Genomic Revolution

Il caso di investimento della rivoluzione genomica

17 April 2024

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Genomic Revolution

Nel nostro caso di investimento nell’innovazione disruptive, abbiamo delineato le cinque piattaforme di innovazione – IA, robotica, sequenziamento multiomico, blockchain pubblica e stoccaggio di energia – che stanno convergendo e definendo l’attuale era tecnologica. In questo articolo ci concentriamo sul potenziale di trasformazione del sequenziamento multiomico, che sta guidando la rivoluzione genomica e che viene seguito dal nostro ARK Genomic Revolution UCITS ETF.

Introduzione

La missione di vincere le sfide mediche più complesse è oggi al centro dell’attenzione del settore sanitario. Gli attuali progressi in campo medico stanno aprendo la strada a importanti scoperte nel campo delle biotecnologie e hanno portato a una nuova era nella medicina di precisione, nella prevenzione delle malattie e nei trattamenti personalizzati. Riteniamo che gli investitori abbiano l’opportunità di investire nell’innovazione che ridefinirà la salute, generando al contempo un valore e un rendimento economico sostanziali.

Cos’è il sequenziamento multiomico

Per comprendere il sequenziamento multiomico, dobbiamo prima capire il sequenziamento genomico. Il sequenziamento genomico è un processo utilizzato per determinare la sequenza completa del DNA del genoma di un organismo. Il genoma è l’intero materiale genetico di un organismo ed è codificato nel suo DNA.

Il sequenziamento multiomico, per estensione, è un approccio alla ricerca biologica e alla medicina che combina dati provenienti da diversi campi “omici”, come la genomica, la trascrittomica, la proteomica e la metabolomica, per ottenere una comprensione completa delle proprietà e delle funzioni biologiche di un organismo. In termini semplici, il dogma centrale¹ della biologia molecolare è una teoria che afferma che l’informazione genetica fluisce solo in una direzione, dal DNA (il Genoma) all’RNA (il Trascrittoma), alle proteine (il Proteoma). Le proteine svolgono praticamente tutte le funzioni critiche per la vita ma, se alterate, possono causare malattie.

The Central Dogma Describes How Information Flows Downstream Through Biological Systems²

The central dogma describes how information flows downstream through biological systems

Comprendendo meglio le interazioni tra i pilastri del dogma centrale, possiamo migliorare la nostra capacità di formulare previsioni, diagnosi e approfondimenti biologici fondamentali. I ricercatori in campo medico possono scoprire meccanismi biologici complessi, percorsi patologici e potenziali bersagli terapeutici, portando a soluzioni sanitarie più personalizzate ed efficaci. Questo approccio integrato offre una visione più olistica dello stato biologico di un organismo, rispetto all’analisi di ciascuno di essi in modo isolato, ovvero studiando solo un insieme specifico di molecole alla volta senza considerare le interazioni con le altre.

La proliferazione di nuove modalità terapeutiche

Negli ultimi trent’anni si è assistito a una proliferazione di modalità terapeutiche con meccanismi d’azione completamente nuovi. Non solo esse hanno ampliato il numero di malattie curabili, ma hanno anche migliorato l’efficacia e la sicurezza. Nel 2023, oltre il 25% delle sperimentazioni cliniche si avvarrà di nuove modalità terapeutiche.

New Therapeutic Modalities are Proliferating³

New therapeutic modalities are proliferating

Precision therapies could reverse the downtrend in returns on R&D

Given regulatory bottlenecks and legacy drug discovery methods, the return on therapeutic Research and Development (R&D) has been falling for nearly 25 years. This has increased the hurdle rate for new drug discovery R&D. But, according to the research of our accredited genomics team, novel therapeutic modalities and R&D methods, coupled with regulatory approval of precision therapies, could reverse this downward trend in return on investment in the pharmaceutical industry.

Average Annual R&D and Incremental Revenue Attributable to Drugs Released⁴

Average annual R&D and incremental revenue attributable to drugs released

The value of curing rare diseases like sickle cell anaemia is high

These advances in could accelerate the pace of scientific drug discovery, personalising medicine to cure disease instead of simply masking its symptoms. Among precision therapies, gene editing treatments like CRISPR-Cas9,have the potential to cure rare genetic diseases such as Sickle Cell Disease (SCD) and Beta Thalassemia. SCD is an inherited red blood cell disorder that affects more than 100,000 people in the US and 20 million people globally, primarily in Africa. Today, therapeutics account for ~16% of the total spent on treating SCD disease in the United States, but they have done little more than manage symptoms, as the life expectancy of SCD patients is only 56% that of the general population.

