TfR1

- Recently presented data demonstrated sustained functional improvement with DYNE-251 treatment through 18 months - - Data from the fully enrolled DELIVER registrational expansion cohort is planned for late 2025 - April 24, 2025 -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage company focused on advancing life-transforming therapeutics for people living with genetically driven neuromuscular diseases, today announced that the European Commission (EC) has granted orphan drug designation for DYNE-251 for the treatment of Duchenne muscular dystrophy (DMD). DYNE-251 is being evaluated in the Phase 1/2 DELIVER global clinical trial in individuals with DMD who are amenable to exon 51 skipping. Long-term clinical data from the ongoing DELIVER trial of DYNE-251 that demonstrated unprecedented and sustained functional improvement at the selected registrational dose were presented in March at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference. Functional assessments in the DELIVER trial include Stride Velocity 95th Centile (SV95C), an objective digital outcome that is accepted as a primary endpoint for DMD clinical trials in Europe. “Our recent long-term DELIVER trial results demonstrated clinically relevant and sustained functional improvement through 18 months, including as assessed by SV95C, which may support a strong rationale for regulatory approval in Europe,” said Doug Kerr, MD, PhD, chief medical officer of Dyne. “We are pleased that the EC has granted orphan drug designation to DYNE-251, reinforcing our belief that our next-generation exon 51 skipping investigational therapy for DMD may be able to bring clinically meaningful functional improvement to those living with this devastating disease. With full enrollment of the registrational expansion cohort in the DELIVER trial complete, we look forward to sharing data from this cohort in late 2025 and the potential to move forward with our first regulatory submissions in early 2026.” The EC grants orphan drug designation to drugs and biologics intended for the treatment, diagnosis or prevention of rare, life-threatening or chronically debilitating diseases or conditions that affect fewer than five in 10,000 people in the European Union (EU). Orphan designation provides companies with certain benefits, including reduced regulatory fees, clinical protocol assistance, research grants and the potential for up to 10 years of market exclusivity in the EU if approved. DYNE-251 was also granted U.S. Food and Drug Administration (FDA) orphan drug and rare pediatric disease designations in March 2023. Key Milestones for the DELIVER Trial Dyne continues to pursue expedited approval pathways globally for DYNE-251 in patients with DMD who are amenable to exon 51 skipping. Dyne has fully enrolled the registrational expansion cohort of 32 patients as part of the DELIVER trial. Data from this cohort are planned for late 2025. Dyne anticipates filing a Biologics License Application (BLA) submission for US accelerated approval in early 2026. DELIVER is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial evaluating the safety, tolerability and efficacy of DYNE-251 in patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping. The multiple ascending dose (MAD) portion of the study resulted in the selection of a registrational dose and regimen of 20 mg/kg every four weeks. A registrational expansion cohort to support potential regulatory submissions for expediated approvals, including accelerated approval in the U.S., is fully enrolled. The primary endpoint for this cohort is the change from baseline in dystrophin protein levels as measured by Western blot. For more information on the DELIVER trial, visit clinicaltrials.gov (NCT05524883) and euclinicaltrials.eu (2023-510351-31-00). DYNE-251 is an investigational therapeutic being evaluated in the Phase 1/2 global DELIVER clinical trial for people living with DMD who are amenable to exon 51 skipping. DYNE-251 consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to a fragment antibody (Fab) that binds to the transferrin receptor 1 (TfR1), which is highly expressed on muscle. It is designed to enable targeted muscle tissue delivery and promote exon skipping in the nucleus, allowing muscle cells to create internally shortened, near full-length dystrophin protein, with the goal of stopping or reversing disease progression. DYNE-251 has been granted fast track, orphan drug and rare pediatric disease designations by