Six key disruptors transforming biosciences into bioengineering
Over the past 10 years, a set of key scientific innovations have transformed the way we understand and interact with human biology. From CRISPR gene editing to AI-powered drug discovery, these innovations are allowing scientists and entrepreneurs to shift their focus from exploration and discovery to the realm of biological design and creation. From the centuries-long study of biosciences, we have stepped into the field of bioengineering.
At Tachyon, we think this marks a turning point in the way we diagnose, treat and manage diseases. In this article, we describe six synergistic “macro trends” that mark the future of innovation in healthcare. As biotech investors, we keep a close eye on these six trends as early-stage companies develop novel ways of harnessing them to revolutionize the industry.
1. Dramatic reduction in DNA sequencing costs
It took $2.7B and 13 years to sequence the reference human genome by 2003. When the endeavor first began, over 200 laboratories were contributing towards sequencing efforts. One company, Celera, adopted a “shotgun approach” to sequencing, whereby DNA was split into tiny fragments and sequenced out of order. The data fragments – over 27 million of them – then had to be painstakingly organized and rearranged into a contiguous sequence.
Today, we can sequence a person’s genome for around $1,000 USD and obtain results in a matter of days. Next-generation sequencing techniques developed by Solexa (acquired by Illumina) allow us to sequence hundreds of millions of DNA fragments in parallel, with great speed and accuracy, and without relying on piecing overlapping fragments back together. A plethora of companies now offer genome sequencing to patients at an affordable cost, but the applications in life sciences go well beyond human genetics. Laboratories small and large routinely sequence the genomes of many types of organism, including animals, bacteria and viruses, in their research. For companies, it opens the doors to faster innovation in the fields of genetic diseases, oncology testing, infectious diseases, microbiome analysis and more.
Cancers, for example, produce tissues riddled with a wide array of mutations, making it challenging to identify which mutations are responsible for disease. The ability to sequence tumor samples rapidly allows us to draw patterns between mutations and responses to different therapies and diagnostic methods.
The technology used for fast and accurate DNA sequencing can also be applied to sequence RNA – the intermediate molecular product used by cells to generate proteins. One of our portfolio companies, Scipher Medicine, is developing diagnostic tools that are the fruit of this effort. The company has developed blood tests that interpret RNA sequence data to predict patients’ responses to drugs for treating autoimmune diseases, helping physicians prescribe drugs that work effectively without delay. Within a year of its launch, Scipher’s PrismRA blood test is being prescribed by 15% of US rheumatologists, making a meaningful dent in the $552 billion wasted annually when patients are prescribed drugs they don’t respond to.
2. Induced Pluripotent Stem Cells
In 2012, Shinya Yamanaka was awarded the Nobel Prize in Physiology or Medicine for discovering a way of reprogramming mature cells to become pluripotent, that is, able to differentiate into any type of cell in the body. These so-called iPSCs (short for “induced pluripotent stem cells”) are revolutionary. Although they hold the same utility as embryonic stem cells, they are not subject to the same regulatory and ethical constraints because they can be derived from adult cell types in the body, such as skin cells.
This seminal research has enabled breakthroughs in regenerative and personalized medicine and advanced the search for treatments of Parkinson’s, heart disease, spinal cord injuries, diabetes and many other diseases. It is a significant stepping stone for other disruptive fields in the industry, such as the ability to grow miniature organs or combining CRISPR’s abilities when creating new iPSCs.
iPSCs can be used, for instance, to replenish depleting dopamine neurons in the brain. Through this method, a patient’s own skin cells can be reprogrammed into pluripotent stem cells and then differentiated into dopamine neurons that can be implanted into the brain. There is currently a clinical trial exploring this application to Parkinson’s disease.
iPSCs can also be used to manufacture tissues to determine which therapies may work in patients. One of our portfolio companies, TARA Biosystems, uses this technique to develop heart tissue and create extensive sets of samples to test the effects of different therapeutic doses and compounds, exponentially accelerating drug discovery for heart diseases.
