On September 20, 2024 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending approval of HANSIZHUANG (serplulimab), Henlius’ independently developed anti-PD-1 monoclonal antibody (mAb), as a first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) (Press release, Henlius Biopharmaceuticals, SEP 20, 2024, View Source [SID1234646769]). In 2023, Henlius entered into an exclusive license agreement with Intas Pharmaceuticals Limited ("Intas") for the development and commercialisation a total of more than 50 countries in Europe and India. This positive opinion from CHMP marks another step closer for both companies to providing serplulimab for patients in Europe. If approved, serplulimab will be marketed by Intas’ subsidiary, Accord Healthcare Ltd, in Europe.

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Dr. Jason Zhu, Executive Director and Chief Executive Officer of Henlius, stated: "The positive opinion from CHMP signifies a major milestone in our efforts to accelerate the global reach of our products, and further validates Henlius’ patient-centred R&D approach and commitment to global strategy. We look forward to the formal approval of this treatment in Europe, bringing more treatment options and hope to patients there and worldwide."

Paul Tredwell, Executive Vice President of EMENA at Accord, said, "I am thrilled with the CHMP’s positive opinion. This not only strengthens our current partnership with Henlius but also means serplulimab is on track to become part of the treatment landscape for extensive stage small cell lung cancer patients who currently have limited options and face a poor prognosis."

Innovative Approach to Address Clinical Needs of SCLC

According to GLOBOCAN 2022, lung cancer is the most diagnosed and the first mortality cancer around the world. There were more than 2.48 million new cases of lung cancer worldwide in 2022, accounting for 12.4% of all new cancer cases.[1] Small cell lung cancer (SCLC) accounts for 15%–20% of the total number of lung cancer, which is featured by high malignancy, early metastasis, and rapid disease progression, with extremely poor prognosis. SCLC is divided into limited-stage and extensive-stage, with approximately 30%-40% of patients diagnosed at the limited stage and the rest at the extensive stage. With a prevalence of 1-5 per 10,000 people in the European community, SCLC has an orphan disease designation.[2] In December 2022, HANSIZHUANG was granted orphan drug designation by the European Commission (EC) for the treatment of SCLC, and in March 2023, EMA validated the marketing authorisation application (MAA) of HANSIZHUANG for ES-SCLC.

The positive opinion from CHMP is primarily based on ASTRUM-005, a randomized, double-blind, placebo-controlled international multi-centre clinical study, which evaluated the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with ES-SCLC. The study has set up a total of 128 sites in various countries including China, Poland, Turkey, and Georgia, and enrolled 585 subjects, among whom 31.5% were Caucasians. The ASTRUM-005 clinical trial results were firstly presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and published in the Journal of the American Medical Association (JAMA), making it the first study published on JAMA in SCLC immunotherapy. Based on the ASTRUM-005 study, HANSIZHUANG has been approved in China and Southeast Asian countries for first-line treatment of ES-SCLC, making it the world’s first anti-PD-1 mAb approved for first-line treatment of SCLC.

Global Strategy to Fuel Innovation-driven Expansion

HANSIZHUANG, Henlius’ first innovative mAb developed in-house, focuses on high-incidence cancers such as lung cancer and gastrointestinal tumours. In China, it has been approved by the NMPA for the treatment of microsatellite instability-high (MSI-H) solid tumours, squamous non-small cell lung cancer (sqNSCLC), ES-SCLC, and esophageal squamous cell carcinoma (ESCC). The company is also conducting more than 10 clinical studies on immuno-oncology combination therapies worldwide.

Notably, Henlius covers the full range of first-line treatment of lung cancer. In addition to sqNSCLC and ES-SCLC, HANSIZHUANG’s marketing application for first-line treatment of non-squamous NSCLC (nsNSCLC) has been accepted by the National Medical Products Administration (NMPA). Additionally, the company is conducting a phase 3 international multi-centre clinical trial of HANSIZHUANG combined with chemotherapy and radiotherapy for limited-stage SCLC (LS-SCLC). Henlius is also running a bridging head-to-head trial in the U.S. to compare HANSIZHUANG with standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC, which is expected to propel the product towards U.S. market approval further.

