Alan Horsager
@horsager.bsky.social
President & CEO of Duet BioTherapeutics • Interested in oncology, oligonucleotides, genetic medicines, and human strength & endurance. Contemplating how to spend more time outdoors.
"The shape of the curve is what matters. Not their origins."
"The shape of the curve is what matters. Not their origins."
The subcutaneous version of the siRNA drug, vutrisiran, generated $558 million, bringing the total revenue for Alnylam's TTR drug class to nearly $1 billion in 2023.
#biotechnology #lifescience #innovation #entrepreneurship #startups
#biotechnology #lifescience #innovation #entrepreneurship #startups
July 13, 2024 at 3:49 AM
The subcutaneous version of the siRNA drug, vutrisiran, generated $558 million, bringing the total revenue for Alnylam's TTR drug class to nearly $1 billion in 2023.
#biotechnology #lifescience #innovation #entrepreneurship #startups
#biotechnology #lifescience #innovation #entrepreneurship #startups
Despite treating a modest number of patients annually, patisiran generated significant global revenues of $355 million.
July 13, 2024 at 3:34 AM
Despite treating a modest number of patients annually, patisiran generated significant global revenues of $355 million.
Patisiran works by using the RNA interference (RNAi) mechanism to target and destroy the mRNA responsible for producing transthyretin protein, reducing its harmful accumulation.
July 13, 2024 at 3:19 AM
Patisiran works by using the RNA interference (RNAi) mechanism to target and destroy the mRNA responsible for producing transthyretin protein, reducing its harmful accumulation.
This groundbreaking medication treats polyneuropathy in adults with hATTR, a rare genetic condition that causes abnormal protein deposits in the body's nerves and organs, leading to symptoms like nerve damage.
July 13, 2024 at 3:04 AM
This groundbreaking medication treats polyneuropathy in adults with hATTR, a rare genetic condition that causes abnormal protein deposits in the body's nerves and organs, leading to symptoms like nerve damage.
Patisiran (marketed as Onpattro by Alnylam Pharmaceuticals) made history in 2018 as the first siRNA-based drug to receive FDA approval.
July 13, 2024 at 2:49 AM
Patisiran (marketed as Onpattro by Alnylam Pharmaceuticals) made history in 2018 as the first siRNA-based drug to receive FDA approval.
To address these issues, scientists have developed various chemical modifications to enhance the stability and safety of siRNAs. There are currently 6 siRNA-based drugs that have been approved for treating various diseases, including hATTR, hyperoxaluria, and hypercholesterolemia.
July 13, 2024 at 2:34 AM
To address these issues, scientists have developed various chemical modifications to enhance the stability and safety of siRNAs. There are currently 6 siRNA-based drugs that have been approved for treating various diseases, including hATTR, hyperoxaluria, and hypercholesterolemia.
This design helps guide the cellular machinery to the target mRNA, leading to its degradation and suppression of gene expression. siRNAs face challenges such as instability in human blood and the potential to trigger the body's immune system.
July 13, 2024 at 2:19 AM
This design helps guide the cellular machinery to the target mRNA, leading to its degradation and suppression of gene expression. siRNAs face challenges such as instability in human blood and the potential to trigger the body's immune system.
Unlike antisense oligonucleotides (ASOs), which are typically single-stranded and can block mRNA without degrading it, siRNAs are designed to be double-stranded and about 20-25 nucleotides long to mimic naturally occurring siRNAs.
July 13, 2024 at 2:04 AM
Unlike antisense oligonucleotides (ASOs), which are typically single-stranded and can block mRNA without degrading it, siRNAs are designed to be double-stranded and about 20-25 nucleotides long to mimic naturally occurring siRNAs.
In 2023, Exondys 51 generated nearly $480 million in revenue.
July 11, 2024 at 5:49 AM
In 2023, Exondys 51 generated nearly $480 million in revenue.
DMD is caused by mutations in the DMD gene that produce a non-functional protein called dystrophin. Exondys 51 targets a specific part of the gene (exon 51) to skip over the faulty section, allowing for the production of a shorter but functional version of dystrophin.
July 11, 2024 at 5:34 AM
DMD is caused by mutations in the DMD gene that produce a non-functional protein called dystrophin. Exondys 51 targets a specific part of the gene (exon 51) to skip over the faulty section, allowing for the production of a shorter but functional version of dystrophin.
For example, Spinraza, developed by Ionis in partnership with Biogen, treats SMA, a disease caused by mutations in the SMN1 gene. Spinraza generated over $1.7 billion in 2023 alone. Another example is Exondys 51, developed by Sarepta, which treats Duchenne muscular dystrophy (DMD).
