There has been a lot of recent attention on the challenges of delivering COVID-19 vaccines. But there are also challenges in making them. For some of the newer options like those from Johnson & Johnson and Oxford-AstraZeneca, the modified cells used in vaccine production are struggling under the scale of demand. But synthetic biology company AbSci’s recent acquisition of the artificial intelligence platform, Denovium, could help mitigate this type of challenge in the future.
Unlike mRNA vaccines, the Johnson & Johnson/Oxford-AstraZeneca class of vaccines rely on a type of virus called adenovirus which is known to cause colds in chimpanzees. To address COVID-19, the adenovirus is genetically altered to express the SARS-CoV-2 spike protein which is what ultimately triggers the body’s immune response. Like mRNA vaccines, adenovirus-based vaccines train the body to recognize and fight COVID-19, foregoing the need to inject a person with a weakened version of SARS-CoV-2.
But producing enough adenovirus cells has been a challenge. To make vaccine doses, large volumes of altered adenovirus are produced by replicating cells in bioreactors. But, the scale of production can also cause the cells to weaken. This can result in a reduced output of adenovirus copies. So while these new vaccines may represent a breakthrough in adenovirus-based therapeutics, the process also highlights some critical roadblocks.
One major issue is that drug discovery and drug manufacturing are often disconnected from one another. Drug discovery typically starts with screening—the process of finding a set of compounds out of 100,000 combinations that can best neutralize a targeted weak point of a disease. But when a promising protein is identified, it often turns out to be difficult to scale effectively.
Once a therapeutic compound is identified, researchers must then determine if it works well with a group of similar cells called a cell-line. By inserting the compound into the cells—which then divide and multiply in a bioreactor—the cells act like factories to produce greater volumes of the compound of choice. But, as in the case with adenovirus-producing cells, not all cells can maintain their functions at large volumes. If the protein compound doesn’t work well in a scalable cell-line, researchers often have to go back to the drawing board to find a new compound and start again.
Many in the biopharma space are aware of this inefficient process. The synthetic biology company AbSci has spent years developing a platform solution that streamlines the workflow. “[Our platform] is simultaneously a drug discovery and manufacturing platform that allows you to discover your drug and the cell line that can manufacture [it],” says AbSci CEO, Sean McClain. “We’re finally uniting drug discovery and manufacturing the first time.”
AbSci refers to their core process as their Protein Printing platform, not because it uses ink and paper to make proteins but as an analogy for ease and speed. “The first technology [in our platform] is our SoluPro E. coli strain. It has been highly engineered to be more mammalian-like to be able to produce mammalian-like proteins that E. coli wasn’t previously capable of doing,” says McClain. AbSci also uses what the company calls a “folding solution” to precisely tailor how proteins fold and therefore function.
Finding the Right Cells Through AI
To find the most effective protein, AbSci alters its folding solutions to create as many protein varieties as possible, often to the order of 10s of millions. The more protein types available, which AbSci refers to as “libraries,” the higher the likelihood of success. But this also creates a challenge: so many options, but which to choose?
To address this, AbSci recently acquired artificial intelligence company, Denovium. By integrating Denovium’s AI platform, AbSci can improve its data analysis via AI models. From there, the company can take the best candidates and find the most effective cell-line to produce the chosen compounds at scale. McClain explains that traditional drug discovery and manufacturing typically takes years. But AbSci’s platform can take that timeline down to weeks. “We’re actually able to manufacture [therapeutics] because the dirty secret in pharma is that so many drugs get shelved because [pharma companies] can’t actually manufacture them,” says McClain.
For McClain, acquiring Denovium is a big step forward for AbSci’s discovery process. “It’s going to change the paradigm. It’s really a perfect marriage of both data and AI technology. If you don’t have good data feeding into your AI model, it’s worthless. But if you don’t have an AI technology, you can’t mine [the data] and get all the benefits,” says McClain.
Denovium’s co-founder and CBO, Imad Ajjawi, also sees the new collaboration as a significant opportunity. “It’s really exciting to be a part of AbSci because they have all the data, billions of points that the deep learning engine can now analyze,” says Ajjawi. AbSci’s acquisition also comes on the heels of the company’s $65 million Series E in late 2020.
Upgrading the union of biology and AI is important for advancing synthetic biology innovation. But the true potential beneficiaries of this advanced discovery platform are those in need of novel drug options.
Getting Drugs to Patients Faster
AbSci’s main goal as a company is to bring therapeutics to market more quickly. “This technology’s impact on healthcare is profound because more drugs and biologics can now enter patients’ hands faster,” says McClain.
McClain believes that AbSci’s technology will help speed the process of clinically testing new medications. Faster clinical trial turnarounds could increase the number of drugs approved to address a range of diseases. This could be most impactful for patients with rare or difficult to treat conditions as drug discovery is often prioritized based on how long it takes to find a scalable cell-line.
But though AbSci is working to accelerate drug discovery, the process still takes time. “Right now, we have six drugs that are in preclinical or clinical trials. And one of them is actually in phase three. So we could have an improved product here in the next couple of years,” says McClain.
Looking Ahead: Partnerships to Tackle Disease
As Absci and Denovium finalize their technology integrations, McClain is also looking ahead to build as many partnerships as possible. “The more partnerships we do, the more patients we’re able to affect that at the end of the day,” says McClain.
In line with that goal, AbSci today announced a continuation of its partnership with Astellas and Xyphos. AbSci will take on screening and identifying an optimal cell-line for a leading variant of Xyphos’ MicAbody, a bispecific antibody-like adaptor molecule used in the company’s immuno-oncology program.
McClain expects more partnership announcements will follow in the first quarter of 2021. “We have some really exciting partnerships that are going to be coming out over this next quarter that I think speak to the [range] of the types of disease states we’re working on and the breadth of how the technology can be used within biopharma,” says McClain.
I’m the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta conference and weekly digest, including AbSci. Thank you to Fiona Mischel and Vinit Parekh for additional research and reporting in this article.