On January 15, 2024 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that CT011, an autologous CAR T-cell product candidate against Glypican-3 (GPC3), has achieved Investigational New Drug (IND) clearance from the National Medical Products Administration (NMPA) for patients with GPC3-positive stage IIIa hepatocellular carcinoma who are at high risk of recurrence after surgical resection (Press release, Carsgen Therapeutics, JAN 15, 2024, View Source [SID1234639237]).

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Raffaele Baffa, MD, PhD, Chief Medical Officer of CARsgen Therapeutics, commented, "Hepatocellular carcinoma (HCC) stands as the predominant histologic subtype of primary liver cancer, ranking as the sixth most prevalent cancer type globally. We initially identified GPC3 as a viable target for CAR T-cell therapy and subsequently progressed it to clinical trials for the treatment of HCC. Case report has shown patients with advanced hepatocellular carcinoma have achieved disease-free survival for more than seven years. We will continue to explore the potential of CAR-T for solid tumors and bring new treatment options for patients."

About CT011

CT011 is an autologous GPC3 CAR T-cell product candidate for the treatment of hepatocellular carcinoma (HCC). CT011 received IND clearance from the NMPA in 2019 for the treatment of patients with GPC3-positive solid tumor which was China’s first IND clearance for CAR T-cell therapy against solid tumors. CARsgen have completed enrollment of a Phase I trial in China.

On January 15, 2024 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported the presentation of oncology research at two upcoming medical meetings taking place in-person in San Francisco, California and virtually (Press release, Eisai, JAN 15, 2024, View Source [SID1234639236]). First, the company will share findings in hepatocellular carcinoma (HCC) and cholangiocarcinoma during the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (#GI24), which is taking place from January 18-20. Eisai will also present research results in renal cell carcinoma (RCC) during the 2024 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (#GU24), which is taking place from January 25-27.

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Key Data from Eisai’s Pipeline and Portfolio to be Presented at ASCO (Free ASCO Whitepaper) GI 2024

Notable findings from Eisai’s pipeline include results from a single-arm Phase 2 trial evaluating tasurgratinib (formerly E7090) as a treatment for patients with fibroblast growth factor receptor 2 (FGFR2) gene fusion positive cholangiocarcinoma (NCT04238715(New Window); Abstract: #471). Tasurgratinib, for which a marketing authorization application was submitted in Japan in December 2023, is an orally available selective tyrosine kinase inhibitor of FGFR1-3. An analysis of tumor biomarkers in patients with advanced HCC from a Phase 1b study of E7386*1, a CREB-binding protein (CBP) / β-catenin interaction inhibitor, in combination with lenvatinib, will also be presented (NCT04008797(New Window); Abstract: #535).

Additional data from the LEAP (LEnvatinib And Pembrolizumab) clinical program include longer term efficacy and safety results from the Phase 3 LEAP-002 trial, which evaluated lenvatinib (LENVIMA), the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, plus pembrolizumab (KEYTRUDA*2), the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA, versus lenvatinib monotherapy as a first-line treatment for patients with unresectable HCC (NCT03713593(New Window); Abstract: #482).

The list of notable ASCO (Free ASCO Whitepaper) GI 2024 presentations is included below. These abstracts will be made available via the ASCO (Free ASCO Whitepaper) website on Tuesday, January 16, 2024, at 2:00 PM PST.

ASCO GI 2024
Cancer Type Study/Compound Abstract Title Abstract Type & Details
(Pacific Standard Time)
Pipeline
Gastrointestinal Cancer E7090 Pivotal single-arm, phase 2 trial of tasurgratinib for patients with fibroblast growth factor receptor-2 gene fusion-positive cholangiocarcinoma
Poster Session
Abstract #471
January 19, 2024
12:30-2:00 PM

E7386 Analysis of tumor biomarkers in patients with advanced hepatocellular carcinoma from a phase 1b study of E7386, a CREB-binding protein/β-catenin interaction inhibitor, in combination with lenvatinib
Poster Session
Abstract #535
January 19, 2024
12:30-2:00 PM

Lenvatinib Plus Pembrolizumab
Gastrointestinal Cancer LEAP-002 Lenvatinib plus pembrolizumab versus lenvatinib alone as first-line therapy for advanced hepatocellular carcinoma: longer-term efficacy and safety results from the phase 3 LEAP-002 study
Poster Session
Abstract #482
January 19, 2024
12:30-2:00 PM

　

Key Data from Eisai’s Pipeline and Portfolio to be Presented at ASCO (Free ASCO Whitepaper) GU 2024

Subgroup analyses from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial, which evaluated lenvatinib plus pembrolizumab versus sunitinib for the first-line treatment of patients with advanced renal cell carcinoma (aRCC), will be featured in a rapid oral abstract session (NCT02811861(New Window); Abstract: #364) and a network meta-analysis to assess the efficacy of lenvatinib plus pembrolizumab compared with other first-line treatment options for patients with aRCC will also be presented in a poster session (Abstract: #482). Extended follow-up results from the Phase 2 KEYNOTE-B61 trial evaluating the combination as a first-line treatment for patients with non-clear cell RCC will be shared in a poster presentation (NCT04704219(New Window); Abstract: #2) by Merck & Co., Inc., Rahway, NJ, USA. Finally, a poster featuring real-world evidence on the use of lenvatinib plus everolimus in previously treated patients with aRCC (Abstract: #437) will also be presented.

