Irinotecan Hydrochloride

May 19, 2025 7:00 am ET BASKING RIDGE, N.J. & RAHWAY, N.J., – The first patient has been dosed in the IDeate-Esophageal01 Phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) versus investigator’s choice of chemotherapy in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) with disease progression following treatment with a platinum-containing systemic therapy and an immune checkpoint inhibitor. Ifinatamab deruxtecan is a specifically engineered, potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed with Merck (NYSE: MRK), known as MSD outside of the United States and Canada. ESCC accounts for nearly 90% of esophageal cancers globally with a five-year overall survival rate around 15% to 20% and has a worse prognosis for those diagnosed at an advanced stage of the disease. While the evolved landscape in the first-line metastatic setting of ESCC has helped to improve outcomes for patients, treatment options are limited for patients progressing after first-line therapy, reinforcing the need for new approaches. “Patients with metastatic esophageal squamous cell carcinoma continue to experience poor outcomes despite currently available treatments,” said Mark Rutstein, MD, head, therapeutic area oncology development, Daiichi Sankyo. “The encouraging clinical activity seen in our early-phase signal finding trial supports further evaluation of ifinatamab deruxtecan as a potential treatment strategy for these patients.” “Advanced esophageal squamous cell carcinoma is a difficult-to-treat disease, and unfortunately overall survival remains low,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “The initiation of the pivotal Phase 3 IDeate-Esophageal01 clinical trial demonstrates our shared commitment with Daiichi Sankyo to further expand our clinical development program evaluating this potentially first-in-class ADC across multiple solid tumors where there are unmet needs for new treatment options.” The initiation of IDeate-Esophageal01 is based on results from the IDeate-PanTumor01 Phase 1/2 trial presented at both the 2022 and 2023 European Society of Medical Oncology (ESMO) where ifinatamab deruxtecan showed promising responses in heavily pretreated patients with ESCC. About the IDeate-Esophageal01 trial IDeate-Esophageal01 is a global, multicenter, open-label, randomized Phase 3 trial evaluating the safety and efficacy of ifinatamab deruxtecan (12 mg/kg) versus treatment of physician’s choice of chemotherapy (paclitaxel, docetaxel or irinotecan hydrochloride) in patients with advanced or metastatic ESCC with disease progression following treatment with platinum-based chemotherapy therapy and an immune checkpoint inhibitor. Eligible patients must have received no more than one prior line of systemic therapy in the advanced or metastatic setting. The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival and objective response rate as assessed by blinded independent central review, and safety. IDeate-Esophageal01 will enroll approximately 510 patients across Asia, Europe and North America. For more information, please visit ClinicalTrials.gov. About esophageal squamous cell carcinoma More than half a million esophageal cancer cases were diagnosed in 2022, with nearly half a million deaths globally.ESCC accounts for nearly 90% of esophageal cancers globally with a five-year overall survival rate around 15% to 20% and has a worse prognosis for those diagnosed at an advanced stage of the disease. ESCC is most prevalent in Eastern Asia where mortality rates are also the highest. While the evolved landscape in the first-line metastatic setting of ESCC has helped to improve outcomes for patients, treatment options are limited for patients progressing after first-line therapy, reinforcing the need for new approaches. About B7-H3 B7-H3 is a transmembrane protein that belongs to the B7 family of proteins which bind to the CD28 family of receptors that includes PD-1. B7-H3 is overexpressed in a wide range of cancer types, including ESCC, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. There are currently no B7-H3 directed medicines approved for the treatment of any cancer. About ifinatamab deruxtecan Ifinatamab deruxtecan is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. In addition to IDeate-Esophageal01, ifinatamab deruxtecan is being evaluated in a global development program that includes IDeate-Lung01, a Phase 2 monotherapy trial in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC); IDeate-Lung02, a Phase 3 trial in patients with relapsed SCLC versus investigator’s choice of chemotherapy; IDeate-Lung03, a Phase 1b/2 trial in patients with ES-SCLC in