Visceral Myopathy Familial External Ophthalmoplegia

21 November 2024 – The United Mitochondrial Disease Foundation’s (UMDF) venture philanthropy arm, The Mito Fund, has invested in Khondrion, a Netherlands-based clinical stage biopharmaceutical company discovering and developing therapies targeting primary mitochondrial disease (PMD). Khondrion is currently preparing to initiate a Phase III study investigating the potential of its lead proprietary drug candidate, sonlicromanol, to treat adult patients with PMD due to the m.3243A>G mutation, the most common genetic defect causing multi-systemic PMD, which has an estimated prevalence of 4.4:100,000 impacting hundreds of thousands of patients worldwide. One of the most advanced drug candidates in development for PMD, sonlicromanol is a disease-modifying, potentially first-in-class, brain-penetrant redox-modulator with anti-inflammatory properties, that targets key metabolic and inflammatory pathways underlying PMD. Its ongoing development is supported by compelling clinical data from Khondrion’s Phase IIb program, published earlier this month in the peer-reviewed scientific journal, Brain, showing strong patient benefits from sonlicromanol in multiple outcome measures of global health, quality of life, mood, fatigue, pain and balance control. "We believe sonlicromanol holds incredible potential for treating primary mitochondrial disease which impacts hundreds of thousands of people worldwide," said Dr. Philip Yeske, UMDF's Interim Managing Director and Science and Alliance Officer. "But it’s not just about numbers. The diseases associated with this mutation are devastating and remarkably progressive. The approval of this therapy would meet an urgent and unmet therapeutic need.” Said Khondrion’s Chief Executive Officer, Prof. Dr. Jan Smeitink: “Patients with primary mitochondrial disease currently have no treatment options available to them. Through our clinical trials to date, we see the great potential sonlicromanol may have on these patients, particularly on their most burdensome symptoms of chronic fatigue and muscle weakness. With the support and investment by the UMDF via The Mito Fund, we look forward to further progressing our clinical work on sonlicromanol at pace in our upcoming Phase III trial in adult patients with PMD.” Like all investments made by The Mito Fund, the Khondrion consideration went through a rigorous review process by UMDF’s Venture Philanthropy Investment Committee, an advisory group consisting of world-class experts in the areas of mitochondrial disease, pharmaceutical development, and private equity investments. After receiving the committee’s recommendation, the investment was then approved by UMDF’s full Board of Trustees. “From an investment perspective, there were several really attractive elements to the investment. First, sonlicromanol represents an innovative treatment for an underserved population. It’s also a mature clinical stage asset, which shortens the runway to approval,” said Dr. Yeske. “UMDF looks forward to partnering with Khondrion in advancing this investigational therapeutic in a patient-centric manner.” Launched in the summer of 2023, The Mito Fund is UMDF’s most ambitious effort to date to ramp up the development of mitochondrial disease treatments and cures. The fund’s venture philanthropy model is designed not only to financially support the development of the next generation of mitochondrial disease treatments, but also to leverage UMDF’s experience and network to accelerate the development process and lower the risk associated with entry into the field for a wide range of investors and researchers. This is the second official investment for The Mito Fund. In April 2024, the fund announced an investment in Pierrepont Therapeutics, Inc., which is working on a preclinical proprietary intracellular enzyme replacement therapy for Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE). Companies exploring the mitochondrial science space are encouraged to start a conversation about investment opportunities at www.themitofund.org. Proposals are accepted on a rolling basis. About UMDF For more than 25 years, The United Mitochondrial Disease Foundation (UMDF) has built a global network of patients, researchers, clinicians, institutions, and industry partners dedicated to fighting mitochondrial disease. Together with the mito community, UMDF is committed to a mission of funding the best science no matter where it is found in the world while at the same time providing critical education, advocacy, and support-focused programs and services to patient families. In the last year … Nearly 1,500 affected patients and families depended upon UMDF for support.More than 400 clinicians listened to UMDF’s Bench-to-Bedside seminars.UMDF advocates had more than 1,000 touchpoints with their congressional offices.UMDF provided hundreds of patients with no-cost genetic testing to help shorten the diagnostic journey. About Khondrion Khondrion is a clinical stage biopharmaceutical company developing therapies for patients with primary mitochondrial disease (PMD). The company’s lead asset, sonlicromanol, is a potentially first-in-class, brain-penetrant