***Scroll along the chart to see this years key data***
About Crispr Therapeutics
CRISPR Therapeutics AG is a gene editing company focused on the development of CRISPR/Cas9- based therapeutics. CRISPR/Cas9 stands for Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and is a technology for gene editing, the process of precisely altering specific sequences of genomic DNA. It aims to apply this technology to disrupt, delete, correct and insert genes to treat genetically-defined diseases and to engineer advanced cellular therapies. They currently lead programs targeting the blood diseases beta-thalassemia and sickle cell disease has entered clinical testing, as has our first allogeneic CAR-T program targeting B-cell malignancies.
What is CRISPR/Cas-9?
Diseases such as cancer, diabetes, down syndrome, and Huntington's disease are the consequence of abnormal proteins that exist because of mutations in specific genes in a patients DNA. These mutations are specific sequences of genomic DNA. CRISPR/Cas-9 is a novel gene editing system that may allow us to modify, correct, or delete specific areas, or sequences, within a patients DNA, allowing us to treat these diseases. CRISPR is comprises of Cas-9; an enzyme that cuts DNA, and a guide RNA whose sequence directs Cas-9 to a specific location within the DNA where the edit should be made. The gene editing process begins when the complex recognizes a specific sequence of DNA and binds to the short segment. This initiates unwinding of the double helix which causes the guide RNA to pair with a specific target sequence within the DNA. Once paired precisely with the desired sequence, Cas-9 cuts out the DNA causing a strand break. Disruption is when the DNA sequence is broken and reconnects, causing inactivation along a specific sequence. Deletion is when two different guide RNAs target separate sites on either side of the desired deletion and the repair process joins the separate ends, deleting the intervening sequence. Corrections can be made by adding a DNA template along with a Cas-9/guide-RNA complex, the template includes DNA sequences that exactly match the DNA sequences adjacent to the target cut site, through a naturally occurring process the correction template is added to the desired break to repair the sequence, thus inserting a new gene.
Pipeline
Hemoglobinopathies
CTX001; Clinical: Autologous CRISPR/Cas9 gene-edited hematopoietic stem cell therapy in development for patients suffering from beta-thalassemia and sickle cell disease
Immuno-Oncology
CTX110; Clinical: Allogeneic CRISPR/Cas9 gene-edited CAR-T cell therapy targeting CD19 in development for the treatment of CD19+ malignancies
CTX120; Clinical: Allogeneic CRISPR/Cas9 gene-edited CAR-T cell therapy targeting BCMA in development for the treatment of multiple myeloma
CTX130; Clinical: Allogeneic CRISPR/Cas9 gene-edited CAR-T cell therapy targeting CD70 in development for the treatment of both solid tumors and hematologic malignancie
Regenerative Medicine
Type I diabetes mellitus; IND-enabling: Allogeneic beta-cell replacement therapy derived from a CRISPR/Cas9 gene-edited immune-evasive stem cell line in development for the treatment of diabetes
In Vivo Approaches
Glycogen storage disease type la (GSD la)
Duchenne muscular dystrophy (DMD)
Myotonic dystrophy type 1 (DM1)
Cystic fibrosis (CF)
*all in Research phase
Programs:
Hemoglobinopathies
About:
The inherited hemoglobinopathies beta-thalassemia and sickle cell disease (SCD) result from mutations in a gene that encodes a key component of hemoglobin, the oxygen carrying molecule in blood. Both diseases currently require lifetime treatment that can result in the need for regular transfusions, painful symptoms and chronic hospitalizations. Both of these diseases result in reduced life expectancy.
CRISPR program:
As a therapy, CTX001 involves isolating a patient’s own blood stem cells, editing them with CRISPR/Cas9 to increase HbF expression, and then returning the edited cells to the patient. We believe that over time these edited blood stem cells will generate red blood cells that have increased levels of HbF, which may reduce or eliminate patients’ symptoms. In 2017, we signed an agreement to co-develop and co-commercialize this program with our partner Vertex Pharmaceuticals.
Immuno-Oncology
About:
Over the past several decades, scientists have sought to engineer immune cells to seek and destroy cancer cells. These efforts eventually led to the approval by the FDA of two chimeric antigen receptor (CAR) T cell therapies in 2017.
