2023-07-26 19:53:59 ET
Summary
- FDA review date of CRISPR Therapeutics AG exa-cel for the treatment of patients with severe sickle-cell disease has been set for December 8, 2023.
- FDA review date of exa-cel for the treatment of patients with transfusion-dependent beta thalassemia had been set for March 30, 2024.
- Analyst at Cantor estimates that exa-cel could generate risk-adjected 2023 peak sales of $1.6 billion.
- Eventual patient population of exa-cel could be expanded upon with the advancement of an anti-CD117 [c-Kit] antibody-drug conjugate [ADC] as a conditioning agent.
CRISPR Therapeutics AG ( CRSP ) had made great progress in advancing a therapy known as exa-cel [exagamglogene autotemcel, formerly known as CTX001. That's because it, along with its partner Vertex Pharmaceuticals ( VRTX ) had the Biologics Licensing Applications [BLAs] to the FDA of exa-cel in the United states for the treatment of patients with transfusion-dependent beta thalassemia [TDT] and severe sickle cell disease [SCD] accepted by the FDA. Not only that but, regulatory applications of exa-cel for both of these indications were also accepted by the European Union and the United Kingdom as well. Why I believe that investors can capitalize on such approvals is because it would be CRISPR's first regulatory approved product as it moves towards commercialization. Not only that, but what's even better is that both approvals are not expected to happen at the same time.
That is, the FDA granted exa-cel for the treatment of patients with severe SCD with Priority Review and set a PDUFA date of December 8, 2023. However, on the other hand, the regulatory review of exa-cel for the treatment of patients with transfusion-dependent beta thalassemia won't be done until March 30, 2024. With these two separate catalysts in place, I believe that investors might be able to benefit from one or both of them. Even though only in pre-clinical testing, there is a goal to expand upon the potential patient population that can be treated with exa-cel with the advancement of its very own pre-conditioning agent. Thus, it is possible that the possible market to be targeted with exa-cel could be expanded upon.
Priority Review Exa-Cel For Severe Sickle Cell Disease Is First On Deck
The first catalyst for CRISPR Therapeutics would be the FDA review of exa-cel for the treatment of patients with severe Sickle Cell Disease. Not only was the application submission of exa-cel accepted, but the FDA did so with a Priority Review date of December 8, 2023. Sickle Cell Disease [SCD] is a group of inherited red blood cell disorders, where red blood cells become c-shaped in the form of "sickles". Thus, the name Sickle Cell Disease. A big thing about this disorder is that cells die early, thus leaving a shortage of healthy red blood cells which are needed to carry oxygen throughout the entire body. They also are responsible for transporting waste such as carbon dioxide back to the lungs to be exhaled.
Several symptoms of SCD are as follows:
- Infections
- Pain
- Fatigue
With respect to pain, these SCD patients can experience something known as vaso-occlusive crisis. A vaso-occlusive crisis occurs when the microcirculation is obstructed by sickled red blood cells, leading the patient to then experience pain.
The second catalyst would be the review of exa-cel for the treatment of patients with transfusion-dependent beta thalassemia [TDT]. The thing to note about this review is that it is being reviewed by the FDA as a standard review. Thus, the FDA has given this indication a review date of March 30, 2024.
Beta thalassemia is a blood disorder whereby there is a reduction in the production of hemoglobin. Hemoglobin is very important, because it is the iron-containing protein found in red blood cells that carries oxygen to cells throughout the body. The thing is that exa-cel is targeting patients with transfusion dependent thalassemia [TDT], thus the most severe form of this disorder. It is because these patients require lifelong regular blood cell transfusions in order to survive. Without them, they can potentially have damaged organs and even die from it. Anemia is a major problem that these patients experience, which leads to some symptoms such as: Weakness, shortness of breath, and feeling tired.
An analyst at Cantor estimates that exa-cel could generate risk-adjected 2023 peak sales of $1.6 billion . In addition to the U.S. approvals of exa-cel for SCD and TDT being catalysts, there are others as well. That is, completed regulatory submission of exa-cel were also accepted by both the European Medicines Agency [EMA] and the Medicines and Healthcare products Regulatory Agency [MHRA] in the EU and United Kingdom. Thus, the review process having been started for both of these territories.