The global expansion of HANSIZHUANG is accelerating. It has already been approved in several countries, including China, Indonesia, Cambodia, and Thailand, and has been licensed to over 70 countries and regions, including the US, Europe, Southeast Asia, the Middle East, and North Africa. On December 2023, Henlius received the European Union (EU) GMP Certificates for the production lines of HANSIZHUANG, marking that the company’s Xuhui Facility and Songjiang First Plant have successfully passed the EU GMP on-site inspection for HANSIZHUANG and meet the EU GMP standards. The first overseas shipment of HANSIZHUANG was completed in Q1 2024, making it the first Chinese anti-PD-1 mAb to enter Southeast Asian, offering new treatment options for more global patients.

Looking ahead, Henlius will continue to prioritize patient needs, address unmet clinical demands, and accelerate efforts to deliver high-quality biologics from China to patients worldwide.

On September 19, 2024, Veru Inc. (the "Company") reported to have entered into an Amended and Restated Forbearance Agreement and Amendment to September 2024 Note (the "Amended Forbearance Agreement") with Onconetix, Inc. f/k/a Blue Water Vaccines Inc. (the "Borrower"). The Amended Forbearance Agreement amends and restates the entirety of the Forbearance Agreement, dated as of April 24, 2024 (the "Original Forbearance Agreement"), which related to certain defaults by the Borrower under a Promissory Note in the principal amount of $5,000,000 due on April 19, 2024 (the "April 2024 Promissory Note") and a Promissory Note in the principal amount of $5,000,000 due on September 30, 2024 (as amended, the "September 2024 Promissory Note" and together with the April 2024 Promissory Note, the "Promissory Notes") that were issued by the Borrower to the Company to reflect payment obligations pursuant to the Asset Purchase Agreement, dated as of April 19, 2023 (the "Asset Purchase Agreement"), between the Company and the Borrower (Filing, 8-K, Veru, SEP 20, 2024, View Source [SID1234646768]).

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Pursuant to the Amended Forbearance Agreement, the forbearance period relating to the Company’s agreement to forbear from exercising its rights and remedies on account of the failure by the Borrower to pay the amounts due under the April 2024 Promissory Note on the due date of April 19, 2024 continues to end on the earlier of (a) March 31, 2025 and (b) the occurrence of an Event of Default (as defined in the Amended Forbearance Agreement) (such period, the "April 2024 Forbearance Period"). The Amended Forbearance Agreement extends the due date for the September Promissory Note until the earlier to occur of: (i) June 30, 2025 or (ii) the occurrence of any Event of Default under the Amended Forbearance Agreement. The Amended Forbearance Agreement also effected certain modifications to the payment terms in the Original Forbearance Agreement and amended certain terms of the September 2024 Promissory Note as summarized below.

The Borrower agreed in the Amended Forbearance Agreement to make the following required payments (the "Required Payments") during the April 2024 Forbearance Period first to accrued and unpaid interest under the April 2024 Promissory Note and then any remainder to the outstanding principal amount of the April 2024 Promissory Note:

•
monthly payments equal to 25% (increased from 15% in the Original Forbearance Agreement) of cash receipts of the Borrower or its subsidiaries from certain sale or licensing revenues or payments, which increased amount shall begin on October 20, 2024 for cash receipts in September 2024; and

•
payment of 20% (increased from 10% in the Original Forbearance Agreement) of the net proceeds from certain financing or other transactions outside the ordinary course of business completed by the Borrower or any of its subsidiaries during the April 2024 Forbearance Period, which increased amount will begin for any net proceeds received after September 19, 2024.

The remaining balance of the April 2024 Promissory Note will be due at the end of the April 2024 Forbearance Period.

The Borrower and the Company also agreed to the following amendments to the September 2024 Promissory Note in the Amended Forbearance Agreement:

•
As noted above, an extension of the maturity date to June 30, 2025;

•
The accrual of interest at the rate of 10% per annum on any unpaid principal balance of the September 2024 Promissory Note commencing on October 1, 2024 through the date that the outstanding principal balance under the September 2024 Promissory Note is paid in full.

•
Any amounts owed on the September 2024 Promissory Note, including but not limited to unpaid principal and accrued interest, will be paid in cash or, upon the mutual written consent of the Borrower and the Company, in shares of the Borrower’s common stock or a combination of cash and the Borrower’s common stock.

•
Following full repayment of all principal and interest under the April 2024 Promissory Note, the Borrower will make the Required Payments first towards accrued and unpaid interest under the September 2024 Promissory Note and then towards the remaining principal balance payable under the September 2024 Promissory Note.

