Uniqure, Inc.

Day 2 of the 2024 Huntington Study Group Conference featured talks on palliative care, clinical trial challenges, and updates from various drug development companies, emphasizing the importance of early intervention and the use of biomarkers in HD treatment.

Despite decades of research, Huntington’s disease lacks a disease-modifying treatment. Clinical trials face challenges due to limited patient numbers and geographic barriers. Prilenia Therapeutics, Sage Therapeutics, uniQure, Wave Life Sciences, and Roche-Ionis are developing potential treatments, though some have faced setbacks. Prilenia’s pridopidine and Sage’s dalzanemdor showed mixed results, while uniQure’s AMT-130 and Wave’s WVE-003 demonstrated promising reductions in mutant huntingtin protein. Roche-Ionis’ tominersen faces ongoing development challenges.

New Huntington's disease therapies are nearing R&D finish lines, aiming to be the first disease-modifying treatments. Despite high-profile failures, companies like Wave, Prilenia, and uniQure are progressing towards regulatory approval. The field has gained momentum after decades of trial and error, with several mid-stage clinical trials underway. The ideal therapy would selectively lower mutant huntingtin and be widely distributed in the brain, though none currently exist.

Despite failed trials, hope is renewed in Huntington's disease treatment with a gene therapy showing 80% slowing of disease progression and another treatment seeking FDA accelerated approval.

uniQure reports financial results for Q3 2024, highlighting progress in gene therapy programs, including positive interim data for AMT-130 in Huntington’s disease, and the initiation of new Phase I/II studies for AMT-162 in SOD1-ALS and AMT-191 in Fabry disease. The company also completed the sale of its Lexington manufacturing facility, reducing operating expenses and extending its cash runway through 2027.

Sangamo Therapeutics' shares surged 69% after FDA alignment on an Accelerated Approval pathway for its Fabry disease gene therapy, isaralgagene civaparvovec (ST-920), using data from its Phase I/II STAAR trial. The company plans to submit a BLA in the second half of 2025, three years ahead of previous estimates.

The first patient has been dosed in uniQure's Phase 1/2 clinical trial of AMT-162, a one-time gene therapy for SOD1-ALS. The open-label EPISOD1 trial is testing three dose levels of AMT-162 for safety and efficacy, aiming to enroll 20 adults with SOD1-ALS. AMT-162 uses an AAV-based vehicle to deliver a microRNA that degrades SOD1 instructions, potentially reducing misfolded protein and slowing disease progression. The therapy is administered via a one-time spinal injection with immunosuppression. AMT-162 has received orphan drug and fast track designations from the FDA.

UniQure has dosed the first patient in its phase 1/2 EPISOD1 trial, evaluating AMT-162, an AAV vector-based gene therapy for SOD1-ALS. AMT-162 uses a miRNA to silence the disease-causing SOD1 gene, delivered via an AAVrh10 vector. The open-label, multicenter study in the US focuses on safety and efficacy, with 4 active sites and plans to activate 7 more by Q1 next year. UniQure also develops AMT-260 for temporal lobe epilepsy, with preclinical data showing potential for a good risk-benefit ratio.

uniQure announced the first patient dosed in the Phase I/II trial of AMT-162 for SOD1-ALS, an AAVrh10-based gene therapy targeting mutated SOD1 protein. The EPISOD1 trial aims to assess safety, tolerability, and efficacy in U.S. patients, with plans to expand to 11 sites by Q1 2025.

uniQure announced the first patient dosed in the Phase I/II trial of AMT-162 for SOD1-ALS, aiming to assess safety, tolerability, and efficacy. AMT-162 is an AAVrh10-based gene therapy designed to knock down mutated SOD1 protein expression, potentially offering a one-time treatment approach. The trial, EPISOD1, is multi-center and open-label, with plans to expand to 11 sites by Q1 2025.