AMO Pharma Ltd.

Earlier this year, Avidity started a pivotal Phase III HARBOR trial evaluating del-desiran inpatients with DM1. Image credit: JHVEPhoto /Shutterstock. The US Food and Drug Administration (FDA) has lifted the partial clinical hold on Avidity Biosciences ’ investigational drug, delpacibart etedesiran (del-desiran). In 2022, the US regulatory agency placed a partial hold after a report of a serious adverse event in a newly enrolled patient in the Phase I/II MARINA trial (NCT05027269), which evaluated del-desiran in patients myotonic dystrophy type 1 (DM1). The company did not disclose the details of the adverse event and the US FDA eased the partial clinical hold the following year, allowing the company to recruit new patients. The clinical hold has not slowed down Avidity’s efforts to advance the clinical development of del-desiran in DM1. Earlier this year, Avidity started a pivotal placebo-controlled Phase III HARBOR trial (NCT06411288). The study is expected to enrol 150 participants with DM1 who will be assessed over 54 weeks. The trial’s primary endpoint is the improvement of myotonia over 30 weeks, measured using video Hand Opening Time (vHOT), the average time to extend the right third and first digits. The study’s secondary endpoints also include the functional assessment of myotonia across 30 weeks, including hand grip strength, quantitative muscle testing composite score and Myotonic Dystrophy Type 1 activity and participation scale c. Del-desiran is an antibody oligonucleotide conjugate (AOC) made up of a monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a small interfering RNA (siRNA) targeting myotonic dystrophy protein kinase (DMPK) mRNA, responsible for producing DMPF protein. If approved, GlobalData expects del-desiran to pull in over $1.2bn in sales by 2030. See Also: BMS receives FDA approval for Opdivo to treat NSCLC Novaliq and Laboratoires Théa announce EC approval for dry eye disease therapy GlobalData is the parent company of Pharmaceutical Technology . mRNA vaccines were instrumental during the Covid-19 pandemic. Since then, there has been increased interest in mRNA therapies beyond the vaccines. GlobalData forecasts the mRNA non-vaccine therapeutics field to reach $2bn by 2028. DM1 is a genetic disorder caused by a triplet-repeat in the DMPK gene. It primarily affects skeletal and cardiac muscle causing muscle weakness and wasting leading to respiratory problems, and cardiac abnormalities. There are no approved treatments for DM1 and management is mostly aimed at symptomatic treatment. Another therapy in development for treating DM1 is AMO Pharma’s AMO-02 (tideglusib). The therapy is an irreversible inhibitor of glycogen synthase kinase 3 (GSK-3), it has the potential to disrupt the RNA repeats that cause congenital DM1. In May, AMO announced plans to start a Phase III trial for AMO-02 in DM1 patients.

Company will conduct Phase 3 trial of AMO-02 (tideglusib) in adults to support a future submission for marketing authorization in Type 1 myotonic dystrophy in both adult and pediatric indications. LONDON, May 2, 2024 /PRNewswire/ -- AMO Pharma Limited ("AMO Pharma"), a privately held clinical-stage specialty biopharmaceutical company focusing on rare genetic disorders with limited or no treatment options, today provided an update on plans to advance the clinical development program for AMO-02 (tideglusib), the company's investigational therapy in development for the treatment of Type 1 myotonic dystrophy (DM1), following a recent meeting with the U.S. Food and Drug Administration (FDA). Based on the input from the meeting, AMO Pharma will conduct a Phase 3 clinical trial to assess the efficacy and safety of AMO-02 in adult patients with adult-onset DM1 to support a future submission for marketing authorization for the treatment of DM1 in children, adolescents and adults. Continue Reading REACH-CDM (PRNewsfoto/AMO Pharma Limited) Results from AMO Pharma's previous REACH-CDM Phase 2/3 clinical study (the "REACH-CDM Study") involving children and adolescents with congenital-onset DM1 showed that AMO-02 was generally safe and well tolerated during the study, with no reported severe adverse events (SAEs) related to treatment. The primary and secondary outcome measures based on clinician administered subjective ratings showed an unexpected placebo effect that may have masked some beneficial effects of treatment. Further post hoc analysis as reviewed with the FDA indicates that there is sufficient evidence to support the continued development of tideglusib for the treatment of DM1 with agreement that AMO Pharma will now advance a Phase 3 study in adults with the adult-onset version of DM1. During the meeting, FDA reviewed data from the REACH-CDM Study to assess the efficacy and safety