redox-modulator with anti-inflammatory properties, that targets key metabolic and inflammatory pathways underlying PMD. One of the most advanced, potentially disease-modifying drug candidates for mitochondrial disease in development, sonlicromanol has been tested in three clinical trials in patients with m.3243A>G PMD, as well as in the first wave of a 6-month Phase 2 study in children with genetically confirmed PMD and who suffer from motor symptoms. Sonlicromanol has been granted orphan drug designations for the treatment of MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes), Leigh disease and patients with maternally inherited diabetes and deafness (MIDD) in Europe, and for all inherited mitochondrial respiratory chain disorders in the US. It has also been granted a rare pediatric disease designation in the US for the treatment of MELAS. Sonlicromanol and other compounds from Khondrion’s proprietary library have the potential to be developed for a wide range of diseases and conditions with the aim of benefiting patients whose daily lives are severely impacted by mitochondrial impairment. For more information visit www.khondrion.com. Contacts: Khondrion BVProf. Dr. Jan Smeitink, CEOE-mail: info@khondrion.comTel: +31-24-7635000www.khondrion.com ICR Healthcare David Daley, Kris Lam, Tom DanielEmail: khondrion@icrhealthcare.com UMDF / The Mito FundAndy Dearth, Director of Marketing & CommunicationsEmail: Andy.dearth@umdf.org

– Initiated a Phase 1 clinical trial of ENTR-601-44 for the potential treatment of Duchenne muscular dystrophy, marking Entrada’s transition to a clinical-stage company – – Expanded the Company’s Duchenne franchise with the selection of its third clinical candidate, ENTR-601-50, for the potential treatment of people living with Duchenne who are exon 50 skipping amenable – – Cash runway expected through 2025 with $354 million in cash, cash equivalents and marketable securities as of September 30, 2023 – BOSTON, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Entrada Therapeutics, Inc. (Nasdaq: TRDA), a biopharmaceutical company aiming to transform the lives of patients by establishing intracellular Endosomal Escape Vehicle (EEV™)-therapeutics as a new class of medicines, today reported financial results for the third quarter ending September 30, 2023, and highlighted recent business updates. “The third quarter marked an important milestone for Entrada, as we transitioned into a clinical-stage company, with the initiation of the Phase 1 clinical trial in healthy volunteers for our lead Duchenne product candidate, ENTR-601-44. Duchenne muscular dystrophy is a relentlessly progressive neurodegenerative disease, and we are committed to bringing forward potential new therapeutic options for people living with Duchenne who have mutations that are amenable to particular exon skipping therapies,” said Dipal Doshi, President and Chief Executive Officer of Entrada Therapeutics. “We are well-positioned to embark upon our next phase of growth, as we further advance our Duchenne franchise and progress indications beyond neuromuscular diseases.” Recent Corporate Highlights In September 2023, Entrada dosed the first participant in its Phase 1 clinical trial evaluating ENTR-601-44 for the potential treatment of individuals with Duchenne muscular dystrophy (DMD) who are exon 44 skipping amenable. The primary objective of Entrada’s Phase 1 clinical trial, which is being conducted in the United Kingdom, is to evaluate the safety and tolerability of a single dose of ENTR-601-44 in healthy male volunteers, with a target enrollment of approximately 40 participants. The trial will also evaluate pharmacokinetics and target engagement, as measured by exon skipping in skeletal muscle. Entrada expects to report data from the Phase 1 clinical trial in the second half of 2024.The Company will provide an update on the clinical hold on its Investigational New Drug (IND) application for ENTR-601-44 with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2023. Entrada announced the selection of a third clinical candidate within its Duchenne franchise, ENTR-601-50, for the potential treatment of people living with Duchenne who are exon 50 skipping amenable. The selection of ENTR-601-50 is based on in vivo preclinical data demonstrating robust exon 50 skipping and dystrophin production across cardiac and skeletal muscle groups. Entrada expects to present these preclinical data in the first half of 2024 and plans to submit a Clinical Trial Application (CTA)/IND submission to initiate clinical development for ENTR-601-50 in 2025. In October 2023, the Company achieved a milestone pursuant to the Vertex Agreement related to preclinical IND-enabling GLP toxicology studies of ENTR-701 that triggered a $17.5 million milestone payment, which the Company expects to receive in the fourth quarter of 2023. In July 2023, Entrada entered into a license agreement to advance the development of ENTR-501 with Pierrepont Therapeutics, Inc., a mitochondrial disease-focused company. ENTR-501 is an intracellular thymidine phosphorylase enzyme replacement therapy in development for the treatment of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is