Infantile Convulsions and Paroxysmal Choreoathetosis, Familial

The prevalence of cholangiocarcinoma has been rising over the past few years, which prompts the growing demand for treatment options. The increasing prevalence of cholangiocarcinoma and the growing research and development activities to develop novel therapies to treat cholangiocarcinoma to drive the market. The companies developing the potential therapies in the last stage of development include Eisai, Janssen Research & Development, 3D Medicines, and several others. LAS VEGAS, June 7, 2023 /PRNewswire/ -- ' Cholangiocarcinoma Pipeline Insight – 2023 ' report provides comprehensive global coverage of pipeline cholangiocarcinoma therapies in various stages of clinical development, major pharmaceutical companies working to advance the pipeline space and future growth potential of the cholangiocarcinoma pipeline domain. Key Takeaways from the Cholangiocarcinoma Pipeline Report DelveInsight's cholangiocarcinoma pipeline report depicts a robust space with 65+ active players working to develop 70+ pipeline therapies for cholangiocarcinoma treatment. Key cholangiocarcinoma companies such as Merck KGaA, Eisai Inc., Janssen Research & Development, LLC, 3D Medicines, Basilea Pharmaceutica, Hutchison Medipharma Limited, Jiangsu HengRui Medicine, TransThera Sciences, RedHill Biopharma, Eli Lilly and Company, Elevation oncology, Senhwa Biosciences, InnoCare Pharma, Genoscience Pharma, Intensity therapeutics, Elucida Oncology, GlaxoSmithKline, Verismo Therapeutics, Sirnaomics, Toray Industries, Inc, Kinnate Biopharma, Boehringer Ingelheim, Wellmarker Bio, Arbele Limited, NGM Biopharmaceuticals, Inc., Elicio Therapeutics, Xencor, Inc., Celon Pharma SA, and others are evaluating new cholangiocarcinoma drugs to improve the treatment landscape. Promising cholangiocarcinoma pipeline therapies in various stages of development include Camrelizumab, Niraparib, Irinotecan Liposome, ABC294640, Bintrafusp alfa, TT-00420, Erdafitinib, E7090, 3D185, HMPL-453, Derazantinib, Abemaciclib, Seribantumab, CX-4945, ICP-192, GNS561, INT230-6, SynKIR-110, STP705, LY3410738, TRK-950, KIN-3248, BI 905711, WM-S1-030, ARB202, NGM831, ELI-002 2P, XmAb20717, CPL304110, and others. In May 2023, Richard Kim discussed the investigation of RLY-4008 for the treatment of patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement. RLY-4008 is a highly selective, irreversible FGFR2 inhibitor currently under evaluation in the phase 1/2 REFOCUS trial (NCT04526106). Preliminary data reported at the 2022 ESMO Congress showed that patients with FGFR inhibitor–naïve cholangiocarcinoma who had an FGFR2 fusion or rearrangement (n = 17) experienced an overall response rate of 88.2%. In April 2023, Nuvectis Pharma provided highlights from the poster presentation of NXP800 at the American Association for Cancer Research ("AACR") Annual Meeting 2023 in Orlando, FL. The robust preclinical activity demonstrated by NXP8000 in these CCA PDX models was believed to be served as good indicators for potential clinical benefit. CCA is a very difficult-to-treat disease with poor outcomes and today's results provide promise for patients in the future. In April 2023, Verismo Therapeutics received fast-track designation from the US Food and Drug Administration (FDA) for its investigational new drug, SynKIR-110.SynKIR-110 is an investigational drug to treat serious diseases and life-threatening conditions, specifically mesothelin-expressing mesothelioma, ovarian cancer, and cholangiocarcinoma. In January 2023, Taiho Oncology, Inc. announced the publication of results from the pivotal Phase 2 FOENIX*-CCA2 clinical trial of futibatinib in the January 19, 2023 issue of The New England Journal of Medicine (NEJM). In the FOENIX-CCA2 trial, futibatinib showed clinically meaningful benefit in previously treated patients with FGFR2 fusion/rearrangement-positive iCCA, including an objective response rate of 42%, as assessed by independent review, and a median response duration of 9.7 months. Treatment with futibatinib resulted in durable responses and survival that surpassed historical data with chemotherapy in patients with previously treated iCCA. In October 2022, Invitae announced a partnership with AstraZeneca to use Invitae's Ciitizen natural history data in a retrospective and prospective study of patients diagnosed with cholangiocarcinoma, a