SCD Healthcare Costs Over Average Patient Lifetime and Reasonable Cost for Sickle Cell Disease Cure⁵

The value of curing rare diseases like sickle cell anemia is high

In 2023, however, the medical community achieved a milestone with the first approvals for gene editing treatments for SCD and Beta Thalassemia in both the United States and Europe, signalling a new dawn for patients burdened by these conditions.⁶ Meanwhile, in the UK in 2022, a young leukaemia patient found hope through a pioneering T-cell therapy, marking another step forward in our battle against cancer.⁷

**Wright’s Law* predicted the cost declines in proteomics**

Mass spectrometry is an analytical technique that identifies the composition of a substance by ionising proteins and measuring their mass-to-charge ratios. As the number of proteomes analysed using this approach has increased, the costs associated with mass spectrometry have dropped significantly. This has unlocked new possibilities in medical research and diagnostics. Our research suggests that for untargeted Proteomics using mass spectrometry, the cost per sample is declining 23% at an annual rate, or ~11% for each cumulative doubling in the number of proteomes sequenced. This aligns with Wright’s Law which predicts that for every cumulative doubling of units produced, costs will decrease by a fixed percentage.

Proteomic discoveries are also paving the way for the identification of novel biomarkers, which are measurable substances in an organism whose presence indicates some biological state or condition. This in turn enables the earlier detection and treatment for unique cancer subtypes.

Wright’s Law has Predicted the Cost Decline for Untargeted Proteomics and US Trails with Patient Biomakers⁸

Wright's law has predicted the cost decline of proteomics

Single-cell RNA sequencing is revolutionising our understanding of cancer

RNA sequencing is a high-throughput sequencing technique used to capture and sequence the complete set of RNA transcripts in a sample, providing insights into gene expression patterns and functional analysis of genes at a given moment. This approach is particularly helpful in developing our understanding in gene expression between healthy and cancerous cells, identifying potential biomarkers for diagnosis and uncovering targets for new treatments. While traditional gene expression analysis using RNA sequencing can measure only the expression of genes in a mixture of different cell types, single-cell RNA sequencing can delineate the expression of different cell types in a complex tissue sample. Theoretically, linking gene expression to specific cells increases the accuracy of measuring by 10x and cuts costs per gigabyte by 76%. In other words, single-cell RNA sequencing provides a more detailed view than traditional RNA sequencing, revealing the cellular heterogeneity within tissues, including tumors that could be masked in bulk RNA sequencing analyses.

Process of the RNA Sequencing⁹

Single-cell RNA sequencing is revolutionising our understanding of cancer

Drug development costs could drop precipitously

We believe advances in fundamental biology, AI and automation and trial design should lower preclinical drug development costs significantly. These technologies enable methods that eliminate less-promising candidates (i.e. potential treatments) earlier in the drug development process (and therefore prevent downstream misallocation of R&D) and create a larger chemical search space early in the discovery phase (i.e. more can be searched and tested earlier in the discovery process).

During the next decade, companies leveraging these techniques fully should be able to lower their costs per regulatory approval (e.g., FDA) by almost 50%, in part by more than doubling the odds of success for those drug candidates that do enter clinical trials.

R&D Cost Per Drug Approval and Clinical Success Probability of Different Efficiency Innovations¹⁰

Drug Development Costs Could Drop Precipitously

Multiomics companies

Twist Biosciences – Twist Biosciences focuses primarily on the synthesis of custom DNA sequences which are pivotal in various multiomic applications. Their technology is used for creating high-quality synthetic DNA and RNA for genetic research, which can play a crucial role in understanding complex biological networks and interactions in diseases. They provide tools and platforms that aid in genomics, transcriptomics and potentially other omic studies, supporting disease research and drug discovery processes.
Exact Sciences – Exact Sciences is primarily known for its diagnostic tools and tests that leverage molecular biomarkers. Their work includes the development of non-invasive screening tests for cancer, such as the Cologuard test for colorectal cancer. In terms of multiomics, Exact Sciences uses genomic and epigenomic data to create and improve diagnostic methodologies, which are vital for early disease detection and monitoring, ultimately aiding in personalized treatment plans.
Recursion Pharmaceuticals – Recursion Pharmaceuticals operates at the intersection of biology and technology, using automated, high-throughput imaging and analysis techniques to discover drugs more efficiently. They utilize a multiomic approach to map diseases and predict the effectiveness of drug candidates. Their platform integrates various types of biological data (genomic, transcriptomic, proteomic, etc.) to identify novel therapeutic targets and develop treatments primarily for rare genetic diseases and other conditions.

Conclusion

Investing in multiomic sequencing presents an unprecedented opportunity to propel the ongoing revolution in medicine and biotechnology. By integrating Genomics, Transcriptomics, Proteomics and Metabolomics, we unlock a deeper understanding of complex biological interactions, fuelling advancements in precision medicine and disease prevention. As new therapeutic modalities emerge and the potential to reverse R&D downtrends becomes clearer, investors stand on the cusp of a transformative era. Beyond the promise of curing rare diseases, Multiomic Sequencing signifies more than just personalised treatment—it signifies a fundamental shift in healthcare, highlighting the importance of holistic biological insights to tackle the most daunting medical challenges of our time.

References

Il dogma centrale della biologia molecolare è una spiegazione del flusso di informazioni genetiche all’interno di un sistema biologico. Spesso si dice che il DNA fa l’RNA e l’RNA fa le proteine. Fu enunciato per la prima volta da Francis Crick nel 1957 e poi pubblicato nel 1958. Il dogma centrale afferma che una volta che l'”informazione” è passata nella proteina, non può uscire di nuovo nell’acido nucleico o nei residui di amminoacidi della proteina.

ARK Investment Management LLC, 2024. This ARK analysis is based on a range of external sources, which may be provided upon request. Forecasts are inherently limited and cannot be relied upon. For informational purposes only and should not be considered investment advice or a recommendation to buy, sell, or hold any particular security. Past performance is not indicative of future results.

Forecasts are inherently limited and cannot be relied upon. For informational purposes only and should not be considered investment advice, or a recommendation to buy, sell or hold any particular security. Source: Malone, Cindy S. “Central Dogma of Genetics – CSUN.EDU.” csun.edu, https://www.csun.edu/~cmalone/pdf360/Ch13-1transcription.pdf.

National Library of Medicine, “Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia”, March 2024. Available at: https://pubmed.ncbi.nlm.nih.gov/38425279/#:~:text=On%208%20December%202023%2C%20the,transfusion%2Ddependent%20%C3%9F%2Dthalassemia

University College London, “Further hope for base-edited T-cell therapy to treat resistant leukaemia”, June 2023. Available at: https://www.ucl.ac.uk/news/2023/jun/further-hope-base-edited-t-cell-therapy-treat-resistant-leukaemia

Wright’s Law states that for every cumulative doubling of units produced, costs will fall by a constant percentage. ARK Investment Management LLC, 2024. This ARK analysis is based on a range of external sources, which may be provided upon request. Forecasts are inherently limited and cannot be relied upon. For informational purposes only and should not be considered investment advice or a recommendation to buy, sell, or hold any particular security. Past performance is not indicative of future results.

Documenti collegati

Introduzione

Cos’è il sequenziamento multiomico

The Central Dogma Describes How Information Flows Downstream Through Biological Systems2

La proliferazione di nuove modalità terapeutiche

New Therapeutic Modalities are Proliferating3

Precision therapies could reverse the downtrend in returns on R&D

Average Annual R&D and Incremental Revenue Attributable to Drugs Released4

The value of curing rare diseases like sickle cell anaemia is high

SCD Healthcare Costs Over Average Patient Lifetime and Reasonable Cost for Sickle Cell Disease Cure5

Wright’s Law* predicted the cost declines in proteomics

Wright’s Law has Predicted the Cost Decline for Untargeted Proteomics and US Trails with Patient Biomakers8

Single-cell RNA sequencing is revolutionising our understanding of cancer

Process of the RNA Sequencing9

Drug development costs could drop precipitously

R&D Cost Per Drug Approval and Clinical Success Probability of Different Efficiency Innovations10

Multiomics companies

Conclusion

References

The Central Dogma Describes How Information Flows Downstream Through Biological Systems²

New Therapeutic Modalities are Proliferating³

Average Annual R&D and Incremental Revenue Attributable to Drugs Released⁴

SCD Healthcare Costs Over Average Patient Lifetime and Reasonable Cost for Sickle Cell Disease Cure⁵

**Wright’s Law* predicted the cost declines in proteomics**

Wright’s Law has Predicted the Cost Decline for Untargeted Proteomics and US Trails with Patient Biomakers⁸

Process of the RNA Sequencing⁹

R&D Cost Per Drug Approval and Clinical Success Probability of Different Efficiency Innovations¹⁰