a slowly progressive and fatal, ultra rare disease for which there are no treatment options available. Third Quarter 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $353.6 million as of September 30, 2023, compared to $188.7 million as of December 31, 2022. Entrada anticipates that its cash, cash equivalents and marketable securities as of September 30, 2023, together with Vertex collaboration ongoing research support and the anticipated achievement of certain milestones, will be sufficient to fund the Company's operating expenses and capital expenditure requirements through 2025. Collaboration Revenue: Collaboration revenue was $43.7 million for the third quarter of 2023. There was no collaboration revenue in the third quarter of 2022. Research & Development (R&D) Expenses: R&D expenses were $22.2 million for the third quarter of 2023, compared to $19.0 million for the same period in 2022. This increase was primarily due to the initiation of the ENTR-601-44 Phase 1 clinical trial, additional investment in IND-enabling studies to support future clinical trials and higher personnel costs, including non-cash, stock-based compensation. General & Administrative (G&A) Expenses: G&A expenses were $7.5 million for the third quarter of 2023, compared to $7.0 million for the same period in 2022. This increase was primarily due to higher personnel costs, including non-cash, stock-based compensation, legal costs and other costs to support its ongoing clinical trial and continued research and development activities. Net Income (Loss): Net income was $35.5 million for the third quarter of 2023, compared to a net loss of $(25.1) million for the same period in 2022. About Entrada TherapeuticsEntrada Therapeutics is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines, Endosomal Escape Vehicle (EEV™)-therapeutics, to engage intracellular targets that have long been considered inaccessible and undruggable. The Company’s EEV therapeutics are designed to enable the efficient intracellular delivery of a wide range of therapeutics into a variety of organs and tissues, resulting in an improved therapeutic index. Through its proprietary, highly versatile and modular EEV platform, Entrada is building a robust development portfolio of RNA-, antibody- and enzyme-based programs for the potential treatment of neuromuscular, immunological, ocular and metabolic diseases, among others. The Company’s lead oligonucleotide programs include ENTR-601-44, ENTR-601-45 and ENTR-601-50 for the potential treatment of people living with Duchenne who are exon 44, 45 and 50 skipping amenable, respectively, as well as our partnered candidate ENTR-701 for the potential treatment of myotonic dystrophy type 1 (DM1). For more information about Entrada, please visit our website, www.entradatx.com, and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Entrada’s strategy, future operations, prospects and plans, objectives of management, Entrada’s ability to continue to recruit for and complete a healthy volunteer trial for ENTR-601-44 in the United Kingdom, expectations regarding the timing of data from its Phase 1 trial for ENTR-601-44 in the second half of 2024, express or implied statements regarding the clinical hold on the IND for ENTR-601-44, Entrada’s ability to address the FDA’s concerns regarding its IND for ENTR-601-44, expectations regarding the timing and content of any update expected in the fourth quarter of 2023 concerning the clinical hold on the IND for ENTR-601-44, expectations regarding the therapeutic benefits of ENTR-601-44, expectations regarding the timing of preclinical data results and planned CTA/IND submission for ENTR-601-50, the continued development and advancement of ENTR-601-44, ENTR-601-45 and ENTR-601-50 for the treatment of DMD, ENTR-501 for the treatment of MNGIE, and ENTR-701 for the treatment of DM1, including the IND-enabling studies, expectations regarding the expected timing, progress and success of our collaboration with Vertex, including any future payments we may receive under our collaboration and license agreements, the ability to develop additional therapeutic programs, including further exon skipping programs, the potential therapeutic benefits of its EEV candidates, statements regarding any future payments Entrada may receive under the Vertex Agreement, and the sufficiency of its cash resources through 2025, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Entrada may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities and the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and Entrada’s ability to submit and obtain regulatory clearance for IND or equivalent foreign applications and initiate or complete clinical trials; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; whether Entrada’s cash resources will be sufficient to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Entrada’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-K and in subsequent filings Entrada may make with the SEC. In addition, the forward-looking statements included in this press release represent Entrada’s views as of the date of this press release. Entrada anticipates that subsequent events and