Just the other day CRISPR Therapeutics announced its Q1 of 2025 financial results. Of course, considering that this is a biotech that is primarily focused on clinical-stage programs, which does matter a bit because of one approved therapy it has known as CASGEVY. This gene therapy was approved to treat patients with sickle-cell disease (SCD) and transfusion-dependent beta thalassemia. It is developed as an ex-vivo CRISPR/Cas9 gene-edited cell therapy to treat both of these patient populations.
While a good opportunity exists with this approved therapy going forward, it is important to note that the Q1 earnings released were also aligned with the reveal of data from the phase 1 study using an in vivo gene-editing therapy with a lipid nanoparticle (LNP) offered as a delivery vehicle. This gene therapy in question is CTX310 and consists of Cas9 messenger RNA (mRNA) and gRNA being delivered to the liver to specifically knock down the protein expression of ANGPTL3.
This is important because ANGPTL3 is responsible for regulating lipoprotein metabolism and plasma lipid levels in a patient’s body. The goal is to reduce this protein, which in turn should see patients achieve a reduction of triglycerides (the most common type of fat found in the body) and low-density lipoprotein (LDL) levels. From what was revealed in this early-stage trial, the company is definitely on the right track.
With released data from the ongoing phase 1 study in the first 4 cohorts of 10 patients, there was a dose-dependent peak reduction of triglycerides (TGs) of 82% and then up to 81% in terms of LDL. This makes sense because with the inhibition of the ANGPTL3 protein, it in turn allowed for the reduction of these biomarkers present in patients with elevated levels of cholesterol.
What’s impressive is that this was observed only with a 30 day follow-up period for each patient, with a cutoff date of April 16th of 2025. Not only that, but even more intriguing is that CTX310 benefited high-risk patient populations in a more efficient manner with cohorts of higher dose levels of therapy.
This goes back to the dose-dependent peak reductions that were observed, as noted above. A dose level 4 (DL4) patient given CTX310 that had severe hypertriglyceridemia (sHTG) is the one that had 82% in TGs from baseline. Then, one dose level 3 (DL3) patent was given, as this therapy had achieved an 81% reduction in LDL-C from baseline. The point here is that the company intends to move to the next stage of clinical testing for patients who are at such high risk of elevated cholesterol levels.
In terms of a catalyst for investors to keep an eye on here, the company intends to release data from this phase 1 study using CTX310 for the treatment of patients with elevated levels of cholesterol and lipid fat levels at a medical conference in the 2nd half of 2025.
Separately, CRISPR is also working on an in vivo gene-editing therapy, also using its LNP delivery of Cas9 mRNA and gRNA to the liver to reduce expression of lipoprotein (a) or Lp(a). The point of this therapy, CTX320, is to reduce plasma levels enough, which in turn should reduce cardiovascular disease.
Top-line data from an ongoing clinical study for this program is on track to be released in Q2 of 2025. Should the data turn out to be positive for this candidate as well, then it would be further proof of delivering Cas9 mRNA and gRNA in an efficient manner to knock down proteins in the liver.
