Today, Kairos Pharma announced that it had achieved positive safety results from its ongoing phase 2 study using ENV-105 (carotuximab) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The stock price closed the day higher by 70% on the back of this news at $1.17 per share. That is, when the company’s CD-105 antagonist was combined with apalutamide (marketed as ERLEADA by Johnson & Johnson), there were no dose-limiting toxicities (DLTs) for the first 10 patients that were enrolled into this mid-stage study. The importance of no DLTs means that the company can potentially, if it wants to, raise the dosing of this drug to a higher level to treat these specific prostate cancer patients.
Most importantly, there were no Grade 3 or 4 toxicities that were noted in these patients. The reason why this announcement was significant is because the company is aiming to do something unique compared to other oncology companies. The science is to specifically reverse the resistance that occurs in patients that take current standard of care (SOC) therapies. With respect to castration-resistant prostate cancer, these patients progress in disease despite receiving androgen deprivation therapies (ADTs). The goal of this SOC therapy is to reduce the hormones present and, in tandem, reduce the spread or growth of the cancer. These patients have limited options, and novel new therapies are needed.
However, this company is using its drug ENV-105 in a unique way. What happens with patients that take current SOC therapies, like ERLEADA for metastatic castration-resistant prostate cancer, is that they develop a resistance to it. There is another phenomenon that happens, which is that the cancer develops proteins on the surface known as CD-105, which allows for the resistance to happen. Kairos deploys ENV-105 to inhibit these proteins and thus theoretically allow such SOC therapies to work again like they normally would. The safety signal is only the beginning, because there is another catalyst to keep an eye on in the coming months. Specifically, the company expects to release interim efficacy data from this phase 2 study targeting mCRPC patients in September of 2025.
The safety data thus far shows that ENV-105 as a CD-105 antagonist is at the very least safe/tolerable for patients to take with current SOC therapies like ERLEADA. Moving forward the company expects to recruit up to 100 mCRPC patients at several leading cancer treatment centers. It remains to be seen whether or not the efficacy data turns out to be good, but in the press release the company noted that it wants to speak to the FDA about possibly being able to design a pivotal phase 3 study for this program. Of course, this is going to depend upon upcoming efficacy data on whether or not such a task is feasible. In addition, the company isn’t enthusiastic just based solely on this phase 2 safety study data.
In a prior phase 2 study for castration-resistant prostate cancer patients who became resistant, they achieved a 62% clinical benefit rate (CBR) when they were given ENV-105. Without this CD-105 antagonist being given, there would only be an expected 0% CBR. As I noted beforehand, the ability to restore SOC therapies function is not just narrowed only to the targeting of prostate cancer patients. Kairos is even in the process of evaluating ENV-105 in a phase 1 study targeting EGFR non-small cell lung cancer (NSCLC) patients. That is, these patients have NSCLC with the EGFR mutation. This cancer is reliant on EGFR to continue to grow and spread. In this instance, TAGRISSO from AstraZeneca is a third-generation tyrosine kinase inhibitor (TKI) that is used to treat this type of NSCLC.
Again, resistance is present with these patients who take Tagrisso or any other TKI for that matter; they develop CD-105 proteins because of it. The goal for ENV-105 is to inhibit these proteins and thus restore a working TKI to treat these specific lung cancer patients. The beauty of this biotech is that both of its ongoing studies are being done through funding by entities of some sort. The phase 2 prostate cancer study is being done through NIH grant funding, while the phase 1 EGFR NSCLC trial is being conducted with non-dilutive donor funding.
All of the potential of this biotech has not been noted, as ENV-105 is just the beginning. There is another preclinical candidate known as KROS-101, a glucocorticosteroid-induced tumor necrosis factor receptor (GITR) ligand agonist with dual mechanisms of action (MOA). One MOA is to boost T-cells and cytokine targeting against solid tumors. Followed by the second MOA, which is to reduce the number of T-regulatory cells, which in turn halts Treg-mediated suppression of the immune system that takes place in the tumor microenvironment (TME).