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Editas Medicine, Inc. (NASDAQ:EDIT) is gearing up for several inflection points in 2024, and I believe that if positive outcomes are achieved for all of them, then that would mean an increase in value for the company and its shareholders. In particular, there are two lead programs that are being advanced with reni-cel for the treatment of patients with sickle-cell disease [SCD] and transfusion dependent thalassemia (TDT). Data readouts for each of these programs are expected in mid-2024 and at the end of 2024, respectively.
This creates several catalysts for investors to look forward to during this year. I don’t believe, though, that this is the only thing to focus on with respect to this biotech. I think a critical turning point is what has become of the phase 1/2 RUBY trial, which is that the FDA will allow it to be used as a pivotal study to support a Biologics Licensing Application [BLA] filing of reni-cel for severe Sickle-Cell Disease (SCD). There is a lot of competition already in place in the SCD and TDT space, with several other approvals already achieved or in the process. However, this biotech is pressing on the idea that reni-cel can be a differentiated treatment option due to a few key factors.
Even then, it might be in good shape, because of another aspect of the pipeline dealing with in-vivo gene editing. Speaking of which, this creates another catalyst opportunity. It is expected that Editas will release in vivo preclinical proof-of-concept data for an undisclosed target by the end of 2024. Besides that, even if you take away the ex-vivo and in-vivo in-house programs, it has been able to establish several partnerships with other pharmaceutical companies. The first two of these are with Bristol-Myers Squibb (BMY) and Immatics (IMTX).
Lastly, in December Editas entered into a license agreement with Vertex Pharmaceuticals (VRTX) providing it with a non-exclusive license to use the Cas9 gene editing technology for ex vivo gene editing targeting the BCL11A gene for the treatment of patients with SCD and beta thalassemia (TDT).
Reni-Cel For The Treatment of Patients With Severe Sickle-Cell Disease
I believe that the most important program for Editas Medicine would be its advancement of reni-cel for the treatment of patients with severe Sickle-Cell Disease (SCD). Why do I believe this to be the most important program as part of its pipeline? That’s because, as I noted directly above, the FDA is allowing the ongoing phase 1/2 RUBY study to be turned into a pivotal one. That is, it will allow a Biologics Licensing Application [BLA] filing of reni-cel for the treatment of patients with severe SCD on the basis of this trial alone. In my opinion, this is very good news, because it would mean a quicker pathway for U.S. marketing approval for this indication.
Sickle-Cell Disease ((SCD)) is a type of disorder characterized by broken down and sickle-shaped red blood cells (RBCs). There are two major problems to consider with this blood disorder specifically. The first is that there is a shortage of healthy RBCs flowing in the body. The second aspect to consider is that the blood cells that become sickle-shaped can cause a block in the flow of blood, which leads to sickle cell crisis or vaso-occlusive crisis. Some symptoms that these patients experience are as follows:
- Jaundice [yellowing] of the skin
- Extreme tiredness
- Stroke
- Severe type of fever being present
- Anemia [inability to have enough healthy red blood cells for oxygen].
The global Sickle-Cell Disease treatment market size is expected to be worth $7.79 billion by 2032. This is a big market opportunity, and success here could be a very good thing. However, as I will describe below, there are a lot of competitors in place which may hinder how well reni-cel ultimately does on the market, even if given regulatory approval.
The use of reni-cel for the treatment of patients with severe Sickle-Cell Disease (SCD) is being explored in the phase 1/2 RUBY study. A Total of 45 patients are going to be given a one-time intravenous infusion of autologous gene edited CD34+ hematopoietic stem cells to treat their disease.
One thing to note is that before patients can be treated with reni-cel they have to be given myeloablative conditioning with busulfan. What is this conditioning agent and why is it important? It eradicates the broken-down red blood cells, provides immunosuppression and prepares for Hematopoietic stem cell transplantation for the patient.
