kg or above and evaluable for tumor assessment, objective response rate (ORR) and disease control rate (DCR) was 43.5% and 81.7%, respectively. In 37 patients with UC who experienced platinum-based chemotherapy and immune checkpoint inhibitors, dosed at 1.25mg/kg and were evaluable for tumor assessment, ORR and DCR was 62.2% and 91.9%, respectively.

Core data reported on ESMO (Free ESMO Whitepaper) from phase I/II study of 9MW2821 showed that among 39 subjects with solid tumor who treated with 9MW2821 at 1.25mg/kg or above and evaluable for tumor assessment, ORR and DCR was 38.5% and 84.6%, respectively. In 18 patients with UC who dosed at 1.25mg/kg and evaluable for tumor assessment, ORR and DCR was 55.6% and 94.4%, respectively. All UC patients have been treated with platinum-based chemotherapy and immune checkpoint inhibitors before enrollment.

The results showed that 9MW2821 had manageable safety profile. Treatment related death was not observed. Objective responses were also observed in patients with breast cancer and cervical cancer. Enrollment continues to determine efficacy of 9MW2821 in certain solid tumors.

Proactive communication on pivotal trial of 9MW2821 is ongoing.

Latest progress & phase III study data to report on ESMO (Free ESMO Whitepaper) 2023 of 8MW0511

Up to now, Mabwell is in the preparation of New Drug Application submission of 8MW0511 within the year.

Core data from phase III study of recombinant (yeast-secreted) human granulocyte-colony stimulation factor fusion protein 8MW0511 for injection, reported at ESMO (Free ESMO Whitepaper), showed that 8MW0511 was clinically effective, non-inferior to the positive control. It is able to improve the incidence and duration of grade 4 neutropenia, with a significantly lower incidence and duration of grade 4 neutropenia observed at cycle 2-3 than in the positive control group. The overall safety profile is similar to that of the positive control group, which indicates manageable safety profile and good tolerance in humans.

About 9MW2821

Developed by Mabwell’s ADC platform and automated high-throughput hybridoma antibody molecular discovery platform, 9MW2821 is the first clinical stage Nectin-4-targeting ADC developed by Chinese company. Multiple clinical studies of 9MW2821 is ongoing to evaluate safety, tolerability, pharmacokinetics, and preliminary antitumor activity in patients with different types of advanced solid tumors.

About 8MW0511

8MW0511 is a recombinant (yeast-secreted) human granulocyte-colony stimulation factor fusion protein, belonging to Category 1 Therapeutic Biological Products. It is indicated for use in adult patients with non-myeloid malignancies to reduce the incidence of infections manifested by febrile neutropenia when treated with myelosuppressive anticancer drugs that predispose to febrile neutropenia.

On October 23, 2023 Luoxin Pharmaceuticals Group Stock Co., Ltd. (Luoxin Pharmaceutical), reported that LX-039, an innovative anti-tumor drug was selected for poster presentation at the 2023 ESMO (Free ESMO Whitepaper) Annual Congress (Press release, Luoxin Pharmaceutical, OCT 23, 2023, View Source [SID1234636279]).

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ESMO is one of the most influential oncology conferences globally, attracting over 30,000 professionals every year from more than 150 countries and regions. The Congress covers basic research, translational research, and the latest advancements in clinical studies, providing an exchange platform in clinical diagnosis, treatment, and academic discussions.

LX-039 is an innovative selective estrogen receptor degrader (SERD) for oral administration. The aims of the dose escalation and expansion phase I study was to explore the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) profiles of LX-039 in postmenopausal patients with ER+ and HER2- advanced breast cancer who have failed endocrine therapy. The study was led by Professor Hu Xichun from Fudan University Shanghai Cancer Center.

In a 3+3 design, the trial evaluated the safety and tolerability from a daily dose of 50 mg to 1200 mg, with two dosage groups selected for expansion. [18F] Fluoroestradiol PET/CT imaging was used for PD study. All 44 enrolled subjects had previously undergone multiple lines of endocrine therapy. Specifically, 72.7% had received second-line therapy or higher. More than half had been treated with fulvestrant, a medication commonly used for hormone receptor-positive breast cancer. Also, over 50% had received advanced chemotherapy, and 40.9% had been treated with CDK4/6 inhibitors.

