A quick introduction to the snowball rolling toward the healthcare system.
Iteration, specialization, and competition
If you believe in the 10,000 hours rule, the difference between a novice and a master is time and repetition. In the field of gene therapy, specialized mastery in fields like genetics, virology, and immunology has curative potential, so bringing innovation to patients quickly is critical. Thankfully, the research and development (R&D) pathway for gene therapies enjoys structural efficiency due to the very nature of gene therapy. By comparing the characteristics of conventional medicine and gene therapy, we’ll reveal the paradigm shift accelerating drug discovery; from traditional medicine’s probabilistic R&D funnel to gene therapy’s deterministic design pathway.
Small molecule research vs. gene therapy design
To see how R&D compares between traditional medicines and gene therapy, consider small molecule pharmaceuticals like aspirin, insulin, and antihistamines. Figure 1, from a study published in The Journal of the American Chemical Society, compares the popularity of certain chemical motifs in medicinal chemistry. Researchers can look to past drug designs to inspire future adaptations, or even blend features from different drugs.
Figure 1: The color-coded areas of the medicinal molecules in the left box have distinct chemical properties. Their relative popularity over time is plotted in the right box. This shows how the design process of small molecule therapeutics evolves over time and builds on previous lessons.
Designing small molecules is an art with unknown outcomes
Piecing together molecular structures with known medicinal value, solubility, stability, and so on, can help in the drug discovery process of small molecules. But designing molecules which interact with the human body is still an art. Testing candidate molecules at the research scale can help screen molecules with unacceptable toxicity or lack of function. However, the drug’s effects across entire organ systems during full scale human testing may differ from initial projections, and unforeseen effects may arise which halt further development. Failure at this scale is expensive, and it is not uncommon.
Small molecules can affect other parts of the body
Since small molecules diffuse throughout the body, affecting many tissue types, it can be incredibly difficult to design a small molecule drug with high specificity. Considering that new medicines must exceed the performance of what is currently available, success is both expensive and difficult to achieve. By contrast, gene therapy development is focused on developing components which can be reused, interchanged, upgraded, or cross-licensed, demonstrated in Figure 2, below, from an article in HemAware, a bleeding disorders magazine.
Viral vectors deliver cargo with cellular precision
Figure 2: While small molecules are one piece, gene therapies are made of separate components. If an empty viral shell has already been tested to deliver gene X to human cell line A, it can be repurposed to deliver any other gene to human cell line A. This way, gene X, gene Y, gene Z, etc can all be tested in human cells to see if they can correct the root cause of disease, simplifying proof-of-concept testing. Likewise, different shells can be tested to maximize delivery of their cargo genes.
Viral vectors, the empty viral shells shown in Figure 2, are some of the smallest, most intricate objects that modern manufacturing can produce. While they’re expensive, they deliver cargo with cellular precision. Repeatedly delivering short-acting medications with viral vectors would be prohibitively expensive, but delivering a one-time gene therapy can justify the cost of these cell-specific precision delivery systems and enable safe, effective gene therapies. Factoring in the cost of producing designer genetic material and conducting the cell culturing methods used in many gene therapies adds to the exorbitant cost of production. The high cost of these advanced components can make gene therapies much more expensive than conventional medicine, but the capacity for long-term therapeutic benefit offsets these costs.
Specialization hones gene therapy components
The component-centric nature of gene therapy allows for multiple market efficiencies which should help lower production costs in the future. For instance, companies may decide to specialize in the design, or the biomanufacturing processes of viral vectors, while other companies may specialize in researching and creating medicinal genes. This layered model allows for competition at every level of gene therapy production, a time-tested way to achieve great results with maximum efficiency.
The gene delivered with a viral vector can be broken down further into genetic components like promoters and coding regions, among others. For example, the promoter specifies when a gene should be expressed and the coding region tells the cell what to produce. Matching promoters, coding regions, and other genetic elements determines how the gene therapy functions. Curing a disease is hard, but breaking it into smaller subproblems can make it an achievable process. Prototyping and refining each component independently lets researchers iterate on a component, honing its function to precisely alter cell behavior.