combination with atezolizumab with or without carboplatin as first-line induction or maintenance therapy; IDeate-PanTumor02, a Phase 2 monotherapy trial in patients with recurrent or metastatic solid tumors; and,IDeate-PanTumor01, a Phase 1/2 first-in-human monotherapy trial in patients with advanced solid malignant tumors in collaboration with Sarah Cannon Research Institute (SCRI) with study operational oversight and delivery provided through SCRI’s early phase oncology clinical research organization, SCRI Development Innovations in Nashville, TN. Ifinatamab deruxtecan has been granted orphan drug designation in the EU, Japan, Taiwan, and U.S. for the treatment of SCLC. About the Daiichi Sankyo and Merck collaboration Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. In August 2024, the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck will maintain exclusive rights. Merck will be solely responsible for manufacturing and supply for gocatamig. About the ADC portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU®, a HER2 directed ADC, and DATROWAY®, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit www.daiichisankyo.com. Merck’s focus on cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). ### Media Contacts: Merck Julie Cunningham (617) 519-6264 julie.cunningham@merck.com Michael McArdle (908) 447-9453 michael.mcardle@merck.com Daiichi Sankyo Global/US Media Jennifer Brennan jennifer.brennan@daiichisankyo.com (908) 900-3183 Japan Media DS-PR@daiichisankyo.co.jp Investor Contacts: Merck Peter Dannenbaum (732) 594-1579 peter.dannenbaum@merck.com Steven Graziano (732) 594-1583 steven.graziano@merck.com Daiichi Sankyo DaiichiSankyoIR_jp@daiichisankyo.com

- 28% confirmed response rate (5/18) per RECIST v1.1 in unselected patients across doses prioritized for expansion (7.2, 8.6 and 10 mg/kg Q3W) - - 3 of 7 evaluable patients (43%) with confirmed responses at upper expansion dose (10 mg/kg Q3W) - - Median progression free survival of 5.8 months as of April 7th 2025 data cutoff - - Encouraging initial safety profile with no dose limiting toxicities at data cutoff - - Planning Phase 2 study initiation in 1H 2026 - - Conference call on Monday, May 12 at 8:00 a.m. ET - SOUTH SAN FRANCISCO, Calif., May 12, 2025 (GLOBE NEWSWIRE) -- CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, today announced positive interim Phase 1 data for its EpCAM PROBODY® ADC candidate, CX-2051, in advanced, late-line CRC. The data are as of an April 7th 2025 data cutoff from the ongoing CTMX-2051-101 Phase 1 study. “EpCAM is a high potential and broadly expressed cancer target that has been challenging to drug historically due to expression on normal tissues. We believe we have broken important new ground with our data announced today, which show potential for markedly improved outcomes for CRC patients,” said Sean McCarthy, D. Phil, chief executive officer and chairman of CytomX. “CX-2051 is showing impressive, durable anti-tumor activity in late line metastatic CRC, an area of high unmet need and a very difficult tumor to treat. Furthermore, CX-2051 has been generally well tolerated, highlighting the power of CytomX PROBODY® masking technology.” Dr. McCarthy added, “Importantly, we believe these results validate EpCAM as an oncology target and unlock a broad development opportunity for CX-2051 in CRC and potentially many other cancer types where EpCAM is expressed. We are excited to rapidly advance CX-2051 for the benefit of CRC patients and to explore the full potential of this novel ADC.” CX-2051 Phase 1a Interim Data Summary in Advanced, Late-line Colorectal Cancer The CTMX-2051-101 study was initiated in April 2024 with dose escalation proceeding through seven dose levels as of April 2025. 25 advanced metastatic CRC patients were treated with CX-2051 across dose levels 1 through 5 as of the April 7, 2025 data cutoff. CX-2051 was administered on a once every three week schedule (Q3W). The 2.4 mg/kg and 4.8 mg/kg doses were single patient dose escalation cohorts not anticipated to be therapeutically active. At the 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg doses, 23 patients were treated in total, 18 of whom were efficacy evaluable, having had at least one post-baseline tumor assessment as of the data cutoff. Patient Characteristics: The 25 patients enrolled in the study across dose levels 1 through 5 had previously received a median of 4 prior lines of therapy and all patients had previously been treated with irinotecan. 