HER3

In the ADC renaissance of the last few years, Japan’s venerable pharma company Daiichi Sankyo has won many of the headlines. But if MediLink Therapeutics has its way, Chinese biotechs will cement the treatments’ dominance in oncology — and prove that China’s new generation of drugmakers can truly compete on the global stage. MediLink has raised $120 million in funding and counts BioNTech and Roche as partners. The Suzhou-based company is at the forefront of a dealmaking wave in which multinational pharma companies have increasingly looked to China as a source of early drug candidates. And MediLink’s licensing deals with multinational pharmas are a bright spot amid growing US-China tensions that have cast a chill over much of the local industry’s work with US companies. The biotech, founded in 2020, came on the scene just as “nearly every pharma was looking for ADCs” again after the drugs had fallen out of favor a decade prior, said Jiaqiang Cai, MediLink’s co-founder and chief scientific officer. That wasn’t always the case. Cai previously worked at Sichuan Kelun-Biotech, which began pursuing ADCs in 2013 after the FDA approval of Roche’s Kadcyla sparked an ADC me-too frenzy in China. While he believed Kelun had a me-better molecule, at 2019’s JP Morgan conference in San Francisco, everyone turned him down for meetings to talk about licensing deals. They saw no future in ADCs, and “nobody believed everything we did in China at that time,” he said. A few months later, Merck came calling after AstraZeneca’s up to $7 billion ADC deal with Daiichi Sankyo stunned the industry. Merck licensed Kelun’s TROP2 ADC and eventually inked two more deals for other programs, each with billions of dollars in potential milestones. By then, Cai had left to work for another domestic pharma company in Shanghai. But Tony Xue, his former ADC partner at Kelun, wondered if they could repeat the success with a new startup and a new platform. “Kelun’s technology is actually very good for TROP2. But for many other targets, [it’s] probably too unstable, and also [the] potency is too high,” Cai said. That fine balance of delivering enough chemotherapy to kill cancer without poisoning the rest of the body has long been the key challenge for ADCs. MediLink works with a version of the standard antibody-linker-payload combo that is stable in healthy tissue and doesn’t require internalization of the antibody — meaning its cancer-killing drugs can be unleashed outside the cell, removing some barriers to efficacy. The concept isn’t new. But the way MediLink turned it into reality is emblematic of the fast, iterative engineering that’s helped many Chinese startups get ahead in the drug discovery race. The tiny team led by Xue, Cai and COO Joey Xiao came up with six different ideas of how to structure the payload-linker complex, then hired a CRO to test them all in parallel. They got to work in December 2020. Three months later, in February 2021, they had a molecule that met their criteria. And in June of that year, optimization was complete. “During six months, they made 200 molecules for us. And only six chemists,” he said. Roche made MediLink the first partner for its Shanghai R&D group, and sees the startup “as a fast-growing China biotech with R&D expertise and proprietary ADC platform technology, including differentiated TOP1 inhibitor payload and linker,” a spokesperson for the Swiss drugmaker said. There can be downsides to speed: MediLink and BioNTech’s HER3 ADC was placed on a clinical hold by regulators earlier this year after patient deaths were deemed related to treatment. The serious toxicity arose as MediLink expanded the patient cohort in a short period of time. “We moved too fast,” Cai told Endpoints. But he said the companies also reacted swiftly to pause enrollment and notify regulators. They ended up adjusting the dose, and the hold was lifted in August . With money from the out-licensing deals, MediLink has been able to grow its team to almost 180 people, even though it hasn’t raised any new venture funding since closing a $70 million Series B in 2022. With many of MediLink’s assets already claimed by a partner (before BioNTech and Roche, it also struck deals with Zai Lab, Harbour BioMed and Henlius) the company’s leaders are hoping to keep some candidates in-house before considering more deals, which Cai said would likely happen at a later phase. “For anything you try to license out, you need to get the idea earlier than others, and then you have something other people don’t have,” he said. When asked about concerns that promising data from Chinese patients wouldn’t translate in trials outside the country, Cai noted that the much higher body weight for US patients could skew the pharmacokinetics, and different dose settings may be required in different countries. “I believe eventually it will work,” he said. Key investors: LYFE Capital, Qiming Venture Partners, Legend Capital, Loyal Valley Capital, Apricot Capital, C&D Emerging Capital, Highlight Capital Find the full list of 2024 Endpoints 11 winners here .