•
If the aggregate unpaid principal outstanding under the April 2024 Promissory Note and the September 2024 Promissory Note and all accrued and unpaid interest thereon is repaid in cash on or before December 31, 2024, then the total principal balance under the September 2024 Promissory Note that will be payable by the Borrower in satisfaction of its obligations under the September 2024 Promissory Note will be reduced from $5,000,000 to $3,500,000.

On September 20, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted positive opinions recommending approval of KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, for two indications in gynecologic cancers (Press release, Merck & Co, SEP 20, 2024, View Source [SID1234646767]). The first opinion recommends the approval of KEYTRUDA in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, for the first-line treatment of adult patients with primary advanced or recurrent endometrial carcinoma who are candidates for systemic therapy. The second positive opinion recommends the approval of KEYTRUDA in combination with chemoradiotherapy (CRT) for the treatment of FIGO (International Federation of Gynecology and Obstetrics) 2014 Stage III-IVA locally advanced cervical cancer in adults who have not received prior definitive therapy. The CHMP’s recommendations will now be reviewed by the European Commission for marketing authorization in the European Union (EU), and final decisions are expected in the fourth quarter of 2024.

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"At Merck, we are deeply committed to expanding the role of KEYTRUDA to improve outcomes for more patients facing difficult-to-treat gynecologic cancers as we work to address the impact of women’s cancers around the world," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "These positive CHMP opinions bring us one step closer to providing new immunotherapy-based regimens to more patients with endometrial and cervical cancer in the European Union who may benefit. We look forward to the European Commission’s decisions."

The recommendation in primary advanced or recurrent endometrial carcinoma is based on the NRG-GY018 trial, also known as KEYNOTE-868, evaluating KEYTRUDA in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent. In this study, the KEYTRUDA-based regimen demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus placebo plus carboplatin and paclitaxel. If approved, this would mark the third indication for KEYTRUDA in endometrial cancer in Europe. KEYTRUDA plus LENVIMA (lenvatinib) was approved in November 2021 for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum‑containing therapy in any setting and who are not candidates for curative surgery or radiation, and KEYTRUDA monotherapy was approved in April 2022 for these patients who have microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors. In June 2024, KEYTRUDA in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, was approved in the U.S. for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

The recommendation in newly diagnosed patients with FIGO 2014 Stage III-IVA locally advanced cervical cancer is based on the KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, in which KEYTRUDA in combination with concurrent CRT demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and PFS versus CRT alone. If approved, this would mark the second indication for KEYTRUDA in cervical cancer in Europe. KEYTRUDA plus chemotherapy, with or without bevacizumab, was approved in April 2022 for the treatment of persistent, recurrent or metastatic cervical cancer in adults whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1). In January 2024, KEYTRUDA in combination with CRT was approved in the U.S. for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.

About endometrial carcinoma

Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. Globally, endometrial cancer is the sixth most common cancer in women and 15th most common cancer overall. Worldwide, it is estimated there were approximately 420,368 patients diagnosed with endometrial cancer and 97,723 patient deaths from the disease in 2022. In Europe, it is estimated there were approximately 124,874 patients diagnosed with endometrial cancer and 30,272 patient deaths from the disease in 2022.

About cervical cancer

Cervical cancer forms in the cells lining the cervix, which is the lower part of the uterus. All women are at risk for cervical cancer, and it is most frequently diagnosed between the ages of 35 and 44. While screenings and prevention have resulted in declining cervical cancer rates, the disease continues to affect many people in the U.S. and around the world. Cervical cancer is the fourth most common cancer in women globally. Worldwide, it is estimated there were approximately 662,301 patients diagnosed with cervical cancer and 348,874 patient deaths from the disease in 2022. In Europe, it is estimated there were approximately 58,219 new cases of cervical cancer diagnosed and 26,950 patient deaths from the disease in 2022.

On September 20, 2024 iBio, Inc. (NYSEA:IBIO), an AI-driven innovator of precision antibody immunotherapies, reported its financial results for the fiscal year ended June 30, 2024, and provided a corporate update (Press release, iBioPharma, SEP 20, 2024, View Source [SID1234646766]).

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"Our fiscal year 2024 was a transformational year for iBio, as we’ve solidified our business and financial position as a next-generation antibody company with a machine-learning-enabled platform for designing and developing difficult-to-drug therapeutics," said CEO and Chief Scientific Officer Martin Brenner, Ph.D., DVM. "We made significant progress entering the fast-growing cardiometabolic and obesity space with our collaboration with AstralBio and strengthened our financial position by eliminating our debt associated with the facility and closing a fully subscribed financing including participation from Ikarian Capital, Lynx1 Capital Management, ADAR1 Capital Management, and other institutional and accredited investors. We continued to build our drug discovery platform, adding innovative technologies that are helping to advance our pipeline and provide critical support to our biopharma partners with best-in-class antibody discovery and development projects."

Business Developments:

Expanded the AI-powered technology stack with the launch of ShieldTx, a patent-pending antibody masking technology designed to enable specific, highly targeted antibody delivery to diseased tissue without harming healthy tissue.

In February, iBio closed the sale of its early-stage PD-1 asset to Otsuka Pharmaceutical Co., Ltd. for $1MM in upfront cash with contingent downstream payments of up to $52.5MM, a pivotal moment that showcased the power of iBio’s platform to discover best-in-class assets.

Added bispecific capabilities with its EngageTx technology. We advanced a Trop2 x CD3 molecule to clinical candidate selection stage by demonstrating in a humanized mouse model of squamous cell carcinoma, a significant 36 percent reduction in tumor size 14 days after tumor implantation and after a single dose. Additionally, we leveraged our EngageTx technology and Epitope Steering technology to successfully develop multiple MUC16 x CD3 molecules, which show potent cell killing against ovarian cancer cells.

Entered into a collaboration with AstralBio, Inc. to provide an exclusive license in the cardiometabolic and obesity space. iBio will develop four targets of interest with rights to license up to three of these targets prior to entering the clinic.
Corporate Developments:

At the Company’s Special Meeting of Stockholders held on November 27, 2023, iBio’s stockholders authorized a reverse stock split, with a ratio ranging from 1-for-5 to 1-for-20 (the "Range"), with the ratio within such Range to be determined at the discretion of the Board of Directors (the "Board"), and thereafter the Board approved a one for twenty (1-for-20) reverse stock split of the Company’s shares of common stock. The reverse stock split was effective November 29, 2023.

Entered into a best-efforts public offering with investors in the fiscal second quarter for gross proceeds of approximately $4.5MM before deducting placement agent fees and offering expenses

Entered into a securities purchase agreement for a private investment in public equity financing with several institutional investors and an accredited investor in the fiscal third quarter and consummated the financing in the fiscal fourth quarter for gross proceeds of approximately $15.0MM before deducting placement agent fees and offering expenses.

During the third and fourth quarters, strengthened the Company’s cash position after previously issued warrants were exercised for proceeds of approximately $4.5MM.

The Company closed the sale of its manufacturing facility located in Bryan, Texas (the "Property") to the Board of Regents of the Texas A&M University System for $8.5MM. Following the issuance of pre-funded warrants having a value of $4.5MM to the lender, Woodforest National Bank, iBio and its wholly owned subsidiary, iBio CDMO LLC, satisfied all of the conditions of the settlement agreement releasing the Company and its subsidiary of all obligations with respect to the debt secured by the Property, which coupled with the release of approximately $915K in restricted cash previously held by Woodforest, eliminated approximately $13.2MM in secured debt from the Company’s balance sheet.

Strengthened its Board of Directors and executive leadership team through the appointments of Dr. Brenner to the Board of Directors, effective June 1, 2024, and Kristi Sarno as Senior Vice President, Business Development, effective August 8, 2024.
"We ended this fiscal year well-positioned to advance our technology to drive value for patients and shareholders," said Chief Financial Officer Felipe Duran. "We strengthened our balance sheet through capital raises and debt extinguishment. In fiscal year 2024, we executed transactions which brought in non-dilutive funding, and we continue to pursue business development projects to strengthen our financial position."

Financial Results:

Revenues for the fiscal year ended June 30, 2024, were approximately $0.2 million, an increase of 100% over fiscal 2023.

R&D and G&A expenses for fiscal 2024 decreased $5.1 million and $7.3 million, respectively, over the comparable period in fiscal 2023. The decrease in R&D and G&A reflects the Company’s cost savings implemented to support its growing investments in its pipeline, platform technologies, employees, and related infrastructure.

iBio’s consolidated net loss for the fiscal year ended June 30, 2024, was $24.9 million, a decreased loss of $40.1 million compared to 2023 primarily because of the decrease in expenses related to the Company’s discontinued operations and cost saving initiatives.

iBio held cash, cash equivalents and restricted cash of $14.4 million as of June 30, 2024.

As disclosed in its Annual Report on Form 10-K for the fiscal year ended June 30, 2024, which was filed on September 20, 2024 with the Securities and Exchange Commission, the audited financial statements contained an audit opinion from its registered public accounting firm that includes an explanatory paragraph related to the Company’s ability to continue as a going concern. See further discussion in footnote 2 to the Company’s financial statements included in the Company’s Annual Report on Form 10-K. This announcement is made pursuant to NYSE American LLC Company Guide Sections 401(h) and 610(b), which requires public announcement of the receipt of an audit opinion containing a going concern paragraph.

On September 20, 2024 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that the European Commission (EC) has approved VYLOY (zolbetuximab) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive (Press release, Astellas, SEP 20, 2024, View Source [SID1234646764]). The European Medicines Agency has recommended that zolbetuximab’s designation as an orphan medicinal product be maintained in recognition of the poor survival outcomes associated with gastric and GEJ cancers.

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Zolbetuximab is currently the first and only approved monoclonal antibody specifically designed to target gastric tumor cells that express the biomarker CLDN18.2, offering a more personalized approach to cancer treatment. In the zolbetuximab Phase 3 clinical trials, approximately 38% of adult patients with advanced and metastatic gastric and GEJ cancers had tumors that were CLDN18.2 positive.1,2 By binding to CLDN18.2 expressed on tumor cell membranes, zolbetuximab results in antibody-dependent cellular cytotoxicity, complement dependent cytotoxicity and tumor growth inhibition.3

Zorana Maravic, Chief Executive Officer of Digestive Cancers Europe (DiCE):
"Sadly, due to similar symptoms to more common stomach conditions, gastric and gastroesophageal junction cancers are often diagnosed at the advanced or metastatic stage when treatment options have traditionally been relatively limited. Ensuring timely diagnosis, followed by personalized treatment and care, will be essential to better survival and quality of life for patients."

Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas:
"We are delighted to bring zolbetuximab, a first-in-class targeted treatment option, to patients in Europe where gastric and gastroesophageal cancers are the sixth leading cause of cancer-related death. With zolbetuximab, we’re entering a new era in precision medicine for these advanced cancers, underpinning our ongoing commitment to pioneering scientific discovery that can advance patient outcomes."

Data from the Phase 3 SPOTLIGHT and GLOW clinical trials, which supported the European Marketing Authorization, showed that treatment with zolbetuximab provided statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to other standard of care chemotherapies in eligible patients with gastric and GEJ cancers.1,2 In the SPOTLIGHT trial, a median PFS of 10.61 months was achieved with zolbetuximab plus mFOLFOX6 as first-line treatment, versus 8.67 months with placebo plus mFOLFOX6. The median OS was 18.23 months versus 15.54 months in the respective treatment groups.1 Similar efficacy findings were seen in the GLOW trial where median PFS was 8.21 months versus 6.80 months, and median OS 14.39 months versus 12.16 months, with zolbetuximab plus CAPOX, compared to placebo plus CAPOX, respectively.2 In both the SPOTLIGHT and GLOW trials, the incidence of serious treatment emergent adverse events (TEAEs) was similar in the zolbetuximab treatment groups compared to the controls. The most common all-grade TEAEs reported in the zolbetuximab treatment groups were nausea, vomiting and decreased appetite.1,2

The European Marketing Authorization for zolbetuximab is valid in all 27 EU member states as well as Iceland, Liechtenstein, and Norway, and is aligned to the recently updated ESMO (Free ESMO Whitepaper) Gastric Cancer Living Guidelines which state that the addition of zolbetuximab to chemotherapy can be considered for patients with CLDN18.2 positive, HER-2 negative tumors in the first-line metastatic disease setting.4 Astellas is working closely with local regulatory authorities and health technology assessment bodies across the EU to ensure that patients who may gain benefit from zolbetuximab are able to access the novel treatment as soon as possible.

This regulatory approval for zolbetuximab follows the August 2024 approval by the UK Medicines and Healthcare products Regulatory Agency and the March 2024 approval by Japan’s Ministry of Health, Labour and Welfare.5,6 Astellas has submitted further applications for zolbetuximab to other regulatory agencies around the world with reviews ongoing.

Astellas has already reflected the impact from this result in its financial forecast for the current fiscal year ending March 31, 2025.

About Zolbetuximab
Zolbetuximab is a claudin 18.2-directed cytolytic antibody investigated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive. In both the SPOTLIGHT and GLOW Phase 3 clinical trials, approximately 38% of patients screened had tumors that were CLDN18.2 positive, defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining, assessed and confirmed using an in-vitro companion diagnostic test or medical device.1,2 Astellas collaborated with Roche on the VENTANA CLDN18 (43-14A) RxDx Assay that, upon approval, is intended to be used by a pathologist or laboratory to identify patients eligible for targeted treatment with zolbetuximab.7 This immunohistochemistry based companion diagnostic test is currently under review by the notified body.

As an investigational first-in-class monoclonal antibody (mAb), zolbetuximab targets and binds to CLDN18.2, a transmembrane protein expressed on cancer cells. In pre-clinical studies, zolbetuximab reduced the number of CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, leading to tumor growth inhibition.3

About Locally Advanced Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer
Gastric and gastroesophageal junction (G/GEJ) cancers are known to be histologically similar, are recommended to be managed in the same way in treatment guidelines, and frequently display aligned responses to treatment.2,8 Across Europe, over 135,000 new cases of G/GEJ cancer were diagnosed in 2022.9 G/GEJ cancer is the sixth most common cause of cancer-related mortality in Europe, responsible for 95,431 deaths in 2022.9,10 GEJ adenocarcinomas start in the first two inches (5 cm) where the esophagus joins the stomach.11 The average five-year survival rate for patients in Europe with G/GEJ cancer is 26% across all stages of the disease, driving the need for new therapeutic options that can slow disease progression and extend lives.12

Because early-stage cancer symptoms frequently overlap with more common stomach-related conditions, G/GEJ cancers are often diagnosed in the advanced or metastatic stage, or once they have spread from the tumor’s origin to other body tissues or organs.13

Early signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, bloating of the stomach after meals, and loss of appetite.13,14 Signs of more advanced G/GEJ cancer can include unexplained weight loss, weakness and fatigue, sensation of food getting stuck in the throat while eating, vomiting blood or having blood in the stool.13,14,15 Risk factors associated with G/GEJ cancer can include older age, male gender, family history, H. pylori infection, smoking, and gastroesophageal reflux disease (GERD).16,17

INVESTIGATIONAL STUDIES

About the SPOTLIGHT Phase 3 Clinical Trial
SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive. The study enrolled 565 patients at 215 study locations in the U.S., Canada, United Kingdom, Australia, Europe, South America, and Asia. The primary endpoint is progression-free survival (PFS) of participants treated with the combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), safety and tolerability, and quality-of-life parameters.1

Data from the SPOTLIGHT clinical trial were presented during the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium in an oral presentation on January 19, 2023, and were subsequently published in The Lancet on April 14, 2023.1

For more information, please visit clinicaltrials.gov under Identifier NCT03504397.

About the GLOW Phase 3 Clinical Trial
GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive. The study enrolled 507 patients at 166 study locations in the U.S., Canada, United Kingdom, Europe, South America, and Asia, including Japan. The primary endpoint is PFS in participants treated with the combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include OS, ORR, DOR, safety and tolerability, and quality-of-life parameters.2

Data from the GLOW study were initially presented at the March 2023 ASCO (Free ASCO Whitepaper) Plenary Series with an updated oral presentation at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting on June 3, 2023, and were subsequently published in Nature Medicine on July 31, 2023.2

For more information, please visit clinicaltrials.gov under Identifier NCT03653507.

Investigational Pipeline in CLDN18.2
An expanded Phase 2 trial of zolbetuximab in metastatic pancreatic adenocarcinoma is in progress and recruiting patients. The trial is a randomized, multi-center, open-label study, evaluating the safety and efficacy of investigational zolbetuximab in combination with gemcitabine plus nab-paclitaxel as a first-line treatment in patients with metastatic pancreatic adenocarcinoma with CLDN18.2 positive tumors (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining based on a validated immunohistochemistry assay). For more information, please visit clinicaltrials.gov under Identifier NCT03816163.

In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology area and is currently recruiting patients. ASP2138 is a bispecific monoclonal antibody that binds to CD3 and CLDN18.2, and it is currently in a Phase 1/1b study in participants with metastatic or locally advanced unresectable gastric or GEJ adenocarcinoma or metastatic pancreatic adenocarcinoma whose tumors have CLDN18.2 expression. The safety and efficacy of the agent under investigation have not been established for the uses being considered. For more information, please visit clinicaltrials.gov under Identifier NCT05365581.

There is no guarantee that the agent(s) will receive regulatory approval and become commercially available for the uses being investigated.