uniQure Acquires Rights to Develop APB-102
Plans afoot for clinical trial of investigational gene therapy for SOD1 ALS
uniQure has entered an agreement to acquire the full rights to Apic Bio‘s investigational gene therapy APB-102, which is being developed for amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations.
uniQure now is planning to start a Phase 1/2 clinical trial of APB-102 later this year.
Under the agreement, Apic Bio will receive an upfront payment of $10 million, and is entitled to up to $45 million in additional payments if certain regulatory milestones are met, and royalties for any sales.
“I am very proud of the contributions Apic Bio has made to bring APB-102 to the cusp of clinical development,” John Reilly, co-founder and CEO of Apic Bio, said in a uniQure press release.
The acquisition reinforces uniQure’s pipeline of innovative gene therapies for ALS. In addition to APB-102, which now will be called AMT-162, the company is developing another gene therapy candidate named AMT-161 for the treatment of ALS patients with C9ORF72 gene mutations.
“The licensing of APB-102 provides uniQure with another clinical stage program that is strategically aligned with our current pipeline and highly complementary with our AMT-161 program for the treatment of ALS caused by mutations in the c9orf72 gene,” said Ricardo Dolmetsch, PhD, president of research and development at uniQure.
Together, the two programs “have the potential to address most familial forms of ALS,” Dolmetsch added.
Mutations in the SOD1 gene are found in up to 20% of people with familial ALS, and in up to 2% of those with sporadic disease. These mutations lead to the production of a misfolded form of the SOD1 protein, which is prone to form toxic clumps and causes damage to nerve cells.
How AMT-162 works
AMT-162 is a one-time gene therapy designed to prevent the production of toxic SOD1 and potentially slow or reverse the progression of SOD1-ALS cases.
It consists of a viral vector containing a small RNA molecule, called microRNA, designed to latch onto the SOD1 messenger RNA molecule and target it for degradation. The SOD1 RNA is an intermediate molecule produced by the SOD1 gene that provides instructions for the protein-making machinery to produce the SOD1 protein.
By eliminating SOD1 RNA, the microRNA prevents the production and accumulation of misfolded SOD1.
The medication is administered via a single injection into the spinal canal (intrathecal). Preclinical studies in mice showed that the viral vector containing the microRNA significantly reduced SOD1 levels, which led to delays in disease onset, better motor function, and improved survival rates. Tests in nonhuman primates also demonstrated that the approach is safe and reduces SOD1 levels in multiple regions of the spinal cord.
Notably, results from a proof-of-concept study in two ALS patients also showed lower SOD1 levels in the brain and spinal cord after the treatment was injected into the spinal canal.
“uniQure is at the forefront of the field of miRNA gene therapies for neurological disorders and is the ideal partner to achieve the goal of rapidly advancing the clinical development of APB-102 for the potential benefit of SOD1-ALS patients,” Reilly added.
Apic Bio received the green light from the U.S. Food and Drug Administration (FDA) in 2021 to conduct a three-part Phase 1/2 clinical trial testing AMT-162 in people with SOD1-ALS.
In the first part of the study, patients will receive single ascending doses of AMT-162 to define an optimal dose. In part 2, participants will be assigned randomly to either AMT-162 — at the dose defined in the first part — or a placebo. Then, the third part will be an open-label extension to determine the long-term safety and efficacy of the treatment.
The FDA also granted AMT-162 fast track and orphan drug designations, which are expected to speed its clinical development and regulatory review.
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