the U.S. Food and Drug Administration for the treatment of DMD mutations amenable to exon 51 skipping. In addition to DYNE-251, Dyne is building a global DMD franchise and has preclinical programs targeting other exons, including 53, 45 and 44. DMD is a rare disease caused by mutations in the gene that encodes for dystrophin, a protein critical for the normal function of muscle cells. These mutations, the majority of which are deletions, result in the lack of dystrophin protein and progressive loss of muscle function. DMD occurs primarily in males and affects an estimated 12,000 to 15,000 individuals in the U.S. and 25,000 in Europe. Loss of strength and function typically first appears in pre-school age boys and worsens as they age. As the disease progresses, the severity of damage to skeletal and cardiac muscle often results in patients experiencing total loss of ambulation by their early teenage years and includes worsening cardiac and respiratory symptoms and loss of upper body function by the later teens. There is no cure for DMD, and currently approved therapies provide limited benefit. Dyne Therapeutics is discovering and advancing innovative life-transforming therapeutics for people living with genetically driven neuromuscular diseases. Leveraging the modularity of its FORCE™ platform, Dyne is developing targeted therapeutics that deliver to muscle and the central nervous system (CNS). Dyne has a broad pipeline for neuromuscular diseases, including clinical programs for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD), and preclinical programs for facioscapulohumeral muscular dystrophy (FSHD) and Pompe disease. 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PALO ALTO, Calif., May 1, 2025 /PRNewswire/ -- Kodiak Sciences Inc. (Nasdaq: KOD), a biopharmaceutical company committed to researching, developing and commercializing transformative therapeutics to treat high prevalence retinal diseases, announced today that seven scientific presentations on its research programs will be made at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting, being held from May 4-8 in Salt Lake City, Utah. "We are pleased to share new data from Kodiak's research and development efforts at this year's ARVO meeting. This body of work further highlights the power and versatility of Kodiak's ABC® (Antibody Biopolymer Conjugate) platform for the design and development of new medicines for complex multifactorial diseases with a high unmet need," said Dr. Victor Perlroth, MD and Chief Executive Officer. "Our bispecific protein platform, the basis for KSI-101 currently in clinical development for macular edema secondary to inflammation (MESI), is fueling two new research programs in two new therapeutic categories: ocular inflammatory disease and geographic atrophy. We also present new data from our ABC® platform extension in which we embed diverse therapeutic payloads, such as oligonucleotides and peptides, into the biopolymer backbone at a high drug-antibody ratio (DAR) and deliver these payloads into targeted cells. We believe this is a promising strategy to power a next generation of targeted, high-DAR, multi-specific and multi-modality therapeutic candidates with relevance for retinal and systemic diseases." The seven poster presentations are listed below, grouped by topic. The posters will also be made available under Kodiak's "Scientific Presentations" page on kodiak.com. Ocular Inflammatory Disease Ocular inflammatory disease, often called uveitis, is the fourth leading cause of vision loss for working aged adults in the developed world. One-third of patients with ocular inflammation develop macular edema, which is the leading cause of vision loss among patients with ocular inflammation. Steroids remain the mainstay treatment but can cause significant and permanent ocular adverse effects especially with long-term use or high doses. This body of work demonstrates Kodiak's strong protein engineering expertise to design innovative therapies, including KSI-101 (currently in Phase 1b) and KSI-102, by targeting the underlying and complex cytokine interactions underlying chronic inflammatory ocular diseases. 