of treatment with AMO-02 in children and adolescents with congenital DM1. The FDA also gave feedback on the design of the new Phase 3 clinical trial for adult patients with adult onset DM1. In this study in adult onset DM1, outcome measures will be similar to those that showed benefit in the REACH-CDM Study. Following discussion with the FDA, AMO Pharma will plan a future submission for approval in children, adolescents and adults with myotonic dystrophy based on a package of safety and efficacy data from the new Phase 3 trial in adults combined with efficacy, pharmacokinetic and safety data from AMO Pharma's REACH-CDM Study. "We are pleased with the outcome of the productive discussions we had with the FDA regarding next steps for AMO-02 and continue to feel strongly that this innovative therapy can represent a significant advance in the treatment of patients with DM1, whether they are children, adolescents or adults," said Alan Rubino, executive chair at AMO Pharma. "We are now focused on progressing a new clinical study in adults with adult-onset DM1. We are very grateful to the FDA and to the patients, families, clinicians and investors who have supported our research thus far and we look forward to working with the community to advance this program as rapidly as possible. We will make an announcement regarding the start date and site locations for the adult onset DM1 study shortly." "The results of the REACH-CDM Study showed measures of efficacy benefit across multiple symptom areas, and we are very excited that this clinical development program will continue to move forward," said Hanns Lochmuller, investigator in the REACH-CDM Study at Children's Hospital of Eastern Ontario, Canada. "We remain very hopeful that this investigational therapy can have a transformative impact on the health of patients living with this ultra-rare, severe muscular dystrophy in the years ahead." About AMO-02 AMO-02 (tideglusib) is an investigational therapy in development for the treatment of DM1 with a dual mechanism disrupting the pathogenic RNA repeat in DM1and inhibiting excess levels of the kinase GSK3β. The REACH-CDM Study was a double-blind, placebo-controlled, randomized study in children and adolescents with congenital DM1 intended to support a future submission for marketing authorization in congenital DM1. The study included 56 participants at leading specialist sites in the US, Canada, New Zealand and Australia. Data associated with functional and objective measures were collected during the study, including motor and muscle assessments (10 meter walk/run, myometry, lip strength and lean muscle mass as assessed by DXA scan), cognitive performance (Peabody Picture Vocabulary Test, NIH Toolbox Picture Sequence Memory Test, NIH Toolbox Dimensional Change Card Sort Test), adaptive (real world) function (Vineland Adaptive Behavior Communication Scale, Vineland Adaptive Behavior Daily Living Scale, Vineland Adaptive Behavior Socialization Scale), bone density (DXA scan) and creatine kinase measurements. In post-hoc analyses more participants showed a positive response following AMO-02 treatment than placebo on 10 of the 12 of these measures. Treatment with AMO-02 was associated with clinically significant improvements in walking and cognition and significant effects on objective biomarkers of muscle and neuronal integrity. AMO-02 also showed significant improvement compared to placebo on a Multi-Domain Responder Index integrating clinically significant responses on measures of ambulation, muscle strength, cognitive performance, activities of daily living and an objective biomarker. Primary analyses of subjective rating assessments showed a placebo effect. Patients from this study and treatment naïve patients with congenital or juvenile onset DM1 are currently being supported in the REACH CDM-X open label extension safety study. About AMO Pharma AMO Pharma is a clinical-stage specialty biopharmaceutical company working to identify and advance promising therapies for the treatment of serious and debilitating diseases in patient populations with significant areas of unmet need, including rare and severe childhood onset neurogenetic disorders with limited or no treatment options. In addition to developing AMO-02 for DM1, the company is also progressing AMO-01 as a clinical stage treatment for Phelan-McDermid syndrome and AMO-04 as a clinic-ready potential medicine for Rett syndrome and related disorders. AMO-02, AMO-01 and AMO-04 are investigational medicines that have not yet been approved for the treatment of patients anywhere in the world. Advice provided to AMO Pharma by regulators is under the condition that any scientific advice given is not legally binding with regards to any future application for the product concerned. Furthermore, advice cannot be taken as indicative of any future agreed position. For more information, please visit the AMO Pharma website at . Media contact: Holly Stevens Berry & Company Public Relations [email protected] 212-253-8881 SOURCE AMO Pharma Limited