CRISPR program:
For our initial allogeneic gene-edited CAR-T product candidates, such as our lead immuno-oncology program CTX110, we make three modifications to healthy donor T cells to allow our CAR-T cells to be used off-the-shelf:
- CAR: The chimeric antigen receptor (CAR) allows CAR-T cells to target and kill cancer cells. We use CRISPR/Cas9 to insert the CAR construct precisely into the TCR alpha constant (TRAC) locus, which we expect to result in a safer, more consistent product.
- TCR: T cells use the T cell receptor (TCR) to recognize and kill cells presenting foreign antigens (a sign of infection), thereby providing immunity from disease. We use CRISPR/Cas9 to eliminate the TCR with high efficiency, which reduces the risk of GvHD occurring during off-the-shelf use.
- MHC I: To improve CAR-T cell persistence and increase the chance for durable remissions, we use CRISPR/Cas9 to eliminate the class I major histocompatibility complex (MHC I) expressed on the surface of our CAR-T product candidates.
Regenerative Medicine
About:
Regenerative medicine, or the use of stem cells to repair or replace tissue or organ function lost due to disease, damage or age, holds tremendous potential in both rare and common diseases. The field is rapidly approaching the point where compelling clinical proofs of concept will likely begin to emerge. Most of these efforts use unmodified stem cells, and the potential to genetically engineer these cells via gene editing is tremendous. We are pursuing gene-editing approaches to allow allogeneic use of stem cell-derived therapies by enabling immune evasion, improving existing cell function and directing cell fate using CRISPR/Cas9.
CRISPR program:
Our gene-editing technology offers the potential to protect the transplanted cells from the patient’s immune system by ex vivo editing immune-modulatory genes within the stem cell line used to produce the pancreatic-lineage cells. The speed, specificity and multiplexing efficiency of CRISPR/Cas9 make our technology ideally suited to this task. We have established significant expertise in immune-evasive gene editing through our allogeneic CAR-T programs. The combination of ViaCyte’s stem cell capabilities and our gene-editing capabilities has the potential to enable a beta-cell replacement product that may deliver durable benefit to patients without triggering an immune reaction.
In Vivo Approaches
About:
Currently, several methods exist to deliver DNA or RNA to cells inside the body, which we can adapt to deliver CRISPR/Cas9 components. These methods fall into two broad categories: viral and non-viral. We are developing therapeutic programs based on technologies in both these areas.
- Viral: For organ systems, including the muscle, lung and central nervous system, we have emphasized viral delivery, primarily using adeno-associated viral (AAV) vectors. These vectors can deliver DNA encoding for Cas9 and guide RNAs into specific tissues of the body.
- Non-viral: Our efforts into non-viral delivery methods have focused on lipid nanoparticles (LNPs), which predominantly target the liver. We can encapsulate messenger RNA (mRNA) encoding Cas9 and guide RNA, and a donor DNA template if necessary, into LNPs to shuttle these components to the liver.
Key Financials:
Balance sheet:
(06/30/2020)
($Mil)
Cash assets: 945.1
Current liabilities: 74.5
Long-term debt: 0
Income statement:
($Mil)
Revenue:
2016: 5.164
2017: 40.997
2018: 3.124
2019: 289.59
Operating income:
2016: (56.648)
2017: (64.648)
2018: (158.943)
2019: 46.74
Financial health: Strong (87/100)
Institutional decisions:
4Q19:
- To buy: 155
- To sell: 71
1Q20:
- To buy: 141
- To sell: 99
2Q20:
- To buy: 148
- To sell: 102
Street consensus:
2.39/Buy
I didn't include too much financial data because the company is still in its research/growth phase (think Apple in the early 2000s). I am long-term bullish on Crispr because I believe genomics along with their therapeutics are the future of medicine for serious human diseases. CRISPR system is one of the most powerful scientific breakthroughs of the decade and we are still yet to see its full potential. The possibilities of gene editing are endless and I can't wait to see the next 10 years of progress within the field of genomics
This post took me hours to create, I'd appreciate a thumbs up! :)
About Crispr Therapeutics
CRISPR Therapeutics AG is a gene editing company focused on the development of CRISPR/Cas9- based therapeutics. CRISPR/Cas9 stands for Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and is a technology for gene editing, the process of precisely altering specific sequences of genomic DNA. It aims to apply this technology to disrupt, delete, correct and insert genes to treat genetically-defined diseases and to engineer advanced cellular therapies. They currently lead programs targeting the blood diseases beta-thalassemia and sickle cell disease has entered clinical testing, as has our first allogeneic CAR-T program targeting B-cell malignancies.