1. Title: Development of Anti-inflammatory Bispecific anti-TNF-α VHH anti-IL-6 Antibody Fusion for the Treatment of Inflammatory Retinal Diseases Session Title: Anti-inflammatory agents, ocular toxicity, cytokines and growth factors Presentation Date and Time: May 4, 2025; 8:00 – 9:45 AM (MT) Presentation Type: Poster Session Poster Number: 195-A0416 Elevated levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) play distinct yet complementary roles in driving inflammatory retinal diseases such as non-infectious uveitis. Treatments targeting these cytokines individually may fail to control inflammation in a comprehensive manner. Here we present preclinical data of KSI-102, a novel bispecific antibody that potently inhibits both TNF-α and IL-6 simultaneously, offering enhanced therapeutic potential for inflammatory ocular diseases. 2. Title: Preserving Endothelial Barrier Function with Novel Bispecific Anti-Inflammatory Agents for the Treatment of Retinal Inflammatory Diseases Session Title: Anti-inflammatory agents, ocular toxicity, cytokines and growth factors Presentation Date and Time: May 4, 2025; 8:00 – 9:45 AM (MT) Presentation Type: Poster Session Poster Number: 196-A0417 Inflammation contributes to ocular disease by triggering a cascade of pathological events, including disruption of the blood-retinal-barrier and recruitment of immune cells to retinal tissues. These processes can lead to edema and tissue damage, which are hallmark features of conditions such as macular edema and uveitis. Adalimumab is an anti-TNF-α biologic approved as a steroid-sparing agent for the treatment of non-infectious uveitis (NIU). However, more than 50% of patients with NIU experienced treatment failure over 85 weeks in the VISUAL I trial. This preclinical presentation demonstrates that Kodiak's anti-TNF-α, anti-IL-6 fusion protein normalizes human endothelial morphology and junctional proteins better than monotherapy agents. 3. Title: Ocular Toxicity Study of KSI-101 Demonstrates Tolerability after Intravitreal Administration in Cynomolgus Monkeys Session Title: Retina/RPE: New drugs, mechanisms of action, and toxicity Presentation Date and Time: May 8, 2025; 11:45 AM – 1:30 PM (MT) Presentation Type: Poster Session Poster Number: 5998-A0183 KSI-101 is a first-in-class, local, high-strength bispecific protein in clinical development for the treatment of macular edema secondary to inflammation (MESI). Early clinical data of KSI-101 in the Phase 1b APEX study, which is enrolling patients with MESI, demonstrates that at all dose levels, KSI-101 rapidly normalizes macular edema and improves vision. To inform and support further clinical development of KSI-101, which has demonstrated a positive safety profile in patients, here we demonstrate that repeated bilateral intravitreal administration of KSI-101 in non-human primates was safe and well tolerated. The following poster was developed in collaboration with Chang Gung Memorial Hospital, Department of Ophthalmology: 4. Title: Systemic Review of Uveitic Macular Edema (UME) Outcomes in Children Versus Adults Session Title: Uveitis Epidemiology and Clinical Characterization Presentation Date and Time: May 6, 2025; 8:30-10:15 AM (MT) Presentation Type: Poster Session Poster Number: 2849-A0142 Macular edema secondary to inflammation affects adults and children, with differing underlying causes, inflammation patterns and clinical presentations. Treatment options vary by etiology, and steroids are generally avoided in children due to serious adverse effects. This study highlights the serious impact UME in particular has on vision, especially in children, and underscores the critical need for dedicated research and the development of safe and effective therapies tailored for pediatric UME. Geographic Atrophy Geographic atrophy (GA), the advanced form of dry age-related macular degeneration, affects approximately one million patients in the U.S. and is characterized by atrophic lesions in the retina that progressively expand to the central macular and fovea, leading to irreversible vision loss. Currently there are two approved therapies for GA, both are anti-complement therapies that offer modest therapeutic benefit and require monthly or every other month intravitreal injections. 