EGFR x HER3 x HER2

- Petosemtamab in 1L HNSCC in combination with pembrolizumab initial interim clinical data planned for 2Q24; preparing for a potential phase 3 trial - Petosemtamab in 2L+ HNSCC phase 3 trial planned to initiate mid-2024; interim clinical data planned for 2H24 - Petosemtamab in 2L CRC: cohort planned to initiate in 2024 - Zeno in NRG1+ cancer: Sufficient clinical data expected in 1H24 to support potential BLA submissions - Based on the Company’s current operating plan, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2027 UTRECHT, The Netherlands and CAMBRIDGE, Mass., Feb. 28, 2024 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics® and Triclonics®), today announced financial results for the fourth quarter and full year and provided a business update. “2024 is poised to be a transformational year for Merus. For petosemtamab, we plan to start a phase 3 registration trial in 2L+ HNSCC in mid-2024. In the first-line setting, we plan to provide initial data on the combination with pembrolizumab in the second quarter and are preparing for a potential first-line phase 3 trial. This year, we also plan to evaluate petosemtamab in 2L colorectal cancer,” said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. “Additionally, for Zeno we are preparing our first potential BLA submissions in NRG1+ lung and NRG1+ pancreatic cancer. We are also excited by continued enhancements to our productive Multiclonics® platforms, which serve as our engine to develop innovative antibodies both for our own pipeline and for our collaborators.” Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics®): Solid Tumors Phase 3 registration trial in 2L+ head & neck squamous cell carcinoma (HNSCC) on track to initiate mid-2024; dose comparison of petosemtamab monotherapy 1100 vs 1500 mg in previously treated (2L+) HNSCC ongoing; evaluation in combination with pembrolizumab as first-line (1L) therapy ongoing; planned initiation of 2L colorectal cancer (CRC) cohort in 2024 Merus plans to initiate a phase 3 clinical trial in mid-2024 to evaluate petosemtamab monotherapy in 2L+ HNSCC. In the planned trial, patients will be randomized to petosemtamab monotherapy or investigators’ choice of single agent chemotherapy or cetuximab. Merus believes a randomized registration trial in HNSCC with an overall response rate (ORR) endpoint could potentially support accelerated approval and the overall survival (OS) results from the same study could potentially verify its clinical benefit to support regular approval. Merus continues to evaluate approximately 40 patients treated with petosemtamab monotherapy at either 1100 or 1500 mg dose levels to confirm a suitable dose for future potential phase 3 trials. Merus plans to share clinical data from this cohort in the second half of 2024. Merus also continues to evaluate patients with untreated advanced PD-L1+ HNSCC treated with petosemtamab 1500 mg in combination with pembrolizumab. Initial safety data from this single arm cohort may support the initiation of a 1L phase 3 trial with this combination. Among the initial patients dosed in the 1L combination cohort, the safety pro been observed to be generally favorable. Merus plans to report initial interim efficacy and safety data from this cohort in the second quarter of 2024. At the American Association of Cancer Research (AACR) Annual Meeting 2023, Merus provided interim data on 49 2L+ HNSCC patients that were treated with petosemtamab at the recommended phase 2 dose of 1500 mg intravenous every two weeks. 43 patients were evaluable for efficacy. As of a February 1, 2023 data cutoff date, the ORR was 37.2% by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment. Petosemtamab continued to demonstrate a manageable safety profile. Merus plans to provide updated efficacy, durability and safety data of this cohort in the second half of 2024. The U.S. Food & Drug Administration (FDA) has granted Fast Track Designation (FTD) for petosemtamab for the treatment of patients with recurrent or metastatic HNSCC whose disease has progressed following treatment with platinum-based chemotherapy and an anti-programmed cell death protein 1 (anti-PD-1) antibody. FTD is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill unmet medical needs. In 2024, Merus is planning to initiate the evaluation of petosemtamab monotherapy in 2L CRC. Zenocutuzumab (Zeno or MCLA-128: HER2 x HER3 Biclonics®): NRG1 fusion-positive (NRG1+) lung, pancreatic and other solid tumors Sufficient clinical data expected in 1H24 to support potential BLA submissions in NRG1+ non-small cell lung cancer (NSCLC) and NRG1+ pancreatic cancer (PDAC) Zeno is being investigated in the phase 1/2 eNRGy trial and Early Access Program (EAP) which are assessing the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancer. In 