Trevor, we last spoke about a year ago. How would you assess the past year’s significance for Mammoth Biosciences?
Over the last year, Mammoth Biosciences has maintained a strong focus on developing differentiated therapeutics, particularly in addressing the high unmet patient need that exists due to genetic disease. More specifically, our efforts have been concentrated on discovering and developing novel CRISPR systems and technologies that are able to cure such diseases. This shift towards curative genetic medicine is a transformative approach in healthcare, and Mammoth is excited to be at the forefront of this change. We believe that our platform's ability to translate into solutions for unmet patient needs is a crucial step forward in the field.
With the shift from pandemic-related testing technology to therapeutics, is Mammoth now entirely focused on therapeutics?
The incredible thing about CRISPR is the truly immense potential of this technology and the breadth of its applications. We have always been committed to exploring various applications of CRISPR technologies. While we continue to see potential across various fields, our primary focus is indeed on therapeutics. This aligns with our overarching goal to leverage CRISPR to address significant unmet medical needs, and, ultimately, make a considerable positive impact to patients.
What are the main promises and achievements of Mammoth Biosciences in gene editing therapeutics?
We at Mammoth see the potential to address a wide range of genetic diseases, especially rare monogenic disorders. Our focus is on developing CRISPR-based therapies that can be administered in vivo and across different tissues, which is challenging yet critical for treating most genetic diseases.
We believe that our portfolio of ultra-compact CRISPR systems are well-positioned to unlock the potential of in vivo delivery, and thereby enable us to go after various genetic diseases that could greatly benefit from our technology.
Can you elucidate on the difference between ex vivo and in vivo approaches in CRISPR technology?
The distinction between these approaches in CRISPR technology is significant. Ex vivo involves editing cells outside the body, like treating blood-based disorders through a process of removing the cells and then putting them back in the patient after editing. This method is limited to certain diseases and is often more technically accessible than in vivo treatments. In contrast, in vivo approaches involve delivering CRISPR technology directly into the body to target specific cells causing the disease. This method is essential for the majority of genetic diseases, as it is not feasible to remove and treat cells, such as those from the brain, outside the body. At Mammoth, we are pioneering in vivo CRISPR applications, focusing on developing CRISPR systems that can safely and effectively reach target cells.
Does Mammoth Biosciences have a specific focus on the type of diseases it targets?
We are primarily focused on in vivo applications of CRISPR technology, differentiating us from many others in the field. Within this domain, we are exploring therapies for various tissues, including the liver, CNS, and muscle. While we have not yet publicly disclosed specific diseases, our internal research is heavily geared towards addressing specific conditions. Our approach is centered on leveraging our advancements in CRISPR technology to access tissues effectively, allowing us to explore a wide range of potential therapeutic applications.
In CRISPR gene editing, is it necessary to edit every cell?
Editing every cell is actually not a requirement for many diseases. The goal is to modify a sufficient number of cells to achieve the desired therapeutic effect, which varies with each disease. For some conditions, editing a smaller percentage of cells may be adequate, while others might require a higher percentage. This variability informs our approach to targeting diseases, where you can even prioritize those where a lower percentage of cell editing can yield significant therapeutic benefits if needed. The feasibility of editing 100% of cells would make some diseases more challenging to tackle than others.
Is Mammoth Biosciences the only company working on in vivo CRISPR applications?
While we are not the only ones working on in vivo CRISPR applications, Mammoth has pioneered the development of new CRISPR technologies that go beyond Cas9 and uniquely enable the development of in vivo therapies. These innovations are a critical part of our founding story and highlight our willingness to push the envelope scientifically to meet unmet patient needs. Our ultra-compact systems allow us to overcome the limitations of larger CRISPR systems, facilitating more efficient and targeted delivery to various tissues. Our platform – discovering, developing, and engineering novel CRISPR systems to cure genetic disease – makes us an incredibly unique player in the CRISPR field, especially when it comes to addressing complex challenges associated with in vivo gene editing.
How has the post-pandemic slump in biotech investment affected your company and the industry?
The post-pandemic investment climate has certainly shifted, affecting not just biotech but the broader economy and startup ecosystem. At Mammoth, we believe that good companies can weather – and even thrive in – any macroeconomic condition. These fluctuations in climate often bring a sharper focus on the value of every dollar, instilling a mindset of how to maximize impact with available resources – which is a beneficial mindset for any startup to have regardless. Despite the current investment landscape, there remains significant excitement and funding opportunities for groundbreaking biotech innovations. Advances in CRISPR technology, for instance, continue to attract substantial interest, indicating a robust appetite for investing in transformative biotech breakthroughs that have the potential to bring a lot of benefit to patients.
How does the biotech sector perceive the Inflation Reduction Act?
The Inflation Reduction Act is a topic of considerable discussion in the biotech industry, particularly as companies move towards commercialization. At Mammoth Biosciences, we have not observed a direct impact from the Act. However, it does raise questions about how it might influence investment behaviors and the types of drugs researched. In the realm of CRISPR technology, there continues to be more excitement than ever .
Does Mammoth Biosciences utilize AI in its research and development?
Machine learning has become integral to our research over the past decade – since even prior to Mammoth’s inception, when our founders were researching CRISPR at UC Berkeley. Our approach involves analyzing vast metagenomic databases containing billions of potential proteins from diverse sources like soil samples and microbes. Machine learning helps us distinguish the most promising CRISPR technologies within these massive datasets. The real challenge lies in identifying these novel systems and then conducting high-throughput experiments to further develop and engineer them.
Why was the company named Mammoth Biosciences?
Mammoth Biosciences was named that for several reasons. One was to embody the concept of the 'elephant in the room', signifying something that is impossible to ignore. We wanted to be that kind of influential and prominent company. The name 'Mammoth' also reflects a sense of humor, given our work on ultra-small CRISPR systems, contrasting with the large size of mammoths. Additionally, the name hints at the wonder associated with CRISPR's potential. The name is memorable and evokes a sense of nostalgia and fascination, aligning with our innovative spirit.