rare bile duct cancer. This partnership will enable sharing of high-quality, patient-consented data from the patient community of the Cholangiocarcinoma Foundation (CCF), a leading patient advocacy group whose mission is to find a cure and improve the quality of life for those with cholangiocarcinoma. In November 2022, The FDA granted orphan drug designation to ZB131 for treatment of cholangiocarcinoma, according to the agent's manufacturer. ZB131 (ZielBio) is a monoclonal antibody with a high affinity and specificity for cancer-specific plectin. Request a sample and discover the recent advances in cholangiocarcinoma drug treatment @ Cholangiocarcinoma Pipeline Report The cholangiocarcinoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage cholangiocarcinoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the cholangiocarcinoma clinical trial landscape. Cholangiocarcinoma Overview Cholangiocarcinoma is an epithelial cell cancer that arises from several places within the biliary network and exhibits cholangiocyte differentiation markers. The most recent anatomical classifications include intrahepatic, perihilar, and distal cholangiocarcinoma. Many occurrences of cholangiocarcinoma occur without a specific risk factor, but a variety of risk factors have been found, including primary hepatobiliary illness, genetic diseases, toxic exposures, and infections. Like many other cancers, cholangiocarcinoma develops from precursor lesions such as the more common biliary intraepithelial neoplasia and the less common intraductal papillary mucinous neoplasm. Mutations in various oncogenes and tumor suppressor genes cause the normal epithelium to become one of these premalignant lesions. Cholangiocarcinomas have mutations in genes such as RAS, BRAF, p52, SMAD4, and others, but the exact molecular mechanism has not been discovered. Basic laboratory tests for the liver should include aminotransferases, alkaline phosphatase, and total/indirect/direct bilirubin. Cholangiocarcinoma can be treated medically or surgically, although surgery is the only curative option. Find out more about drugs for cholangiocarcinoma @ New Cholangiocarcinoma Drugs A snapshot of the Cholangiocarcinoma Pipeline Drugs mentioned in the report: Learn more about the emerging cholangiocarcinoma pipeline therapies @ Cholangiocarcinoma Clinical Trials Cholangiocarcinoma Therapeutics Assessment The cholangiocarcinoma pipeline report proffers an integral view of cholangiocarcinoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Cholangiocarcinoma Pipeline Report Coverage: Global Cholangiocarcinoma Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Cholangiocarcinoma Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Cholangiocarcinoma Therapeutics Assessment By Route of Administration: Oral, Parenteral, Intravitreal, Subretinal, Topical Cholangiocarcinoma Therapeutics Assessment By Molecule Type: Monoclonal Antibody, Peptides, Polymer, Small molecule, Gene therapy Cholangiocarcinoma Therapeutics Assessment By Mechanism of Action: Type 1 fibroblast growth factor receptor antagonists, Type 3 fibroblast growth factor receptor antagonists, Type 4 fibroblast growth factor receptor antagonists, Type-2 fibroblast growth factor receptor antagonists, Programmed cell death-1 receptor antagonists, Bcr-abl tyrosine kinase inhibitors, EphA2 receptor antagonists, Platelet-derived growth factor beta receptor antagonists, Proto oncogene protein c-kit inhibitors, Src-Family kinase inhibitors, Antibody-dependent cell cytotoxicity, Programmed cell death-1 receptor antagonists, T lymphocyte stimulants, Poly(ADP-ribose) polymerase 1 inhibitors, Poly(ADP-ribose) polymerase 2 inhibitors Key Cholangiocarcinoma Companies: Merck KGaA, Eisai Inc., Janssen Research & Development, LLC, 3D Medicines, Basilea Pharmaceutica, Hutchison Medipharma Limited, Jiangsu HengRui Medicine, TransThera Sciences, RedHill Biopharma, Eli Lilly and Company, Elevation oncology, Senhwa Biosciences, InnoCare Pharma, Genoscience Pharma, Intensity therapeutics, Elucida Oncology, GlaxoSmithKline, Verismo Therapeutics, Sirnaomics, Toray Industries, Inc, Kinnate Biopharma, Boehringer Ingelheim, Wellmarker Bio, Arbele Limited, NGM Biopharmaceuticals, Inc., Elicio Therapeutics, Xencor, Inc., Celon Pharma SA, and others. Key Cholangiocarcinoma Pipeline Therapies: Camrelizumab, Niraparib, Irinotecan Liposome, ABC294640, Bintrafusp