Maximum tolerated dose (MTD) was not reached in this study. Most adverse events are graded as mild to moderate (grade 1-2). The exposure of LX-039 increased along with the dose escalation, and no obvious accumulation after multiple doses. Inhibition of the ER pathway is observed in all subjects participating in the PD exploration. Four subjects achieved partial response, with an objective response rate of 10.8% and a clinical benefit rate at 24 weeks of 40%. LX-039 demonstrates good tolerability and PK/PD properties in ER+ and HER2- advanced breast cancer and shows preliminary anti-tumor activity. These encouraging results suggest that LX-039 holds great potential for further development. Consequently, a phase II study is under planning.

About 75% of breast cancer cases are classified as ER+. This subtype of breast cancer relies on the estrogen signaling pathway for its growth and progression. The primary therapeutic approach for ER+ breast cancer involves inhibiting the estrogen signaling pathway through various methods. Notably, drugs like tamoxifen and fulvestrant have been utilized in clinical settings to target the ER pathway. However, tamoxifen resistance and treatment non-compliance with fulvestrant have led to unmet clinical needs.

LX-039, an orally administered selective ER degrader (SERD) developed by Louxin Pharmaceutical, specifically focuses on modulating the estrogen signaling pathway. It antagonizes ER actions and promotes its ubiquitination and degradation within breast cancer cells, downregulating ER expression. LX-039 offers unique therapeutic benefits compared to selective ER modulators and aromatase inhibitors. Additionally, its oral formulation enhances patient convenience and compliance, as it eliminates the need for injections. There are currently no domestically available oral drugs with a similar mechanism of action to LX-039 in the market.

References:

Wang Y, Ayres K L, Goldman D A, et al. 18F-fluoroestradiol PET/CT measurement of estrogen receptor suppression during a phase I trial of the novel estrogen receptor-targeted therapeutic GDC-0810: using an imaging biomarker to guide drug dosage in subsequent trials[J]. Clinical Cancer Research, 2017, 23(12): 3053-3060.
Patel H K, Bihani T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment[J]. Pharmacology & therapeutics, 2018, 186: 1-24.

On October 23, 2023 Sumitomo Pharma Canada, Inc., reported that Health Canada has approved ORGOVYX (relugolix), an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, for the treatment of men with advanced prostate cancer (Press release, Sumitomo Pharmaceuticals, OCT 23, 2023, View Source [SID1234636278]). The approval is based on efficacy and safety data from the Phase 3 HERO study of ORGOVYX in men with advanced prostate cancer. ORGOVYX is expected to be available for prescription in Canada in Q1 2024.

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"Roughly 1 in 8 Canadian men will develop prostate cancer in their lifetime, and the ability to suppress testosterone, primarily achieved through androgen deprivation therapy (ADT), is foundational in the treatment of the advanced stages of the disease," said Fred Saad, M.D., FRCS, Professor and Chairman of the Department of Surgery and Director of Genitourinary Oncology at the University of Montreal. "In the HERO study, ORGOVYX demonstrated rapid, sustained, and profound testosterone suppression when compared to leuprolide. ORGOVYX is the first approved ADT in Canada that can be administered orally, and once daily, offering a safe and effective option for advanced prostate cancer patients in the country."

"We’re pleased that with Health Canada’s approval of ORGOVYX, we are helping to expand upon treatment options for Canadian men living with advanced prostate cancer," said Lisa Mullett, General Manager of Sumitomo Pharma Canada, Inc. "We are committed to making ORGOVYX available to patients across Canada early in the new year."

The Health Canada approval was based on the results of the Phase 3 HERO study, a randomized, open-label, parallel-group, multinational clinical study evaluating the safety and efficacy of ORGOVYX in over 1,000 men with androgen-sensitive advanced prostate cancer who required at least one year of continuous ADT. In the Phase 3 study, ORGOVYX met the primary endpoint and demonstrated superiority in sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks compared to those receiving leuprolide acetate injections, the current standard of care. The most frequent adverse events reported in at least 10% of men in the ORGOVYX group were hot flush, musculoskeletal pain, fatigue, constipation, and mild to moderate diarrhea.

ORGOVYX was previously approved by the U.S. Food and Drug Administration on December 18, 2020 and granted marketing authorization by the European Commission for advanced hormone-sensitive prostate cancer on April 29, 2022.

About Advanced Prostate Cancer
Prostate cancer is the most common cancer in Canadian men, and, in 2023 an estimated 24,700 men will be diagnosed.1 Prostate cancer is considered advanced when it has spread or come back after initial treatment and may include biochemical recurrence (rising prostate-specific antigen in the absence of metastatic disease on imaging), locally advanced disease, or metastatic disease.