5. Title: Development of Potent Bispecific Inhibitors Targeting Complement Activation and Cytokines for the Treatment of Geographic Atrophy (GA) Session Title: New drugs, delivery systems, and mechanisms of action II Presentation Date and Time: May 7, 2025; 10:15 AM – 12:00 PM (MT) Presentation Type: Poster Session Poster Number: 4337-A0493 Here we present new data on a promising therapeutic strategy to treat GA by combining complement regulators with an anti-VEGF antibody to prevent wet AMD conversion and anti-IL-6 antibody to further reduce GA progression, to achieve potent concurrent inhibition of complement pathway activation and VEGF pathway signaling. Enhancing Therapeutic Efficacy with the ABCD Platform Antibody Drug Conjugates (ADCs) and Antibody Oligonucleotide Conjugates (AOCs) are promising platforms for targeted drug delivery but have a limited drug-antibody ratio (DAR), which poses significant challenges in optimizing therapeutic efficacy. Kodiak's Antibody Biopolymer Conjugate Drug (ABCD) platform addresses this limitation by utilizing a customizable biopolymer to enable the design and development of multifunctional, high DAR therapeutics for ophthalmic and systemic applications. 6. Title: Delivery of Therapeutic Oligonucleotides by Antibody Biopolymer Conjugates (ABC®) Session Title: New drugs, delivery systems, and mechanisms of action II Presentation Date and Time: May 7, 2025; 10:15 AM – 12:00 PM (MT) Presentation Type: Poster Session Poster Number: 4334-A0490 Here we demonstrate the intracellular drug delivery capability and target knockdown potency of Antibody Biopolymer Conjugate Oligonucleotides (ABCO) in the target cells, providing a proof of concept for ABC® mediated intracellular delivery of oligonucleotide therapeutics. We demonstrate that (a) anti-TfR1 ABCO maintains high binding affinity to TfR1, (b) the antibody and its conjugates exhibit concentration dependent uptake in HepG2 cells, enabling delivery of RNA payloads, and (c) anti-TfR1 ABCOs with siRNA or ASO effectively modulate target gene expression. 7. Title: Effect of Polymer Architecture on Properties of Antibody Biopolymer Conjugates Session Title: New drugs, delivery systems, and mechanisms of action II Presentation Date and Time: May 7, 2025; 10:15 AM – 12:00 PM (MT) Presentation Type: Poster Session Poster Number: 4325-A0481 This study demonstrates how polymer architecture, specifically molar mass and number of arms in homopolymers, influences conjugate properties and explores the role of structural design. These findings guide optimization and further development of biopolymer conjugated therapeutic candidates with Kodiak's ABCD platform. About Kodiak Sciences Inc. Kodiak Sciences (Nasdaq: KOD) is a biopharmaceutical company committed to researching, developing, and commercializing transformative therapeutics to treat a broad spectrum of retinal diseases. We are focused on bringing new science to the design and manufacture of next generation retinal medicines to prevent and treat the leading causes of blindness globally. Our ABC Platform® uses molecular engineering to merge the fields of protein-based and chemistry-based therapies and has been at the core of Kodiak's discovery engine. We are developing a portfolio of three clinical programs, two of which are late-stage today and derived from our ABC Platform and one which is platform-independent and which we believe can progress rapidly into pivotal studies. Kodiak's lead investigational medicine, tarcocimab, is a novel anti-VEGF antibody biopolymer conjugate under development for the treatment of high prevalence retinal vascular diseases. Tarcocimab is currently being studied in two Phase 3 clinical trials, GLOW2 in patients with diabetic retinopathy and DAYBREAK in patients with wet AMD. GLOW2 enrollment is complete, and DAYBREAK is actively enrolling patients. KSI-501 is our second investigational medicine, a first-in-class anti-IL-6, VEGF-trap bispecific antibody biopolymer conjugate designed to inhibit both IL-6 mediated inflammation and VEGF-mediated angiogenesis and vascular permeability. KSI-501 is being developed for the treatment of high prevalence retinal vascular diseases to address the unmet needs of extended durability and targeting disease biology beyond VEGF for differentiated efficacy. The Phase 3 DAYBREAK study of KSI-501 in wet AMD is actively enrolling patients. KSI-101, our third product candidate, is a novel anti-IL-6, VEGF-trap bispecific protein. Kodiak is developing KSI-101 for the treatment of retinal inflammatory diseases, as currently there are no available intravitreal biologic therapies addressing the spectrum of inflammatory conditions of the retina. The Phase 1b APEX study of KSI-101 is actively enrolling patients, as a precursor to activating the Phase 2b/3 PEAK and PINNACLE studies in patients with macular edema secondary to inflammation ("MESI"). Kodiak is advancing its platform technology to embed small molecules and other active pharmaceutical ingredients ("APIs") into Kodiak's proprietary biopolymer backbone to enable high drug-antibody-ratio ("DAR") medicines. The diverse APIs are designed to be released over time to achieve targeted, multi-specific and tailored modulation of biological pathways. The unique combination of high DAR and tailored therapeutic benefit offers potential for broad application to multifactorial diseases and builds directly from our Antibody Biopolymer Conjugate technology and its 15 years of design, development and manufacturing experience. We call this platform extension our Antibody Biopolymer Conjugate Drug ("ABCD") Platform because we are extending our platform capabilities to include the conjugation of small molecule drugs and other APIs whereas historically, we primarily conjugated biologics such as antibodies. For more information, please visit www.kodiak.com. Kodiak®, Kodiak Sciences®, ABC®, ABC Platform®, ABCD™ and the Kodiak logo are registered trademarks or trademarks of Kodiak Sciences Inc. in various global jurisdictions Forward-Looking Statements This release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding: the power and versatility of Kodiak's ABC® platform; the enhanced therapeutic potential of KSI-102 for inflammatory ocular diseases; the potential of KSI-101 for the treatment of MESI; the potential for Kodiak's ABCD platform to enable the design and development of multifunctional, high DAR therapeutics for ophthalmic and systemic applications; and the optimization and further development of biopolymer conjugated therapeutic candidates with Kodiak's ABCD platform. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "could," "expect," "plan," "believe," "intend," "pursue," and other similar expressions among others. Any forward-looking statements are based on management's current expectations of future events and are subject to risks and uncertainties that could cause actual results to differ materially and adversely from those in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that cessation, modification or delay of any of the ongoing clinical studies may occur; the risk that our research and development efforts and our ability to advance our product candidates into later stages of development may fail; the risk that any one or more of our product candidates may not be successfully developed, approved or commercialized; the risk that adverse economic conditions may significantly impact our business and operations, including our clinical trial sites, and those of our manufacturers, contract research organizations or others with whom we conduct business; the risk that sufficient capital may not be available as expected, or at all, to complete the development of any products; as well as the other risks identified in our filings with the Securities and Exchange Commission (SEC). For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. These forward-looking statements speak only as of the date hereof and Kodiak undertakes no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. View original content:https://www.prnewswire.com/news-releases/kodiak-sciences-data-at-arvo-2025-highlight-power-and-versatility-of-abc-platform-in-addressing-complex-multifactorial-ocular-diseases-302444839.html SOURCE Kodiak Sciences Inc. John Borgeson, Chief Financial Officer, Tel (650) 281-0850, ir@kodiak.com

NEW YORK and TRUMBULL, Conn., April 30, 2025 /PRNewswire/ -- Apertura Gene Therapy, a biotechnology company focused on innovative gene therapy solutions, and the Rett Syndrome Research Trust (RSRT), an organization working to cure Rett Syndrome, today announced a collaboration to license Apertura's human transferrin receptor 1 capsid (TfR1 CapX). This partnership aims to advance innovative genetic medicine approaches for the treatment of Rett Syndrome, a rare genetic neurological disorder caused by random mutations in the MECP2 gene on the X chromosome that primarily affect females, causing developmental regression and severe motor and language impairments. Apertura's TfR1 CapX is an intravenously delivered adeno-associated virus (AAV) capsid engineered to bind the transferrin receptor 1(TfR1), enabling efficient delivery of genetic medicines across the blood-brain barrier (BBB). TfR1 is a well-characterized BBB-crossing receptor, broadly and consistently expressed throughout life—even in the context of neurological disease—making it an attractive target for CNS delivery in disorders like Rett syndrome. Developed by Apertura's academic