Sarepta gains rights to Arrowhead Huntington’s treatment candidate
Companies to collaborate on ARO-HTT, other therapies
Sarepta Therapeutics has entered a global licensing and collaboration agreement with Arrowhead Pharmaceuticals covering Arrowhead’s therapy candidates, including ARO-HTT, an experimental treatment for Huntington’s disease.
Sarepta will obtain exclusive global rights to ARO-HTT and other preclinical programs, as well as clinical and discovery-stage programs for rare genetic diseases.
Arrowhead will be responsible for Phase 1 and 2 clinical trials currently testing four clinical candidates for rare muscular, respiratory, and neurodegenerative diseases. The company will also complete studies and activities required to seek clearance from the U.S. Food and Drug Administration to test the preclinical assets, such as ARO-HTT, in clinical trials.
ARO-HTT is expected to be ready for a clinical trial application next year.
Sarepta brings “a wealth of clinical, regulatory, and commercial expertise in key areas outside of our cardiometabolic focus,” Christopher Anzalone, PhD, Arrowhead’s president and CEO, said in a company press release.
Advancing ‘next steps’ for treatment candidates
“We have a very efficient drug discovery engine that continues to generate many promising programs and we have great confidence in Sarepta’s ability to take the next steps to advance and commercialize multiple Arrowhead-discovered drug candidates, which we believe have the potential to be best-in-class,” Anzalone said.
All therapy candidates use Arrowhead’s Targeted RNAi Molecule (TRiM) platform, which develops molecules known as small interfering RNAs (siRNAs) designed to lower the production of specific disease-driving proteins, and in a tissue-specific manner.
“The agreement marks the start of a synergistic relationship with Arrowhead’s leading siRNA technology and Sarepta’s proven success in bringing rare disease treatments to patients,” said Doug Ingram, Sarepta’s president and CEO. “Together, we will expedite the development of Arrowhead’s promising scientific approach and bring best-in-class treatments to patients with devastating rare diseases where treatment options are limited or do not exist.”
Huntington’s is a genetic, neurodegenerative disease characterized by a progressive decline in movement, cognitive function, and mental health. It is caused by a mutation in the huntingtin (HTT) gene that results in the production of a longer-than-usual huntingtin protein. This abnormally long protein is prone to form toxic clumps in nerve cells, affecting their function and eventually causing them to die.
Arrowhead’s TRiM platform designs siRNAs bound to tissue-specific ligand molecules that allows them to target specific tissues and cell types throughout the body, including the central nervous system, or CNS, which consists of the brain and spinal cord. These candidates are delivered via an under-the-skin, or subcutaneous, injection.
ARO-HTT is designed to interrupt the production of the abnormal huntingtin protein that drives Huntington’s, which is expected to potentially slow disease progression.
Crossing the blood-brain barrier
Like other Arrowhead CNS-targeting candidates, ARO-HTT is able to cross the blood-brain barrier and enter the deep brain structures where nerve cells die in Huntington’s patients. The blood-brain barrier is an important protective layer that prevents potentially harmful molecules in circulation from reaching the CNS. However, it is also an obstacle for many medications designed to target conditions affecting the brain and/or spinal cord.
“The targeted ligand approach, combined with Arrowhead’s clinically validated siRNA chemistry, suggests the potential for deep and durable knockdown of proteins that are over-expressed in these conditions,” Louise Rodino-Klapac, PhD, Sarepta’s chief scientific officer, said in a company press release. “Arrowhead’s innovative approach to cross the blood brain barrier with subcutaneous dosing represents a potential paradigm shift for the CNS preclinical and discovery programs as part of this collaboration.”
The agreement covers two preclinical candidates for another neurodegenerative disease, spinocerebellar ataxia.
As an additional part of the deal, the companies have entered into a discovery program collaboration that aims to use Arrowhead’s technologies to develop siRNA-based therapies based on up to six new muscle, heart, or CNS targets, which will be proposed by Sarepta.
“Robust and compelling early data from Arrowhead’s differentiated siRNA approach platform suggests potentially best-in-class treatments that will profoundly improve the lives of those with rare, genetic diseases,” Rodino-Klapac said.
Under the agreement, which the companies expect to complete early next year, Arrowhead will receive $500 million in cash and $325 million as an equity investment, in addition to $250 million in annual installments over five years. The company is also eligible to receive $300 million in near-term payments, royalties on commercial sales, and up to approximately $10 billion in future potential milestone payments.
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