Biotecnología
Tratando lo Incurable con Terapias de Precisión – ¿Una Oportunidad de $4 billones?
Terapias de Precisión para Resultados Dirigidos
Precision therapies have always been the ultimate goal of medicine. Instead of drugs acting on multiple parts of the body, these therapies would only target one organ, one cell, or even one gene.
En teoría, no solo sería mucho más eficiente, sino que también reduciría drásticamente los efectos secundarios y permitiría curar enfermedades que hasta ahora han resistido el tratamiento, desde enfermedades genéticas hasta parálisis o incluso cáncer.
Con el progreso en la comprensión de la biología y la bioquímica, esto finalmente está siendo posible. La pandemia ha demostrado el poder de la tecnología de ARNm. En la última década o dos se han descubierto muchas herramientas igualmente poderosas: edición genética CRISPR, edición de bases, CAR‑T, RNAi, siRNA, zinc‑fingers, etc.
De teorías o ideas de nicho, estas tecnologías ahora forman gran parte del esfuerzo de I+D biomédica. En 2023, más del 25 % de los ensayos clínicos utilizaban nuevas modalidades terapéuticas.
Fuente: ARK Invest
Una Revolución que Llega Justo a Tiempo
And the surge in clinical trials relying on precision therapies could not have come at a better time. In the last 20 years, the budget for finding new drugs has grown constantly, but the financial returns have been less than impressive.
Fuente: ARK Invest
Esta tendencia persistió hasta 2016‑2020, con una inesperada recuperación, gracias a las terapias de precisión. Esta reversión de la tendencia se confirmó aún más con un rebote aún mayor en los ingresos incrementales comparado con el gasto en I+D en 2021‑2023.
Hasta ahora, este repunte en los rendimientos de la investigación médica ha sido impulsado mayormente por terapias innovadoras contra el cáncer. Esto se logró principalmente mediante el uso de anticuerpos personalizados y terapias celulares.
Pero con la aprobación de la primera terapia génica CRISPR en 2023, las compuertas podrían estar abriéndose para una cura generalizada de la mayoría de las enfermedades genéticas en menos de una generación.
Fuente: ARK Invest
RNA therapies and precision small molecules could solve the rest of medical concerns, including non-genetic rare diseases, neurodegenerative diseases, and infectious diseases.
Terapias de Precisión
Degradadores de Proteínas Dirigidos” (TPDs)
Only 864 out of 20,000 proteins in the human body are currently targeted by FDA-approved drugs. This is just 4% of the total, with another 17% potentially targetable. This is mostly due to the extreme difficulty of finding a chemical compound that efficiently targets a specific protein.
Una nueva tecnología, los TPDs, podría dirigirse al 56 % del proteoma humano total (el catálogo completo de proteínas, como el genoma lo es para los genes). Esto podría generar resultados masivos en enfermedades intratables asociadas a proteínas anormales, como la enfermedad de Alzheimer.
Fuente: ARK Invest
Enfermedades Raras
Most rare diseases are associated with premature deaths, as well as poor quality of life. Current treatments mostly focus on managing the symptoms as well as possible, which are mostly poorly improved.
Esto significa que enfermedades raras, como, por ejemplo, la enfermedad de células falciformes (SCD), generan costos masivos a lo largo del tiempo, a menudo medidos en millones de dólares por paciente durante toda una vida.
Fuente: ARK Invest
Como resultado, terapias de precisión como la terapia génica CRISPR podrían cambiar la vida y ser rentables para la sociedad en general, aun cuando tengan un precio de 6 a 7 cifras.
EE. UU. gastan alrededor de $450 B al año en el tratamiento de enfermedades raras. Una cura para cada enfermedad rara (mayormente causadas por problemas genéticos) representaría entre 8 y 16 billones de dólares ahorrados en los próximos 50 años. Y, por supuesto, esto es mirando solo desde un punto de vista contable, sin incluir la reducción del sufrimiento humano y de muertes innecesarias.
Fuente: ARK Invest
Terapias de ARN
mRNA is now well known for its possibilities in treating infectious diseases. This concept is going to be expanded quickly thanks to the efforts of companies like BioNTech and Moderna.
También están trabajando en desplegar ARNm hacia terapias contra el cáncer, ambos temas que exploramos con mayor profundidad en nuestro artículo “The Next Application for mRNA Technology: Cancer Therapies”.
