On March 19, 2024 Mabwell (688062.SH), an innovative-driven biopharmaceutical company with entire industry chain, reported the clinical study data of the 9MW2821 for patients with cervical cancer as focused plenary oral presentation at the Society of Gynecologic Oncology (SGO) annual meeting on March 16, 2024 (Press release, Mabwell Biotech, MAR 19, 2024, View Source;the-first-published-clinical-data-of-nectin-4-targeting-adc-developed-by-mabwell-in-cervical-cancer-demonstrates-its-outstanding-therapeutic-potential-302092792.html [SID1234641277]).

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The data showed good efficacy and safety of 9MW2821 in patients with cervical cancer, which is expected to bring new breakthroughs for the treatment of recurrent or metastatic cervical cancer, meeting a large number of unmet clinical needs.

9MW2821 is the first drug to report clinical data for the indication of cervical cancer among the drugs with the same target in the world.

Report on Study Data of Nectin-4-Targeting Antibody-drug Conjugate (ADC) for the Treatment of Recurrent or Metastatic Cervical Cancer

This phase I/II, multicenter, open-label, clinical study was led by Professor Zhang Jian of Fudan University Shanghai Cancer Center, and Professor Yang Huijuan of Fudan University Shanghai Cancer Center represented the study team to give an in-depth report at the meeting. The study results were highly recognized by experts on site. Further clinical study data are expected to provide more treatment options for patients with recurrent or metastatic cervical cancer.

Clinical Findings

The systemic treatment drug options and efficacy for recurrent or metastatic cervical cancer are relatively limited. The cervical cancer cohort in the phase I/II study of 9MW2821 enrolled patients with Nectin-4-positive recurrent or metastatic cervical cancer who had progressed on or after doublet platinum-containing chemotherapy with or without bevacizumab and received no more than two previous systemic regimens for recurrent or metastatic disease. Eligible patients received intravenous 9MW2821 1.25mg/kg on days 1, 8 and 15 of each 28-day cycle until confirmed disease progression, death, intolerable adverse effects or withdrawal from the study.

As of September 25, 2023, in the cervical cancer expansion cohort of the study, the detection rate of Nectin-4 expression was 89.67%, and the rate of Nectin-4 IHC 3+ was 67.82%. A total of 40 patients were enrolled in the study, 57.5% of the patients had previously received platinum-based doublet chemotherapy combined with bevacizumab, and 60% of the patients had previously received platinum-based doublet chemotherapy and immune checkpoint inhibitor therapy.

In terms of efficacy, the overall response rate (ORR) and disease control rate (DCR) of 37 patients evaluable for efficacy were 40.54% and 89.19%, respectively, with one complete response (2.70%) and 14 partial responses (37.84%). Median progression-free survival (PFS), overall survival (OS), and duration of response (DOR) were not reached yet. Among patients with Nectin-4 IHC 3+, the ORR and DCR of 26 patients evaluable for efficacy were 50.00% and 92.31%, respectively. Among patients on or after doublet platinum-containing chemotherapy, the ORR and DCR of 21 patients evaluable for efficacy were 38.10% and 85.71%, respectively.

In terms of safety, treatment-related adverse events (TRAEs) occurred in 92.50% of participants. Grade3-4 TRAEs occurred in 70.00% of participants, with neutropenia (40.00%), rash (17.50%) and gamma-glutamyl transferase increased (12.50%) being the most frequently reported. Nodeaths related to treatment were reported.

The above study results indicate that 9MW2821 has controllable safety and positive efficacy in patients with cervical cancer.

About 9MW2821

9MW2821 is the first site-specific conjugated novel ADC targeting Nectin-4 developed by Mabwell using ADC platform and automated high-throughput hybridoma antibody molecular discovery platform, and is the first product to enter clinical study among the products with the same target developed by Chinese companies. Multiple clinical studies of 9MW2821 have been conducted in China to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of 9MW2821 in patients with various advanced solid tumors.

The phase III clinical study of 9MW2821 monotherapy has officially been initiated in patients with locally advanced or metastatic urothelial carcinoma who have previously received platinum-based chemotherapy and PD-(L)1 inhibitor therapy. The phase I/II clinical study of 9MW2821 in combination with PD-1 inhibitors is also ongoing, with the first patient already enrolled. The phase II clinical study for the indication of esophageal carcinoma will continue enrollment and evaluation, and communication for the initiation of phase III clinical study will be expedited. 9MW2821 was granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) in February 2024 for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma. Currently, 9MW2821 is the first therapeutic drug targeting Nectin-4 in the world to disclose clinical efficacy and safety data for indications of cervical cancer and esophageal carcinoma.

About Cervical Cancer

Cervical cancer is the 4th most common neoplasm and the 4th leading cause of cancer death in females worldwide (excerpted from "Worldwide trends in cervical cancer incidence and mortality, with predictions for the next 15 years, Cancer 2021"). According to the "World Cancer Report 2020" released by the International Agency for Research on Cancer (IARC), there were 600 thousand new cases of cervical cancer worldwide in 2020 and up to 340 thousand deaths caused by cervical cancer. In February 2024, the National Cancer Center published the Cancer Burden Data in China in 2022 on Journal of the National Cancer Center (JNCC), showing that there were 150.7 thousand new cases of cervical cancer and 55.7 thousand deaths in China, ranking 8th and 9th respectively in terms of new cases and number of deaths. Compared with the 119 thousand new cases and 37 thousand deaths released in February 2022 for the same period in 2016, significant increases are observed.

