CRISPR in 5 years’ time: Late-phase trials in major markets, predicts CEO

ERS Genomics was co-founded by French researcher, Emmanuelle Charpentier, to commercialise her genome editing intellectual property.

“Genome editing is essentially where you introduce a cut in DNA, in a cell, and allow the cell to repair itself in one of two ways. Either the cell repairs in a way that makes a mistake – if you want to disrupt the gene and stop it from functioning – or, it repairs after you have added a piece of DNA intended for the cut site,” ​ERS Genomics CEO, Eric Rhodes, explained when we caught up at BIO Europe earlier this month.

The CRISPR/Cas9 patent has been filed broadly around the world and approved in more than 45 countries. On a commercial level, ERS Genomics is licensing the technology to a growing number of firms, including recent deals​ with Thermo Fisher and Oxford Genetics.

“CRISPR/Cas9 is one of four technologies available that enable genome editing, along with meganuclease, zinc finger protein, and transcription activator-like effector nuclease (TALEN),”​ he continued.

However, according to Rhodes, Charpentier’s technology sets itself apart in the genome editing landscape. Biopharma-Reporter (BPR) ​spoke with Rhodes (ER) ​to ask about competitor technologies, what we should expect from the gene and cell therapy landscape, and the risks involved in cutting DNA.

BPR: How does CRISPR/Cas9 set itself apart from the competition?​

ER: ​While meganuclease, zinc finger protein, and TALEN essentially achieve the same result as CRISPR/Cas9, our technology sets itself apart in two significant ways: It is so easy to use and cheap to make. In addition, CRISPR/Cas9 is slightly more effective in some cases.

Other technologies either require a lot of design knowledge, or in the case of TALEN, construction knowledge. You can design a zinc finger that is very precise and cuts at a very high efficiency, but your first few designs might not be quite as precise, not quite as effective, until you repeat the manoeuvre a few times.

TALEN sometimes cuts really well, but has a less effective cut-rate – for reasons not well understood.  Depending on the location, a zinc finger might give you a 25% cut-rate, a TALEN might give you a 30% cut-rate, whereas nine times out of 10, CRISPR/Cas9 will give you a 40% cut-rate or just slightly better than the competition.

While the CRISPR/Cas9 cut-rate difference may not be big enough to make a huge difference, the fact that it is cheap and quick to order, and slightly more effective, means that there is a preference for our technology. 

BPR: CRISPR/Cas9 attracted negative attention earlier this year, following a report​ from the Wellcome Sanger Institute. Can the technology cause DNA damage and increase potential cancer risks?​

ER: ​That risk is known for every one of the genome editing technologies previously mentioned – there is the potential to cause unwanted cuts. It can happen that you unintentionally cut into an essential gene, a gene that usually supresses cancers, for example. If that happens, you essentially ‘take the brakes off’ and cancers can emerge.

The Wellcome Sanger Institute paper wasn’t pointing out anything that we didn’t already know, but what the report did alert us to, was the focus area observed after a cut. Prior to the report, scientists would usually introduce a cut, check the space around the cut to see if any damage had occurred, and also check a few other isolated, similar spots in the DNA to see if cells had been mistakenly targeted.

The report pointed out that the window we were looking at wasn’t nearly large enough. Significant damage was found well away from where we were generally looking. The scientists were right to point that out, it was a well controlled and executed study.

Since the study, some researchers have opened up that window and found that potential risks are not as scary as the paper might have first implied. However, the report still acted as a warning to the wider world.

BPR: What does the current CRISPR landscape look like?​

ER: ​The main users of this technology are in the human healthcare field. Scientists are using it mostly for discovery and validation purposes, but there is a select group looking into the cell and gene therapy potential of it. CRISPR Therapeutics has instigated the first in-human clinical trial in the US.

What is really exciting to me, is that now people who wouldn’t usually think about using genome editing in their studies because it was considered too difficult, or not applicable, are beginning to experiment with the technology. Now, we are seeing applications in environmental remediation, aquaculture, and areas that had not previously been associated with genome editing. Yes, it is having a huge impact on human healthcare markets, but it is also spreading beyond.

BPR: How does ERS Genomics help firms access CRISPR/Cas9 technology?​

ER: ​ERS Genomics has a unique business model in this industry. Whereas most companies are developing therapeutic products, providing services, or selling products, we do not do any of that. Rather, we enable companies in this field, by giving them license to use CRISPR technology commercially.

Essentially, we license the technology to pharma companies for their internal R&D to develop and validate new targets, as well as to develop small molecules and monoclonal antibodies.

We also license the technology to service providers for screening purposes and to test small molecules and monoclonal antibodies in preclinical settings. Diagnostics firms also license the technology.

BPR: Does ERS Genomics also license to academic institutions?​

ER: ​Academics are free to use this technology. In fact, there is no license required for anyone not-for-profit or in academia. That is something that all licensing bodies have agreed.

BPR: Where is CRISPR going? What should we predict for the next five years?​

ER: ​Soon we will be seeing all kinds of CRISPR-based cell and gene therapies. Looking to monogenic diseases, we might be able to cure cystic fibrosis, sickle cell anaemia, or hemoglobinopathies, as a result of a single change in the DNA.

Whether these therapies will be approved in five years’ time might be borderline, but I predict that they would be in late-phase trials, getting ready for approval. 

While of course it depends on the therapeutic application, and whether a disease is specific to a certain region, I imagine we’ll see CRISPR-based therapies being used across China, Japan, the US and Europe.

Prior to accepting the role of CEO at ERS Genomics, Eric Rhodes was SVP of R&D and CTO at Horizon Discovery. At Horizon, Rhodes was responsible for commercialising Horizon’s genome editing technologies. He has also held positions at Sigma-Aldrich and at Sangamo Biosciences.​​