64% of patients had liver metastases, 64% had KRAS mutations, and 96% were microsatellite stable. Patients were not preselected based on EpCAM expression levels. Efficacy Results: As of the data cutoff, 18 patients were efficacy-evaluable at the expansion doses of 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg Q3W. Overall response rate (ORR): 28% of patients (5/18) achieved confirmed partial RECIST v. 1.1 responses. Overall response rates for currently approved therapies in 3rd line or later CRC are in the low to mid-single digit percentages1. At the 10 mg/kg dose, 3 of 7 evaluable patients (43%) achieved confirmed partial responses. The Disease Control Rate2 was 94% across the three dose groups (17/18). Durability: Median progression free survival was 5.8 months as of the data cutoff. 10 of 18 patients remained on study treatment as of the data of cutoff. 28% of patients (5/18) achieved confirmed partial RECIST v. 1.1 responses. Overall response rates for currently approved therapies in 3rd line or later CRC are in the low to mid-single digit percentages1. At the 10 mg/kg dose, 3 of 7 evaluable patients (43%) achieved confirmed partial responses. The Disease Control Rate2 was 94% across the three dose groups (17/18). Median progression free survival was 5.8 months as of the data cutoff. 10 of 18 patients remained on study treatment as of the data of cutoff. Safety Results: As of the data cutoff, 25 patients were evaluable for safety. CX-2051 was generally well-tolerated with manageable adverse events, with no observed dose limiting toxicities. Most treatment related adverse events (TRAEs) were Grade 1 or Grade 2 in severity. The most common reported TRAEs were diarrhea (18 patients, 5 Grade 3), nausea (11 patients, 1 Grade 3), vomiting (8 patients, No Grade 3), fatigue (8 patients, 1 Grade 3), anemia (5 patients, 3 Grade 3), hypokalemia (3 patients, 1 Grade 3), neutrophil count decrease (2 patients, 2 Grade 3) and neutropenia (2 patients, 1 Grade 3). TRAEs included serious adverse events in 5 patients (1 Grade 2, 4 Grade 3). No Grade 4 or 5 TRAEs were observed. No events of pancreatitis, interstitial lung disease or febrile neutropenia were reported at time of data cutoff. CX-2051 Phase 1 Dose Expansions Initiated: Dose expansions have been initiated at doses of 7.2 mg/kg, 8.6 mg/kg and 10 mg/kg Q3W. A total of 20 patients are expected to be enrolled at each dose level to inform the selection of recommended phase 2 dose. CX-2051 Anticipated Milestones: CX-2051 Monotherapy for Advanced Late-Line CRC: Additional Phase 1 data update by Q1 2026 Planning Phase 2 study initiation in 1H 2026 CX-2051 CRC Combinations: Potential to initiate CX-2051 combination studies in earlier lines of CRC in 2026 CX-2051 Pan-tumor Potential: Evaluate non-CRC, EpCAM-expressing tumor indications for potential Phase 1b study initiation in 2026 Additional Phase 1 data update by Q1 2026 Planning Phase 2 study initiation in 1H 2026 Potential to initiate CX-2051 combination studies in earlier lines of CRC in 2026 Evaluate non-CRC, EpCAM-expressing tumor indications for potential Phase 1b study initiation in 2026 CytomX Investor Event Information Additional details will be provided on the Company’s Investor Call on May 12, 2025 at 8 a.m. EST. Participants may access the live webcast of the conference call from the Events and Presentations page of CytomX’s website at https://ir.cytomx.com/events-and-presentations. Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. An archived replay of the webcast will be available on the company’s website for at least 30 days. About CTMX-2051-101 Study Additional information about the CTMX-2051-101 study can be found here on clinicaltrials.gov. About CX-2051 (EpCAM PROBODY® ADC) CX-2051 is an investigational masked, conditionally activated ADC directed toward epithelial cell adhesion molecule (EpCAM) and armed with a topoisomerase-1 inhibitor payload. CX-2051 has potential applicability across multiple EpCAM-expressing epithelial cancers, including CRC, and was discovered in collaboration with ImmunoGen, now part of AbbVie. EpCAM (Epithelial Cell Adhesion Molecule) is a highly expressed but previously undruggable tumor antigen due to expression on normal tissues. CX-2051 is designed to open a therapeutic window for this high potential target and to deliver meaningful anti-cancer activity in solid tumors, including CRC. About CytomX Therapeutics CytomX is a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel conditionally activated, masked biologics designed to be localized to the tumor microenvironment. By pioneering a novel pipeline of localized biologics, powered by its PROBODY® therapeutic platform, CytomX’s vision is to create safer, more effective therapies for the treatment of cancer. CytomX’s robust and differentiated pipeline comprises