On March 19, 2024 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that results of its preclinical studies on ATG-101 (PD-L1/4-1BB bispecific antibody) were published in Cancer Research in a paper titled ATG-101 is a tetravalent PD-L1×4-1BB bispecific antibody that stimulates anti-tumor immunity through PD-L1 blockade and PD-L1-directed 4-1BB activation[1] (Press release, Antengene, MAR 19, 2024, View Source [SID1234641276]). Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), publishes impactful original studies, reviews, and opinion pieces of high significance to the broad cancer research community. It has a 5-year impact factor of 13.

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"Although immune checkpoint inhibitors (ICIs) have transformed cancer treatment, many patients do not achieve desired treatment outcomes due to innate or acquired resistance," said Dr. Bing Hou, Antengene’s Head of Discovery Science & Translational Medicine, and the corresponding author of the paper. "While 4-1BB has been recognized as a powerful immune stimulating target, the development of therapeutic 4-1BB agonists has been hampered by hepatotoxicity and suboptimal efficacy. In the Cancer Research paper, we present studies used to characterize the differentiated preclinical features and mechanism of action of ATG-101, a tetravalent PD-L1/4-1BB bispecific antibody. ATG-101 activates 4-1BB+ T cells in a PD-L1-crosslinking dependent manner, which minimizes the hepatotoxicity associated with existing 4-1BB agonists and suppresses the growth of ICI-resistant tumors. We wish to continue contributing to the academic community through publications in the future."

"The dedication and relentless efforts of our research team have led to the publication of the preclinical work in the prestigious journal Cancer Research and the development of a new clinical program," said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO." The Phase I study of ATG-101 is currently in the sixth dose escalation cohort and the drug is approaching its biologically active dose with good tolerability. Early observations indicate that a partial response has been observed in a patient with microsatellite stable (MSS) metastatic colon adenocarcinoma with liver metastasis. Moreover, there have also been multiple patients with durable stable disease. These early observations are indeed very encouraging. Moving forward, we will continue working closely with the study sites and investigators to bring a new treatment option to patients who have previously relapsed/progressed on ICIs."

Reference

[1] ATG-101 is a tetravalent PD-L1×4-1BB bispecific antibody that stimulates anti-tumor immunity through PD-L1 blockade and PD-L1-directed 4-1BB activation. Cancer Res (2024). DOI:10.1158/0008-5472.CAN-23-2701.

About ATG-101

ATG-101 is a novel PD-L1/4-1BB bispecific antibody that was designed to block the binding of immunosuppressive PD-1/PD-L1 and conditionally induce 4-1BB stimulation, thus activating anti-tumor immune effectors, while delivering enhanced anti-tumor activity, with an improved safety profile. ATG-101 is currently being developed in Australia, China, and the U.S. in the Phase I study for the treatment of advanced/metastatic solid tumors and B-cell non-Hodgkin lymphoma (B-NHL).

On March 19, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, reported that the Company’s President and Chief Executive Officer, Kristin Yarema, Ph.D., will participate in a virtual fireside chat at the H.C. Wainwright 2nd Annual Cell Therapy Virtual Conference on Tuesday, March 26, 2024 at 1:00pm PT | 4:00pm ET (Press release, Poseida Therapeutics, MAR 19, 2024, View Source [SID1234641275]).

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A live webcast of the fireside chat will be available on the Investors & Media Section of Poseida’s website, www.poseida.com. A replay of the webcast will be available for approximately 90 days following the presentation.

On March 19, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, reported that it will be participating in the H.C. Wainwright 2nd Annual Cell Therapy Virtual Conference on March 26, 2024 (Press release, MediGene, MAR 19, 2024, View Source [SID1234641274]).

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Members of Medigene’s management team will join a fireside chat and will be available for virtual one-on-one meetings with registered investors.

On March 19, 2024 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported financial results for the fourth quarter and full year ended December 31, 2023 and highlighted recent corporate progress (Press release, Tyra Biosciences, MAR 19, 2024, View Source [SID1234641272]).

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"2023 was an outstanding year for TYRA and we are pleased to have positive momentum at the start of 2024," said Todd Harris, CEO of TYRA. "We have strong conviction in our pipeline and believe our lead program TYRA-300 has the potential to become a best-in-class agent for multiple high-value indications. TYRA-300 remains our top priority and we are focused on submitting our Phase 2 IND for achondroplasia, while optimizing dose in SURF301 in preparation for Phase 2 studies in NMIBC and metastatic urothelial carcinoma."

"TYRA is in our strongest financial position to date, with a pro-forma cash position of over $400 million following our PIPE last month. Our ability to retain and attract high quality investors reflects the excitement around our pipeline to deliver value for both shareholders and patient communities," added Alan Fuhrman, Chief Financial Officer of TYRA. "Our current cash, cash equivalents and marketable securities on hand allow us to execute on our plans through at least 2026."