The primary endpoint of this trial is going to look at what I described above, which is the proportion of patients achieving complete resolution of severe vaso-occlusive events (VOE) over a two-year period. One thing to note is that the focus first is to specifically treat adults only and then move on to recruiting adolescents. Speaking of which, in 2024 it was able to initiate the cohort with the sole focus being to recruit such adolescent severe SCD patients.
I believe that there is a good chance for investors to benefit here with respect to the advancement of Editas’ ex-vivo gene editing technology. How so? That’s because it is gearing up for several value-generating inflection points during 2024. For starters, it is expected to report updated results from the phase 1/2 RUBY study using reni-cel for the treatment of patients with SCD in mid-2024 and end of 2024, respectively. Should the updated data provided at both time points be good, then this will translate for the ability of the company to file a Biologics Licensing Application (BLA) to the FDA of reni-cel for the treatment of this specific patient population.
Reni-cel For The Treatment Of Patients with Transfusion Dependent Thalassemia
The other program being advanced in the pipeline would be the use of reni-cel for the treatment of patients with transfusion dependent thalassemia [TDT]. The use of this ex-vivo gene editing medicine is being advanced in the phase 1/2 EdiTHAL study. This provides another shot on goal for reni-cel and could be another program to possibly generate value for shareholders.
TDT is a genetic red blood cell disorder, whereby patients must receive life-long red blood cell transfusions to restore hemoglobin. Without such hemoglobin being present in the body, organs lack oxygen necessary to survive. The global thalassemia treatment market is expected to reach $1.5 billion by end of 2031. The phase 1/2 EdiTHAL trial is expected to enroll up to a total of 9 patients who are to be given a one-time intravenous infusion of reni-cel for TDT.
Once again, it is important to note that the population being sought out would be adults only. In this case, to recruit patients who are specifically age 18 to 35 years of age. Like the other trial design above, it is going to only dose patients with this treatment after having gone through myeloablative conditioning with busulfan. The primary endpoint of this study is to look at the number of patients who achieve a successful engraftment, which will be defined as neutrophil engraftment. This will be considered a success if absolute neutrophil count (ANC) is ≥ 0.5 x 10^9/L post reni-cel.
The bad news for TDT patients is that they require life-long blood transfusions to increase hemoglobin. However, a treatment like reni-cel can help here, because it was shown that all EdiTHAL patients [6 of them] had achieved early and robust increase in total hemoglobin, above the transfusion independence threshold level of 9 g/dl. Why is this important? That’s because a treatment that can achieve this means no need for constant red blood cell transfusions being necessary. This is another program, which has a few catalysts for investors to look forward to. Additional results from the phase 1/2 EdiTHAL study, using reni-cel for the treatment of patients with TDT, are expected in mid-2024 and end of 2024 respectively.
Financials
According to the 8-K SEC Filing, Editas Medicine had cash, cash equivalents and marketable securities of $427.1 million as of December 31st of 2023. The current cash position of this company is going to be helped with respect to the license agreement that it had made with Vertex Pharmaceuticals. This was a non-exclusive license agreement developed, where Vertex would be able to use Editas’ Cas9 editing technology for ex vivo use targeting the BCL11A gene for the treatment of patients with SCD and TDT. This also includes CASGEVY as well.
That’s because Editas owns exclusive license rights to certain CRISPR patent estates for development of human medicines. For example, it holds patent rights for Cas9 owned by Harvard University, Broad Institute, the Massachusetts Institute of Technology and the Rockefeller University. This is a win for Editas for two reasons. One reason is that it allows for the advancement of ex-vivo Cas9 CRISPR technology for both SCD and TDT. Secondly, it extends it cash runway significantly. Matter of fact, with this deal generated with Vertex, Editas believes that it would have enough cash to fund its operations into 2026.
Risks To Business
There are several risks that investors should be aware of before investing in Editas Medicine. The first risk to consider would be with respect to the advancement of reni-cel for the treatment of patients with severe Sickle-Cell Disease (SCD) in the ongoing phase 1/2 RUBY study. It has been shown thus far that all 10 patients who had received one intravenous infusion of reni-cel were able to be vaso-occlusive free since then for many months. There is no assurance that additional data to be released from this trial will continue to show this very same trend. If that happens, then this could end up being a major problem for the biotech and its ability to compete in the SCD and TDT space.