2023, Merus met with the FDA and based on these productive and collaborative discussions, the Company believes it will have sufficient clinical data in the first half of 2024 to support potential Biologics License Application (BLA) submissions in NRG1+ NSCLC and NRG1+ PDAC. Merus believes that obtaining a commercialization partnership agreement will be an essential step in bringing Zeno to patients with NRG1+ cancer, if approved. In 2023, the FDA granted Breakthrough Therapy Designation (BTD) to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ pancreatic cancer following progression with prior systemic therapy or who have no satisfactory alternative treatment options. Additionally, the FDA granted BTD to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ NSCLC, following progression with prior systemic therapy. Merus shared updated interim clinical data on our Zeno program (eNRGy trial and EAP) in patients with NRG1+ NSCLC and NRG1+ PDAC at the European Society for Medical Oncology (ESMO) Congress 2023. In 78 evaluable NRG1+ NSCLC patients, as of a July 31, 2023 data cutoff date, a 37% ORR per RECIST v1.1 by investigator assessment and 14.9 months median duration of response (DOR) was reported. In 33 evaluable NRG1+ PDAC patients, a 42% ORR per RECIST v1.1 by investigator assessment and 9.1 months median DOR was reported. Zeno continued to demonstrate a well-tolerated safety profile. Merus also evaluated patients with castration resistant prostate cancer (CRPC) treated with Zeno in combination with an androgen deprivation therapy (enzalutamide or abiraterone), irrespective of NRG1+ status. Enrollment is complete and Merus plans to continue monitoring these patients. The Company also continues to monitor and evaluate patients treated with Zeno in combination with afatinib but no further enrollment is planned at this time. The Company is also conducting ongoing translational work on potential biomarkers outside of NRG1+ cancer which may support development opportunities for Zeno in additional areas of unmet need. MCLA-129 (EGFR x c-MET Biclonics®): Solid Tumors Investigation of MCLA-129 continues in the MET ex14 NSCLC expansion cohort in the phase 1/2 trial; MCLA-129 in combination with chemotherapy in 2L+ EGFR mutant (EGFRm) NSCLC planned to start in 2024 MCLA-129 is in clinical development in a phase 1/2, open-label clinical trial evaluating MCLA-129 monotherapy in patients with MET ex14 NSCLC and Merus plans to start a cohort of MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC in 2024. In December at the ESMO Asia Congress 2023 interim data was presented on MCLA-129 from ongoing expansion cohorts in NSCLC and in previously treated HNSCC. Patients with advanced/metastatic EGFRm NSCLC were treated with MCLA-129 combined with osimertinib as first-line therapy or in the 2L+ setting after progression on osimertinib. In the 1L setting, all 16 evaluable patients experienced tumor shrinkage. In the 2L+ setting, 34 patients were evaluable for response with 11 experiencing confirmed PRs and 1 unconfirmed PR by RECIST v1.1. per investigator assessment. We continue to monitor these patients and evaluate potential for biomarkers to maximize efficacy, while proactively addressing safety signals seen to date. We also remain interested in exploring partnering MCLA-129 with other companies to sufficiently resource the development of MCLA-129 and potential benefit it may have for patients. MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains global rights outside of China. MCLA-145 (CD137 x PD-L1 Biclonics®): Solid Tumors Investigation continues of the phase 1 trial of MCLA-145 in combination with pembrolizumab MCLA-145 is in clinical development in a global, phase 1, open-label, clinical trial evaluating MCLA-145 in patients with solid tumors. The trial is in the dose expansion phase, with the Company monitoring and evaluating patients on treatment with the combination of MCLA-145 with pembrolizumab. Collaborations Incyte Corporation Since 2017, Merus has been working with Incyte Corporation (Incyte) under a global collaboration and license agreement focused on the research, discovery and development of bispecific antibodies utilizing Merus’ proprietary Biclonics® technology platform. The agreement grants Incyte certain exclusive rights for up to ten bispecific and monospecific antibody programs. The collaboration is progressing, with multiple programs in various stages of preclinical and clinical development. For each program under the collaboration, Merus receives reimbursement for research activities and is eligible to receive potential development, regulatory and commercial milestones and sales royalties for any products, if approved. Further, Incyte announced, in 2023, that