Non-viral delivery technology + gene editing: Sarepta collaborates to develop innovative neuromuscular disease therapy Maimeng

February 9, 2022 / eMedClub News / -- On February 1, 2022, Sarepta Therapeutics and GenEdit jointly announced that they have entered into a research collaboration agreement whereby the two companies will utilize GenEdit's polymer nanoparticles The delivery platform and Sarepta's gene editing technology to jointly develop gene editing therapies for the treatment of neuromuscular diseases
.

As part of the agreement, Sarepta will receive an exclusive option for polymer nanoparticles developed by GenEdit for use in up to 4 neuromuscular indications selected by Sarepta
.

Preliminary trial results from a collaboration between Sarepta and GenEdit have demonstrated the potential of polymer nanoparticles to deliver therapeutics to specific muscle tissues following systemic administration, allowing targeted gene drug delivery independent of viral vectors
.

GenEdit's polymer nanoparticle delivery platform (NanoGalaxy) contains thousands of chemically diverse polymers, each with unique properties that enable them to target different tissues and cell types and carry different payload
.

▲ NanoGalaxy platform (Image source: GenEdit's official website) According to public information, the NanoGalaxy platform has the following advantages: Tissue selectivity: NanoGalaxy uses the systematic screening process to screen hundreds of polymers with different chemical properties in human primary cells and in vivo Nanoparticles to determine key structure-activity relationships for tissue selectivity
.

Through several rounds of optimization, the optimal polymer is selected for delivery to specific tissues in the body, which improves efficacy and reduces potential safety concerns
.

Flexible delivery of payloads (DNA, RNA, CRISPR RNP) beyond AAV: NanoGalaxy polymer nanoparticles can encapsulate many different payloads, including nucleic acids (e.
g.
mRNA, ASOs or siRNA), therapeutic proteins, and CRISPRs
.

NanoGalaxy polymer nanoparticles can also carry large nucleic acids and enzymes required for gene editing, with payloads ranging from 20bp siRNA to 10kbp constructs
.

Multiple Dosing: Unlike viral delivery systems, NanoGalaxy polymer nanoparticles avoid problems that can result from an immune response, which could make the treatment accessible to more people
.

The low immunogenicity of NanoGalaxy polymer nanoparticles is expected to allow patients who require multiple doses the opportunity to be re-administered to achieve the desired therapeutic benefit
.

Simple and low cost to manufacture: NanoGalaxy polymer nanoparticles are manufactured with a process designed for batch-to-batch purity, repeatability, and scalability, and can be lyophilized for long-term cold-chain storage and shipping logistics
.

And NanoGalaxy polymer nanoparticles are water-soluble, which enables them to encapsulate not only nucleic acids, but also ribonucleoprotein payloads without denaturation
.

The whole production process is simple and low cost
.

▲ NanoGalaxy platform (Image source: GenEdit's official website) In addition to research payments, under the terms of the partnership agreement, GenEdit will receive up to $57 million in near-term payments and is also eligible for future development, regulatory and commercial milestone payments and future product sales tiered royalties
.

"We were impressed by the variety of GenEdit's NanoGalaxy platform and its screening process, which resulted in many completely different polymers that can be targeted to muscle
.

"Sarepta is committed to developing treatments for rare neuromuscular diseases, and we look forward to continuing to work with the team at GenEdit to advance effective gene editing-based therapies for these patients," said Mr.
Doug Ingram, President and CEO of Sarepta Therapeutics
.

"GenEdit has demonstrated in this collaboration and our own research that the NanoGalaxy platform can overcome historic challenges in the field to enable tissue selectivity for a broad range of gene medicine therapies," said GenEdit co-founder and CEO Kunwoo Lee, Ph.
D.
delivery
.

GenEdit is pleased to continue to advance its collaboration with Sarepta to jointly develop gene editing candidates for neuromuscular diseases
.

"Leaders in DMD: Sarepta Therapeutics Sarepta Therapeutics has been working to discover and develop precision gene therapies for rare neuromuscular diseases
.

It has established a leading position in the field of gene therapy for disease type IIIA, charcot-mary-tooth (CMT) and other central nervous system-related diseases, with more than 40 projects in various stages of development
.

▲Sarepta's product pipeline (Image source: Sarepta) Official website) At this stage, Sarepta has three DMD drugs approved for marketing, namely Exondys 51 (eteplirsen), Vyondy 53 (golodirsen), and Amondys 45 (casimersen)
.

On September 19, 2016, Sarepta's Exondys 51 was not available It was approved by the FDA for the treatment of DMD patients with exon 51 mutations amid the huge controversy over the significant efficacy data.
This is also the first drug approved for the treatment of DMD.

.

Sarepta's second DMD drug, Vyondy 53, despite its twists and turns, finally received the green light from the FDA on December 12, 2019, for the treatment of exon 53 skipping DMD patients
.

On February 25, 2021, the FDA granted accelerated approval to Sarepta's third DMD drug, Amondys 45, for the treatment of patients with exon 45 skipping DMD
.

Like the previous two new drugs, Exondys 51 and Vyondy 53, the treatment principle of Amondys 45 is to use oligonucleotides (ASO) to bind to exon 45 of the messenger nucleic acid (mRNA) of dystrophin precursor, thereby skipping the Genetic coding for genetic defects
.

Compared with the previous two drugs, Sarepta provided more reliable data on the new drug Amondys 45
.

Sarepta's three new drugs will nearly reach about 30% of DMD patients
.

In addition to nucleic acid drugs, Sarepta has developed a potentially curative therapy SRP-9001 (rAAVrh74.
MHCK7.
micro-dystrophin) for all DMD patients
.

SRP-9001 uses an AAVrh74 vector isolated from non-human primates, which has the advantage of being able to cause robust expression of the transgene in muscle without crossing the blood-brain barrier into the central nervous system
.

Also, fewer patients have immunity against this viral vector
.

SRP-9001 gene therapy drives the expression of the transgene by the MHCK7 promoter
.

This promoter not only drives transgene expression in skeletal muscle, cardiac muscle, and diaphragm, but also enhances transgene expression especially in the heart
.

The advantage of gene therapy is that it can work in patients with any type of DMD genetic mutation
.

In addition to the traditional gene therapy for DMD, Sarepta is also deploying a more cutting-edge treatment technology - DMD gene editing therapy
.

Reference: 1.
https:// -Announce-Agreement-to-Develop-Gene-Editing-Therapeutics-for-Neuromuscular-Diseases.
html