LONDON, Feb. 15, 2024 /PRNewswire/ -- AMO Pharma Limited ("AMO Pharma"), a privately held clinical-stage specialty biopharmaceutical company focusing on rare genetic disorders with limited or no treatment options, today announced a collaboration with Population Health Research Institute (PHRI), a joint institute of McMaster University and Hamilton Health Sciences in Canada, to advance a clinical proof of concept trial to assess the efficacy of AMO-02 (tideglusib), AMO Pharma's investigational oral glycogen synthase kinase 3 beta (GSK3β) inhibitor, in the treatment of genotype positive arrhythmogenic cardiomyopathy (ACM). The study, entitled "Targeted Therapy with Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy" (TaRGET), will be led by the research team at PHRI and will involve collaboration with multiple organizations in addition to AMO Pharma including the Hearts in Rhythm Organization (HiRO). Enrollment is set to begin in mid-2024 at 20 sites across Canada and will include a total of 120 participants who will be randomized in a 1:1 ratio. "It can be a helpless feeling to carry a gene for ACM and know that, no matter how you live your life, you may someday develop a deadly form of heart disease," said Jason Roberts, scientist at PHRI and TaRGET study principal investigator, adding, "Encouraged by earlier studies in animal models, we are hopeful that tideglusib may serve as an effective treatment that can dramatically improve the health of people living with ACM. The TaRGET trial is a critical first step in evaluating this potential." ACM is a form of genetic heart disease characterized by scarring in the heart muscle. This scarring increases the risk of dangerously fast heart rhythms that can lead to sudden cardiac death (SCD). There are currently no approved medical therapies that have been shown to prevent progression of ACM. An implantable cardioverter defibrillator (ICD) is recommended for prevention of SCD for ACM patients considered at high risk for SCD. In prior research, a high-throughput screen of bioactive compounds against a zebrafish model of ACM identified a small molecule classified as a GSK3β inhibitor that successfully prevented and rescued the phenotype, findings that have subsequently been reproduced in a series of ACM murine models. GSK3β is an enzyme that modulates the activity of a broad spectrum of intracellular signaling pathways, including the canonical Wnt/β-catenin pathway whose suppression has been suggested to exert an important role in ACM pathogenesis. "As we continue to advance our research to assess the potential benefits of AMO-02 in the treatment of myotonic dystrophy, we are very pleased to be supporting this landmark research effort in ACM with the outstanding team at PHRI," said Mike Snape, chief scientific officer at AMO Pharma. "Based on extensive research that highlights the proven MOA of AMO-02 as a clinically safe and well tolerated GSK3β inhibitor, we look forward to progress in advancing this promising program that can bring new hope to people living with ACM and their families in the years ahead. This new data has the potential to build on the cardiac efficacy data previously reported in studies conducted in Duchenne muscular dystrophy by Professor Val Fajardo's team at Brock University." About AMO Pharma AMO Pharma is a clinical-stage specialty biopharmaceutical company working to identify and advance promising therapies for the treatment of serious and debilitating diseases in patient populations with significant areas of unmet need, including rare and severe childhood onset neurogenetic disorders with limited or no treatment options. In addition to developing AMO-02 for myotonic dystrophy, the company is also progressing AMO-01 as a clinical stage treatment for Phelan-McDermid syndrome and AMO-04 as a clinic-ready potential medicine for Rett syndrome and related disorders. AMO-02, AMO-01 and AMO-04 are investigational medicines that have not yet been approved for the treatment of patients anywhere in the world. Advice provided to AMO Pharma by regulators is under the condition that any scientific advice given is not legally binding with regards to any future application for the product concerned, neither on the part of MHRA/Commission on Human Medicines (CHM) nor on the Company. Furthermore, advice cannot be taken as indicative of any future agreed position. For more information, please visit the AMO Pharma website at . Media Contact Holly Stevens Berry & Company Public Relations 212 253 8881 [email protected] Logo -