INCA33890, a novel TGFBr2xPD-1 bispecific antibody developed through the collaboration is currently being evaluated in clinical trials. Merus achieved a milestone and received a payment of $2.5 million related to the advancement of this program in the third quarter of 2023. Merus also achieved an additional milestone of $1 million for candidate nomination in the fourth quarter of 2023. This is the third program to undergo candidate nomination under the collaboration. Loxo Oncology at Lilly In January 2021, Merus and Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (Lilly), announced a research collaboration and exclusive license agreement to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies utilizing Merus’ Biclonics® platform and proprietary CD3 panel along with the scientific and rational drug design expertise of Loxo Oncology at Lilly. The collaboration is progressing with multiple active research programs underway. Cash Runway, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2027 As of December 31, 2023, Merus had $411.7 million cash, cash equivalents and marketable securities. Based on the Company’s current operating plan, the existing cash, cash equivalents and marketable securities are expected to fund Merus’ operations into 2027. Full Year 2024 Financial Results Collaboration revenue for the year ended December 31, 2023 increased $2.4 million as compared to the year ended December 31, 2022, primarily as a result of increases in Incyte revenue of $2.6 million, and Lilly revenue of $1.0 million, offset by decreases in Other revenue of $1.2 million. The increase in Incyte revenue is primarily the result of increases in milestone revenue of $5.0 million and upfront payment amortization of $0.4 million due to changes in foreign exchange rates, partially offset by decreases in reimbursement revenue of $2.8 million. The increase in Lilly revenue is primarily the result of increases in reimbursement revenue of $0.7 million and upfront payment amortization of $0.3 million. Research and development expense for the year ended December 31, 2023 decreased $8.8 million as compared to the year ended December 31, 2022, primarily as a result of decreases in external clinical services and drug manufacturing costs, including costs to fulfill our obligations under our collaboration agreements related to our programs of $18.8 million and partner expenses of $0.7 million, partially offset by increases to personnel related expenses including share-based compensation of $6.5 million due to an increase in employee headcount, consultancy expenses of $2.9 million, facilities expenses of $1.1 million, consumables expenses of $0.3 million, and travel expenses of $0.3 million. General and administrative expense for the year ended December 31, 2023 increased $7.6 million as compared to the year ended December 31, 2022, primarily as a result of increases in consultancy expenses of $3.1 million, personnel related expenses including share-base compensation of $2.1 million due to an increase in employee headcount, intellectual property and licenses expenses of $1.0 million, facilities and depreciation expense of $0.9 million, legal expenses of $0.8 million and travel expenses of $0.5 million, partially offset by decreases in finance and human resources expenses of $0.9 million. Other income, net consists of interest earned on our cash and cash equivalents held on account, accretion of investment earnings and net foreign exchange gains or losses on our foreign denominated cash, cash equivalents and marketable securities, and payables and receivables. MERUS N.V. CONSOLIDATED BALANCE SHEETS (Amounts in thousands, except share and per share data) ASSETS Current assets: Cash and cash equivalents 204,246 147,749 Marketable securities 150,130 142,480 Accounts receivable 2,429 4,051 Prepaid expenses and other current assets 12,009 12,163 Total current assets 368,814 306,443 Marketable securities 57,312 36,457 Property and equipment, net 12,135 12,222 Operating lease right-of-use assets 11,362 12,618 Intangible assets, net 1,800 1,950 Deferred tax assets 1,199 2,041 Other assets 2,872 4,811 Total assets 455,494 376,542 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable 4,602 9,834 Accrued expenses and other liabilities 38,482 35,590 Income taxes payable 1,646 2,400 Current portion of lease obligation 1,674 1,684 Current portion of deferred revenue 22,685 29,418 Total current liabilities 69,089 78,926 Lease obligation 10,488 11,790 Deferred revenue, net of current portion 19,574 38,771 Total liabilities 99,151 129,487 Commitments and contingencies (Note 10) Stockholders’ equity: Common shares, €0.09 par value; 67,500,000 and 67,500,000 shares authorized at December 31, 2023 and 2022, respectively; 57,825,879 and 46,310,589 shares issued