What is CRISPR/Cas-9?
Diseases such as cancer, diabetes, down syndrome, and Huntington's disease are the consequence of abnormal proteins that exist because of mutations in specific genes in a patients DNA. These mutations are specific sequences of genomic DNA. CRISPR/Cas-9 is a novel gene editing system that may allow us to modify, correct, or delete specific areas, or sequences, within a patients DNA, allowing us to treat these diseases. CRISPR is comprises of Cas-9; an enzyme that cuts DNA, and a guide RNA whose sequence directs Cas-9 to a specific location within the DNA where the edit should be made. The gene editing process begins when the complex recognizes a specific sequence of DNA and binds to the short segment. This initiates unwinding of the double helix which causes the guide RNA to pair with a specific target sequence within the DNA. Once paired precisely with the desired sequence, Cas-9 cuts out the DNA causing a strand break. Disruption is when the DNA sequence is broken and reconnects, causing inactivation along a specific sequence. Deletion is when two different guide RNAs target separate sites on either side of the desired deletion and the repair process joins the separate ends, deleting the intervening sequence. Corrections can be made by adding a DNA template along with a Cas-9/guide-RNA complex, the template includes DNA sequences that exactly match the DNA sequences adjacent to the target cut site, through a naturally occurring process the correction template is added to the desired break to repair the sequence, thus inserting a new gene.
Pipeline
Hemoglobinopathies
CTX001; Clinical: Autologous CRISPR/Cas9 gene-edited hematopoietic stem cell therapy in development for patients suffering from beta-thalassemia and sickle cell disease
Immuno-Oncology
CTX110; Clinical: Allogeneic CRISPR/Cas9 gene-edited CAR-T cell therapy targeting CD19 in development for the treatment of CD19+ malignancies
CTX120; Clinical: Allogeneic CRISPR/Cas9 gene-edited CAR-T cell therapy targeting BCMA in development for the treatment of multiple myeloma
CTX130; Clinical: Allogeneic CRISPR/Cas9 gene-edited CAR-T cell therapy targeting CD70 in development for the treatment of both solid tumors and hematologic malignancie
Regenerative Medicine
Type I diabetes mellitus; IND-enabling: Allogeneic beta-cell replacement therapy derived from a CRISPR/Cas9 gene-edited immune-evasive stem cell line in development for the treatment of diabetes
In Vivo Approaches
Glycogen storage disease type la (GSD la)
Duchenne muscular dystrophy (DMD)
Myotonic dystrophy type 1 (DM1)
Cystic fibrosis (CF)
*all in Research phase
Programs:
Hemoglobinopathies
About:
The inherited hemoglobinopathies beta-thalassemia and sickle cell disease (SCD) result from mutations in a gene that encodes a key component of hemoglobin, the oxygen carrying molecule in blood. Both diseases currently require lifetime treatment that can result in the need for regular transfusions, painful symptoms and chronic hospitalizations. Both of these diseases result in reduced life expectancy.
CRISPR program:
As a therapy, CTX001 involves isolating a patient’s own blood stem cells, editing them with CRISPR/Cas9 to increase HbF expression, and then returning the edited cells to the patient. We believe that over time these edited blood stem cells will generate red blood cells that have increased levels of HbF, which may reduce or eliminate patients’ symptoms. In 2017, we signed an agreement to co-develop and co-commercialize this program with our partner Vertex Pharmaceuticals.
Immuno-Oncology
About:
Over the past several decades, scientists have sought to engineer immune cells to seek and destroy cancer cells. These efforts eventually led to the approval by the FDA of two chimeric antigen receptor (CAR) T cell therapies in 2017.