A second risk to consider would be with respect to the use of reni-cel for the treatment of patients with TDT, which is being explored in the phase 1/2 EdiTHAL study. Additional data from this study is going to be released at two time points in 2024 and there is no assurance that it will end up being positive. Nor that, the market will end up viewing this data favorably compared to other biotechs who have already received regulatory approval for TDT or in clinical development for it.
A third risk to consider for the reni-cel program would be competition in the Sickle-Cell Disease and Transfusion dependent thalassemia (TDT) space. That’s because several other companies have received regulatory approval. For example, Vertex and CRISPR Therapeutics (CRSP) have already received FDA approval of Casgevy for the treatment of patients with SCD and TDT. Matter of fact, FDA approval of Casgevy for the treatment of patients with TDT was achieved two months before the projected regulatory approval date.
This is only one competitor that Editas Medicine will have to deal with. The other one would be bluebird Bio (BLUE), which also received FDA approval of its gene therapy Lyfgenia for the treatment of patients with Sickle-Cell Disease (SCD)).
How can Editas Medicine do well in light of all this competition? For starters, I think it may have a shot at doing so because of all the Cas9 CRISPR patents it holds. However, there is something else to consider, which may ultimately provide it with a competitive edge. That is, reni-cel deploys an entirely different type of ex-vivo CRISPR technology which deploys Cas12a. This can possibly help fend off competition and it is because of flexibility.
There is more flexibility of where and how to edit DNA. Consider that AsCas12a CRISPR is highly differentiated with greater specificity and efficiency. It is believed that this differentiation will be enough to help it overcome competition in this space. With respect to the treatment of patients with SCD, reni-cel could provide superior VOC efficacy, but this remains to be seen depending upon data this year. In terms of treating patients with TDT, the advantage here is that Editas’ AsCas12 CRISPR was able to achieve robust total Hemoglobin levels for 8 months above the transfusion independence threshold of total Hb 9 g/dL. It is believed that robust total hemoglobin may provide a competitive advantage, but this remains to be seen if and when marketing approval of reni-cel for TDT is achieved.
The fourth and final risk to consider would be with respect to the partnership I noted above in the financials about Vertex Pharmaceuticals. That’s because even though there is potential to advance an ex-vivo gene editing Cas9 CRISPR targeting the BCL11A gene for the treatment of patients with SCD and TDT, there is no assurance that this will end up being better than currently approved marketed treatments.
Conclusion
Editas Medicine, Inc. is gearing up for a lot of data releases in 2024, which is why I believed it was important to note its prospects. Between the advancement of reni-cel for the treatment of patients with severe Sickle-Cell Disease [SCD] and transfusion dependent thalassemia (TDT), there are roughly four data readouts here alone. That’s not even including the positive development gained from the FDA, in that the phase 1/2/3 RUBY study is allowed to be a pivotal one, which would allow for the Biologics Licensing Application [BLA] of reni-cel for the treatment of patients with SCD.
Even if you take out reni-cel for SCD and TDT, long-term the biotech might be okay if it can advance its preclinical treatments towards human clinical testing. How so? Well, for instance it is also advancing an in-vivo CRISPR candidate.
Thus, this brings about another possible catalyst for investors to keep an eye on. By the end of 2024, it is expected that the company will release in vivo preclinical proof-of-concept for an undisclosed indication. To be clear, the initial focus here will be to initially focus on hematopoietic stem cell transplantation [HSCT[ for this program. Besides these pipeline advancements, it has also already established partnerships with Immatics and Bristol-Myers Squibb. That is, to modify allogeneic Gamma T-cells from Immatics with CRISPR gene editing to improve clinical outcomes for the treatment of patients with cancer. In terms of the Bristol-Myers Squibb deal, it is to advance Alph-Beta T-cells genetically modified for the treatment of patients with cancer.
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