MeiraGTx Announces the Presentation of Four Posters at the American Society of Gene and Cell Therapy (ASGCT) 2025 Annual Meeting
MeiraGTx (Nasdaq: MGTX) presented four posters at the ASGCT 2025 Annual Meeting showcasing their gene and cell therapy technology platforms. Key presentations included:
1. An ultra-low dose CNS gene therapy for pediatric obesity using optimized BDNF clinical construct, showing 40% weight loss in mice vs 12% with semaglutide
2. Novel CAG-based promoters that are shorter and more potent than traditional ones, with one variant (C178) showing superior performance in muscle, liver, heart, and brain while being 700 base pairs shorter
3. Research on transcription factor binding sites (TFBS) to enhance synthetic promoter activity, identifying optimal combinations for gene expression
4. Development of optimized AAV-hUPF1 gene therapy for ALS and FTD, showing improved efficacy in multiple disease models while reducing construct size by 1.5kb
MeiraGTx (Nasdaq: MGTX) ha presentato quattro poster al ASGCT 2025 Annual Meeting illustrando le loro piattaforme tecnologiche per terapie geniche e cellulari. Le presentazioni principali includevano:
1. Una terapia genica CNS a dose ultra-bassa per l'obesità pediatrica utilizzando un costrutto clinico BDNF ottimizzato, con una perdita di peso del 40% nei topi rispetto al 12% con semaglutide.
2. Nuovi promotori basati su CAG, più corti e potenti rispetto a quelli tradizionali, con una variante (C178) che ha mostrato prestazioni superiori in muscoli, fegato, cuore e cervello, pur essendo più corta di 700 paia di basi.
3. Ricerca sui siti di legame dei fattori di trascrizione (TFBS) per migliorare l'attività dei promotori sintetici, identificando combinazioni ottimali per l'espressione genica.
4. Sviluppo di una terapia genica AAV-hUPF1 ottimizzata per SLA e FTD, con efficacia migliorata in diversi modelli di malattia e una riduzione della dimensione del costrutto di 1,5 kb.
MeiraGTx (Nasdaq: MGTX) presentó cuatro pósteres en la Reunión Anual ASGCT 2025 mostrando sus plataformas tecnológicas de terapia génica y celular. Las presentaciones clave incluyeron:
1. Una terapia génica CNS de dosis ultra baja para obesidad pediátrica usando un constructo clínico BDNF optimizado, mostrando una pérdida de peso del 40% en ratones frente al 12% con semaglutida.
2. Nuevos promotores basados en CAG que son más cortos y potentes que los tradicionales, con una variante (C178) que mostró un rendimiento superior en músculo, hígado, corazón y cerebro, siendo 700 pares de bases más corta.
3. Investigación sobre sitios de unión de factores de transcripción (TFBS) para mejorar la actividad de promotores sintéticos, identificando combinaciones óptimas para la expresión génica.
4. Desarrollo de terapia génica AAV-hUPF1 optimizada para ELA y FTD, mostrando mejor eficacia en múltiples modelos de enfermedad y reduciendo el tamaño del constructo en 1.5 kb.
MeiraGTx(Nasdaq: MGTX)는 ASGCT 2025 연례 회의에서 유전자 및 세포 치료 기술 플랫폼을 소개하는 4개의 포스터를 발표했습니다. 주요 발표 내용은 다음과 같습니다:
1. 최적화된 BDNF 임상 구성체를 사용한 소아 비만 초저용량 중추신경계 유전자 치료로, 쥐에서 체중 40% 감소를 보여 세마글루타이드의 12% 대비 우수한 효과를 나타냈습니다.
2. 기존보다 더 짧고 강력한 새로운 CAG 기반 프로모터로, 변이체 하나(C178)는 근육, 간, 심장, 뇌에서 우수한 성능을 보이며 700 염기쌍 더 짧습니다.
3. 합성 프로모터 활성을 향상시키기 위한 전사 인자 결합 부위(TFBS) 연구로, 유전자 발현에 최적의 조합을 확인했습니다.