BOSTON, Sept. 23, 2024 /PRNewswire/ -- Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation (FTD) to EO-3021, a differentiated antibody drug conjugate (ADC), for the treatment of patients with advanced or metastatic gastric and gastroesophageal junction (GC/GEJ) cancer expressing Claudin 18.2 that has progressed on or after prior therapy. "We are delighted to receive Fast Track designation for EO-3021, which marks an encouraging recognition of the unmet medical need in patients with Claudin 18.2-expressing tumors, as well as the potential for EO-3021 to deliver improved therapeutic outcomes," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "This designation is based on nonclinical and initial clinical data from our ongoing Phase 1 clinical trial. As we announced in August, early results showed a confirmed overall response rate of 42.8% in a Claudin 18.2-enriched subset of gastric and GEJ cancer. In addition, we observed differentiated tolerability, with minimal MMAE-associated toxicities, including no neutropenia or peripheral neuropathy/hypoesthesia. We are grateful for the opportunity to potentially expedite the delivery of EO-3021 and look forward to advancing through monotherapy dose expansion and reporting additional data from our ongoing trial in the first half of 2025, and to initiating the combination portion of our study later this year." Fast Track is a process designed by the FDA to facilitate the development and expedite the review of therapeutic candidates intended to treat serious or life-threatening conditions, for which nonclinical or clinical data demonstrate the potential to address unmet medical needs. Therapeutic candidates that receive FTD may be eligible for more frequent interactions with the FDA to discuss the candidate's development plan. Therapeutic candidates with Fast Track designation may also be eligible for priority review and accelerated approval if supported by clinical data. About EO-3021 EO-3021 is a differentiated, clinical-stage antibody drug conjugate (ADC) with best-in-class potential comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2 and a monomethyl auristatin E (MMAE) payload with a cleavable linker that is site-specifically conjugated to Glutamine 295 providing a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 trial (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers. Elevation Oncology has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China. About Elevation Oncology, Inc. Elevation Oncology is an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs. We are leveraging our antibody-drug conjugate (ADC) expertise to advance a novel pipeline, initially targeting two clinically validated targets in oncology, Claudin 18.2 and HER3. Our lead candidate, EO-3021, is a potential best-in-class ADC designed to target Claudin 18.2 and is currently being evaluated in a Phase 1 trial (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers. Additionally, we expect to nominate a development candidate for our second program, a HER3-targeting ADC for the treatment of patients with solid tumors that overexpress HER3, in 2024. For more information, visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated clinical and preclinical development activities, expected timing of announcements of clinical results, potential benefits of Elevation Oncology's product candidates, potential market opportunities for Elevation Oncology's product candidates and the ability of Elevation Oncology's product candidates to treat their targeted indications. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These forward-looking statements may be accompanied by such words as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "goal," "intend," "may," "might," "plan," "possible," "potential," "will," "would," and other words and terms of similar meaning. Although Elevation Oncology believes that the expectations reflected in such forward-looking statements are reasonable, Elevation Oncology cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval are inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause Elevation Oncology's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to Elevation Oncology's ability to advance its product candidates, the timing and results of preclinical studies and clinical trials, approvals and commercialization of product candidates, the receipt and timing of potential regulatory designations, Elevation Oncology's ability to fund development activities and achieve development goals, Elevation Oncology's ability to protect intellectual property, Elevation Oncology's ability to establish and maintain collaborations with third parties, and other risks and uncertainties described under the heading "Risk Factors" in documents Elevation Oncology files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Elevation Oncology undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Elevation Oncology Investor and Media Contact Hannah Deresiewicz, 212-362-1200 EVP, Managing Director, Precision AQ [email protected] SOURCE Elevation Oncology WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