Exa-cel continues to show substantial efficacy for both of these TDT and SCD patients. With respect to TDT patients, 27 of them were evaluable for the primary analysis endpoint, which was transfusion-independence for at least 12 consecutive months. It was shown that 24 out of 27 patients [88.9%] achieved this primary endpoint when given exa-cel treatment. With respect to SCD patients, 17 of them were evaluable for the primary analysis endpoint. It was shown that 16 out of 17 [94.1%] had achieved the primary endpoint of "freedom from vaso-occlusive crisis [VOCS] for at least 12 consecutive months.
With this data on hand, there is a pretty good chance at CRISPR receiving regulatory approvals for the intended territories. However, there is also potential for it to possibly be able to expand upon the population that can be targeted with exa-cel. That's because CRISPR Therapeutics is advancing its own anti-CD117 [c-Kit] antibody-drug conjugate [ADC].
What's the purpose of this? This is its internal targeted conditioning program, which is being advanced in preclinical studies. Should this conditioning agent advance through multiple studies, then it could become a tool that it could use to target additional patients for exa-cel.
Financials
According to the 10-Q SEC Filing CRISPR Therapeutics had cash, cash equivalents and marketable securities of $1.889.5 million as of March 31, 2023. One thing to note is that it was able to earn total collaboration revenue of $100 million for this reported Q1 2023 financial results. This revenue was recognized in connection with an upfront payment that it had received from Vertex.
It has a lot of cash on hand and I don't foresee a major risk of dilution in the near-term. The reason why I state that is because it expects that its existing cash will be enough to fund its operations for at least the next 24 months. This doesn't include the ability to raise additional proceeds from either capital raising transactions that it might do or that it may receive under its collaboration agreement with Vertex.
Not only that, but if it does need to raise additional cash, then it can do so under a prior agreement it had made. This was an August 2019 Sales Agreement it entered into with Jefferies, with a prospectus supplement of $419.8 million in July of 2021. As of March 31, 2023 it issued and sold an aggregate of 1.1 million common shares under this prospectus supplement at an average price of $168.79 per share for aggregate proceeds of $178.8 million.
Risks To Business
There are several risks that investors should be aware of before investing in CRISPR Therapeutics.
The first risk to consider would be with respect to the BLA filing of exa-cel for severe Sickle-Cell Disease [SCD] and transfusion-dependent beta thalassemia [TDT] that was accepted by the FDA. A decision date for U.S approval of exa-cel for SCD had been established for December 8, 2023, whereas the decision date for TDT patients is not expected until March 30, 2024. There is no guarantee that CRISPR will receive regulatory approvals for one or both of these indications for marketing in the United States.
A second risk to then consider would be with the European and United Kingdom regulatory filings that were accepted for review by both of these territories of exa-cel for both of these indications. There is no assurance that one or both of these territories will approve exa-cel for either one of these indications.
A third risk to consider would be a potential competitor. That's because bluebird bio ( BLUE ) had its Biologics Licensing Application [BLA] of lovo-cel accepted by the FDA for review for the treatment of patients with Sickle-Cell Disease. Its PDUFA date is set for December 20, 2023 for this indication. A regulatory approval for bluebird bio would mean a competitor that CRISPR and Vertex would have to deal with.
A fourth and final risk to consider would be the pricing of gene therapies. That's because it remains to be seen if insurers or payers are willing to pay for the heavy price tag for these gene therapies. That's because these types of gene therapy treatment could have a price tag of up to $2 million . Thus, it remains to be seen if CRISPR Therapeutics can become profitable with such a big price tag.
Conclusion
Crispr Therapeutics AG has made great progress in being able to advance exa-cel with its partner Vertex Pharmaceuticals as noted above. The regulatory filings of exa-cel for both SCD and TDT in several territories, means that there are several catalyst opportunities in play.
The first catalyst to be expected for this company would be the review of exa-cel for the treatment of patients with severe SCD. A PDUFA date of December 8, 2023 has been set to review this CRISPR gene therapy for the treatment of this patient population. The other review of exa-cel for the treatment of patients with TDT won't be reviewed until March 30, 2024.
Crispr Therapeutics AG is already moving towards possibly being able to expand upon the potential SCD and TDT populations that it could target. How so? Well, this will be through the use of advancing its own anti-CD117 [c-Kit] antibody-drug conjugate [ADC] as a conditioning agent. With the regulatory submissions of exa-cel accepted for several territories, plus the ability to possibly eventually expand upon the indications being targeted with its own conditioning agent, I believe that investors can capitalize on any potential gains made.
For further details see:
Crispr Therapeutics: Biotech To Watch With Regulatory Approvals Of Exa-Cel On Deck