The field of genome editing is hot and growing. Despite legal battles over key patents on the CRISPR technology, the important work of genome editing goes on. Even the layperson can understand the potential to change medicine and human health as we know it. There are still hurdles to be overcome, both scientific and practical, from minimizing off-target effects to regulation and safety issues. Insight recently spoke with Jennifer King, Vice President Business Development at Intellia Therapeutics Inc., a genome editing company, about their ambitious mission to develop curative therapeutics using a recently developed biological tool known as the CRISPR/Cas9 system. Founded in 2014, Intellia has gone from founding to IPO in just under two years, and has grown from two employees to 83 in that time.
Insight: What is unique about Intellia’s strategy?
King: The simplest way to think about it is we are using genome editing to fix the broken gene. Our mission is to bring therapies to patients with no other hope. For the first time, we have the opportunity to go to the root cause of the disease and really transform patients’ lives.
Insight: Intellia is developing proprietary therapeutics using the CRISPR/Cas9 system. CRISPR is a revolutionary gene-editing technology. Up to now, there have been challenges in creating gene therapies. In particular, RNA interference attempts to manipulate/inhibit gene function thus far have temporary effects, as well as having off-target effects. How does genome editing differ?
King: In layman terms, CRISPR is essentially a programmable molecular scissors which cuts DNA at a particular site. This is special because it is a genome editing tool that is easy to use, and straightforward to optimize. There are other genome editing tools out there, and man-made proteins designed to cut DNA, but there are key differences between CRISPR/Cas9 and other tools.
First, Zinc fingers and TALENs are man-engineered proteins. They are powerful, but CRISPR has the advantage in that it is a naturally occurring enzyme, found in bacteria, and is thought to be a primordial immune system for bacteria. This naturally occurring system has been honed over millions of years of evolution to be specific and rapid in cutting DNA. This is the advantage. We have been able to harness this activity, optimize CRISPR/Cas9 and use it to cut DNA in a wide variety of ways, and in a wide variety of cell types.
Another advantage over other gene editors is the DNA specificity. The programmable nature of the cut is determined by an RNA molecule, and this RNA can easily be swapped out using CRISPR/Cas9. This allows for efficient identification of the best cut site in a target or gene of interest for your desired outcome. CRISPR/Cas9 is better for industrial use because it is so rapidly optimized.
One more advantage is that CRISPR/Cas9 is a one-protein system. . What this means is that for CRISPR/Cas9 you can multiplex, i.e., you make multiple cuts at the same time using different RNA guides – this is not easily done with other genome editing tools.
Insight: The promise of genome editing, as opposed to gene therapy, is that genome editing has the potential to make permanent, precise changes at the cellular level, repairing the underlying genetic mutation. This attribute may provide a significant competitive edge over gene therapy, more closely mimicking the body’s own repair system while also addressing a broader spectrum of diseases. What does this mean in real life for real people?
King: I think first we have to say that these are early days of genome editing. The paper was published in 2012 (Jinek et al Science v:337;i:6096;p:816-21); we have had just four years to develop these products. There has been an unprecedented amount of work in the field of genome editing, but there is much more work to be done. The vision and promise is that of potentially curative therapies for patients with genetic diseases. That is what Intellia is working toward.
Insight: CRISPR/Cas9 technology has the potential to treat a broad range of disease but it is expensive and time consuming. How will you overcome these obstacles?
King: I think one of the key points is we are in the very early days and Intellia is advancing therapies that will bring value to patients.. I do believe as we think about developing products, what we are calling sentinel indications, these are indications that can teach us about what the platform can do and what the problems are.
We have to think in terms of the intersection of the edit type, whether you are knocking out or knocking down, whether you are repairing a certain indication or replacing expression. And you must consider delivery technology; your genome editor is only as good as where you can deliver it. As we think about these sentinel indications, we are thinking about ex-vivo, and looking to edit CAR T-cells and have collaborated with Novartis to developed eXtellia, a new division of Intellia that focuses on ex-vivo application of CRISPR/Cas9 largely in immunology, autoimmune and inflammatory diseases focus.
That’s the ex-vivo space. On the in-vivo side, we are looking to administer CRISPR/Cas9 to patients systemically, and we are looking at the liver, primarily since Intellia has access to a proprietary delivery system, lipid nanoparticles or LNPs. As well, we have a partnership with Regeneron largely focused on the liver.
Insight: Intellia went public in May, 2016, closing at USD $112.9 million. No doubt this gave you a huge leap forward in capital and put Intellia on the biopharma radar, so to speak. What types of partnerships are you looking for now to further your technology?
King: We’re really focused on partnerships that meet three main criteria: First, we seek partners that are industry leaders that share our vision to bring potentially curative therapies to patients who need them. We are also looking for partners who are open to a focused deal structure that gives us flexibility. And, we’re looking for partners who are willing to collaborate to expand the genome editing field and level of expertise, to bring technology to the fore to further genome editing capabilities. We are actively seeking partnerships for new delivery options for the eye, muscle and CNS, for example. Our focus is in bringing forward innovative products to patients, the ultimate in precision medicine.
Insight: At the end of the day, why do you do what you do?
King: I’ve been in the rare disease space over 10 years, and I have met many patients and families over that time. Families grappling with devastating rare disease. These diseases impact not just patients but whole families. I have been moved by their bravery. In the past, we could only offer these patients limited hope or palliative care. Really, for the first time, we can make a true difference in these patients’ and families’ lives.
I am really cautious about the idea of a cure, but I am really excited about the potential impact CRISPR/Cas9 can make for these families. It will take time, good science and flexibility in the healthcare system, but for the first time I think it will be possible to do what we are setting out to do, to bring cures or transformative therapies to patients.
Insight: Why Is Intellia attending BioPharm America™ in September?
King: I really value EBD Group partnering events and the BioPharm America conference. I have actively participated in the BIO-Europe® and BIO-Europe Spring® conferences, as well. BioPharm America brings industry leaders and dealmakers together to be able to initiate and further partnering conversations. Participating in these events is key to our BD strategy. The panels are directly related to the topics of the day, as well. Our Chief Scientific Officer, Thomas Barnes, will be attending, as well as my colleague John Grant, Director of Business Development, who will provide an introduction to Intellia at BioPharm America.
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