founder, Dr. Ben Deverman, Director of Vector Engineering at the Broad Institute, TfR1 CapX has shown strong CNS selectivity in preclinical studies, achieving over 50% neuronal and 90% astrocyte transduction across multiple brain regions. Because Rett syndrome affects the brain diffusely, broader cellular transduction may correlate with greater symptomatic improvement. "Efficient, safe, and widespread delivery of genetic medicines to the brain is the ultimate goal for treating CNS disorders such as Rett syndrome. Successfully addressing this challenge would dramatically accelerate the development of genetic medicines for Rett and other neurological diseases. My colleagues and I have extensively evaluated advanced delivery technologies, and Apertura's capsid stands out for its impressive CNS biodistribution capabilities," said Monica Coenraads, Founder and CEO of RSRT and parent to an adult daughter with Rett. "We're enthusiastic about integrating this innovative capsid into our internal gene-editing programs and facilitating its adoption for external Rett syndrome programs as well. This collaboration represents a major step forward for patients." Last year RSRT launched the MECP2 Editing Consortium, a collaboration among six labs, developing next-generation genetic medicines for Rett syndrome. The Consortium's editing programs will be utilizing the Apertura capsid to deliver genetic medicine cargoes diffusely across the brain non-invasively. Furthermore, the license allows RSRT to sublicense the capsid for Rett programs. "RSRT has made remarkable progress in advancing Rett syndrome therapies, and Apertura is committed to accelerating this momentum with TfR1 CapX. Our engineered capsid addresses the critical need for more potent and less invasive treatments, significantly benefiting patients and caregivers. This collaboration reflects the innovative efforts of both organizations and serves as a pioneering example of how industry partnerships can rapidly advance vital therapies for patients in need," said Diego Garzón, PhD, Vice President of Corporate Development, Apertura Gene Therapy. "Apertura's TfR1 capsid has the potential to transform treatments for CNS diseases. We are committed to partnering with both for-profit and non-profit organizations to maximize this innovation's impact for patients." About Rett Syndrome Rett syndrome is a rare genetic neurodevelopmental disorder caused by random mutations in the MECP2 gene on the X chromosome. The disorder predominantly affects girls but can also rarely affect boys. Symptoms typically become apparent between the ages of 12 to 18 months. Rett syndrome is devastating as it deprives toddlers of speech, hand use, and normal movement often including the ability to walk. As childhood progresses the disorder brings anxiety, seizures, tremors, breathing difficulties, and severe gastrointestinal issues. While their bodies suffer, it is believed that their cognitive abilities remain largely intact. Although most children survive to adulthood, they require total round- the-clock care. About Rett Syndrome Research Trust The Rett Syndrome Research Trust is a non-profit organization exclusively focused on advancing genetic medicines for Rett syndrome. Multiple clinical trials in gene therapy for Rett syndrome are now underway, all possible because of RSRT-funded research. In 2024 RSRT launched a $40 million initiative, Roadmap to Cures, with a goal to bring three genetic medicines, beyond the current gene therapies, to clinical trials by 2028. RSRT's mission is clear, urgent, and personal: to cure Rett syndrome and transform the lives of the people we love. To learn more, please visit . Follow us on Facebook, Instagram and YouTube. About Apertura Gene Therapy Apertura Gene Therapy is a biotechnology company unlocking new opportunities for treating currently intractable diseases. The company is uniquely positioned to develop genetic medicines to overcome limitations in cellular access, gene expression, pre-existing immunity and manufacturability. Founded in 2021 on technology from the Broad Institute, and with support from Deerfield Management Company, the company is based in New York City. For more information, please visit our website at and follow us on LinkedIn. Contact: Apertura Gene Therapy Diego Garzón [email protected] Rett Syndrome Research Trust Amanda Breeding Scient PR [email protected] SOURCE Apertura Gene Therapy WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED