What is SKY-0515?
Skyhawk’s objective is to change the way diseases are treated by creating oral medicines that target RNA, the body's instructions for making proteins.
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​These medicines are designed to fix or adjust how cells function, helping to treat diseases at their root cause.
A once-a-day pill taken by mouth
Potential to slow the progression of Huntington's Disease
Works by reducing levels of harmful proteins linked to the disease
Shown to be well-tolerated in healthy volunteers
*14-day study with healthy volunteers
Therapy types being developed for Huntington’s Disease
Small Molecules
Small, lab-made compounds
Usually taken as a pill
May easily spread throughout the body, enter cells, and can be designed to reach the brain
Nucleic Acids
Medium-sized, lab-made molecules
Must be given by injection into the blood, tissue, or spinal cord
May not spread easily throughout the body
Biologics
Large molecules, made from living sources
Must be given by injection into the blood, tissue, or spinal cord
May not spread easily in the body and some may have trouble entering cells
Certain technologies can help them reach the brain and improve how well they work
SKY-0515 is a daily pill designed to potentially slow down or reduce the damage caused by HD
The pill is taken by mouth, once-a-day
The pill spreads throughout the body, including the brain
It lowers the amount of harmful HD protein (HTT), which might prevent brain cell damage
It also reduces another protein (PMS1), which might slow the CAG repeats expansion
HD happens because of a mutation in a gene called HTT
Mutation
People inherit too many copies of a small DNA sequence called CAG
Result
This causes the body to make a harmful protein that keeps growing
Damage
The harmful protein hurts brain cells eventually leading to cell death
Effect
Over time, this leads to brain shrinkage, affecting movement, thinking, and emotions
CAG is a small piece of DNA that repeats too many times (36 or more) in people with HD, causing harmful effects in the brain
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PMS1 promotes CAG repeats and makes mutant HTT more harmful and worsens Huntington’s Disease
HD is caused by mutant HTT and worsened by PMS1
Mutant HTT is a damaged protein caused by extra CAG repeats in the DNA. The CAG can continue to expand over time affecting the severity of the Huntington’s disease
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PMS1 is one of the proteins that help control CAG expansion, linked to the development of HD
SKY-0515 also reduces PMS1: PMS1 and somatic CAG expansion contribute to HD progression
Reducing PMS1 may slow the disease
Born with Extra
CAG Repeats
People who have HD are born with more CAG repeats in their HTT gene
More CAG Repeats
= Earlier Disease
Higher number of CAG repeats can lead to earlier onset of disease and symptoms
CAG Repeats Increase Over Time
Over time, the number of CAG repeats expands in brain cells. This can occur at different rates in individuals and further impacts onset and progression of symptoms
Reduced PMS1 Slows CAG Expansion
A protein called PMS1 affects the rate of increase in CAG repeats
Somatic CAG Expansion is the increase in CAG repeats in specific cells over time
SKY-0515 affects mRNA splicing
Splicing is like editing a set of instructions for a recipe—taking out or adding ingredients can modify the final dish, helping make good proteins or stop bad ones.
SKY-0515 adjusts how RNA is processed to change protein production
1
DNA stores instructions
Your genes contain the code for making proteins
Transcription
2
Pre-mRNA is created
The body copies part of the DNA into a temporary message called pre-mRNA
Splicing
3
mRNA is formed
This message gets edited (splicing) to remove extra parts, leaving only the important instructions
SKY-0515 changes splicing
This drug adjusts the editing step to stop mRNA from making harmful proteins that contribute to Huntington’s disease
Translation
4
Proteins are made
The body reads the mRNA and builds proteins based on the instructions
SKY-0515 has a dual mechanism of action
SKY-0515 lowers the amount of harmful HD protein and reduces another protein, PMS1 which may help stop the increase in CAG repeats
Clinical effects of SKY-0515 on HTT mRNA in blood after 14 days of dosing in healthy volunteers
Multiple Dose Study (daily dosing for 14 days)
Average Reduction in HTT mRNA Level in Blood over 24 Hours
Error bars represent standard error of the mean