Glycogen Storage Disease Type II

Investigational, next-generation therapy for Pompe disease delivers GYS1 siRNA to muscle tissue Phase 1a safety and bioactivity data in normal healthy volunteers supports moving into first-in-patient LOPD trial PHILADELPHIA, PA, USA I October 29, 2024 I Aro Biotherapeutics , a clinical-stage biotechnology company working to develop potent and tissue-targeted medicines, today announced the initiation of the Phase 1b portion of its clinical trial of ABX1100, a novel potential treatment for late-onset Pompe disease (LOPD). By targeting a known receptor called CD71, ABX1100 delivers siRNA therapy to muscle tissue, where it inhibits the production of the GYS1 enzyme, which is responsible for synthesizing glycogen. In the planned 1b study, investigators seek to enroll adults with LOPD to evaluate the safety and bioactivity of ABX1100. More information about the trial is available at ClinicalTrials.gov using the identifier NCT06109948. “The limitations of enzyme replacement therapy for Pompe disease underscore the need for new therapies with novel mechanisms of action,” said Aneal Khan, MD, principal investigator of the trial and a pediatrician and medical geneticist at the Metabolic and Genetic in Calgary (MAGIC) Clinic in Alberta, Canada. “ABX1100 is being evaluated as a new therapeutic approach for individuals with late-onset Pompe disease, and we are eager to begin this trial in the underserved Pompe disease population.” Pompe disease is a rare neuromuscular disorder driven by the toxic buildup of glycogen, a stored form of sugar used for energy, in the muscle. This over-accumulation of glycogen leads to progressive loss of muscle function, weakness, and disability that can eventually progress to death from respiratory failure. 1 Currently available enzyme replacement therapies (ERTs) for Pompe disease have limited long-term efficacy. Preclinical studies suggest that inhibiting the production of GYS1 may be a valuable addition or alternative to ERT. “The encouraging preclinical and clinical evidence generated to date provides a solid foundation for ongoing clinical studies of ABX1100, which has the potential to be the first new treatment for Pompe disease beyond ERT. We anticipate dosing the first patient with Pompe disease in the Phase 1b study before the end of 2024,” noted Susan Dillon, Ph.D., co-founder, president and chief executive officer of Aro. “ABX1100 was well tolerated in a recently completed Phase 1a trial conducted in normal healthy volunteers, and it showed durable GYS1 mRNA knockdown in muscle biopsies, with effects lasting through at least 10 weeks following a single dose,” added Dr. Dillon. “The study achieved the goal of identifying a safe and effective starting dose for studies in patients with LOPD. We plan to present the Phase 1a results at a future medical conference.” About ABX1100 ABX1100, an investigational treatment for Pompe disease, is comprised of a CD71 receptor-binding Centyrin conjugated to a small interfering RNA (siRNA) that specifically interferes with expression of GYS1 messenger RNA (mRNA), thereby reducing levels and overall activity of the GYS1 enzyme in muscle tissues. ABX1100 demonstrated a favorable safety profile in toxicology studies, with durable reductions in GYS1 mRNA in muscles, supporting the potential for quarterly dosing. ABX1100 has received Orphan Drug Designation and Rare Pediatric Disease status from the United States Food and Drug Administration (FDA). About Aro Biotherapeutics Aro Biotherapeutics is a biotechnology company working to develop potent and versatile tissue-targeted genetic medicines with a platform based on a proprietary protein technology called Centyrins. The company is developing a wholly owned pipeline of Centyrin-based therapeutic candidates for tissue-specific targeting of therapeutics for a diverse set of diseases. For more information, visit www.arobiotx.com . Reference SOURCE : Aro Biotherapeutics

- Presentations Will Feature Recent Clinical Data From DYNE-251 and DYNE-101 as Well as Preclinical Data in FSHD and Pompe Disease - WALTHAM, Mass., Oct. 09, 2024 (GLOBE NEWSWIRE) -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases, today announced that previously reported clinical and preclinical data across its pipeline will be featured in poster presentations at the 29th Annual Congress of the World Muscle Society, held virtually and in Prague, Czech Republic, October 8-12, 2024. The presentations highlight the promise of the FORCE™ platform to deliver targeted therapeutics to address neuromuscular diseases. “The full breadth and versatility of our FORCE platform is on display at this year’s World Muscle Society Congress, with presentations covering both of our co-lead clinical programs in DM1 and DMD, along with preclinical work in FSHD and Pompe disease,” said John Cox, president and chief executive officer of Dyne. “We’ve observed targeted delivery with the FORCE platform showing broad distribution to key tissues like skeletal, cardiac, smooth muscle and the CNS – which has the potential to transform the lives of individuals living with these diseases.” Poster Highlights The Phase 1/2 DELIVER trial evaluating DYNE-251 in males with