Gene therapy R&D is more design-centric than conventional medicines
The human body is massively complex, and precisely targeting drugs to specific cells or tissues can simplify the drug development process. Conventional medications can only be targeted to a degree, making their higher-order interactions with a live human hard to predict until human trials begin. This inherent randomness makes pharmaceutical R&D a probabilistic process, where failure sets companies back to square one with a new drug candidate. In contrast, R&D in gene therapy may be better described as deterministic. Under the deterministic model, success and failure are not binary, and limited success simply sends companies back to the drawing board to refine a component, instead of gambling on another therapeutic altogether.
The efficiencies described here are both scientific and economic. At a glance, the market for conventional medicines has historically been characterized by large barriers to entry, and a risky probabilistic drug development model where a single failure in clinical trials could put small companies out of business. This made it difficult, expensive, and risky for new companies to enter the market for conventional medicine, favoring giant companies and stifling competition. Gene therapy, on the other hand, rewards efficiency over power. The component-centric nature of genetic medicine encourages cross-licensing, collaboration within an industry of specialized mid-sized companies, and an iterative design process that builds on itself version after version in pursuit of cures instead of treatments.
The interplay between physical aspects of gene therapy and financial aspects of the market poetically parallel a motif biology: form fits function. As these new technologies reform the classical pharmaceutical model to incorporate today’s biotechnologies, correctly allocating resources may add power to the R&D efficiencies described here. A cursory glance at the cost of a one-time gene therapy compared to daily medication gives plenty of incentive to spend the time designing a gene therapy, even if a reasonably effective small molecule already exists for a condition; and that doesn’t even account for the conditions which conventional medication is unable to address. For a more detailed dive into the financial side, check out this article on the Cost of Gene Therapy.
Gene therapies can achieve previously impossible feats
Gene therapies on the market today can address previously incurable forms of cancer and multiple inherited diseases in a way that was previously impossible. Considering the features of gene therapy that naturally accelerate R&D, we look forward to a bright future with more cures and fewer treatments. Addimmune’s focus is to extend the reach of gene therapy to chronic viral infections, namely HIV, and we are currently conducting human trials. We are optimistic that our therapeutic product or therapy will join the ever-expanding ranks of curative gene therapies delivering value to patients that was previously unattainable. We encourage everyone to watch this industry for innovations that will revolutionize the healthcare system through better technology
A quick introduction to the snowball rolling toward the healthcare system.
Iteration, specialization, and competition
If you believe in the 10,000 hours rule, the difference between a novice and a master is time and repetition. In the field of gene therapy, specialized mastery in fields like genetics, virology, and immunology has curative potential, so bringing innovation to patients quickly is critical. Thankfully, the research and development (R&D) pathway for gene therapies enjoys structural efficiency due to the very nature of gene therapy. By comparing the characteristics of conventional medicine and gene therapy, we’ll reveal the paradigm shift accelerating drug discovery; from traditional medicine’s probabilistic R&D funnel to gene therapy’s deterministic design pathway.
Small molecule research vs. gene therapy design
To see how R&D compares between traditional medicines and gene therapy, consider small molecule pharmaceuticals like aspirin, insulin, and antihistamines. Figure 1, from a study published in The Journal of the American Chemical Society, compares the popularity of certain chemical motifs in medicinal chemistry. Researchers can look to past drug designs to inspire future adaptations, or even blend features from different drugs.
Figure 1: The color-coded areas of the medicinal molecules in the left box have distinct chemical properties. Their relative popularity over time is plotted in the right box. This shows how the design process of small molecule therapeutics evolves over time and builds on previous lessons.
Designing small molecules is an art with unknown outcomes
Piecing together molecular structures with known medicinal value, solubility, stability, and so on, can help in the drug discovery process of small molecules. But designing molecules which interact with the human body is still an art. Testing candidate molecules at the research scale can help screen molecules with unacceptable toxicity or lack of function. However, the drug’s effects across entire organ systems during full scale human testing may differ from initial projections, and unforeseen effects may arise which halt further development. Failure at this scale is expensive, and it is not uncommon.
Small molecules can affect other parts of the body
Since small molecules diffuse throughout the body, affecting many tissue types, it can be incredibly difficult to design a small molecule drug with high specificity. Considering that new medicines must exceed the performance of what is currently available, success is both expensive and difficult to achieve. By contrast, gene therapy development is focused on developing components which can be reused, interchanged, upgraded, or cross-licensed, demonstrated in Figure 2, below, from an article in HemAware, a bleeding disorders magazine.
