Recently, Kairos Pharma announced positive interim efficacy data from its phase 2 study using its drug ENV105 (carotuximab) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The data comes from a total of 10 patients with advanced prostate cancer who were only enrolled into the study if they were said to have failed at least one prior androgen receptor inhibitor therapy. The actual analysis, though, happened with a total of 8 remaining patients, because two of the patients had withdrawn from the trial for unrelated reasons. Regardless, the data was highly ideal because it was noted that when this drug was added to standard of care (SOC) therapy, apalutamide (marketed as ERLEADA) was shown to achieve a progression-free survival (PFS) rate of 13 months.
The company wanted to release some interim data to establish proof-of-concept that the drug could improve PFS rates in these patients with advanced prostate cancer. The truth is that the rate that was shown far exceeded what has been achieved by other therapies. For example, a chemotherapy agent like cabazitaxel has a PFS rate of 8 months, which is good, except for the fact that it’s highly toxic. Standard of care hormone therapies in the 2nd-line or 3rd-line setting tend to have a median PFS rate of 3.7 months. I think that this data is encouraging, and the company seems pretty enthusiastic as well. The reason why I say that is because on the back of the release of this data, they set a key opinion leader (KOL) virtual event to discuss it.
The positive interim efficacy data comes from the very same 10 patients who had completed the safety lead in of this phase 2 study using ENV105 to target patients with mCRPC. Beyond the drug being able to help patients overcome resistance observed in SOC therapies, it was safe and tolerable for patients to take. For starters, there were no Grade 3 or Grade 4 adverse events (AEs) to speak of. In addition, there were no dose-limiting toxicities. This is important because the company may have the freedom to increase the dose of ENV105 for other studies. Speaking of overcoming resistance, this is what is ideal with this drug. The whole problem stems from the fact that apalutamide is the SOC.
This androgen receptor inhibitor works by blocking androgens, male hormones, from causing the cancer cells to spread and grow. To that end, it can work for a period of time, but there is a resistance that kicks in, and this is where ENV105 could end up being a good addition to it. The resistance that happens causes the cancer cells to develop a protein on the surface known as CD105. In essence, the cancer adapts and learns to counter a therapy like apalutamide. What ENV105 does is it blocks this protein and allows the drug to work as if it had done so beforehand. The point is that it restores a tumor’s sensitivity to the SOC therapy. In this case the addition of ENV105 allows apalutamide to work well again.
This interim analysis was just a small batch of 10 patients. What’s next to keep an eye on would be the completion of this phase 2 study and then the reporting of additional data. With added proof from a larger pool of patients, it reinforces the data that Kairos just released. Speaking of which, it intends to recruit up to a total of 100 advanced prostate cancer patients to prove that this data was not achieved just by chance. While the biotech is making headway in terms of targeting advanced prostate cancer patients, it’s also evaluating its use in targeting patients with EGFR-mutant non-small cell lung cancer (NSCLC). This is being explored in a phase 1 study.
Just like ENV105 helped sensitize the tumor of prostate cancer, this might also extend to the targeting of patients with EGFR-mutant NSCLC. It is not going to be long before investors can get a glimpse of data from this early-stage study either. The company intends to release data from this early-stage trial soon. If it is shown that the drug causes Tagrisso (marketed as Osimertinib) to work well again, then this will be further confirmation for the data that was released from this advanced prostate cancer study. There is definitely room for this company to do better with ENV105, and this is thanks to another strategy it is deploying. This is in terms of an ongoing valuation of using biomarkers to recruit the correct patients.
What this means is that each patient is measured and recruited based on biomarkers, which could potentially predict whether or not they are likely to respond. As shown above, the company did well with ENV105 regardless of deploying a biomarker strategy. For example, one common biomarker that helps in terms of early screening to determine whether or not a patient has prostate cancer is known as prostate-specific antigen (PSA). Thus, a strategy the company could use is to measure those with certain levels of PSA that are likely to respond when given ENV105 with apalutamide or another androgen receptor inhibitor.
The opportunity for this company goes beyond the scope of ENV105. The company received IND authorization from the FDA for KROS 201, which is a T-cell therapy that is set to go after cancer stem cells, which are believed to be the root cause of the cancer. This might be another candidate worth exploring for the company; of course, that’s if it is able to obtain additional funding.