therapeutic candidates across multiple treatment modalities including antibody-drug conjugates (ADCs), T-cell engagers, and immune modulators such as cytokines. CytomX’s clinical-stage pipeline includes CX-2051 and CX-801. CX-2051 is a masked, conditionally activated ADC directed toward epithelial cell adhesion molecule (EpCAM), armed with a topoisomerase-1 inhibitor payload. CX-2051 has potential applicability across multiple EpCAM-expressing epithelial cancers, including CRC. CX-801 is a masked interferon alpha-2b PROBODY® cytokine with broad potential applicability in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. CytomX has established strategic collaborations with multiple leaders in oncology, including Amgen, Astellas, Bristol Myers Squibb, Regeneron and Moderna. For more information about CytomX and how it is working to make conditionally activated treatments the new standard-of-care in the fight against cancer, visit www.cytomx.com and follow us on LinkedIn and X (formerly Twitter). CytomX Therapeutics Forward-Looking Statements This press release includes forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that are difficult to predict, may be beyond our control, and may cause the actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied in such statements, including those related to CX-2051. Accordingly, you should not rely on any of these forward-looking statements, including those relating to the potential benefits, safety and efficacy or progress of CytomX’s or any of its collaborative partners’ product candidates, including CX-2051 and CX-801, the potential benefits or applications of CytomX’s PROBODY® therapeutic platform, CytomX’s or its collaborative partners’ ability to develop and advance product candidates into and successfully complete clinical trials, including the ongoing and planned clinical trials of CX-2051 and CX-801 and the timing of initial and ongoing data availability for our clinical trials, including CX-2051 and CX-801, and other development milestones. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include: the unproven nature of CytomX’s novel PROBODY® therapeutic technology; uncertainties around the Company’s ability to raise sufficient funds to carry out its planned research and development; CytomX’s clinical trial product candidates are in the initial stages of clinical development and its other product candidates are currently in preclinical development, and the process by which preclinical and clinical development could potentially lead to an approved product is long and subject to significant risks and uncertainties, including the possibility that the results of preclinical research and early clinical trials, including initial CX-2051 results, may not be predictive of future results; the possibility that CytomX’s clinical trials will not be successful; the possibility that current preclinical research may not result in additional product candidates; CytomX’s dependence on the success of CX-2051 and CX-801; CytomX’s reliance on third parties for the manufacture of the Company’s product candidates; possible regulatory developments in the United States and foreign countries, including China and the European Union; and the risk that we may incur higher costs than expected for research and development or unexpected costs and expenses or may not obtain expected savings from our announced restructuring. Additional applicable risks and uncertainties include those relating to our preclinical research and development, clinical development, and other risks identified under the heading "Risk Factors" included in CytomX’s Quarterly Report on Form 10-Q filed with the SEC on May 12, 2025. The forward-looking statements contained in this press release are based on information currently available to CytomX and speak only as of the date on which they are made. CytomX does not undertake and specifically disclaims any obligation to update any forward-looking statements, whether as a result of any new information, future events, changed circumstances or otherwise. PROBODY is a U.S. registered trademark of CytomX Therapeutics, Inc. All other trademarks are the properties of their respective owners. Company Contact: Chris Ogden SVP, Chief Financial Officer cogden@cytomx.com Investor Contact: Precision AQ (formerly Stern Investor Relations) Stephanie Ascher Stephanie.Ascher@precisionaq.com Media Contact: Redhouse Communications Teri Dahlman teri@redhousecomms.com 1 Lonsurf®, Fruzaqla®, Stivarga® package inserts 2 Disease Control Rate: Patients achieving a best response of stable disease, partial response, or complete response. Source: CytomX Therapeutics Inc.