Viral vectors deliver cargo with cellular precision
Figure 2: While small molecules are one piece, gene therapies are made of separate components. If an empty viral shell has already been tested to deliver gene X to human cell line A, it can be repurposed to deliver any other gene to human cell line A. This way, gene X, gene Y, gene Z, etc can all be tested in human cells to see if they can correct the root cause of disease, simplifying proof-of-concept testing. Likewise, different shells can be tested to maximize delivery of their cargo genes.
Viral vectors, the empty viral shells shown in Figure 2, are some of the smallest, most intricate objects that modern manufacturing can produce. While they’re expensive, they deliver cargo with cellular precision. Repeatedly delivering short-acting medications with viral vectors would be prohibitively expensive, but delivering a one-time gene therapy can justify the cost of these cell-specific precision delivery systems and enable safe, effective gene therapies. Factoring in the cost of producing designer genetic material and conducting the cell culturing methods used in many gene therapies adds to the exorbitant cost of production. The high cost of these advanced components can make gene therapies much more expensive than conventional medicine, but the capacity for long-term therapeutic benefit offsets these costs.
Specialization hones gene therapy components
The component-centric nature of gene therapy allows for multiple market efficiencies which should help lower production costs in the future. For instance, companies may decide to specialize in the design, or the biomanufacturing processes of viral vectors, while other companies may specialize in researching and creating medicinal genes. This layered model allows for competition at every level of gene therapy production, a time-tested way to achieve great results with maximum efficiency.
The gene delivered with a viral vector can be broken down further into genetic components like promoters and coding regions, among others. For example, the promoter specifies when a gene should be expressed and the coding region tells the cell what to produce. Matching promoters, coding regions, and other genetic elements determines how the gene therapy functions. Curing a disease is hard, but breaking it into smaller subproblems can make it an achievable process. Prototyping and refining each component independently lets researchers iterate on a component, honing its function to precisely alter cell behavior.
Gene therapy R&D is more design-centric than conventional medicines
The human body is massively complex, and precisely targeting drugs to specific cells or tissues can simplify the drug development process. Conventional medications can only be targeted to a degree, making their higher-order interactions with a live human hard to predict until human trials begin. This inherent randomness makes pharmaceutical R&D a probabilistic process, where failure sets companies back to square one with a new drug candidate. In contrast, R&D in gene therapy may be better described as deterministic. Under the deterministic model, success and failure are not binary, and limited success simply sends companies back to the drawing board to refine a component, instead of gambling on another therapeutic altogether.
The efficiencies described here are both scientific and economic. At a glance, the market for conventional medicines has historically been characterized by large barriers to entry, and a risky probabilistic drug development model where a single failure in clinical trials could put small companies out of business. This made it difficult, expensive, and risky for new companies to enter the market for conventional medicine, favoring giant companies and stifling competition. Gene therapy, on the other hand, rewards efficiency over power. The component-centric nature of genetic medicine encourages cross-licensing, collaboration within an industry of specialized mid-sized companies, and an iterative design process that builds on itself version after version in pursuit of cures instead of treatments.
The interplay between physical aspects of gene therapy and financial aspects of the market poetically parallel a motif biology: form fits function. As these new technologies reform the classical pharmaceutical model to incorporate today’s biotechnologies, correctly allocating resources may add power to the R&D efficiencies described here. A cursory glance at the cost of a one-time gene therapy compared to daily medication gives plenty of incentive to spend the time designing a gene therapy, even if a reasonably effective small molecule already exists for a condition; and that doesn’t even account for the conditions which conventional medication is unable to address. For a more detailed dive into the financial side, check out this article on the Cost of Gene Therapy.
Gene therapies can achieve previously impossible feats
Gene therapies on the market today can address previously incurable forms of cancer and multiple inherited diseases in a way that was previously impossible. Considering the features of gene therapy that naturally accelerate R&D, we look forward to a bright future with more cures and fewer treatments. Addimmune’s focus is to extend the reach of gene therapy to chronic viral infections, namely HIV, and we are currently conducting human trials. We are optimistic that our therapeutic product or therapy will join the ever-expanding ranks of curative gene therapies delivering value to patients that was previously unattainable. We encourage everyone to watch this industry for innovations that will revolutionize the healthcare system through better technology
