Editas: End Of Year Data Readouts For SCD & Rare Eye Disease Studies

Editas Medicine (NASDAQ:EDIT) is a speculative biotech that should be on your radar. That’s because it has achieved a few positive events as it relates to the use of EDIT-301, which is being developed for the treatment of patients with sickle cell disease (SCD). It achieved successful engraftment of the first patient dosed with EDIT-301 and it had the partial clinical hold for EDIT-301 in the RUBY study removed. Not only that, but it intends to provide a data readout from the RUBY trial before the end of 2022. I believe this could act as a great catalyst for the stock and its investors if successful. In addition, it also hopes to use EDIT-301 for the treatment of patients with transfusion dependent thalassemia. Having said that, it remains on track to dose the 1st TDT patient in 2022 any day now. I want to state that as it relates to EDIT-301 for SCD, the first dosing is a huge milestone because it is a first time that Editas’ AsCas12a enzyme is being used to edit human cells. If data from the RUBY study before the end of this year establishes proof of concept with clinical success, then it could also possibly mean success for the use of EDIT-301 in TDT as well. Another catalyst for investors would be a trial update from the in vivo gene editing pipeline using EDIT-101 in the BRILLIANCE study to treat patients with Leber Congenital Amaurosis 10 (LCA10). Clinical results from this study are expected in the 2nd half of 2022. With two data readouts before the end of 2022, plus advancements of in vivo and ex vivo gene editing pipeline being expanded with INDs, these are the reasons why I believe it is a great speculative biotech play to look into.

EDIT-301 For Treatment Of Patients With Sickle Cell Disease

The use of EDIT-301 is being developed for the treatment of patients with sickle cell disease (SCD). SCD occurs when red blood cells become misshapen and then start to breakdown. In other words, they turn into a sickle shape where they die early. In turn, these leaves a shortage of the necessary red blood cells to have oxygen-rich blood. Without this oxygen damage occurs to nerves and organs which can ultimately end up being fata. Another consequence of this disease is blocking blood flow. This happens when the sickled cells become entangled in small blood vessels blocking such blood flow and causing the patient pain, also known as vaso-occlusive crisis (VOC). Several treatment options for SCD include taking medication, going through multiple blood transfusions and if possible a bone-marrow transplant. The global sickle cell disease market is expected to reach $6.4 billion by 2027. This is a large market opportunity and the hope is that gene editing using EDIT-301 can achieve this function.

How exactly will EDIT-301 be able to actually help patients with SCD? For starters, it’s important to mention that the pipeline uses two methods for CRISPR technology, which are CRISPR/Cas9 and CRISPR/AsCas12a. CRISPR/Cas9 is what’s being used mainly at the moment, but Cas12a if produced correctly is better in every way. But getting back to CRISPR technology itself there are two molecules necessary for Editas to use CRISPR gene editing successfully. These are the nuclease (Cas9 or AsCas12a) and then guide RNAs. The nuclease is the protein that does the editing and the guide RNA shows exactly where a cut/editing must be made. Why the advancement to AsCas12a nuclease (to be used for DNA editing)? That’s because it provides a far more enhanced approach compared to Cas9. Engineered AsCas12a gives the research team more options on where it can actually edit DNA and not only that but it gives the option for a shorter guide RNA as well. In addition, for the ability to achieve staggered DNA edits to reduce unwanted effects. Shorter guide RNAs also reduce off target adverse effects and could provide greater specificity. These enhancements may be important and as such why I described the milestone of Editas being able to achieve successful engraftment of the first patient using EDIT-301 for SCD being a good thing. It is the first CRISPR/Cas12a to be used for gene editing in humans. The intention is for EDIT-301 to edit beta-globin locus, which in turn would increase fetal hemoglobin for these SCD patients. Why are higher levels of fetal hemoglobin (HbF) necessary to help these patients? That’s because higher levels of HbF inhibits HbS polymerization, which in turn reduces the sickling (mis-shaped red blood cells) occurring in the patient body. If done successfully, this would improve oxygen levels and reduce VOC at the same time.

The use of EDIT-301 is being explored in a phase 1/2 single-arm open-label study (known as “RUBY”) as an autologous hematopoietic stem cell transplant (HSCT) in patients with severe SCD. The trial intends to enroll up to a total of 40 patients who will are between the ages of 18 to 50. There were two great achievements with respect to EDIT-301 for the treatment of patients with SCD, both of which were announced in July of 2022. The first achievement was that the partial clinical hold for EDIT-301 of the RUBY study was lifted. The second achievement was what I briefly highlighted above, in that successful engraftment of the first patient was achieved. That is, following the transplant treatment, the cells made it to the bone marrow. This is a necessary first step in order for the treatment to be successful. The goal now is to see if fetal hemoglobin (HbF) can be restored as noted above. This is where a major catalyst comes into play. Results from the phase 1/2 RUBY study are expected to be released by the end of 2022. Again, this needs to be watched closely because it will be important to see if CRISPR/AsCas12a is successful as a gene editing tool. One that provides greater specificity in removing unwanted side effects and also being a proper form of long-term treatment for these SCD patients.