4. ALS 및 FTD에 대한 최적화된 AAV-hUPF1 유전자 치료 개발로, 여러 질환 모델에서 효능이 향상되었으며 구성체 크기를 1.5kb 줄였습니다.
MeiraGTx (Nasdaq : MGTX) a présenté quatre posters lors du ASGCT 2025 Annual Meeting mettant en avant leurs plateformes technologiques de thérapie génique et cellulaire. Les présentations clés comprenaient :
1. Une thérapie génique CNS à dose ultra-faible pour l’obésité pédiatrique utilisant un construct clinique BDNF optimisé, montrant une perte de poids de 40 % chez la souris contre 12 % avec le sémaglutide.
2. De nouveaux promoteurs basés sur CAG, plus courts et plus puissants que les traditionnels, avec une variante (C178) affichant de meilleures performances dans le muscle, le foie, le cœur et le cerveau tout en étant plus courte de 700 paires de bases.
3. Recherche sur les sites de liaison des facteurs de transcription (TFBS) pour améliorer l’activité des promoteurs synthétiques, identifiant les combinaisons optimales pour l’expression génique.
4. Développement d’une thérapie génique AAV-hUPF1 optimisée pour la SLA et la DFT, montrant une efficacité accrue dans plusieurs modèles de maladie tout en réduisant la taille du construct de 1,5 kb.
MeiraGTx (Nasdaq: MGTX) präsentierte auf dem ASGCT 2025 Jahreskongress vier Poster, die ihre Plattformen für Gen- und Zelltherapien zeigten. Wichtige Präsentationen umfassten:
1. Eine ultra-niedrig dosierte ZNS-Gen-Therapie zur Behandlung von pädiatrischer Adipositas mit einem optimierten BDNF-Klinikkonstrukt, die bei Mäusen einen Gewichtsverlust von 40 % gegenüber 12 % mit Semaglutid zeigte.
2. Neue CAG-basierte Promotoren, die kürzer und potenter als herkömmliche sind, wobei eine Variante (C178) in Muskel, Leber, Herz und Gehirn eine überlegene Leistung zeigte und dabei 700 Basenpaare kürzer ist.
3. Forschung zu Bindungsstellen von Transkriptionsfaktoren (TFBS) zur Steigerung der Aktivität synthetischer Promotoren, wobei optimale Kombinationen für die Genexpression identifiziert wurden.
4. Entwicklung einer optimierten AAV-hUPF1-Gen-Therapie für ALS und FTD, die in mehreren Krankheitsmodellen eine verbesserte Wirksamkeit zeigte und die Konstruktgröße um 1,5 kb reduzierte.
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Insights
MeiraGTx's conference posters demonstrate promising advancements in gene therapy technologies with potential applications in obesity, neurodegeneration, and vector optimization.
MeiraGTx's presentations at ASGCT 2025 showcase significant technical advancements across multiple gene therapy platforms that strengthen their competitive position in the genetic medicine space. The first poster describes an AAV-BDNF therapy for severe pediatric obesity that demonstrates remarkable efficacy in preclinical models, achieving approximately
Two subsequent posters detail MeiraGTx's advances in promoter technology – critical DNA sequences that drive gene expression. Their novel CAG-based promoters are both
Their fourth poster highlights an optimized AAV-hUPF1 program for ALS/FTD that works through a mechanism targeting TDP-43 pathology – present in over
What's particularly valuable in these presentations is the demonstration of MeiraGTx's integrated capabilities across vector design, promoter optimization, and therapeutic development. Their approach of increasing expression efficiency while reducing viral load represents an important advance for addressing safety concerns in the field. While these are preclinical findings requiring clinical validation, they demonstrate how MeiraGTx is solving fundamental challenges in gene therapy development through rational engineering approaches.
Multiple Poster Presentations Highlight the Depth and Novelty of MeiraGTx’s Technology Platforms for Gene and Cell Therapy
LONDON and NEW YORK, May 13, 2025 (GLOBE NEWSWIRE) -- MeiraGTx Holdings plc (Nasdaq: MGTX), a vertically integrated, clinical stage genetic medicines company, today announced the Company will exhibit four poster presentations at the American Society of Gene and Cell Therapy (ASGCT) 2025 Annual Meeting, which is being held from May 13-17, 2025, in New Orleans, LA.
The posters will be available on the Posters and Publications page of the Company’s website.