TOKYO, Japan & BASKING RIDGE, NJ, USA I September 23, 2024 I Topline results from the TROPION-Breast01 phase 3 trial of datopotamab deruxtecan (Dato-DXd) compared to investigator’s choice of chemotherapy, which previously met the dual primary endpoint of progression-free survival (PFS), did not achieve statistical significance in the final overall survival (OS) analysis in patients with inoperable or metastatic hormone receptor (HR) positive, HER2 low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). This analysis follows the positive PFS results presented at the 2023 European Society for Medical Oncology Congress which showed datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS. An improvement in patient-reported outcomes was also seen. 1 The PFS data and additional results for key secondary endpoints were published this month in the Journal of Clinical Oncology . The safety profile of datopotamab deruxtecan was consistent with that observed in the previous analysis, including lower rates of grade 3 or higher treatment-related adverse events compared to chemotherapy, and no new safety concerns identified. All grade interstitial lung disease (ILD) rates remained low with no new grade 3 or higher ILD events observed. With ADCs approved during the course of the trial, including ENHERTU ® (trastuzumab deruxtecan), subsequent treatment following patients’ disease progression or treatment discontinuation is likely to have affected survival results. “Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in TROPION-Breast01, a result supported by multiple meaningful secondary measures including patient-reported outcomes,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We are proud to have brought forth a new standard of care for patients with metastatic breast cancer with ENHERTU and we remain committed to making datopotamab deruxtecan another potential option for patients who can benefit.” “The metastatic HR positive breast cancer treatment landscape has advanced remarkably in the last several years to the benefit of patients,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting. We will continue discussions with regulatory authorities and apply insights from these results to our clinical development program for datopotamab deruxtecan in breast cancer.” The data will be presented at an upcoming medical meeting and shared with regulatory authorities currently reviewing applications for this indication. In addition to TROPION-Breast01, Daiichi Sankyo and AstraZeneca are evaluating datopotamab deruxtecan alone and with immunotherapy as treatment for patients with triple negative or HR low, HER2 negative breast cancers in the TROPION-Breast02 , TROPION-Breast03 , TROPION-Breast04 and TROPION-Breast05 phase 3 trials. About TROPION-Breast01 TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR positive, HER2 low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease. Following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy, patients had the option to receive subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted. The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov . About Hormone Receptor Positive Breast Cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 2 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally. 2 While survival rates are high for those diagnosed with early breast cancer, less than 35% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 3 Approximately 70% of diagnosed cases are considered what has been historically called HR positive, HER2 negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-). 3 Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer. 4 However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited. 4 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 4,5,6,7 TROP2 is a protein broadly expressed in HR positive, HER2 negative breast cancer and is associated with increased tumor progression and poor survival. 8,9 About Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including non-small cell lung cancer, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan. 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 datopotamab deruxtecan (Dato-DXd), 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. Datopotamab deruxtecan, 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. ENHERTU U.S. Important Safety Information Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide . 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 need. For more information, please visit www.daiichisankyo.com . References: 1 Pernas S, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer: Patient-reported outcomes (PROs) from the TROPION-Breast01 study. Presented at: ASCO Congress 2024; 31 May – 4 June, 2024; Chicago, IL. Abstract 1006. 2 Bray F, et al. CA Cancer J Clin . 2024; 10.3322/caac.21834. 3 National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes . Accessed September 2024. 4 Manohar P, et al. Cancer Biol Med . 2022 Feb 15; 19(2):202–212. 5 Cortes J, et al. Lancet . 2011;377:914-923. 6 Yuan P, et al. Eur J Cancer . 2019;112:57-65. 7 Jerusalem G, et al. JAMA Oncol . 2018;4(10):1367–1374. 8 Goldenberg D, et al. Oncotarget . 2018;9(48): 28989-29006. 9 Vidula N, et al. Breast Cancer Res Treat . 2022 Aug;194(3):569-575. SOURCE: Daiichi Sankyo