EDIT-301 For Treatment Of Patients With Transfusion Dependent Beta Thalassemia

EDIT-301 is also being used to treat patients with transfusion dependent beta thalassemia (TDT). What occurs with this disease is that the production of hemoglobin is greatly reduced, which in turn can cause anemia. For patients to overcome this, they must undergo several blood transfusions. The problem with having to keep up blood transfusions is the possibility to get iron overload. If iron overload is left untreated, then it can lead to organs being impaired and even death. There needs to be a more prominent treatment option for these patients. This is where EDIT-301 comes into play in that once again increasing fetal hemoglobin (HbF) can provide a one-time long-term sustainable treatment option for these patient with TDT. A catalyst that investors should be looking forward to would be the dosing of the first patient in the phase 1/2 stud which is expected any day now in 2022.

Financials

According to the 10-Q SEC Filing, Editas Medicine had $527.6 million in cash as of June 30, 2022. It should be good on cash for now and that’s because it believes that it has enough to fund its operations into 2024. It has basically obtained additional cash over the years by selling shares of its common stock at performing at-the-market offerings. If it does need cash in the coming months then it’s possible it could choose to utilize an ATM Facility with Cowen, which was entered into back in May of 2021. To date as of June 30, 2022 it has not sold ay common stock under this ATM Facility. However, if it does need this option if it can’t obtain funding by other means, then it won’t hesitate to do so. Where I think it could raise additional cash is if announces positive results from a few studies in the 2nd half of 2022. Either with the phase 1/2 BRILLIANCE study using EDIT-101 for the treatment of patients with Leber Congenital Amaurosis 10 (LCA10) or from the phase 1/2 RUBY study using EDIT-301 for the treatment of patients with SCD. Results from both of these studies are expected before the end of this year. If they turn out to be successful, then I expect the stock price to rise significantly. In turn, I believe that management won’t hesitate to raise cash by taking advantage of such a gain. Again, this will only be the case with data being very good.

Risks To Business

There are several risk factors that investors should be aware of. The first risk pertains to the use of EDIT-301 itself. This is using AsCas12a for the very first time in humans, as such proof of concept has not yet been established. What has been established thus far is that engraftment was successful (in that edited cells made root into the bone marrow). What needs to be seen next is that these cells are active in increasing fetal Hemoglobin (HbF) in SCD patients. One other possible risk is safety concern. The reason why I state this is because even though the partial clinical hold has been lifted, doesn’t necessarily remove the possibility of another safety issue arising in late-stage development. A Second risk to consider would be the use of EDIT-301 for TDT, in that it proof of concept fails in SCD using AsCas12a nuclease for gene editing, then it wouldn’t be good news for this particular program either. The final risk to consider would be the other data readout which is expected in the 2nd half of 2022. This involves the use of EDIT-101, which is being developed to treat patients with Leber Congenital Amaurosis 10 (LCA10) from the phase 1/2 BRILLINACE study. This makes use of the in vivo gene editing EDIT-101 CRISPR/Cas9 nuclease editor in the pipeline. It is a good thing that there is use of both a Cas9 and AsCas1a nuclease in the pipeline. It is possible that one nuclease may perform better than the other. It also provides an additional option in case one CRISPR editing technology doesn’t pan out.

Conclusion

I believe that Editas Medicine is a great speculative biotech play to look into. That’s because as I noted above, there are two data readouts expected before the end of 2022. In addition, you get a chance to see a glimpse of both CRISPR types of technologies being deployed. One set of results will be with CRISPR/Cas9 EDIT-101 for the treatment of patients with LCA10 and then the other using CRISPR/AsCas12a EDIT-301 for the treatment of patients with SCD. I think it will be important to see if AsCas12a performs in a superior fashion compared to Cas9. That’s because AsCas12a can be used for much more target indications (Due to the ability to cut in more areas compared to Cas9), use of a shorter RNA guide strand to reduce off-target effects and many other improvements. It’s quite possible that EDIT-101 can perform well with the Cas9 nuclease, but ultimately I believe it will be that AsCas12a nuclease should end up being superior. Lastly, it is even advancing the use of the AsCas12a nuclease, it is employing gene editing to a new approach it developed known as SLEEK. SLEEK stands for SeLection by Essential-gene Exon Knock-in. The goal is to advance cell therapy for its oncology programs. SLEEK enable the ability for multi-transgene knock in over several cells such as: T-cells, natural killer (NK) cells and induced pluripotent stem cells (iPSCs). I think the main thing to note here is that AsCas12a was deployed in SLEEK. Which makes sense, because AsCas2a nuclease provides greater efficiency for gene editing with reduced off-target effects. With two trial readouts expected in the 2nd half of 2022, plus the patents established with both Cas9a and Cas12a CRISPR gene editing technologies, these are the reasons why I believe that Editas Medicine is a great speculative biotech play to look into.