July 11, 2024 at 5:19 AM
For example, Spinraza, developed by Ionis in partnership with Biogen, treats SMA, a disease caused by mutations in the SMN1 gene. Spinraza generated over $1.7 billion in 2023 alone. Another example is Exondys 51, developed by Sarepta, which treats Duchenne muscular dystrophy (DMD).
There are currently 12 ASO-based drugs approved for treating diseases such as spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD), and hereditary transthyretin amyloidosis (hATTR). Some of these drugs have become financial blockbusters.
July 11, 2024 at 5:04 AM
There are currently 12 ASO-based drugs approved for treating diseases such as spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD), and hereditary transthyretin amyloidosis (hATTR). Some of these drugs have become financial blockbusters.
These modifications protect ASOs from being broken down in the body and improve their ability to bind to their target mRNA.
July 11, 2024 at 4:49 AM
These modifications protect ASOs from being broken down in the body and improve their ability to bind to their target mRNA.
3. Translational Arrest: ASOs can block the machinery that reads mRNA to make proteins by binding to the starting point of the mRNA, directly preventing protein production. To make ASOs more stable and effective, they can be chemically modified.
July 11, 2024 at 4:34 AM
3. Translational Arrest: ASOs can block the machinery that reads mRNA to make proteins by binding to the starting point of the mRNA, directly preventing protein production. To make ASOs more stable and effective, they can be chemically modified.
By altering this process, ASOs can sometimes increase the production of beneficial proteins, which can help treat diseases like Duchenne muscular dystrophy and spinal muscular atrophy.
July 11, 2024 at 4:19 AM
By altering this process, ASOs can sometimes increase the production of beneficial proteins, which can help treat diseases like Duchenne muscular dystrophy and spinal muscular atrophy.
1. RNA Cutting: ASOs bind to mRNA in a way that recruits an enzyme called RNase H1, which cuts the RNA, silencing the gene. These ASOs are often called "gapmers."
2. Splicing Modification: ASOs can change how mRNA is processed before it is used to make proteins.
July 11, 2024 at 4:04 AM
1. RNA Cutting: ASOs bind to mRNA in a way that recruits an enzyme called RNase H1, which cuts the RNA, silencing the gene. These ASOs are often called "gapmers."
2. Splicing Modification: ASOs can change how mRNA is processed before it is used to make proteins.
This customization allows ASOs to be stable and effective in different therapeutic situations. ASOs work in three main ways to influence gene expression in the body:
July 11, 2024 at 3:49 AM
This customization allows ASOs to be stable and effective in different therapeutic situations. ASOs work in three main ways to influence gene expression in the body:
ASOs can be made from various materials, including single-stranded DNA, modified DNA, RNA-like compounds, or specially structured molecules such as locked nucleic acids (LNA) and morpholino oligonucleotides. Each type is tailored to bind precisely to its target RNA, blocking its function.
July 11, 2024 at 3:34 AM
ASOs can be made from various materials, including single-stranded DNA, modified DNA, RNA-like compounds, or specially structured molecules such as locked nucleic acids (LNA) and morpholino oligonucleotides. Each type is tailored to bind precisely to its target RNA, blocking its function.
Additionally, while natural microRNAs regulate many mRNAs all at once and non-specifically, ASOs target very specific mRNAs.
July 11, 2024 at 3:19 AM
Additionally, while natural microRNAs regulate many mRNAs all at once and non-specifically, ASOs target very specific mRNAs.
Binding blocks the mRNA from making proteins, effectively silencing the gene's expression. Unlike other RNA-based therapies like small interfering RNA (siRNA), which typically destroy mRNA via the RNA-induced silencing complex (RISC), ASOs can block protein production without breaking down the mRNA.
July 11, 2024 at 3:04 AM
Binding blocks the mRNA from making proteins, effectively silencing the gene's expression. Unlike other RNA-based therapies like small interfering RNA (siRNA), which typically destroy mRNA via the RNA-induced silencing complex (RISC), ASOs can block protein production without breaking down the mRNA.
July 9, 2024 at 1:04 AM
The attached image covers the various modalities of RNA-based treatments in depth, from antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to the promising realms of microRNAs (miRNAs) and aptamers.
July 9, 2024 at 12:49 AM
The attached image covers the various modalities of RNA-based treatments in depth, from antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to the promising realms of microRNAs (miRNAs) and aptamers.
Each modality offers unique mechanisms and strategies for combating a wide range of diseases, illustrating the innovative scope of RNA as a therapeutic class.
July 9, 2024 at 12:34 AM
Each modality offers unique mechanisms and strategies for combating a wide range of diseases, illustrating the innovative scope of RNA as a therapeutic class.