The details of the poster presentations are below:
Poster 507: An Ultra-Low Dose of a Localized CNS Gene Therapy for Severe Pediatric Obesity
Poster Session: Tuesday, May 13, 6:00-7:30 pm CDT
Abstract:
Brain-derived neurotrophic factor (BDNF) is a secreted growth factor that promotes neuronal health throughout the central nervous system and is a key signaling component of metabolic homeostasis. In the ventromedial hypothalamus (VmH), elevated leptin signals melanocortin 4 receptor (MC4R) expressing neurons to release BDNF, which then acts through tropomyosin receptor kinase B (TrkB) to signal fullness and reduce food intake. Patients with loss-of function mutations along this pathway develop severe early-onset obesity syndromes characterized by hyperphagia and food-related distress as young as six months old. Current therapeutic approaches such as bariatric surgery and glucagon-like peptide 1 (GLP1) agonists may be effective for generalized obesity, but do not result in significant, durable treatment for individuals with MC4R or BDNF deficiency. By directly delivering BDNF to the VmH through an adeno-associated virus (AAV)-based gene therapy, we aim to treat these individuals early in childhood in a safe, effective, and lasting way. Treating these children early could significantly improve their physical and emotional well-being and prevent the development of irreversible sequelae such as cancer and diabetes.
To achieve this, we developed a more potent vector which could decrease the AAV gene therapy dose required to maintain effective weight loss, potentially mitigating adverse effects associated with high levels of AAV administration. Our optimized BDNF clinical construct, designed by altering various cis-regulatory components, expresses BDNF up to 143-fold greater than basal levels in vivo, significantly higher than the original academic construct. This is well in excess of the levels shown to prevent weight gain in the diet-induced obesity (DIO) wild-type mouse model. This highly potent AAV-BDNF vector showed efficacy in DIO mice with significant dose-dependent weight loss observed across a wide therapeutic window, with a 60-fold-dose range. Delivery of AAV-BDNF to a single hemisphere of obese mice on high-fat diet resulted in dramatic weight loss up to approximately
To assess the safety of AAV-BDNF gene therapy administered directly to the hypothalamus, we performed biodistribution, hematology, serum chemistry, and brain histology. Because the hypothalamus controls additional behaviors besides feeding, we also assessed animals using the open field, novelty-suppressed feeding, food intake measurements, and standard opponent tests to survey other behavioral attributes. As previously reported, locomotion increased in AAV-BDNF-treated animals. More importantly, animals did not display heightened aggression after AAV-BDNF treatment and exhibited normal pro-social behaviors. Furthermore, AAV-BDNF treatment did not ablate the ability of animals to feed. Overall, our data suggest that AAV-BDNF is an effective and safe therapeutic strategy for severe-early onset pediatric obesity syndromes.
Poster 893: Novel Rationally Designed Promoters Surpass CAG in Mouse and Human Models
Poster Session: Tuesday, May 13, 6:00-7:30 pm CDT
Abstract:
Promoters are essential for gene expression and can be engineered to develop optimized gene therapies. Ideal promoters are short in length and confer tissue specificity as well as potent transgene expression. Approximately
The CAG promoter is a hybrid promoter, 1.8 kb in length, consisting of the CMV immediate early enhancer, the chicken β-actin promoter, and a hybrid rabbit β-globin intron. We rationally designed a series of 82 new CAG promoter variants by systematically introducing modifications to each of the promoter elements and tested them in human and mouse in vitro and in vivo models. In our library of engineered CAG promoter variants, 51 are smaller than the original CAG, of which 22 are fewer than 1000 base pairs in length.
In HEK293T cells, 67 CAG promoter variants are stronger than the original CAG sequence with the strongest promoter exhibiting 13-fold improvement in potency. In both primary human hepatocytes and primary human myotubes, four CAG variants drove 15-fold higher transgene expression than the original while being ~
Here, we have shown several rationally designed CAG-based constitutive promoters which are both shorter than the original CAG sequence and yield higher transcriptional activity in human and mouse in vitro and in vivo models. These promoters show potential for the development of future gene therapies. In particular, these smaller, more potent CAG variants could be advantageous for the design of gene therapies for the muscle and central nervous system where transgenes are typically large, and packaging constraints are of major concern.