In an interesting example of combining the advances we identified in the first and second macro trends, TARA Biosystems has partnered with another of our other portfolio companies, Scipher Medicine. In addition to predicting patients’ response to treatment, Scipher has developed an AI-driven platform “Spectra”, which exploits the proteomic data generated from blood tests to identify novel therapeutic targets. Through this specific partnership, the Spectra platform will be used to identify novel targets in genetic heart diseases such as cardiac laminopathies. These targets will then be evaluated using TARA’s platform, potentially reducing target discovery and validation from years down to months.
3. Organoid Technologies
The formation of complex three-dimensional cellular structures, or organoids, is a natural extension to the development of induced pluripotent stem cell technology. With the use of organoids, scientists can generate useful models of brain and heart diseases and test different therapies during drug discovery and development, widening the realm of possibilities for personalized medicine.
We have already mentioned TARA Biosystems, which leverages iPSCs differentiated into heart cells to create heart organoids. Another one of our portfolio companies, EpiBone, harvests stem cells from patients’ fat tissue and grows them into a scaffold using a proprietary bioreactor. In just three weeks, complex personalized bone grafts can be grown and used for surgical procedures - enabling faster and simpler surgeries with fewer risks of complications and faster recovery times for patients. EpiBone is currently conducting clinical trials of their technology in facial reconstruction and knee surgery.
4. Genome Editing
Perhaps the most thrilling technology development of the last few years, the use of CRISPR as a precise and versatile genome-editing tool, has accelerated innovation across multiple domains since its discovery in 2011. While the first macro trend – the dramatic reduction in the cost of DNA sequencing – is revolutionizing our understanding of cause and effect, editing genomes precisely has been a major challenge to developing therapeutics based on genomic findings.
As a discovery adopted from bacteria in nature, CRISPR works as a ‘molecular scissor’ that can cut DNA at a specified location in the genome so that sequences of DNA can be added or removed. Using CRISPR, we can engineer bacteria to produce biofuels for industrial applications or alter human genomes to correct genetic defects, thereby manipulating the outcome of diseases caused by single-gene mutations. Importantly, the changes that can be introduced with CRISPR are not the conventional symptom-reducing remedies offered by most drugs on the market but are potentially cures that last a lifetime, targeting disease at the source and permanently improving health for patients.
Gene editing using CRISPR-based therapies has shown promise in a range of clinical trials for diseases including cancer, HIV, sickle cell disease (SCD) and eye disorders. In the case of SCD, for instance, Vertex Pharmaceuticals has made significant headway towards treating the disease using gene editing technology. SCD is a debilitating illness caused by the formation of abnormal hemoglobin, the protein responsible for carrying oxygen throughout the body. SCD patients have a median life expectancy of approximately 45 years and suffer from severe pain and a greatly increased risk of stroke and organ damage. Using Vertex’s approach, blood stem cells from patients with sickle cell are harvested and modified using CRISPR-Cas9 to delete a gene responsible for suppressing the production of fetal hemoglobin, a form of hemoglobin which is normally only produced up to the first few months after birth but is highly effective at binding oxygen. Once the edited cells are reintroduced into the patient’s body, hemoglobin levels have been shown to rise and disease symptoms decline significantly in severity.
The versatility of the CRISPR mechanism extends its use beyond gene editing. CRISPR’s core function to identify and target DNA sequences precisely means it can also be used for fast and accurate disease detection. A unique application of CRISPR in this capacity has been underway at Mammoth Biosciences (also in our portfolio), a company co-founded by Jennifer Doudna, who won the 2020 Nobel Prize in Chemistry for her development (alongside Emmanuelle Charpentier) of CRISPR-Cas9 gene-editing tools. Mammoth Biosciences uses CRISPR to detect nucleotide sequences through rapid (<30min), cheap (<$30), and non-invasive at-home testing. These tests will disrupt the consumer testing space by enabling accessible and accurate detection of a wide range of conditions, from infectious diseases to cancer. The technology can also be used outside the medical field, by helping agriculturists identify viruses or bacteria spreading in crops, for example.