Front-line medical therapy for advanced prostate cancer typically involves androgen deprivation therapy, which reduces testosterone to very low levels, commonly referred to as castrate levels (< 50 ng/dL). Luteinizing hormone-releasing hormone (LHRH) receptor agonists, such as leuprolide acetate, are depot injections and the current standard of care for androgen deprivation therapy. However, LHRH receptor agonists may be associated with mechanism-of-action limitations, including the potentially detrimental initial surge in testosterone levels that can exacerbate clinical symptoms, which is known as clinical or hormonal flare, and delayed testosterone recovery after the drug is discontinued.

About ORGOVYX (relugolix)
ORGOVYX (relugolix) is the first and only oral gonadotropin-releasing hormone (GnRH) receptor antagonist approved by the U.S. Food and Drug Administration, the European Commission and Health Canada for the treatment of adult patients with advanced prostate cancer. As a GnRH antagonist, ORGOVYX blocks the GnRH receptor and reduces production of testicular testosterone, a hormone known to stimulate the growth of prostate cancer.

On October 23, 2023 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer, reported submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for the use of TCB-008 in the treatment of relapse/refractory Acute Myeloid Leukemia (Press release, TC Biopharm, OCT 23, 2023, View Source [SID1234636277]). TCB-008, an allogeneic unmodified gamma delta t-cell, is the Company’s lead product and is currently in Phase 2b trials in the U.K. for the treatment of AML.).

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The IND application leverages pioneering research on the use of Gamma Deltas in the treatment of relapse/refractory Acute Myeloid Leukemia. TCB-008 has been designated Orphan Drug Status in the treatment arena of AML previously.

"Filing of the IND for TCB-008 is the next step in the clinical development of TCB-008 and aligns with our strategic refocus announced in Q2 of this year to target our clinical strategy to US trials in the future." said Bryan Kobel, Chief Executive Officer of TC BioPharm. "The IND application leverages supporting clinical study data from ongoing studies in patients with Acute Myeloid Leukemia and is also a reflection of substantial pre-clinical IND enabling work done over the course of the last 6 months by the TCB team. I would like to thank our entire team, who worked tirelessly to complete the Company’s first ever US FDA trial filing. We look forward to working closely with the FDA to garner acceptance of our IND over the coming 30 days and advancing our lead candidate through clinical phases of development."

The FDA will review the application and determine the acceptability of the data before TC BioPharm begins its first clinical trial for TCB-008 It is possible that the FDA will require additional information.

About OmnImmune

OmnImmune an allogeneic unmodified cell therapy consisting of activated and expanded gamma delta T cells. The trial, for treatment of patients suffering from relapse/refractory Acute Myeloid Leukemia (AML). The therapeutic comprises GDT cells sourced from healthy donors, expanded and activated in large numbers before being purified and formulated for infusion into patients. OmnImmune is a frozen and thawed product, now "banked" from donor derived cells.

On October 23, 2023 Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical-stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, reported that it has presented updated efficacy data from the expansion cohort of the TranStar102 of Osemitamab (TST001) plus CAPOX chemotherapy study as the first-line treatment of advanced G/GEJ Cancer at the ESMO (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain (Press release, Transcenta, OCT 23, 2023, View Source [SID1234636276]). The updated data continued to show encouraging efficacy from previously disclosed data in patients with CLDN18.2 expression ≥10%, ≥1+ per the LDT assay used to select patients. Two additional posters were presented: one on preclinical data supporting the triple combination of Osemitamab (TST001), nivolumab and chemotherapy over Osemitamab (TST001) and chemotherapy including in PD-L1 negative tumors; and one detailing the clinical pharmacology explorations supporting the recommended Phase III dose.

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"These latest datasets further solidify the evidence affirming the efficacy that Osemitamab (TST001) plus CAPOX chemotherapy can provide as a first-line treatment for advanced gastric and gastroesophageal cancer including in tumors with lower levels of CLDN18.2 expression, and provide the rationale to explore the triple combination of Osemitamab (TST001), nivolumab and chemotherapy regardless of the PD-L1 CPS levels." said Dr. Caroline Germa, Transcenta’s Executive Vice President, Global Medicine Development and Chief Medical Officer. "We are highly encouraged by the compelling efficacy outcomes from this study in addition to the recent FDA approval to initiate a global Phase III clinical trial, which signifies that Osemitamab (TST001) is poised to redefine the prevailing standard of care for patients with CLDN18.2 positive, HER2 negative gastric and gastroesophageal cancers."

Study Design

Cohort C from Transtar102 study (NCT04495296) was designed to explore the safety and efficacy of Osemitamab (TST001) plus CAPOX as first-line treatment in advanced G/GEJ cancer. In this study, 49 patients were enrolled and treated with 6mg/kg Q3W Osemitamab (TST001) and CAPOX in the efficacy expansion cohort.

Among the 49 patients enrolled, 41 patients had CLDN18.2 positive tumors, and the other 8 patients did not have the biomarker tested. CLDN18.2 expression were tested using the IHC 14G11 LDT assay in a central laboratory. CLDN18.2 positive tumor was defined as ≥ 10% tumor cells staining at least 1+ by the LDT assay, which represents approximately 55% of all the G/GEJ cancer patients.

Encouraging and Durable mDOR and mPFS

At the cut-off date reported here, the median follow-up for the 49 patients was 11.3 months with the longest treatment duration over 1.5 years. Among the 49 patients, 42 patients had measurable lesions at baseline and at least one post-baseline tumor assessment, and 28 of them achieved partial response, with 23 as confirmed response (54.8%, 23/42). The median duration of response (DoR) of these 23 responders was 12.7 months. 20 patients of the 49 patients had progression of disease or death, with an estimated median progression-free survival (PFS) of 14 months. The median overall survival (OS) was not reached because of the limited number of events, the 12-month survival rate for the overall population of cohort-C (64 patients, all doses) was 88.9% (95% CI: 74.2, 95.4). This further supports the Phase III trial strategy of combining Osemitamab (TST001) with nivolumab and chemotherapy in 1L CLDN18.2 positive G/GEJ cancer which Transcenta received FDA clearance recently.

Favorable and Manageable Safety Profile

The safety profile of these 49 patients was mainly characterized by manageable on-target-off-tumor effects, including nausea, hypoalbuminemia, and vomiting, most of them were grade 1 or 2 and occurred during the first 2 cycles.

In addition, preclinical data presented at the congress (#1560P) showed significant upregulation of PD-L1 in gastric cancer cells and increased TIL infiltration into tumor upon treatment with Osemitamab (TST001). The combination of anti-CLDN18.2 Osemitamab (TST001) with PD1 inhibitor nivolumab and chemotherapy resulted in significant synergy including in a CLDN18.2 positive/PD-L1 negative PDX model of gastric cancer. 5/8, 2/8, 0/8, 0/8 of the mice treated with Osemitamab (TST001) plus nivolumab and chemotherapy, Osemitamab (TST001) and chemotherapy, nivolumab and chemotherapy or chemotherapy only achieved tumor clearance in the mouse model respectively.

In an ER analysis of data from 58 patients with 1L G/GEJ adenocarcinoma treated with Osemitamab (TST001) and CAPOX, trends of longer PFS/DoR and higher durable ORR were associated with higher Osemitamab (TST001) exposure and was aligned with exposure range achieved by 6 mg/kg Q3W. Safety ER analyses didn’t demonstrate clinically significant increase in risk when dose increased from 3 to 6 mg/kg Q3W. Preliminary efficacy, safety and PK/PD data demonstrates favorable benefit risk profile and support future exploration of Osemitamab (TST001) at the dose of 6mg/kg Q3W or 4mg/kg Q2W.

About Osemitamab (TST001)

Osemitamab (TST001) is a high affinity humanized anti-CLDN18.2 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity ("ADCC"). It has shown potent anti-tumor activities in tumor xenograft models. Osemitamab (TST001) is the second most advanced CLDN18.2 targeting antibody being developed globally. Osemitamab (TST001) was generated using Transcenta’s Immune Tolerance Breaking Technology (IMTB) platform. Osemitamab (TST001) kills CLDN18.2 expressing tumor cells by mechanisms of ADCC. Leveraging advanced bioprocessing technology, the fucose content of Osemitamab (TST001) was significantly reduced during the production, which further enhanced NK cells mediated ADCC activity of Osemitamab (TST001). Clinical trials for Osemitamab (TST001) are ongoing in the U.S. and China (NCT05190575, NCT04396821, NCT04495296, NCT05608785 / CTR20201281). Osemitamab (TST001) was granted Orphan Drug Designation in the U.S. by FDA for the treatment of patients with gastric or gastroesophageal junction (G/GEJ) and pancreatic cancer.