Poster 897: Differential Usage of Transcription Factor Binding Sites to Boost Synthetic Promoter Activity
Poster Session: Tuesday, May 13, 6:00-7:30 pm CDT
Abstract:
Transcription factor binding sites (TFBS) play a crucial role in regulating gene expression and can either enhance or repress expression depending on their function and context. Here, we designed a library of short synthetic promoters to evaluate the effect of differential TFBS usage in N2A, mouse neuroblastoma, and C2C12, mouse myoblasts, cell lines.
A massively parallel reporter assay was created to assess the transcriptional strength of 244,000 synthetic promoter sequences. These 182 bp sequences include a variable regulatory upstream region and one of six core promoters with known tissue specificity. Two ubiquitous, JeT and AdML, two muscle-specific, MCK and DES, and two liver-specific promoters, mTTR and AAT, were chosen to assess the impact of alternative TFBS usage on promoter specificity. Regulatory regions were generated to evaluate (i) the effect of each TFBS in isolation, and (ii) the combinatorial effect of selected and tissue-enriched TFBS. Promoter activity in each cell line was calculated as a normalized expression score, referred to as SoR, using Illumina-based sequencing data. Subsequently, the TFBS fold change, or Boost SoR, over the activity of the parent core promoter without any regulatory region was calculated.
Using Boost SoR, we categorized all TFBS as activators (Boost SoR ≥ 0.1, n=85,711), repressors (Boost SoR ≤ -0.1, n=53,146), or as having minimal impact on promoter performance (Boost SoR between -0.1 and 0.1, n=13,814). The top five activating TFBS tested with muscle-specific MCK achieved a four-fold or greater increase in expression compared to MCK alone, with the top boosting TFBS exhibiting a six-fold Boost SoR. The five most repressive TFBS combined with MCK reduced transcription by over five-fold. For JeT, the five strongest activating TFBS increased expression by three-fold or more, while the five most repressive TFBS decreased expression by four-fold or more. In total,
We successfully characterized TFBS that positively and negatively boost the expression from core promoters. By quantifying the boosting effects of differential TFBS, we demonstrated the ability to enhance the performance of the widely used and optimized JeT promoter. Furthermore, we identified TFBS uniquely associated with each promoter and sequences that should be excluded from active regulatory element design. This analysis represents a key asset when designing stronger synthetic promoters for gene therapy.
Poster 1040: Preclinical Efficacy and Potency Assay Development of An Optimized AAV-hUPF1 Gene Therapy for Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)
Poster Session: Wednesday, May 14, 5:30-7:00 pm CDT
Abstract:
Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease that damages motor neurons in the brain and spinal cord. While the pathogenesis of ALS can result from either sporadic or familial inherited mutations, the underlying pathology in over
To improve AAV packaging and thus convey manufacturing benefits, we reduced the size of the original hUPF1 construct by 1.5kb while improving therapeutic efficacy in both in vitro and in vivo models. Using an efficient capsid for CNS delivery and a highly potent expression cassette, our therapeutic strategy is to minimize AAV dosage while maintaining a high level of expression and subsequent efficacy. The optimized AAV-hUPF1 effectively mitigated toxicity in TDP-43 and C9orf72 iNeuron models and restored the normal function of neurons derived from C9orf72 patient cell lines at a lower multiplicity of infection (MOI) than used for the original. Mechanistically, UPF1 target engagement was confirmed in transduced C9orf72 patient-derived neurons by the downregulation of known NMD targets. In a Fused in Sarcoma (FUS) mouse model of ALS, optimized AAV-hUPF1 significantly improved motor neuron survival to levels comparable to wild-type controls at approximately
To further develop the AAV-hUPF1 program, we piloted different TDP-43 induced toxicity models as in vitro potency assays for manufacturing release. To induce cell death, TDP-43 was overexpressed in primary mouse neurons using AAV9 transduction, and in human SH-SY5Y cells using the doxycycline-inducible TET-ON system. While toxicity was reliably and robustly induced in the primary neuronal model, UPF1 co-expression did not result in a measurable global effect and thus did not meet the requirements for our assay development. In contrast, repeated experimentation in the stably transduced and differentiated SH-SY5Y cells showed that TET-inducible overexpression of TDP-43 caused significant toxicity in only about
Collectively, the data from in vitro and in vivo studies using FUS, TDP-43, and C9orf72 models demonstrate that hUPF1 holds significant potential for treating the majority of patients with ALS and other degenerative diseases caused by TDP43 pathology such as Frontotemporal Dementia, as we continue the development of this program.