The list of notable ASCO (Free ASCO Whitepaper) GU 2024 presentations is included below. These abstracts will be made available via the ASCO (Free ASCO Whitepaper) website on Monday, January 22, 2024, at 2:00 PM PST.

ASCO GU 2024
Cancer Type Study/Compound Abstract Title Abstract Type & Details
(Pacific Standard Time)
Lenvatinib Plus Pembrolizumab
Genitourinary Cancer CLEAR Subgroup analyses of efficacy outcomes by baseline tumor size in the phase 3, open‐label CLEAR trial
Rapid Oral Abstract Session
Abstract #364
January 27, 2024
1:00-2:15 PM

Network Meta-Analysis Network meta-analysis to assess comparative efficacy of lenvatinib plus pembrolizumab compared with other first-line treatments for management of advanced renal cell carcinoma
Poster Session
Abstract #482
January 27, 2024
7:00 AM

KEYNOTE-B61 First-line pembrolizumab plus lenvatinib for non-clear cell renal carcinomas: Extended follow-up of the Phase 2 KEYNOTE-B61 Study
(Presented by Merck & Co., Inc., Rahway, NJ, USA)
Poster Session
Abstract #2
January 27, 2024
7:00 AM

Lenvatinib Plus Everolimus
Genitourinary Cancer Real World Evidence Lenvatinib plus everolimus in patients with pre-treated advanced renal cell carcinoma: Real world evidence
Poster Session
Abstract #437
January 27, 2024
7:00AM

　

In March 2018, Eisai and Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA, pembrolizumab. Eisai and Merck & Co., Inc., Rahway, NJ, USA are studying the lenvatinib plus pembrolizumab combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various tumor types across multiple clinical trials.

This release discusses investigational compounds and investigational uses for Food and Drug Administration (FDA)-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

On January 14, 2024 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, will present new data across its dermatologic portfolio of commercially available and pipeline gene expression profile (GEP) tests at the 2024 Winter Clinical Dermatology Conference – Hawaii, being held Jan. 12-17 in Honolulu, Hawaii (Press release, Castle Biosciences, JAN 14, 2024, View Source;Hawaii%C2%AE [SID1234639225]).

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"We are committed to challenging current disease management paradigms and building the evidence supporting our portfolio of clinically actionable molecular tests and their use to improve decision-making for patients with skin cancers and inflammatory skin diseases," said Robert Cook, Ph.D., senior vice president of research and development at Castle Biosciences. "As such, we are proud to share our latest data at Winter Clinical – Hawaii in collaboration with leading physicians who we believe share our vision of transforming the management of these potentially serious diseases."

Highlights from Castle’s posters at Winter Clinical – Hawaii are included below. Posters will be displayed for viewing in the Coral Ballroom 2 through Jan. 16 at 1 p.m. Hawaii Standard Time.

DecisionDx-Melanoma

Real-world evidence confirms risk stratification of the 31-GEP and i31-GEP in prospectively tested patients with stage I-III cutaneous melanoma
Summary: To further advance personalized patient care, Castle’s DecisionDx-Melanoma test result, based on a patient’s tumor biology, was integrated with clinical and pathological factors using a validated proprietary algorithm (i31-GEP for risk of recurrence, or ROR). The i31-GEP ROR provides a more personalized, precise risk of tumor recurrence to guide clinical management of CM. This study aimed to validate the DecisionDx-Melanoma test and i31-GEP ROR algorithm in a real-world cohort of patients with stage I-III CM (n=1,831) who received the DecisionDx-Melanoma test as part of their routine clinical care. The study confirmed the independent and significant risk-stratification provided by DecisionDx-Melanoma and its integrated i31-GEP ROR algorithm, identifying patients at high risk of melanoma recurrence to guide important, risk-appropriate interventions, such as imaging surveillance and immunotherapy, that can potentially improve patient outcomes.
View poster here.
DecisionDx-SCC

