Nearly $1 billion!

January 13, 2022 / eMedClub News / -- Acadia Pharmaceuticals and Stoke Therapeutics recently announced that the two companies have entered into a nearly $1 billion collaboration to jointly discover, develop and commercialize novel RNA-based medicines, For the treatment of severe and rare inherited neurodevelopmental disorders of the central nervous system (CNS)
.

The collaboration includes SYNGAP1 syndrome, Rett syndrome (MECP2) and an undisclosed neurodevelopmental disorder
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➤ Terms of partnership Under the terms of the agreement, Stoke will receive an upfront payment of $60 million from Acadia, as well as potential milestone payments of up to $907 million and royalties on future sales
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For the SYNGAP1 project, the two companies will share global research, development and commercialization responsibilities, with global costs and future profits each split in half
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Additionally, Stoke is eligible for potential development, regulatory, first commercial sales and sales milestone payments
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For Rett syndrome (MECP2) and undisclosed neurodevelopmental disease programs, Stoke will lead research and preclinical development efforts, while Acadia will lead clinical development and commercialization efforts
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Acadia will fully fund research and preclinical development work related to these two goals, and Stoke is eligible to receive potential development, regulatory, first commercial sales and sales milestones, as well as tiered royalties on global sales (up to 15% )
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➤ TANGO technology platform TANGO (Targeted Augmentation of Nuclear Gene Output) is Stoke's proprietary research platform
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Stoke initially applied the technique to the disease haploinsufficiency, which occurs when two chromatids of a gene in diploid animals are mutated and the other normal.
The encoded gene product (often referred to as protein) is not sufficient to maintain the body's function or to exhibit the same state as the WT individual
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The mutated gene does not affect the normal gene, but the residual normal gene product is not competent for all functions, leading to the occurrence of disease
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How TANGO Works: Haploinsufficiency patients produce only half the protein needed to stay healthy due to a genetic mutation
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And these genes are transcribed into pre-mRNA
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Most pre-mRNAs are processed into productive mRNAs and serve as templates for protein production
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However, some pre-mRNAs are processed into non-productive mRNAs
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Both types of mRNA can exist in cells at the same time
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Non-productive mRNA is degraded and no protein is produced
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Only mRNA produced from a functional copy of the gene can produce the desired protein
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  ▲ Image source: Stoke Therapeutics official website Using TANGO methods and a deep understanding of RNA science, Stoke researchers designed an antisense oligonucleotide (ASO) that binds to pre-mRNA and helps functional ( or wild-type) gene to produce more protein
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TANGO is designed to restore the missing protein by increasing or stimulating the protein output of the healthy gene, thereby compensating for the mutated copy of the gene
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▲ Image source: Stoke Therapeutics' official website SYNGAP1 syndrome SYNGAP1 syndrome is a rare neurological disorder characterized by moderate-to-severe intellectual disability that manifests in early childhood
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Mutations in the SYNGAP1 gene (which produces the SynGAP protein) were first identified in 2009, and since then, more and more children with SYNGAP1 syndrome have been identified
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Normal levels of SynGAP protein are essential for normal brain function and development
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Mutations in the SYNGAP1 gene also play an important role in the development of epileptic encephalopathy (DEEs)
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The severity and onset of symptoms may vary from patient to patient
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SYNGAP1 syndrome is characterized by developmental delay or intellectual disability, generalized epilepsy, autism spectrum disorder (ASD), and other behavioral abnormalities
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More than 80% of SYNGAP1 syndrome cases are caused by haploinsufficiency of the SYNGAP1 gene
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SYNGAP1 syndrome is estimated to account for 1% to 2% of all cases of intellectual disability
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There is currently no approved treatment for SYNGAP1 syndrome
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Rett syndrome Rett syndrome is a rare inherited neurological disorder that primarily affects women, with an incidence of approximately 1 in 10,000
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It is characterized by normal early growth and development, followed by clinical features such as slow development, distinctive hand movements, slow brain and head growth, walking problems, seizures, and intellectual disability
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Almost all cases of Rett syndrome are caused by mutations in the MECP2 gene, which is located on the X chromosome
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Scientists identified the gene in 1999, and studies have shown that it controls the function of many other genes
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The MECP2 gene synthesizes a methylcytosine-binding protein 2 (MeCP2), which is necessary for brain development, and plays a role in regulating gene expression at the transcriptional level
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▲ Image source: Reference 2 Worldwide, approximately one in every 10,000 to 15,000 baby girls suffers from Rett syndrome, and in the United States, 6,000 to 9,000 patients suffer from Rett syndrome
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Rett syndrome causes problems with the functions of the brain responsible for cognitive, sensory, emotional, motor, and autonomic functions
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Symptoms of Rett syndrome usually appear when the patient is 6-18 months old, and the patient will experience a period of rapid decline with marked retardation of head development, gradual loss of purposeful hand skills and language skills, and rapid progression of the disease.
Slow; begins to exhibit typical hand movements, such as twisting, washing, clapping, or tapping, and repeatedly moving hands to mouth; holds hands behind or at sides, touching, grasping, and releasing at will, The above repetitive movements disappear during sleep; irregular breathing, such as apnea and hyperventilation, occurs; some female children also have autism-like performance at this stage, with unstable walking and difficulty in movement
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Currently, there are no FDA-approved drugs for Rett syndrome
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➤ Both company CEOs are bullish on the collaboration Acadia CEO Steve Davis said: "Stoke's RNA-based approach to upregulate healthy proteins offers exciting new hope for the treatment of rare neurodevelopmental diseases such as Rett syndrome.
Combining Stoke's capabilities with Acadia's extensive expertise in neuroscience drug development and commercialization allows us to explore some new areas of rare CNS diseases faster and better
.
We are excited about the opportunity to build on this further Our Rett syndrome series and seek treatment options for SYNGAP1 syndrome and other neurodevelopmental disorders .
" Stoke CEO Edward M.
Kaye, MD, said: "Rett syndrome and SYNGAP1 syndrome are two serious central nervous system Intractable disease, both associated with developmental delay, loss of motor function, autism, epilepsy, and other comorbidities that affect the quality of life of patients and their families.
Acadia shares our commitment to improving outcomes for patients with neurodevelopmental disorders .
We believe their neuroscience expertise, as well as late-stage development and commercialization capabilities, complement our ability to develop drugs for Dravet syndrome .
We believe we can deliver new disease control medicines to those who need them.
increase its treatment options .













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