As a co-founder of Mammoth Biosciences, will you please introduce us to the company and the circumstances that bled to its formation?
Of course. The company was founded five years ago, spun out of Jennifer Doudna‘s lab, who recently won the Nobel prize for her pioneering work in the CRISPR technology. What really catalyzed the creation of Mammoth Biosciences was the idea of pushing the envelope of CRISPR technology and tackling the grand challenges of gene editing. One major question was how we could progress from ex vivo (external to the body) to in vivo (within the body) and find permanent cures for genetic diseases.
The majority of the field at the time, and to a large extent still today, was focused on one version of the CRISPR technology called Cas9 - but this version poses challenges for going in vivo, especially beyond certain tissues like the liver. It is also a physically large protein - think of it as a semi-truck, whereas something the size of a smart car can go more places, easier. What we came up with is an ultra-compact CRISPR system, which allows us to go in vivo for these one-time, permanent cures. Another area was going beyond double-strand breaks - we all have DNA in our cells and any changes to it can lead to genetic diseases. One of the traditional approaches was to cut the DNA and allow it to form new bonds that would eventually cure the disease. Instead, we considered the situation as if it were a Word document, and instead of simply deleting sentences, we would insert new ones, change the spelling, and so on.
It has been exciting to see the growth of the company. We are now a team of 190 people and managed to strike several great partnerships with pharma companies like Bayer and Vertex, working together to bring these technologies to patients.
CRISPR technology has now been around for a decade. Why is this technology so important to the future of the life sciences industry?
What makes CRISPR really exciting is that it allows us to move from treating disease to curing them.
Rather than receiving treatment for the rest of your life you can access this one-time, potentially curative therapy that goes to the root cause of the disease.
It is also a philosophical shift that transforms biology into engineering: we can make changes to our DNA rather than shooting in the dark and hoping that the molecule will affect the gene. If you cure one disease it makes it easier to tackle others, because you have already figured out delivery, dosage, etc., and all you are doing is switching up the guide RNA, a very reproducible and effective method. It simply changes the game of how we do drug development. There are 4,000 genetic diseases that we could target through our work.
What are your next milestones, and how close are you to delivering the technology to patients?
Our timeline is not public yet, but broadly speaking we are excited to drive these systems toward the clinics as fast as possible. We have seen how efficacious these systems can be even in vivo in model systems, a huge milestone not just for us but for our sector — when people first saw these ultra-compact systems, they were skeptical that they would work. We are still proving that they can do what we want them to do, after which we will consider the quickest way to get them to patients.
What has proved most challenging on your journey so far?
When you have a platform technology you are in an interesting spot because you can do so many things, go after any of the 4000 diseases I was mentioning earlier. This means you really need to think about your focus and the hardest thing becomes choosing what to say no to, and what should remain a priority.
The global pandemic has affected all industries; what is a notable mark that has been left of the innovative side of the life sciences sector?
What is interesting about the pandemic is that it highlighted mRNA, another platform technology, and it has been a powerful demonstration of how quickly we can spin up this type of technology. It really showed what is possible and the potential of these new biotech platforms to make an impact, even beyond Covid. These changes are going to reverberate across the industry and give way to new and unexpected therapies.
Innovation in the life sciences space is known to require massive capital. How do you assess the current investment landscape for biotechs?
The biotech markets are dislocated at the moment, but this is also true of other sectors. We try not to be too concerned with macro-cycles; I believe that good companies will always be able to obtain the capital they require, albeit at slightly different costs. These situations come and go; you can't control the macro-cycles, but you can control your execution and prioritize to ensure your company is adequately capitalized.
Looking at the coming 3-5 years, what are the main priorities of your business?
The ultimate goal is to turn the systems into functional technologies that will provide patients with viable solutions. Keeping the balance between innovation and development is a difficult task, but it is ultimately what builds long-term biotech companies. Hopefully, an increasing number of scientists will choose to make the transition from academia to the field of technology, where they can materialize their knowledge into promising projects.
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