5. RNA Interference
Permanently altering the genetic code isn’t always the most desirable way of imparting change. RNA interference techniques present a different approach to modulating gene expression. While DNA permanently stores and encodes genetic information, RNA acts as a messenger for DNA, in the form of short sequences transcribed from DNA that are then translated into specific proteins. These RNA molecules enable the cell machinery to create proteins without interacting with DNA directly.
Techniques have been developed that interfere with specific RNA molecules, allowing us to silence the effect of a particular genetic mutation by suppressing the expression of proteins stemming from the gene it lies in. With RNA interference (RNAi), we can create therapeutics with direct biological targets inside cells, but without entering the nucleus or manipulating the genome.
DTx Pharma is one portfolio company of ours that is working on advancing RNAi technology so that it can be widely used for therapeutic purposes. So far, RNAi medicines have found success in treating liver diseases, but have faced obstacles in entering other organs due to poor cellular uptake. DTx Pharma has an enabling technology allowing RNA medicines to be used to treat other organs and enter most cells without toxicity.
6. Large-scale datasets and predictive algorithms
Computational prediction and discovery platforms are one of the narratives we’re the most driven towards at Tachyon. Ever-growing large-scale genomic and imaging datasets comprise a treasure trove of potential therapeutic targets and disease indicators. However, signals within these datasets are often buried in substantial noise, requiring careful data sorting and interpretation.
The applications of machine learning to discovery are wide-reaching: from antimicrobials to monoclonal antibodies, most of the traditional drug discovery methods previously involved a slow process of screening hundreds of compounds found in nature for potential therapeutic benefit.
New computational and statistical approaches are able to leverage large datasets and advanced simulation techniques to simultaneously take into account a myriad of factors and narrow down candidates with high rates of success. 3D protein structure simulation, biomarker discovery, designing small molecules, predicting drug response across different patient segments and image analysis are only a few of many platform applications.
Today, many biotechnology companies have adopted a platform-first approach: developing know-how around data of a particular type in a niche sector and then expanding the potential applications of their findings by aggregating and analyzing the resulting data. We’ve already discussed how Scipher Medicine does this, and two other portfolio companies of ours are also developing powerful platforms.
Peptilogics is tackling the rising prevalence of drug-resistant bacteria (largely engendered by excessive use of antibiotics) through an improved ability to design antimicrobial peptide therapeutics. Their lead product shows potent efficacy against 900+ drug-resistant bacterial strains, both gram-positive and gram-negative, the latter of which is especially significant, as no new antibiotics against gram-negative bacteria have been developed since the 1960s. These discoveries are driven by a platform-based approach that connects and extracts insights from diverse biomedical data and iterates novel peptide molecule designs while taking into consideration factors such as the complexity and cost of manufacture.
Another one of our companies, Totient - acquired by AbSci in 2021 - processes thousands of samples from infectious, autoimmune, and neurological disorders to identify potentially therapeutic monoclonal antibodies and their corresponding antigens. Human blood contains a huge diversity of antibodies and it is not straightforward to identify which subsets are therapeutically valuable. For this reason, antibody therapies have been slow and costly to develop, and Totient’s approach is especially disruptive – enabling faster discovery of mAbs in fields like oncology.
The six macro trends described above present tremendous untapped therapeutic and discovery opportunities across almost every major field of disease. Yet, while we have focussed on progress made in the context of these specific trends, each of these trends faces a multitude of nuanced challenges that must be overcome in order to make the progress required to bring new products and services to market.
This is where our role at Tachyon Ventures fits in as investors in the field. Brilliant teams across industry and academia are pushing the boundaries of these six frontiers every day, and a tremendous amount of resources are required to make their undertakings a success. The potential rewards – economic, but most importantly, in terms of human lives and wellbeing – are equally impressive. We are grateful to have the opportunity to be part of this journey and are very excited about the future of biotechnology.