and outstanding at December 31, 2023 and 2022, respectively 5,883 4,751 Additional paid-in capital 1,126,054 870,874 Accumulated deficit (753,061 (598,122 Accumulated other comprehensive (loss) income (22,533 (30,448 Total stockholders’ equity 356,343 247,055 Total liabilities and stockholders’ equity 455,494 376,542 MERUS N.V. CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (Amounts in thousands, except share and except per share data) Year Ended December 31, Collaboration revenue 43,947 41,586 19,503 Collaboration revenue (related party) 29,604 Total revenue 43,947 41,586 49,107 Operating expenses: Research and development 140,658 149,424 98,187 General and administrative 59,836 52,200 40,896 Total operating expenses 200,494 201,624 139,083 Operating loss (156,547 (160,038 (89,976 Other income (loss), net: Interest (expense) income, net 14,510 2,722 Foreign exchange (losses) gains, net (9,710 26,022 24,663 Other (losses) gains, net 1,059 (1,135 Total other income (loss), net 4,800 29,803 23,399 Loss before income tax expense (151,747 (130,235 (66,577 Income tax expense 3,192 Net loss (154,939 (131,194 (66,816 Other comprehensive income (loss): Currency translation adjustment 7,915 (21,227 (18,292 Comprehensive loss (147,024 (152,421 (85,108 Net loss per share allocable to common stockholders: Basic and diluted (3.00 (2.92 (1.73 Weighted-average common shares outstanding: Basic and diluted 51,605,444 44,919,084 38,638,434 About Merus N.V. Merus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding the content and timing of clinical trials, data readouts and clinical, regulatory, strategy and development updates for our product candidates; our belief that 2024 is poised to be a transformational year for Merus; our plan to start a phase 3 registration trial in 2L+ HNSCC in mid-2024; our plan to provide initial interim efficacy and safety data on the combination with pembrolizumab in the second quarter of 2024; our preparation for a potential first-line phase 3 trial of petosemtamab in combination with pembrolizumab in untreated advanced PD-L1+ HNSCC; our plan to initiate investigation of petosemtamab in 2L colorectal cancer patients; our preparing for potential BLA submissions for Zeno in the treatment of NRG1+ PDAC and NRG1+ NSCLC; the continued enhancements to our productive Multiclonics® platforms, which serve as our engine to develop innovative antibodies both for our own pipeline and for our collaborators; our belief that we expect to have data in the 1H of 2024 in NRG1+ NSCLC and NRG1+ PDAC for potential BLA submissions; our preparation for a phase 3 study in 2L+ expected to start mid-2024; the potential design and details of our planned phase 3 trial investigating monotherapy petosemtamab in 2L HNSCC; the enrollment of approximately 40 patients in previously treated HNSCC with petosemtamab monotherapy at the 1100 or 1500 mg dose levels to confirm a suitable dose for future randomized trials and plan to share the clinical data form this cohort in the second half of 2024; our plan to provide updated efficacy, durability and safety data in the second half of 2024 of the cohort disclosed at the AACR Annual Meeting 2023; our plan to initiate a cohort investigating petosemtamab in 2L colorectal cancer; the potential benefits of FTD for petosemtamab and BTD designations for Zeno and the ability of Merus to maintain such designations; our belief that obtaining a commercialization partnership agreement will be an essential step in bringing Zeno to patients with NRG1+ cancer, if approved; our continued monitoring and evaluation of patients with CRPC receiving Zeno in combination with ADT, and patients with NRG1+ NSCLC receiving Zeno in combination with afatinib; our conduct of ongoing translational work on potential biomarkers outside of NRG1+ tumors, which may support development opportunities for Zeno in additional areas of unmet need; statements regarding the sufficiency of our cash, cash equivalents and marketable securities, and expectation that it will fund the Company into 2027; the ongoing monitoring and evaluation of patients the phase 1 trial of MCLA-145 in combination with pembrolizumab; the advancement of the phase 1/2 trial for MCLA-129 in the dose expansion phase, in monotherapy in Met ex14 NSCLC; the ongoing monitoring and evaluation of patients receiving MCLA-129 in combination with osimertinib; our plan to initiate a cohort of MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC in 2024; the benefits of the collaboration between Loxo Oncology at Lilly and Merus, its potential for future value generation, including whether and when Merus will receive any future payment under the collaboration, including milestones or royalties, and the amounts of such payments; whether any programs under the collaboration will be successful; Merus’ and Lilly’s activities under the agreement; our global collaboration and license agreement with Incyte, its progress and potential development and commercialization of up to ten bispecific and monospecific antibodies from our Biclonics® platform, including whether and when Merus will receive any future payment under the collaboration, including milestones or royalties, and the amounts of such payments; whether any programs under the collaboration will be successful; and our collaboration and license agreement with Betta, which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains full ex-China rights, including any future clinical development by Betta of MCLA-129. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the COVID-19 pandemic; we may not identify suitable Biclonics® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks; and risks related to our ceasing to qualify as an emerging growth company and a smaller reporting company after December 31, 2021. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-Q for the period ended September 30, 2023, filed with the Securities and Exchange Commission, or SEC, on November 2, 2023, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Multiclonics®, Biclonics® and Triclonics® are registered trademarks of Merus N.V. Investor and Media Inquiries: Sherri Spear Merus N.V. VP Investor Relations and Corporate Communications 617-821-3246 [email protected] Kathleen Farren Merus N.V. Investor Relations and Corporate Communications 617-230-4165 [email protected]

BASKING RIDGE, NJ & RAHWAY, NJ, USA I December 22, 2023 I Daiichi Sankyo (TSE: 4568) and Merck (known as MSD outside of the United States and Canada) (NYSE: MRK) announced today that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to the Biologics License Application (BLA) for patritumab deruxtecan (HER3-DXd) for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with two or more systemic therapies. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is June 26, 2024. The Priority Review follows receipt of Breakthrough Therapy Designation granted by the FDA in December 2021. The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The BLA is being reviewed under the Real-Time Oncology Review (RTOR) program, an initiative of the FDA which is designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and Merck. The BLA is based on the primary results from the HERTHENA-Lung01 pivotal phase 2 trial and data results presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23), which were simultaneously published in the Journal of Clinical Oncology In HERTHENA-Lung01, patritumab deruxtecan was studied in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy, which demonstrated an objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2), including one complete response and 66 partial responses. The median duration of response was 6.4 months (95% CI: 4.9-7.8). The safety profile of patritumab deruxtecan observed in HERTHENA-Lung01 was consistent with previous phase 1 clinical trials in NSCLC with a treatment discontinuation rate of 7.1% due to treatment-emergent adverse events (TEAEs). Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common (≥5%) grade 3 or higher TEAEs were thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) and asthenia (5%). Twelve patients (5.3%) had confirmed treatment-related interstitial lung disease (ILD) as determined by an independent adjudication committee. One grade 5 ILD event was observed. “The FDA’s prioritization of the BLA submission reflects the strength of the data from HERTHENA-Lung01 and emphasizes the need to provide new options to patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer previously treated with two or more systemic therapies,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “If approved, patritumab deruxtecan could become the first HER3 directed medicine approved in the US and the second DXd antibody drug conjugate approved from Daiichi Sankyo’s oncology pipeline.” “The acceptance of the BLA submission of patritumab deruxtecan marks an important step in potentially bringing this new medicine to previously treated patients with EGFR-mutated non-small cell lung cancer who often experience recurrence and have few remaining treatment options,” said Marjorie Green, MD, Senior Vice President and Head of Late-Stage Oncology, Global Clinical Development, Merck Research Laboratories. “Today is the first of many important milestones from our collaboration with Daiichi Sankyo, as we work together to bring new and potentially first-in-class antibody drug conjugates to people living with cancer.” About HERTHENA-Lung01 HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from the phase 1 trial assessing the doses in a similar