Duchenne muscular dystrophy (DMD) mutations amenable to exon 51 skipping includes 6-month biomarker and functional data from patients enrolled in the 20 mg/kg (approximate PMO dose) cohort and 12-month functional data from the 10 mg/kg cohort. DYNE-251 demonstrated dose dependent exon skipping and dystrophin expression and improvement in multiple functional endpoints in both cohorts. Patients treated with 20 mg/kg of DYNE-251 Q4W had a mean absolute dystrophin expression of 3.7% of normal (unadjusted for muscle content) and when adjusting for muscle content, it reached 8.7%. Importantly, treatment with DYNE-251 resulted in meaningful improvements in Stride Velocity 95th Centile (SV95C), a digital objective outcome measure of ambulatory performance in a patient’s normal daily environment. The change from baseline in SV95C met the published minimal clinically important difference as defined by the European Medicines Agency (0.1 m/sec) at 6 months for both the 10 and 20 mg/kg cohorts (approximately 0.2 m/sec change from baseline for both cohorts).The Phase 1/2 ACHIEVE trial evaluating DYNE-101 in adult participants with myotonic dystrophy type 1 (DM1) includes 12-month data from the 1.8 mg/kg Q4W (approximate ASO dose) cohort, 6-month data from the 3.4 mg/kg Q4W cohort, and 3-month data from the 5.4 mg/kg Q8W cohort. DYNE-101 demonstrated robust muscle delivery and dose-dependent, consistent splicing correction while also showing improvement in myotonia, muscle strength, and timed function tests and in the Myotonic Dystrophy Type 1 Activity and Participation Scale (DM1-ACTIVc) and the Myotonic Dystrophy Health Index (MDHI) patient reported outcomes. Patients in the 5.4 mg/kg Q8W cohort had a 27% mean splicing correction from baseline across a broad, 22-gene panel at 3 months, with all participants demonstrating splicing correction.Both DYNE-251 and DYNE-101 have demonstrated favorable safety profiles. 1 2Preclinical data for DYNE-302 in facioscapulohumeral muscular dystrophy (FSHD), demonstrated robust and durable DUX4 suppression and functional benefit in an innovative hTfR1/iFLExD mouse model developed by Dyne. In hTfR1/iFLExD mice, a single intravenous dose of DYNE-302 resulted in dose-dependent and robust reduction of the DUX4 transcriptome (D4T) that lasted up to three months, with benefit on muscle structure and function.Preclinical data in a Pompe disease model demonstrated the potential of the FORCE platform to deliver enzyme replacement therapy to cardiac and skeletal muscle and the central nervous system (CNS), potentially expanding the modularity of the platform beyond oligonucleotides. Presentation Information Title: Initial Data from the DELIVER Trial of DYNE-251 in Males with DMD Mutations Amenable to Exon 51 SkippingDate/Time: October 9, 2024, 2:30 p.m. CEST/8:30 a.m. ETPresenter: Liesbeth De Waele, M.D., Ph.D., Pediatric Neurologist at University Hospital Leuven, Belgium Title: Initial Data from the ACHIEVE Trial of DYNE-101 in Adults with Myotonic Dystrophy Type 1 (DM1)Date/Time: October 9, 2024, 2:30 p.m. CEST/8:30 a.m. ETPresenter: Joost Kools, M.D., Neuromuscular Department at Radboud University Medical Center, Netherlands Title: The FORCE™ Platform Achieves Robust and Durable DUX4 Suppression and Improves Muscle Function in Facioscapulohumeral Muscular Dystrophy Mouse ModelDate/Time: October 9, 2024, 5:15 p.m. CEST/11:15 a.m. ETPresenter: Tyler Picariello, Ph.D., Director, Neuromuscular Research, Dyne Therapeutics Title: The FORCE™ Platform Enables Tfr1-mediated Delivery of Enzyme Replacement Therapy to Muscle and Central Nervous System, Resolving Pompe Pathology in MiceDate/Time: October 11, 2024, 3:45 p.m. CEST/ 9:45 a.m. ETPresenter: Tyler Picariello, Ph.D., Director, Neuromuscular Research, Dyne Therapeutics The presentations will be available in the Scientific Publications & Presentations section of Dyne’s website following the session. Additionally, a symposium titled “Potential of the FORCE™ Platform to Address Unmet Needs in Rare Neuromuscular Diseases” will be held on October 10 at 8:15 a.m. CEST/ 2:15 a.m. ET. About the FORCE™ Platform The proprietary FORCE™ platform drives Dyne’s efforts to develop targeted, modern oligonucleotide innovative therapeutics with the potential to be life-transforming for patients with serious muscle diseases. Dyne designed the FORCE platform using its deep knowledge of muscle biology and oligonucleotide therapeutics to overcome the current limitations in delivery to muscle tissue with the goal of stopping or reversing disease progression. The FORCE platform leverages the importance of transferrin receptor 1 (TfR1) in muscle biology as the foundation for its novel approach. TfR1, which is highly expressed on the surface of muscle cells, is required for iron transport into muscle cells. Dyne links therapeutic payloads to its TfR1-binding fragment antibody (Fab) to develop targeted therapeutics for muscle diseases. About Dyne Therapeutics Dyne Therapeutics is a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases. With its proprietary FORCE™ platform, Dyne is developing modern oligonucleotide therapeutics that are designed to overcome limitations in delivery to muscle tissue. Dyne has a broad pipeline for serious muscle diseases, including clinical programs for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and preclinical programs for facioscapulohumeral muscular dystrophy (FSHD). For more information, please visit https://www.dyne-tx.com/, and follow us on X, LinkedIn and Facebook. 