Fourth Quarter 2023 and Recent Corporate Highlights

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Closed a $200M Private Placement Financing. In February 2024, TYRA entered into a securities purchase agreement with new and existing institutional and accredited investors to sell securities in a private placement financing (the PIPE) for gross proceeds of approximately $200 million. The financing was led by RA Capital Management, with participation by new and existing institutional investors, including Boxer Capital, BVF Partners, Nextech Invest Ltd (on behalf of one or more funds managed by it), OrbiMed, 5AM Ventures, a large investment management firm and a life-sciences focused institutional investor.

TYRA-300

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Received FDA Rare Pediatric Disease Designation for the Treatment of Achondroplasia. In January 2024, TYRA-300 was granted Rare Pediatric Disease (RPD) Designation for the treatment of achondroplasia from the U.S. Food and Drug Administration (FDA). TYRA-300 has also received Orphan Drug Designation (ODD) for the treatment of achondroplasia from the FDA.
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SURF301 Phase 1/2 Study for Oncology Continued to Advance. The SURF301 Phase 1 study for oncology (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552) continues to advance. The study is a multi-center, open label study designed to determine the optimal and maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. TYRA expects that the Phase 1 portion of SURF301 will provide data to inform multiple doses and schedules of TYRA-300 in future studies in metastatic urothelial carcinoma (mUC), non-muscle invasive bladder cancer (NMIBC) and achondroplasia. As of March 2024, the Part A Phase 1 portion of SURF301 has completed

dose escalation, and the current expansion cohorts in Part B are evaluating potentially therapeutic once daily and twice daily doses. TYRA expects to submit initial results from its SURF301 Phase 1 portion for presentation at a scientific congress in the second half of 2024.
•
Phase 2 Achondroplasia (ACH) Study On Track. TYRA is planning to initiate a Phase 2 clinical trial testing multiple doses of TYRA-300 to support children with achondroplasia. TYRA expects that the primary objective of this study will be to assess safety and tolerability in children with achondroplasia and determine the dose(s) for further development. TYRA also expects that secondary objectives will include evaluating change in growth velocity, growth proportionality and pharmacokinetics (PK). TYRA is also planning exploratory assessments of clinical outcomes and quality of life measures, and an evaluation of biomarkers to determine dose-response relationships to TYRA-300. TYRA’s current expectation is that the study will initially evaluate treatment naïve children ages 5-12 to determine optimal dose ranges and will also include a separate cohort and analysis of children ages 5-12 with achondroplasia who have received and did not tolerate or respond to a prior growth accelerating therapy. TYRA plans to submit an Investigational New Drug (IND) application to the FDA in the second half of 2024 for the initiation of the Phase 2 study.

TYRA-200

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Phase 1 SURF201 Study Initiated. SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752) is a multi-center, open label study designed to evaluate the safety, tolerability, and PK of TYRA-200 and determine the optimal and MTD and RP2D, as well as evaluate the preliminary antitumor activity of TYRA-200.

TYRA-200 is an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The SURF201 study is currently enrolling and dosing adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations.

SNÅP Platform and Pipeline

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TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions including FGF19+/FGFR4-driven cancers and others.

Fourth Quarter and Full Year 2023 Financial Results

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Fourth quarter 2023 net loss was $22.8 million compared to $12.9 million for the same period in 2022.
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Fourth quarter 2023 research and development expenses were $20.7 million compared to $10.4 million for the same period in 2022.
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Fourth quarter 2023 general and administrative expenses were $5.0 million compared to $4.6 million for the same period in 2022.
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Full year 2023 net loss was $69.1 million compared to $55.3 million for the same period in 2022.
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Full year 2023 research and development expenses were $62.5 million compared to $43.0 million for the same period in 2022.
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Full year 2023 general and administrative expenses were $17.4 million compared to $15.9 million for the same period in 2022.
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As of December 31, 2023, TYRA had cash, cash equivalents, and marketable securities of $203.5 million. Following completion of the approximately $200 million PIPE in February 2024, TYRA’s pro-forma cash position of approximately $403.5 million is expected to support the Company’s important clinical and operational milestones through at least 2026.

About TYRA-300

TYRA-300 is the Company’s lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasias, including achondroplasia. In oncology, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors). SURF301

(NCT05544552) was designed to determine the optimal and MTD and the RP2D of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. SURF301 is currently enrolling adults with advanced urothelial carcinoma and other solid tumors with FGFR3 gene alterations. In skeletal dysplasias, TYRA-300 has demonstrated positive preclinical results, and the Company expects to submit an IND in the second half of 2024 for the initiation of a Phase 2 clinical study in pediatric achondroplasia. In July 2023 and January 2024, the FDA granted ODD and RPD Designation to TYRA-300, respectively, for the treatment of achondroplasia.

About TYRA-200

TYRA-200 is an investigational, oral, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations currently in development for the treatment of cancer. TYRA-200 is being evaluated in a multi-center, open label Phase 1 clinical study, SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors). SURF201 (NCT06160752) was designed to determine the optimal and MTD and the RP2D of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2.