About MeiraGTx
MeiraGTx (Nasdaq: MGTX) is a vertically integrated, clinical-stage genetic medicines company with a broad pipeline with four late-stage clinical programs. Each of these programs use local delivery of small doses resulting in disease modifying effects in both inherited and more common diseases, in the eye, Parkinson’s disease and radiation-induced xerostomia. MeiraGTx uses its innovative technology in optimization of capsids, promoters and novel translational control elements to develop best in class, potent, safe viral vectors. MeiraGTx’s broad pipeline is supported by end-to-end in-house manufacturing. MeiraGTx has built the most comprehensive manufacturing capabilities in the industry, with 5 facilities globally, including two that are licensed for GMP viral vector production and a GMP QC facility with clinical and commercial licensure. In addition, MeiraGTx has developed a proprietary manufacturing platform process over 9 years based on more than 20 different viral vectors with leading yield and quality aspects and commercial readiness. Uniquely, MeiraGTx has developed a novel technology for in vivo delivery of any biologic therapeutic using oral small molecules. This transformative riboswitch gene regulation technology allows precise, dose-responsive control of gene expression by oral small molecules. MeiraGTx is focusing the riboswitch platform on the regulated in vivo delivery of metabolic peptides, including GLP-1, GIP, Glucagon, Amylin, PYY and Leptin, as well as cell therapy, CAR-T for liquid and solid tumors and autoimmune diseases, and additionally PNS targets addressing long term intractable pain. MeiraGTx has developed the technology to apply genetic medicine to common diseases, increasing efficacy, addressing novel targets, and expanding access in some of the largest disease areas where the unmet need remains high.
For more information, please visit www.meiragtx.com
Forward Looking Statement
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 our product candidate development and our pre-clinical data and reporting of such data and the timing of results of data, as well as statements that include the words “expect,” “will,” “intend,” “plan,” “believe,” “project,” “forecast,” “estimate,” “may,” “could,” “should,” “would,” “continue,” “anticipate” and similar statements of a future or forward-looking nature. 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 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, our incurrence of significant losses; any inability to achieve or maintain profitability, raise additional capital, repay our debt obligations, identify additional and develop existing product candidates, successfully execute strategic transactions or priorities, bring product candidates to market, expansion of our manufacturing facilities and processes, successfully enroll patients in and complete clinical trials, accurately predict growth assumptions, recognize benefits of any orphan drug or rare pediatric disease designations, retain key personnel or attract qualified employees, or incur expected levels of operating expenses; the impact of pandemics, epidemics or outbreaks of infectious diseases on the status, enrollment, timing and results of our clinical trials and on our business, results of operations and financial condition; failure of early data to predict eventual outcomes; failure to obtain FDA or other regulatory approval for product candidates within expected time frames or at all; the novel nature and impact of negative public opinion of gene therapy; failure to comply with ongoing regulatory obligations; contamination or shortage of raw materials or other manufacturing issues; changes in healthcare laws; risks associated with our international operations; significant competition in the pharmaceutical and biotechnology industries; dependence on third parties; risks related to intellectual property; changes in tax policy or treatment; our ability to utilize our loss and tax credit carryforwards; litigation risks; and the other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, as such factors may be updated from time to time in our other filings with the SEC, which are accessible on the SEC’s website at www.sec.gov. These and other important factors 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, unless required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. Thus, one should not assume that our silence over time means that actual events are bearing out as expressed or implied in such forward-looking statements. 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.
Contacts
Investors:
MeiraGTx
Investors@meiragtx.com
or
Media:
Jason Braco, Ph.D.
LifeSci Communications
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FAQ
What were the key findings from MGTX's BDNF gene therapy for obesity presentation at ASGCT 2025?
How did MeiraGTx's new CAG promoter variants perform compared to traditional ones?
What improvements did MGTX make to their AAV-hUPF1 gene therapy for ALS?
What is the significance of MeiraGTx's TFBS research presented at ASGCT 2025?