alfa, TT-00420, Erdafitinib, E7090, 3D185, HMPL-453, Derazantinib, Abemaciclib, Seribantumab, CX-4945, ICP-192, GNS561, INT230-6, SynKIR-110, STP705, LY3410738, TRK-950, KIN-3248, BI 905711, WM-S1-030, ARB202, NGM831, ELI-002 2P, XmAb20717, CPL304110, and others. Dive deep into rich insights for new drugs for cholangiocarcinoma treatment; visit @ Cholangiocarcinoma Medications Table of Contents For further information on the cholangiocarcinoma pipeline therapeutics, reach out @ Cholangiocarcinoma Drug Treatment Related Reports Cholangiocarcinoma Market Cholangiocarcinoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key cholangiocarcinoma companies, including AstraZeneca, Decalth Systems, Basilea Pharmaceutica, Taiho Oncology, Eisai Pharmaceuticals, TransThera Sciences, Incyte Corporation, Roche, among others. Cholangiocarcinoma Epidemiology Forecast Cholangiocarcinoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and cholangiocarcinoma epidemiology trends. Intrahepatic Cholangiocarcinoma Pipeline Intrahepatic Cholangiocarcinoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key intrahepatic cholangiocarcinoma companies, including Basilea Pharmaceutica, AstraZeneca, Delcath Systems Inc., Jiangsu HengRui Medicine Co., Ltd., Syndax Pharmaceuticals, Hutchison Medipharma Limited, Medivir, Newish Technology (Beijing) Co., Ltd., Relay Therapeutics, Inc., among others. Intrahepatic Cholangiocarcinoma Market Intrahepatic Cholangiocarcinoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key intrahepatic cholangiocarcinoma companies, including Kinnate Biopharma, Taiho Oncology, Inc., Sirtex Medical, Virogin Biotech Ltd, TriSalus Life Sciences, among others. Bile Duct Cancer Pipeline Bile Duct Cancer Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key bile duct cancer companies, including Merck, BMS, Elicio Therapeutics, among others. Biliary Tract Cancers Pipeline Biliary Tract Cancers Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key biliary tract cancers companies, including companies involved such as Merck, RemeGen, EMD Serono, SMT bio Co., Ltd., among others. Related Healthcare Services Healthcare Consulting Healthcare Competitive Intelligence Services Healthcare Asset Prioritization Services About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

NEW YORK, March 27, 2023 /PRNewswire/ -- Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, today reported business highlights and financial results for the fourth quarter and full year ended December 31, 2022. Recent Business Highlights During and since the fourth quarter, Delcath Systems, Inc. (Delcath or the Company): Received an acceptance of the NDA resubmission from the U.S. Food and Drug Administration (FDA) for Hepzato Kit® (melphalan hydrochloride for injection/Hepatic Delivery System) with a Prescription Drug User Fee Act (PDUFA) target action date of August 14, 2023, Priced a financing that is expected to provide an initial upfront funding of $25 million, with up to an additional $60 million tied to satisfaction of milestones, in gross proceeds to Delcath through a private placement. The financing was led by Vivo Capital with participation from Logos Capital, BVF Partners LP, Stonepine Capital Management, LLC, Serrado Capital LLC and existing investor, Rosalind Advisors, Completed in December a private placement with existing investors priced at market for a total of $11.2 million funds raised in 2022, Announced the rotation of its Board of Directors with John R. Sylvester appointed as Chairman, and Reached terms of settlement to end its dispute with medac, its former distributor in Europe. In addition, during and since the fourth quarter, independent investigators published: Updated results from the CHOPIN phase 1B trial in which seven patients with advanced uveal melanoma treated with CHEMOSAT and ipilimumab plus nivolumab show a median PFS of 29.1 months at a median follow-up of 29.1 months, and Results of a Single Center Study in the treatment of Cholangiocarcinoma (CCA) in which the authors concluded that percutaneous hepatic perfusion (PHP) with CHEMOSAT is an effective and safe treatment option for patients with advanced CCA and has the potential to prolong life in patients with inoperable, treatment-refractory liver metastases. The authors highlighted the increasing importance of locoregional forms of therapy in the treatment of CCA and that the new edition of the German S3 cancer guideline "Diagnostics and Therapy of Hepatocellular Carcinoma and Biliary Carcinomas" now includes PHP with melphalan for the treatment of inoperable iCCA or eCCA liver metastases. "With the FDA setting an August 14, 2023, PDUFA date we have crossed a significant milestone for the Company." said Gerard Michel, Chief Executive Officer of Delcath. Mr. Michel added, "We are gratified with the support from both our existing investors and our new investors, all of whom are highly regarded healthcare-focused funds. Their support, potentially totaling up to $85 million, subject to satisfaction of milestones, we believe validates the clinical relevance of and the commercial opportunity for Hepzato in metastatic ocular melanoma. Further, it positions Delcath to execute on HEPZATO commercialization plans upon potential FDA approval. Finally, we eagerly await the publication of interim results from the phase II portion of the CHOPIN study which should provide critical additional information about the potential utility of CHEMOSAT used in sequence with immune checkpoint inhibitors." Income Statement Highlights. Fourth Quarter 2022 Results Product revenue for the three months ended December 31, 2022 was approximately $0.6 million, compared to $0.2 million for the prior year period, from our sales of CHEMOSAT in Europe. This increase in product revenue is primarily due to direct product sales for the fourth quarter of 2022 compared to the revenue share arrangement with our distribution partner in Europe during the fourth quarter of 2021. Other income for the three months ended December 31, 2022 was $1.9 million due to the acceleration of deferred revenue caused by the termination of the medac license agreement. Research and development expenses for the three months ended December 31, 2022 were $4.4 million, compared to $3.6 million in the prior year quarter. The growth in R&D expense is primarily due to increased activity related to the expenses incurred for the preparation of our NDA resubmission which occurred on February 14, 2023. Selling, general and administrative expenses for the three months ended December 31, 2022 were approximately $3.8 million, compared to $3.0 million in the prior year quarter. The increase in general and administrative expenses was primarily due to higher headcount related costs such as higher share-based compensation expense. The Company recorded a net loss for the three months ended December 31, 2022 of $8.5 million, $0.86 per share (basic and diluted), compared to a net loss of $5.3 million, $0.69 per share (basic and diluted), for the same period in 2021. Full Year 2022 Results Product revenue for the year ended December 31, 2022 was approximately $2.5 million, compared to $1.3 million for the prior year from sales of CHEMOSAT in Europe. Other income for the year ended December 31, 2022 was $0.2 million compared to $2.3 million in the prior year primarily due to the termination of the medac license agreement in December last year. Research and development expenses for the year ended December 31, 2022 were $18.6 million compared to $13.8 million in the prior year with the increase due to preparation for the pre-NDA meeting in April 2022 and expenses related to the NDA resubmission. Selling, general and administrative expenses for the year ended December 31, 2022 were approximately $17.3 million compared to $13.6 million in the prior year with the increase primarily due to the pending launch of HEPZATO in the United States and the accrual for the settlement of the medac litigation. The Company recorded a net loss for the year ended December 31, 2022, of $36.5 million, $4.12 per share (basic and diluted), compared to a net loss of $25.6 million $3.59 per share (basic and diluted) for the year ended December 31, 2021. Balance Sheet Highlights On December 31, 2022, the Company had cash, cash equivalents and restricted cash totaling $11.8 million, as compared to cash, cash equivalents and restricted cash totaling $26.9 million on December 31, 2021. During the years ended December 31, 2022, and December 31, 2021, the Company used $25.0 million and $22.6 million, respectively, of cash in our operating activities. The use of cash in operating activities was partially offset by two private placements during 2022 resulting in net proceeds of $10.9 million. On March 15, 2023, the Company returned to Avenue Venture Opportunity Fund L.P. the $4.0 million held in the restricted cash to paydown a portion of the outstanding loan balance. On December 13, 2022, the Company closed a private placement for the issuance and sale of 1,448,889 shares of common stock and 692,042 pre-funded warrants to purchase common stock to certain investors. Each share of common stock was sold at a price per share of $2.90 and the pre-funded warrants were sold at a price of $2.89 per pre-funded warrant. The pre-funded warrants have an exercise price of $0.01 per share of common stock and are immediately exercisable. The Company received gross proceeds from the private placement of approximately $6.2 million before deducting offering expenses. Conference Call Information Delcath will host a conference call today, on March 27, 2023, at 4:30 PM Eastern Time to discuss results for its fourth quarter and full year ended December 31, 2022 and provide a business update. To participate in this event, dial approximately 5 to 10 minutes before the beginning of the call. Event Date: Monday March 27, 2023 Time: 4:30 PM Eastern Time Participant Numbers: Toll Free: 1-833-630-1960 International: 1-412-317-1841 Webcast: CONFERENCE REPLAY US Toll Free: 1-877-344-7529 International Toll: 1-412-317-0088 Replay Access Code: 7305121 End Date: April 03, 2023 About Delcath Systems, Inc. Delcath Systems, Inc. is an interventional oncology company focused on the treatment of primary and metastatic liver cancers. The Company's proprietary products, HEPZATO Kit (melphalan hydrochloride for Injection/Hepatic Delivery System) and CHEMOSAT® Hepatic Delivery System for Melphalan percutaneous hepatic perfusion (PHP) are designed to administer high-dose chemotherapy to the liver while controlling systemic exposure and associated side effects during a PHP procedure. In the United States, HEPZATO Kit is considered an investigational drug/device combination product regulated as a drug by the United States Food and Drug Administration (FDA). HEPZATO Kit is comprised of the chemotherapeutic drug melphalan and Delcath's proprietary Hepatic Delivery System (HDS). The HDS is used to surgically isolate the liver while simultaneously filtrating hepatic venous blood during melphalan infusion and washout. The use of the HDS results in loco-regional delivery of a relatively high melphalan dose, which can potentially induce a clinically meaningful tumor response with minimal hepatotoxicity and reduce systemic exposure. In the US, HEPZATO Kit was the subject of a February 14, 2023 new drug application resubmission to FDA for the treatment of patients with unresectable hepatic-dominant metastatic ocular melanoma (mOM), also known as metastatic uveal melanoma (mUM). The FDA has established an August 14, 2023 PDUFA target action date for the resubmission. In Europe, the device-only configuration of the HDS is regulated as a Class III medical device and is approved for sale under the trade name CHEMOSAT Hepatic Delivery System for Melphalan, or CHEMOSAT, where it has been used in the conduct of percutaneous hepatic perfusion procedures at major medical centers to treat a wide range of cancers of the liver. Safe Harbor / Forward-Looking Statements The Private Securities Litigation Reform Act of 1995 provides a safe harbor for forward-looking statements made by the Company or on its behalf. This news release contains forward-looking statements, which are subject to certain risks and uncertainties that can cause actual results to differ materially from those described in particular, the statements regarding our private placement and expected gross proceeds and the expected uses of the proceeds from the private placement. Factors that may cause such differences include, but are not limited to, uncertainties relating to: achievement of milestones, the likelihood and timing of the FDA's potential approval of the NDA for HEPZATO by the FDA by the PDUFA date of August 14, 2023, the Company's ability to commercialize HEPZATO, the receipt of stockholder approval to allow for the conversion of the Series F Preferred Stock into shares of the Company's common stock; the Company's ability to generate revenue from HEPZATO, clinical adoption, use and resulting sales, if any, for the CHEMOSAT system to deliver and filter melphalan in; the Company's ability to successfully commercialize the HEPZATO KIT/CHEMOSAT system and the potential of the HEPZATO KIT/CHEMOSAT system as a treatment for patients with primary and metastatic disease in the liver; approval of the current or future HEPZATO KIT/CHEMOSAT system for delivery and filtration of melphalan or other chemotherapeutic agents for various indications in the U.S. and/or in foreign markets; actions by the FDA or foreign regulatory agencies; uncertainties relating to the timing and results of research and development projects; and uncertainties regarding the Company's ability to obtain financial and other resources for any research, development, clinical trials and commercialization activities. These factors, and others, are discussed from time to time in our filings with the SEC. You should not place undue reliance on these forward-looking statements, which speak only as of the date they are made. We undertake no obligation to publicly update or revise these forward-looking statements to reflect events or circumstances after the date they are made. Investor Relations Contact: Ben Shamsian Lytham Partners 646-829-9701 shamsian@lythampartners.com Company Codes: NASDAQ-NMS:DCTH

Treatment with futibatinib resulted in durable responses and survival surpassing historical data with chemotherapy in patients with previously treated disease. Patients in the study reported stable quality of life over nine months of treatment. Data supported U.S. Food and Drug Administration accelerated approval of LYTGOBI® (futibatinib) tablets in September 2022; continued approval may be contingent upon a confirmatory trial(s). PRINCETON, N.J., Jan. 18, 2023 /PRNewswire/ -- Taiho Oncology, Inc. today announced the publication of results from the pivotal Phase 2 FOENIX*-CCA2 clinical trial of futibatinib in the January 19, 2023 issue of The New England Journal of Medicine (NEJM). The article, "Futibatinib for Intrahepatic Cholangiocarcinoma with FGFR2 Fusions/Rearrangements," reports on data from the FOENIX-CCA2 trial, a global open-label study evaluating patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements. These data supported the U.S. Food and Drug Administration (FDA) accelerated approval of futibatinib tablets – brand name LYTGOBI® – in September 2022 for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic iCCA harboring FGFR2 gene fusions or other rearrangements. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1 In the FOENIX-CCA2 trial, futibatinib showed clinically meaningful benefit in previously treated patients with FGFR2 fusion/rearrangement-positive iCCA, including an objective response rate of 42%, as assessed by independent review, and a median response duration of 9.7 months. Treatment with futibatinib resulted in durable responses and survival that surpassed historical data with chemotherapy in patients with previously treated iCCA. According to the investigators, these data suggest that a molecularly-targeted agent like futibatinib can substantially improve outcomes for patients with iCCA harboring FGFR2 fusions/rearrangements. "The FOENIX-CCA2 trial results demonstrate that futibatinib is an effective treatment for FGFR2 fusion/rearrangement positive cholangiocarcinoma. Its activity and safety profile offer a new treatment in this setting. These data reinforce the importance of molecular profiling in cholangiocarcinoma and represent a step forward for patients facing a difficult disease," said Lipika Goyal, MD, MPhil, the lead investigator for FOENIX-CCA2 and previously a medical oncologist at Mass General Cancer Center and now Associate Professor and Director of Gastrointestinal Cancer at the Stanford School of Medicine. Cholangiocarcinoma is an aggressive cancer of the bile ducts and is diagnosed in approximately 8,000 individuals each year in the U.S.2 This includes both intrahepatic (inside the liver) and extrahepatic (outside the liver) forms of the disease. Approximately 10-16% of patients with iCCA have FGFR2 gene rearrangements, including fusions, which promote tumor proliferation.3,4,5,6,7 Historically, patients with iCCA have a five-year overall survival rate of less than 8% with a median overall survival of approximately one year in advanced stages,8,9 underscoring the unmet need for additional second-line therapies. Futibatinib is an oral, potent, selective small-molecule inhibitor of FGFR1, 2, 3 and 4.1 It covalently binds to FGFR and inhibits the signaling pathway,1 a unique mode of binding compared to the other currently approved FGFR inhibitors, which are reversible ATP-competitive inhibitors.10,11,12 Key Findings From the FOENIX-CCA2 Trial Among the 103 patients enrolled in the study, futibatinib showed a confirmed objective response rate of 42% (95% confidence interval [CI], 32%-52%), according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as the primary endpoint of the study. Patients responding to futibatinib had a median duration of response, a key secondary endpoint, of 9.7 months (95% CI, 7.6-17.0). The disease control rate was 83% (95% CI, 74%-89%). At data cutoff for the primary analysis on October 1, 2020, median follow-up was 17.1 months (range, 10.1-29.6) and median treatment duration was 9.1 months. Objective responses were observed across all protocol-specified subgroups, including in patients aged at least 65 years and those with one, two or three or more prior treatment lines. Median progression-free survival was 9.0 months (95% CI, 6.9-13.1) and median overall survival was 21.7 months (95% CI, 14.5 to not reached). Similar response and survival data were documented at extended follow-up, 8.0 months after the primary analysis. Patient-reported outcomes were evaluated as a prespecified secondary objective and results showed stable quality of life over 9.0 months for trial participants. Throughout the observed time period, there were no meaningful changes from baseline across the observed study period in any of the EORTC-QLQ-c30 quality of life (QoL) scales, including physical, role, cognitive, emotional or social domains. In addition, the EQ-5D Visual Analog Scale did not reveal any significant changes in perceived health status across the observed study period. All patients experienced at least one adverse event of any cause. The most common (≥25%) treatment-related adverse reactions were hyperphosphatemia (85%), alopecia (33%), dry mouth (30%), diarrhea (28%), dry skin (27%) and fatigue (25%). Treatment-related adverse events led to treatment discontinuation in 2% of patients, and no new safety concerns were reported with extended follow-up. No treatment-related deaths occurred. Genomic Profiling Analysis to Identify FGFR2 Rearrangements The tumor molecular-profile analysis indicated that responses did not correlate with FGFR2 fusion-partner status or co-occurring alterations in tumor suppressor or oncogenes. Response rates were 42% and 45% in patients with BICC1- and non-BICC1 fusions, respectively, and ORR ranged from 35% to 49% in patients with or without BAP1, TP53, CDKN2A or CDKN2B co-alterations. Of note, response rates and PFS were similar in patients with and without TP53 co-alterations. As FGFR2 fusions and other rearrangements are an important actionable alteration in cholangiocarcinoma, utilizing a practical, high-performance method for identifying this therapeutic target will contribute to improved care of patients with this disease. Accurate tumor profiling to identify individuals with FGFR2 gene rearrangements can be challenging if tissue from tumor biopsy is limited. In addition, the failure rate of tissue biopsy profiling in metastatic CCA is as high as 26.8%.13 Circulating tumor DNA (ctDNA) profiling offers a non-invasive alternative for patients with no tumor tissue available or failed attempts at tissue profiling. Although the FGFR2 fusion/rearrangement detection rate from blood samples by ctDNA assays has historically been low with some platforms,14 the fusion partner-agnostic ctDNA platform utilized in the correlative analyses in the FOENIX-CCA2 trial identified FGFR2 fusions or rearrangements in 87% of patients evaluated.15 Impact on Treatment Guidelines for Biliary Tract Cancers In October 2022, futibatinib was included in the latest National Comprehensive Cancer Network® Clinical Practice Guidelines (NCCN Guidelines®) in Oncology for Hepatobiliary Cancers as a subsequent-line therapy for biliary tract cancers if disease progression occurs. Futibatinib is listed as Category 2A, useful in certain circumstances for CCA with FGFR2 fusions or rearrangements. In addition, the latest European Society for Medical Oncology (ESMO) Clinical Practice Guideline for diagnosis, treatment and follow-up of biliary tract cancer include that, where available, FGFR inhibitors, including futibatinib, are recommended for the treatment of patients with FGFR2 fusions whose disease has progressed after ≥1 prior line of systemic therapy. Futibatinib was discovered by Taiho Oncology's parent company, Taiho Pharmaceutical Co., Ltd., which continues to co-develop this product for other potential tumor types. About LYTGOBI INDICATION AND USAGE LYTGOBI is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Ocular Toxicity: Retinal Pigment Epithelial Detachment (RPED), which may cause symptoms such as blurred vision, occurred in 9% of 318 patients who received LYTGOBI across clinical trials. The median time to first onset of RPED was 40 days. Perform a comprehensive ophthalmological examination, including optical coherence tomography (OCT) of the macula, prior to initiation of therapy, every 2 months for the first 6 months, and every 3 months thereafter. For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of LYTGOBI. Withhold or reduce the dose of LYTGOBI as recommended. Dry Eye/Corneal Keratitis: Among 318 patients who received LYTGOBI across clinical trials, dry eye occurred in 15% of patients. Treat patients with ocular demulcents as needed. Hyperphosphatemia and Soft Tissue Mineralization: Hyperphosphatemia, which can cause soft tissue mineralization, calcinosis, nonuremic calciphylaxis, and vascular calcification was reported in 88% of 318 patients treated with LYTGOBI across clinical trials with a median time of onset of 5 days (range 3-117). Phosphate binders were received by 77% of patients who received LYTGOBI. Monitor for hyperphosphatemia throughout treatment. Initiate a low-phosphate diet and phosphate-lowering therapy when serum phosphate level is ≥5.5 mg/dL; initiate or intensify phosphate-lowering therapy when >7 mg/dL; reduce dose, withhold, or permanently discontinue LYTGOBI based on duration and severity of hyperphosphatemia. Embryo-fetal Toxicity: LYTGOBI can cause fetal harm. Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential, and males with female partners of reproductive potential, to use effective contraception during treatment with LYTGOBI and for 1 week after the last dose. ADVERSE REACTIONS Serious adverse reactions occurred in 39% of patients receiving LYTGOBI, and in ≥2% of patients included pyrexia, gastrointestinal hemorrhage, ascites, musculoskeletal pain, and bile duct obstruction. The most common adverse reactions (≥20%) were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting. The most common laboratory abnormalities (≥20%) were increased phosphate, increased creatinine, decreased hemoglobin, increased glucose, increased calcium, decreased sodium, decreased phosphate, increased alanine aminotransferase, increased alkaline phosphatase, decreased lymphocytes, increased aspartate aminotransferase, decreased platelets, increased activated partial thromboplastin time, decreased leukocytes, decreased albumin, decreased neutrophils, increased creatine kinase, increased bilirubin, decreased glucose, increased prothrombin international normalized ratio, and decreased potassium. DRUG INTERACTIONS Dual P-gp and Strong CYP3A Inhibitors: Avoid concomitant use of drugs that are dual P-gp and strong CYP3A inhibitors. Dual P-gp and Strong CYP3A Inducers: Avoid concomitant use of drugs that are dual P-gp and strong CYP3A inducers. USE IN SPECIFIC POPULATIONS Lactation: Because of the potential for serious adverse reactions from LYTGOBI in breastfed children, advise women not to breastfeed during treatment and for 1 week after the last dose. Please see accompanying full Prescribing Information for complete details. For more information, visit About Taiho Oncology, Inc. The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development of orally administered anti-cancer agents and markets these medicines for a range of tumor types in the U.S. Taiho Oncology's growing pipeline of antimetabolic and selectively targeted anti-cancer agents is led by a world-class clinical development organization. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company's European and Canadian operations, which are located in Zug, Switzerland and Oakville, Ontario, Canada. For more information, visit LYTGOBI is a registered trademark of Taiho Pharmaceutical Co., Ltd. *FGFR Oral SElective Novel Inhibitor X [across] tumors Taiho Oncology Media Contact: Judy Kay Moore Taiho Oncology, Inc. 574-526-2369 [email protected] SOURCE Taiho Oncology, Inc.