Other types of RNA, like RNAi, siRNA, ASOs, miRNA, and asRNA, can also be leveraged for innovative therapies. Each has unique medical potential, which we explored in our article: “RNA Based Therapeutics are Gaining Traction: What Are Investors Options?“.
Un Mercado Masivo y en Crecimiento
ARK Invest’s research led them to forecast a tremendous opportunity in this sector:
The enterprise value of companies focused on precision therapies could appreciate 28% at an annual rate during the next seven years, from ~$820B in 2023 to ~$4.5T by 2030.
Fuente: ARK Invest
Esto es impresionante pero también tiene sentido al considerar la enorme ganancia tanto en salud como en costos de atención que estas terapias pueden aportar.
The recent approval of the first CRISPR therapy for sickle cell disease, Casgevy, from Vertex Pharmaceuticals (VRTX) and CRISPR Therapeutics (CRSP), came with a price tag of $2.2M per patient.
You can read more about Vasgevy approval in our article “Sickle Cell Disease Gene Therapies Approved by FDA Highlighting Potential of CRISPR/Cas9 Technologies”.
The FDA also announced another sickle cell disease gene therapy, Bluebird Bio’s lentiviral therapy, Lyfgenia, at a $3.1M price tag. So not only do these therapies save lives, but they can also prove extremely successful for the companies that made them possible.
Acciones de Terapias de Precisión de ARK
1. CRISPR Therapeutics
(CRSP )
As the company that made history with the first CRISPR gene therapy to ever be approved, it makes sense for CRISPR Therapeutics also to be the second largest holding in the ARK Genomic ETF.
Fuente: ARK Invest
Casgevy’s approval is by far the biggest news for the company, as it validates the potential of CRISPR technology as an actual lifelong solution for uncurable genetic diseases.
Reducing CRISPR Therapeutics to a “genetic disease” biotech would be, however, too reductive. The company also has clinical trials for CAR-T therapies and cardiovascular diseases.
Ultimately, by far, the largest potential is in CRISPR Therapeutics’ diabetes therapy, developed in collaboration with Vertex (as was Casgevy). This could be a much larger potential market, with the total number of patients an order of magnitude larger than for the now-approved hemoglobinopathies.
Fuente: CRISPR Therapeutics
2. Exact Sciences Corporation
(EXAS )
Cancer is especially deadly because it is often a silent disease. Most of the time, symptoms get visible only when it is already too late. This is why early detection can radically improve the survival rate of cancer patients.
For successful monitoring, the technology must be non-invasive and cheap enough to run regular testing.
This is the idea behind Exact Sciences, which is using both DNA & RNA data to detect early cancer, which “simple” DNA tests might miss. Exact Sciences is the largest holding in ARK Genomics ETF.
This detection method also gives much more insight into the characteristics of cancer and opens the door for more targeted therapies.
The company develops solutions for all stages of cancer detection.
Fuente: Exact Sciences
Such cancer detection is done from a simple blood sample and is also called liquid biopsy.
In the long term, liquid biopsy will likely become routine testing, as early cancer detection is a lot cheaper (and safer) than finding it later, making it a very cost-efficient option for insurance and society at large.
3. Ionis Pharmaceuticals, Inc.
(IONS )
While mRNA has been spotlighted in the last 3 years, RNA is a complex molecule with many other sub-types. Among them are micro-RNA (miRNA) & antisense-RNA (asRNA).
They are naturally occurring RNA that do not encode any genes. Instead, they regulate standard mRNA activity, changing the cells’ genetic activity. Both miRNA and asRNA have been discovered to be involved in multiple diseases.
Ionis Pharmaceuticals(IONS) is a leader in antisense-RNA therapies. It is also the the 7th largest holding in ARK Genomics ETF, its 3rd largest in precision therapies, and its largest holding dealing with RNA-based therapies.
It currently has 4 commercialized drugs and a rich pipeline of potential new drugs, of which 10 are in phase III of clinical trials:
- 11 terapias neurológicas.
- 6 terapias cardiovasculares.
- 2 terapias para enfermedades raras.
- 7 otras enfermedades (Hepatitis B, enfermedades renales, etc.…)
Ionis has also created a joint venture with RNAi-leader Alnylam (ALNY): Regulus (RGLS). The joint company will use unique patents from both companies to create synergies between the 2 companies’ proprietary technologies.
How far RNAi, miRNA, and asRNA can go as a therapeutic class is yet to be seen. But if mRNA taught us anything, we are just at the beginning of applications relying on induced or regulated gene expression. RNA molecules will be central to this new field of biotech and medicine.