developments will cause its views to change. However, while Entrada may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Entrada’s views as of any date subsequent to the date of this press release. ENTRADA THERAPEUTICS, INC.Condensed Consolidated Statements of Operations (Unaudited)(In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Collaboration revenue 43,735 — 87,165 — Operating expenses: Research and development 22,191 18,958 71,593 50,924 General and administrative 7,532 6,978 23,639 20,745 Total operating expenses 29,723 25,936 95,232 71,669 Income (loss) from operations 14,012 (25,936) (8,067) (71,669)Other income: Interest and other income 4,051 799 10,926 1,682 Total other income 4,051 799 10,926 1,682 Income (loss) before benefit from income taxes 18,063 (25,137) 2,859 (69,987)Benefit from income taxes 17,398 — — — Net income (loss) 35,461 (25,137) 2,859 (69,987)Net income (loss) per share, basic$1.07 $(0.80) $0.09 $(2.24)Net income (loss) per share, diluted$1.02 $(0.80) $0.08 $(2.24)Weighted‑average common shares outstanding, basic 33,281,287 31,298,052 32,942,958 31,273,612 Weighted‑average common shares outstanding, diluted 34,775,451 31,298,052 34,289,411 31,273,612 ENTRADA THERAPEUTICS, INC.Condensed Consolidated Balance Sheet Data (Unaudited)(In thousands) September 30,2023 December 31,2022 Cash, cash equivalents and marketable securities$353,578 $188,712Total assets 485,033 252,056Total liabilities 238,370 39,502Total stockholders’ equity 246,663 212,554 Investor and Media ContactKarla MacDonaldChief Corporate Affairs Officerkmacdonald@entradatx.com

In what is turning out to be a strong year for biotech initial public offerings (IPOs), three companies are either launching or planning their IPOs. Here’s a look. Vaxxinity Raises $76 Million Dallas-based Vaxxinity set its initial public offering (IPO) price at $13 per share, raising $76 million. The company was launched in April via consolidation of the vaccine development efforts of COVAXX and United Neuroscience. Based in Dallas, it has operations in Asia, Europe, Latin America, and the U.S. Both COVAXX and United Neuroscience are wholly-owned subsidiaries of Vaxxinity. The company’s proprietary tech platform allows synthetic peptide vaccines to treat and prevent chronic diseases, including Alzheimer’s, Parkinson’s, migraine, high cholesterol, and various infectious diseases, including COVID-19. The technology uses the immune system to become a drug factory, creating antibodies that have a therapeutic or protective effect. The company was originally planning to see 7 million shares at a price range of $14 to $16 per share but instead sold 6 million at $13. It is trading on the Nasdaq under the “VAXX” ticker symbol. The company’s lead compound is UB-311 for Alzheimer’s disease. It targets beta-amyloid. A Phase IIb trial is expected to launch in 2022. It also has UB-612, which activates B- and T-cells to attack SARS-CoV-2, the virus that causes COVID-19. It is currently in several ongoing clinical trials around the world. Genenta to Raise $35 Million Italian company Genenta Science filed with the U.S. Securities and Exchange Commission (SEC) to launch an IPO to raise $35 million. The company is developing stem cell gene therapies for solid tumors. Its lead candidate is Temferon and carries interferon-alpha, a drug used to treat several cancers but isn’t used often because of toxicity. Genenta is developing glioblastoma multiforme (GBM) drug in patients whose GBM has an unmethylated MGMT gene promoter. The Phase I/IIa trial for this indication is ongoing in Italy and is expected to complete patient enrollment and treatment by the second quarter of 2022. It intends to trade on the Nasdaq under the ticker symbol “GNTA.” Entrada Raised $181.5 Million IPO Ohio State University spinoff Entrada Therapeutics raised $181.5 million in its IPO just a week ago. The company, based in Boston, sold 9.1 million shares at $19 per share. The company spun out of Ohio State in 2018 and brought in more than $175 million in venture capital. In March, it brought in $116 million in a Series B round. That round was led by Wellington Management Company and joined by Redmile Group, TCG Crossover, Greenspring Associates, Point72, Qatar Investment Authority, Moore Strategic Ventures, Goldman Sachs, CureDuchenne Ventures and an undisclosed investment firm. Existing investors also participated, including 5AM Ventures, MPM Capital, Roche Venture Fund, MRL Ventures Fund and Agent Capital. The company focuses on using peptides to deliver therapeutics inside cells. Its pipeline includes treatments for various neuromuscular diseases, including Duchenne muscular dystrophy (DMD). In addition to DMD, it has preclinical programs in Myotonic Dystrophy Type 1, Pompe disease, and discovery-level programs in other neurodegenerative diseases, inflammatory diseases, solid tumors and Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE). Its proprietary technology platform is dubbed Endosomal Escape Vehicle (EEV), and they plan to use it to expand beyond neuromuscular diseases. EEV harnesses the inherent endocytic mechanism of cells to allow greater access for therapeutics to the inside of a cell.