patient population. The primary endpoint of HERTHENA-Lung01 was ORR as assessed by blinded independent central review (BICR). Secondary endpoints included duration of response, progression-free survival (PFS), disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, overall survival, safety and tolerability. HERTHENA-Lung01 enrolled patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov About EGFR-Mutated Non-Small Cell Lung Cancer Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide. NSCLC accounts for approximately 85% of all lung cancers – 55% having distant spread at diagnosis – with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide. 2,3,4 About HER3 HER3 is a member of the EGFR family of receptor tyrosine kinases. It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment. There is currently no HER3 directed therapy approved for the treatment of any cancer. About Patritumab Deruxtecan Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Patritumab deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in December 2021 for the treatment of patients with EGFR-mutated locally advanced or metastatic NSCLC with disease progression on or after treatment with a third-generation TKI and platinum-based therapies. Patritumab deruxtecan is currently being evaluated as both a monotherapy and in combination with other therapies in a global development program, which includes HERTHENA-Lung02 , a phase 3 trial versus platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression on or after treatment with a third-generation EGFR TKI; a phase 1 trial in combination with osimertinib in EGFR-mutated locally advanced or metastatic NSCLC; and a phase 1 trial in previously treated patients with advanced NSCLC. A phase 1/2 trial in HER3 expressing metastatic breast cancer also has been completed. 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. About the DXd ADC Portfolio of Daiichi Sankyo The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, 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. Designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, 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. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 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 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 LinkedIn References World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Accessed September 2023. Economopoulou P, et al. Ann Transl Med . 2018; 6(8):138. Chen R, et al. J Hematol Oncol . 2020; 13(1):58. Zhang Y-L, et al. Oncotarget . 2016; 7(48):78985-78993. Mishra R, et al. Onco Rev . 2018; 12(355):45-62. Scharpenseel H, et al. Scientific Reports 2019; 9:7406. Yonesaka K, et al. Clin Cancer Res 2022; 15:28(2):390-403. SOURCE: Merck

REDMOND, Wash., Dec. 5, 2023 /PRNewswire/ -- SystImmune, Inc (SystImmune), a clinical-stage biopharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) authorized the company to proceed with the planned clinical study of the HER2-specific HIRE platform ADC, BL-M07D1, in the Investigational New Drug (IND) application on November 28, 2023. This milestone paves the way for the multicenter Phase 1 study evaluating the safety, tolerability, pharmacokinetic profile, and initial efficacy of BL-M07D1 in subjects with metastatic or unresectable HER2 expressing cancers in the United States. Dr. Yi Zhu, Chief Executive Officer of SystImmune, remarked, "The FDA's approval of our IND application for BL-M07D1 underscores our commitment to advancing innovative therapies in the field of oncology with our HIRE platform of ADCs. We look forward to collaborating with our clinical partners, trial treatment centers, and global regulatory agencies to contribute meaningfully to the ongoing evolution of cancer treatment." The clearance of this IND application marks a significant milestone for SystImmune as the company continues to advance its pipeline of therapeutic candidates into global clinical development. Updated Clinical Trial Results New results from the ongoing study with the EGFRxHER3 bi-specific HIRE platform ADC, BL-B01D1, in patients with breast cancer treated in the trial registered as NCT05470348, are presented for the first time. Preliminary results demonstrated overall response rates of 44.7%, 31.4% and 39.1% and disease control rates of 91.4%, 94.7% and 87% in an analysis of 38, 35 and 23 pretreated patients with HER2-/HR+, TNBC and HER 2+ patients with breast cancer respectively. No interstitial lung disease (ILD) was observed in 127 patients treated with at least one dose. For more information visit poster: PS08-07 2024 San Antonio Breast Cancer conference. Updated analysis from an ongoing phase 1 study of the HIRE platform HER2-specific ADC, BL-M07D1 in the trial registered as NCT05461768, continues to demonstrate