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 Dyne’s strategy, future operations, prospects and plans, objectives of management, the potential of the FORCE platform, the potential of DYNE-101, DYNE-251 and DYNE-302, expectations regarding the timing and outcome of interactions with global regulatory authorities, and plans to provide future updates on pipeline programs, 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. Dyne 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 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 Dyne’s ability to enroll patients in clinical trials; whether results from preclinical studies and initial data from early clinical trials will be predictive of the final results of the clinical trials or future trials; uncertainties as to the FDA’s and other regulatory authorities’ interpretation of the data from Dyne's clinical trials and acceptance of Dyne's clinical programs and the regulatory approval process; whether Dyne’s cash resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Dyne’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-Q and in subsequent filings Dyne may make with the SEC. In addition, the forward-looking statements included in this press release represent Dyne’s views as of the date of this press release. Dyne anticipates that subsequent events and developments will cause its views to change. However, while Dyne 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 Dyne’s views as of any date subsequent to the date of this press release. Safety data as of August 21, 2024Safety data as of August 20, 2024 Contacts: InvestorsAmy Reillyareilly@dyne-tx.com 857-341-1203 MediaStacy Nartkersnartker@dyne-tx.com 781-317-1938

As it works to rebuild from an earlier gene therapy setback, Astellas is doubling down on the one-and-done modality in a new deal with a London-based startup already in the clinic. Astellas said Tuesday it will pay $30 million upfront and invest $20 million in AviadoBio in exchange for the chance to exclusively develop and commercialize the startup’s AAV-based gene therapy for people with frontotemporal dementia with progranulin mutations, or FTD-GRN. Investigators dosed the first patient with the experimental medicine, codenamed AVB-101, in April. The Phase 1/2 also opened in the US in July. Astellas could deliver up to $2.18 billion in license fees and milestone payments, the companies said. Astellas could develop AVB-101 for FTD-GRN and potentially other indications, the duo added. AviadoBio mentions ALS as another focus area for the startup, according to its website. Patients with FTD, an early form of dementia, can die within three to 13 years after diagnosis, the companies said. Attention, memory, mobility, problem solving and other functions deteriorate in adults with the neurodegenerative disease. AviadoBio’s gene therapy delivers a working copy of the GRN gene into the brain with the goal of halting the disease’s progress. The Astellas investment provides a boost to AviadoBio, which does not appear to have raised another financing round since unveiling an $80 million Series A in December 2021. Leading the upstart is former Novartis Gene Therapies chief business officer Lisa Deschamps. “Together, we can further accelerate delivering this investigational medicine to families around the world who so desperately need treatment options for FTD-GRN and other neurological diseases,” Deschamps said in a press release, noting the company is completing dosing in the first cohort of the ASPIRE-FTD study. The AviadoBio tie-up marks a further bet on gene therapy for Astellas, which ran into a major setback in 2020 and 2021, when four boys died after receiving the company’s gene therapy for a rare neuromuscular disease known as X-linked myotubular myopathy. “People tend to look at the four boys’ deaths. And that’s a very unfortunate and tragic situation,” Astellas CEO Naoki Okamura told Endpoints last month . “On the other hand, there are healthier boys who received [the therapy] and survived for three to five years already. So we believe in the power of gene therapy to really make the difference.” Astellas is working with Kate Therapeutics to improve the safety of the Audentes gene therapy, which is known as resamirigene bilparvovec, or AT132. The drugmaker also has Phase 1-stage gene therapies for Pompe disease (zocaglusagene nuzaparvovec, or AT845) and ASP2016 for cardiomyopathy associated with Friedreich’s ataxia. It also took a write-down in April on a preclinical Friedreich’s ataxia gene therapy known as AT808 from the Audentes buyout. Meanwhile, multiple drugmakers are pulling back from gene therapy R&D, including Pfizer, while a small number of startups have been able to reel in large financing rounds to carry forward their work in the field. The Japanese pharmaceutical company has a gene therapy R&D and manufacturing footprint in the Bay Area; Sanford, NC; and Tsukuba, Japan.