The 40-gene expression profile (40-GEP) test identifies cutaneous squamous cell carcinoma (cSCC) patients at high risk of metastasis within lower-staged tumors to better guide treatment decisions
Summary: This study evaluated the ability of DecisionDx-SCC to independently improve the identification of lower-staged tumors at increased risk of metastasis. Improved risk assessment in these lower-staged subsets is important as up to one-third of all metastatic events have been reported for patients originally staged with T1 tumors. Within a cohort of SCC patients considered lower risk by current staging alone, DecisionDx-SCC identified those at a substantially higher risk of metastasis. These results represent a clinically significant improvement in risk assessment for SCC patients with observed rates of metastasis over 10% and 20%, respectively, which are clinically actionable for nodal staging or post-operative adjuvant radiation. Combining traditional risk classification systems with a patient’s individual biologic risk, as provided by the DecisionDx-SCC test, can improve the accuracy of risk assessment to inform important patient treatment decisions.
View poster here.
MyPath Melanoma

Diagnostic discordance among histopathological reviewers for difficult-to-diagnose melanocytic lesions
Summary: Diagnostic discordance in cutaneous melanocytic lesions is well documented and prevalent among difficult-to-diagnose cases, for which histopathology may be insufficient for a definitive diagnosis. MyPath Melanoma testing is available for ambiguous melanocytic neoplasms to add clarity to these diagnoses. This study showed that in a large cohort of patients with suspicious lesions (n=3,317), approximately 24% were difficult to diagnose, supporting the need for an objective diagnostic tool like MyPath Melanoma to aid in providing an accurate diagnosis to help ensure appropriate patient management.
View poster here.
Inflammatory Skin Disease Pipeline Program

Gene expression differences identified in skin samples of mycosis fungoides, atopic dermatitis and psoriasis
Summary: The goal of Castle’s innovative pipeline initiative is to develop a genomic test aimed at guiding systemic therapy selection for patients with moderate-to-severe atopic dermatitis (AD), PSO and related conditions. The test in development would help personalize therapy selection for patients based on their molecular profile and help determine which therapy may best help to manage their symptoms. At the recent 2023 Fall Clinical Dermatology Conference, Castle presented data showing the ability of its pipeline test in development to identify distinct gene expression profiles of super-responders to an AD therapy and also distinguish between AD, PSO and mycosis fungoides (MF) skin lesions. Castle’s poster at Winter Clinical – Hawaii builds on this data by showing the ability of the pipeline test in development to determine the gene expression profile of super-responders to a PSO therapy.
View poster here.
About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile risk stratification test. It is designed to inform two clinical questions in the management of cutaneous melanoma: a patient’s individual risk of sentinel lymph node (SLN) positivity and a patient’s personal risk of melanoma recurrence and/or metastasis. By integrating tumor biology with clinical and pathologic factors using a validated proprietary algorithm, DecisionDx-Melanoma is designed to provide a comprehensive and clinically actionable result to guide risk-aligned patient care. DecisionDx-Melanoma has been shown to be associated with improved patient survival and has been studied in more than 10,000 patient samples. DecisionDx-Melanoma’s clinical value is supported by more than 40 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test’s results. Through Sept. 30, 2023, DecisionDx-Melanoma has been ordered more than 146,000 times for patients diagnosed with cutaneous melanoma.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), Class 2A (higher) or Class 2B (highest) risk category, predicts individual metastatic risk to inform risk-appropriate management. Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

About MyPath Melanoma

MyPath Melanoma is Castle’s gene expression profile test designed to provide an accurate, objective result to aid dermatopathologists and dermatologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately two million suspicious pigmented lesions biopsied annually in the U.S., Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. For these cases, the treatment plan can also be uncertain. Obtaining accurate, objective ancillary testing can mean the difference between a path of overtreatment or the risk of undertreatment. Interpreted in the context of other clinical, laboratory and histopathologic information, MyPath Melanoma is designed to reduce uncertainty and provide confidence for dermatopathologists and help dermatologists deliver more informed patient management plans.

On January 12, 2024 BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of first-in-class immune-modulatory antibodies for cancer immunotherapy, reported that its early discovery partner Exelixis, Inc. has provided a notice of termination for the option and license agreement for novel antibodies for use in immuno-oncology therapeutics (Press release, BioInvent, JAN 12, 2024, https://www.bioinvent.com/en/press/bioinvent-regains-rights-immuno-oncology-targets-exelixis-2191491 [SID1234642491]). It follows a recently announced corporate restructuring program within Exelixis, prioritizing its pipeline of clinical and near-clinical programs. BioInvent regains the full rights to all targets and resulting candidates developed under the collaboration.

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"We have appreciated the excellent partnership with Exelixis which has identified very interesting new pathways," said Dr. Martin Welschof, CEO of BioInvent. "These novel targets, generated from our proprietary F.I.R.S.T platform, formed the basis for generation of unique antibodies for immuno-oncology therapy. BioInvent has a long track record of successful collaborations and the positive progress on these exciting immuno-oncology targets opens the door to further opportunities."

The companies will collaborate on a wind-down and effective transition over the next 90 days. Today’s news has no material financial impact on BioInvent.

On January 12, 2024, Eagle Pharmaceuticals, Inc. (the "Company"), reported to have entered into a Limited Waiver and First Amendment to Third Amended and Restated Credit Agreement (the "Amendment Agreement") with JPMorgan Chase Bank, N.A., as administrative agent (the "Agent"), and the lenders party thereto (the "Lenders"), which (i) provides a waiver of previously disclosed defaults and events of default that occurred and were continuing under the Company’s Third Amended and Restated Credit Agreement, dated as of November 1, 2022 (the "Credit Agreement") and (ii) amends the Credit Agreement (the Credit Agreement as amended by the Amendment Agreement, the "Amended Credit Agreement") (Filing, 8-K, Eagle Pharmaceuticals, JAN 12, 2024, View Source [SID1234639257]).

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Pursuant to the terms of the Amendment Agreement, the Agent and the Lenders have agreed to a limited waiver subject to the terms and conditions described below and set forth in the Amendment Agreement, with respect to, among other things, the defaults and events of default that occurred in connection with (i) the non-reliance determination by the Company in respect of the Company’s financial statements for the quarter ended June 30, 2023 and (ii) the Company’s failure to timely deliver financial statements for the fiscal quarter ended September 30, 2023. As previously disclosed in the Company’s Current Report filed with the SEC on Form 8-K filed on December 15, 2023, the Company was required to deliver to the Agent and lenders, by not later than November 14, 2023, quarterly financial statements certified by one of its officers as presenting fairly in all material respects the financial condition and results of operations of the Company and its consolidated subsidiaries for the fiscal quarter ended September 30, 2023 (the "September 2023 Financials") pursuant to a covenant requiring delivery of quarterly financials within 45 days of the end of each of the first three fiscal quarters of each fiscal year. The Company failed to timely deliver the September 2023 Financials, which such failure constituted a default under the Credit Agreement, subject to a 30-day cure period ending December 14, 2023. The Company failed to timely deliver the September 2023 Financials and accordingly failed to cure such default within the 30-day cure period, which gave rise to an event of default under the Credit Agreement. In addition, in connection with the planned restatement of the financial statements for the quarter ended June 30, 2023 (the "June 2023 Financials"), the Company concluded that the June 2023 Financials previously delivered to the Agent and lenders did not present fairly in all material respects the financial condition and results of operations of the Company and its consolidated subsidiaries and accordingly were not prepared in accordance with generally accepted accounting principles, which gave rise to events of default under the Credit Agreement.

Pursuant to the terms of the Amended Credit Agreement, the Company is required to deliver to the Agent and the Lenders, by not later than February 29, 2024, quarterly financial statements for the fiscal quarters ended June 30, 2023 and September 30, 2023, in each case certified by one of its officers as presenting fairly in all material respects the financial condition and results of operations of the Company and its consolidated subsidiaries for the respective quarter (the "Financial Statement Requirement").

Pursuant to the terms of the Amendment Agreement, until the Company satisfies the Financial Statement Requirement, (i) availability under the Amended Credit Agreement will be reduced from $100 million to $50 million, (ii) the Company will not be permitted to utilize any negative covenant flexibility that is based on a pro forma compliance with any of the Fixed Charge Coverage Ratio, Senior Secured Net Leverage Ratio and/or the Total Net Leverage Ratio test (each as defined in the Amended Credit Agreement), which restricts the Company’s flexibility to, among other things, incur certain additional indebtedness, complete certain corporate transactions, including certain acquisitions and dispositions, or make certain additional restricted payments and (iii) compliance with the minimum liquidity covenant shall be waived.

Pursuant to the terms of the Amended Credit Agreement, failure to timely satisfy the Financial Statement Requirement will result in an event of default. During the continuance of an event of default, the Agent may, with the consent of the required lenders, and shall, at the request of the required lenders, by notice to the Company, terminate undrawn commitments, declare the loans then outstanding to be due and payable in full and/or exercise other remedies available to it, among other things. In addition, the Company’s obligations under the Amended Credit Agreement are secured by a pledge of substantially all of the Company’s assets. If the Company is unable to pay its obligations, the Agent on behalf of the lenders could proceed to protect and enforce their rights under the Amended Credit Agreement, including by foreclosure on the assets securing the Company’s obligations under the Amended Credit Agreement. The foregoing would materially and adversely affect the Company’s business and financial condition. There can be no assurance that the Company will be able to satisfy the Financial Statement Requirement on the required timing or at all, or comply with the terms of the Agreement Amendment and the Amended Credit Agreement.

The foregoing description of the Amendment Agreement is not intended to be complete and is qualified in its entirety by reference to the full text of the Amendment Agreement, which is filed as Exhibit 10.1 to this Current Report on Form 8-K.