impressive results in patients with breast cancer. Reported are response rate of 80%, confirmed responses over 60%, and disease control rate of 100% in 50 patients with HER2+ metastatic breast cancer. Prior treatment with HER2 ADCs did not prevent responses to BL-M07D1, as 18 subjects who had received prior ADC therapies showed similar overall response. Preliminary results from the same study demonstrated an overall response rate of 50%, confirmed responses in 28.9% and disease control rate of 86% in an analysis of 38 heavily pretreated patients with HER2 low-expressing metastatic breast cancer. Only 1 patient experienced ILD which was grade 2, in the 130 patients treated. For more information visit poster: PO2-04-03 2024 San Antonio Breast Cancer conference. Dr. Martin S. Olivo, the Chief Medical Officer at SystImmune, reports the preliminary findings showcased in these two studies, underscoring their backing of the promising activity seen in the HIRE platform. Dr. Olivo emphasized the significance of the FDA clearance for the IND application of BL-M07D1, expressing optimism. "As the clinical development of BL-M07D1 and BL-B01D1 progress, we're closer to assessing our potential to offer therapeutic pathways for patients diagnosed with breast cancer." About BL-B01D1 BL-B01D1 is a first-in-class bispecific antibody-drug conjugate (ADC) developed by SystImmune, targeting both EGFR and HER3, proteins that are highly expressed in most epithelial tumors. The tetravalent BL-B01D1 possesses two binding domains blocking each Growth Factor Receptor, which both drive cancer cell proliferation and survival. Inheriting the SI-B001 mechanisms of action, BL-B01D1 effectively blocks EGFR and HER3 signals to cancer cells, thereby reducing proliferation and survival signals. Upon antibody-mediated internalization, BL-B01D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death. The two targets of BL-B01D1 are broadly expressed in epithelial tumors, including NSCLC, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal carcinoma, Gastrointestinal tumors, Gynecological tumors, and others. The therapeutic conjugated toxin of BL-B01D1 comprises SystImmune's Ex-0115 linker-payload platform, a proprietary Topo1 inhibitor conjugated to the bi-specific antibody by a stable, cleavable linker. Each BL-B01D1 carries 7-8 units of SystImmune's proprietary ED-04 toxin. About BL-M07D1 BL-M07D1 is a HER2 specific antibody-drug conjugate (ADC) developed by SystImmune, targeting cancers that express HER2. The trastuzumab-based BL-M07D1 possesses two binding domains specific for the commonly overexpressed cancer growth factor receptor HER2, which drive cancer cell proliferation and survival. BL-M07D1 binding to HER2 leads to its internalization by cancer cells. Upon antibody-mediated internalization, BL-M07D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death. The target of BL-M07D1, HER2, is highly expressed in solid tumors, including breast cancer, gastric cancer, endometrial cancer, cervical cancer, ovarian cancer, urothelial cancer, biliary tract cancer and others. The therapeutic conjugated toxin of BL-M07D1 comprises SystImmune's Ex-0115 linker-payload platform, a proprietary Topo1 inhibitor conjugated to the antibody by a stable, cleavable linker. Each BL-M07D1 carries 7-8 units of SystImmune's proprietary ED-04 toxin. Clinical studies conducted thus far have demonstrated compelling results for BL-M07D1. In 107 subjects with HER2+ Breast cancer and other HER2+ cancer BL-M07D1 exhibited promising preliminary antitumor activity in patients with both breast cancer and non-small cell lung cancer. The maximum tolerated dose for BL-M07D1 was not reached. The observed toxicities were predominantly hematologic. These findings were recently presented at the European Society for Medical Oncology (ESMO) Congress in October 2023, and the abstract of the clinical study can be accessed at the following link: BL-M07D1 ESMO Abstract. These results indicate that further investigations and clinical trials are warranted to fully assess the efficacy and safety profile of BL-M07D1 in a larger and more diverse patient population. About SystImmune SystImmune is a clinical-stage biopharmaceutical company located in Redmond, WA. It specializes in developing innovative cancer treatments using its established drug development platforms, focusing on bi-specific, multi-specific antibodies, and antibody-drug conjugates (ADCs). SystImmune has several assets in various stages of clinical trials for solid tumor and hematologic indications. Alongside ongoing clinical trials, SystImmune has a robust preclinical pipeline of potential cancer therapeutics in the discovery or IND-enabling stages, representing cutting-edge biologics development. Forward-Looking Statements