CRISPR program:
For our initial allogeneic gene-edited CAR-T product candidates, such as our lead immuno-oncology program CTX110, we make three modifications to healthy donor T cells to allow our CAR-T cells to be used off-the-shelf:
- CAR: The chimeric antigen receptor (CAR) allows CAR-T cells to target and kill cancer cells. We use CRISPR/Cas9 to insert the CAR construct precisely into the TCR alpha constant (TRAC) locus, which we expect to result in a safer, more consistent product.
- TCR: T cells use the T cell receptor (TCR) to recognize and kill cells presenting foreign antigens (a sign of infection), thereby providing immunity from disease. We use CRISPR/Cas9 to eliminate the TCR with high efficiency, which reduces the risk of GvHD occurring during off-the-shelf use.
- MHC I: To improve CAR-T cell persistence and increase the chance for durable remissions, we use CRISPR/Cas9 to eliminate the class I major histocompatibility complex (MHC I) expressed on the surface of our CAR-T product candidates.
Regenerative Medicine
About:
Regenerative medicine, or the use of stem cells to repair or replace tissue or organ function lost due to disease, damage or age, holds tremendous potential in both rare and common diseases. The field is rapidly approaching the point where compelling clinical proofs of concept will likely begin to emerge. Most of these efforts use unmodified stem cells, and the potential to genetically engineer these cells via gene editing is tremendous. We are pursuing gene-editing approaches to allow allogeneic use of stem cell-derived therapies by enabling immune evasion, improving existing cell function and directing cell fate using CRISPR/Cas9.
CRISPR program:
Our gene-editing technology offers the potential to protect the transplanted cells from the patient’s immune system by ex vivo editing immune-modulatory genes within the stem cell line used to produce the pancreatic-lineage cells. The speed, specificity and multiplexing efficiency of CRISPR/Cas9 make our technology ideally suited to this task. We have established significant expertise in immune-evasive gene editing through our allogeneic CAR-T programs. The combination of ViaCyte’s stem cell capabilities and our gene-editing capabilities has the potential to enable a beta-cell replacement product that may deliver durable benefit to patients without triggering an immune reaction.
In Vivo Approaches
About:
Currently, several methods exist to deliver DNA or RNA to cells inside the body, which we can adapt to deliver CRISPR/Cas9 components. These methods fall into two broad categories: viral and non-viral. We are developing therapeutic programs based on technologies in both these areas.
- Viral: For organ systems, including the muscle, lung and central nervous system, we have emphasized viral delivery, primarily using adeno-associated viral (AAV) vectors. These vectors can deliver DNA encoding for Cas9 and guide RNAs into specific tissues of the body.
- Non-viral: Our efforts into non-viral delivery methods have focused on lipid nanoparticles (LNPs), which predominantly target the liver. We can encapsulate messenger RNA (mRNA) encoding Cas9 and guide RNA, and a donor DNA template if necessary, into LNPs to shuttle these components to the liver.
Key Financials:
Balance sheet:
(06/30/2020)
($Mil)
Cash assets: 945.1
Current liabilities: 74.5
Long-term debt: 0
Income statement:
($Mil)
Revenue:
2016: 5.164
2017: 40.997
2018: 3.124
2019: 289.59
Operating income:
2016: (56.648)
2017: (64.648)
2018: (158.943)
2019: 46.74
Financial health: Strong (87/100)
Institutional decisions:
4Q19:
- To buy: 155
- To sell: 71
1Q20:
- To buy: 141
- To sell: 99
2Q20:
- To buy: 148
- To sell: 102
Street consensus:
2.39/Buy
I didn't include too much financial data because the company is still in its research/growth phase (think Apple in the early 2000s). I am long-term bullish on Crispr because I believe genomics along with their therapeutics are the future of medicine for serious human diseases. CRISPR system is one of the most powerful scientific breakthroughs of the decade and we are still yet to see its full potential. The possibilities of gene editing are endless and I can't wait to see the next 10 years of progress within the field of genomics
This post took me hours to create, I'd appreciate a thumbs up! :)