Hello everyone. Thank you so much for being with us today. I am happy to introduce to you John Yu, the CEO and Chairman of Kairos Pharma.
Good afternoon. Thank you for being here. My name is John Yu, and I'm representing Kairos Pharma, KAPA, on the New York Stock Exchange American. These are forward-looking statements. As a neurosurgeon, one of the difficult parts of my job is to give the patient a diagnosis of a brain cancer, but it's much more difficult when the tumor comes back and we're talking about recurrence and how to deal with that. Kairos Pharma is dedicated to developing therapies that target cancer drug resistance and immune suppression. The problem is that drug resistance develops for even blockbuster drugs, reducing their effectiveness over time. CD105 is a cell surface protein that becomes elevated in association with resistance, and our lead candidate, ENV-105, reverses resistance for hormone therapy and EGFR-targeted therapy for prostate and lung cancer respectively.
We have three clinical programs in progress. ENV-105 is in a phase II trial for prostate cancer, a phase I trial for EGFR-driven lung cancer. KROS 201 received an IND for glioblastoma, we acquired or are acquiring KROS-741, which is a c-Met antagonist that targets a resistance mechanisms that develops for EGFR therapy in non-small cell lung cancer. We will be starting a phase I trial treating a biomarker-driven lung and esophageal gastric cancers with this. This was attained from Celyn Therapeutics, which is an OrbiMed company, we are happy to have this healthcare fund as part of our cap table and involved in our development. We are in a phase II trial in castration-resistant prostate cancer.
This is a $6.5 billion market for anti-androgen agents, and it's in three centers at the Cedars-Sinai Medical Center, University of Utah, and City of Hope. We are in a phase I trial with EGFR-driven lung cancer at Cedars-Sinai Medical Center. This is a $2 billion market at least, and glioblastoma, which targets activated T-cell therapy, and this is a $3.6 million market. The small molecule c-Met antagonist will be in a lung and gastric trial, which we hope to get an IND for over the next quarter. KROS 101 is a small molecule that targets the GITR ligand and is a checkpoint inhibitor that increases T-cells and decreases inhibitory Tregs that we're developing for clinical trial.
The problem is that cancers develop resistance to standard of care therapies, and this is due to the expression of CD105 on the cell surface. CD105 has two functions. One is to target and increase BMP4 signaling. The other is to turn off TGF-β signaling. What BMP4 does is that it makes the cell more stem cell-like and more primordial. In a parallel fashion to normal stem cells, as a cancer becomes more stem cell-like, it becomes more resistant to the therapies that are used to treat it. Normal stem cells are resistant to the toxins in the environment and radiation so that it can survive and replenish the normal organ. Unfortunately, when cancer stem cells develop that characteristic, they become more resistant to the drugs that are used to treat it.
We want to turn off the stem cell function by a neutralizing antibody that targets the CD105 on the cell surface and turns off this dedifferentiating or stem cell marker. This is broadly applicable to many cancers, and we've shown it in models of colon cancer, breast cancer, and head and neck cancer, widely applicable to many drugs and widespread cancers. This is in preclinical data in prostate cancers, and you can see a very dedifferentiated or stem cell-like phenotype in a patient who was treated with enzalutamide. When you treat with enzalutamide plus ENV-105, it loses that stem cell aggressive phenotype and becomes more like a normal prostate organ.
It does this by turning off the Androgen Receptor Splice Variant 7, which is a decoy receptor for androgen agents, and turns off the effectiveness of anti-androgen therapy. Only when ENV-105 is used will patients become susceptible again to enzalutamide and castration, and this was shown in a previous paper. We then went on to a phase II trial and had a safety lead in of 10 patients and are now randomizing patients to receive either apalutamide, which is a second-generation anti-androgen agent, or apalutamide plus ENV-105 with the primary endpoint being progression free survival benefit over apalutamide alone and secondary endpoints being a companion biomarker validation.
This is supported by a $3.2 million grant from the NIH that supports the biomarker validation from a previous phase I and II trial. This is the patient summary of the safety cohort of 10 patients that we reported previously. These patients were treated with at least one or two anti-androgen agents. Some were treated with PLUVICTO, which is the drug of choice after failure of these anti-androgen agents and the responses of these patients over time. The expected progression-free survival in these patients when you change an anti-androgen agent, as demonstrated by these two past trials in The New England Journal of Medicine and The Lancet, is a survival of or PFS of four months or six months when you change out the anti-androgen agent.
In contrast, what we saw was a median progression-free survival of 13.7 months or 59 weeks, which is still progressing or increasing as we speak because all of these patients have not progressed so far. We hope to update these results over the next quarter. One interesting finding that we showed preclinically was that ENV-105, when in combination with radiation therapy, shows increased efficacy in the metastatic mouse model of prostate cancer. You can see the tumor growth with ENV-105 with radiation alone, and when you add them, there's a significant drop in the tumor growth.
Based on these results, we have initiated a preclinical collaboration with a large pharmaceutical with an alpha-emitting isotope in animal models of bone metastatic prostate cancer, which we hope, based on its results, will turn into a phase II trial that they will support and move to a phase II clinical trial in that way. In lung cancer, we showed previously that when you have a high CD105 expression on the tumor cell, patients have a much lower survival or shorter survival than those patients with a high CD105 expression, suggesting that CD105 expression is highly correlated with survival.
In order to test this hypothesis, we added ENV-105 to osimertinib in animal models with lung cancer and showed there's a significant decrease in the growth of these tumors when added to osimertinib. These results led to a phase I trial where we're presently enrolling in which patients are treated with ENV-105 on top of TAGRISSO when they have become resistant to TAGRISSO and they've recurred, or in patients that have incomplete treatment with TAGRISSO with persistent circulating DNA. This represents 80% of patients that are treated with TAGRISSO.
The safety lead-in, we hope to report within this quarter and this will be safety results as well as interim efficacy responses in this dose escalating cohort of patients. One very interesting development at Cedars-Sinai Medical Center where all of these therapies were derived and where I'm an investigator as well as our CSO, our Chief Scientific Officer and VP of Research and Development, is that we formed an academic CRO or consortium with the Mayo Clinic, Stanford, Vanderbilt, Rutgers, and the Cleveland Clinic.
What this allows us to do is efficiently start our trials all together, do it at an academic rate, and thereby bypass these very expensive and very slow-moving commercial consortia so that we can bring innovative therapies to clinical trial and complete the clinical trials in a rapid fashion. As pharmaceutical data in China becomes not acceptable to the FDA for their clinical data, I think it's all the more important to be able to obtain these data rapidly and efficiently as it was in China in a form in the States. where it's acceptable to the FDA.
We've had significant non-dilutive funding after we became public with a $3.2 million grant from the NIH to look at a biomarker companion study with our phase II trial that shows that a biomarker can determine which patients will respond or not, and that will determine how you enter patients to a clinical trial, improving the likelihood of a positive phase III trial from 55% to 76%. We've had a donor that supports our lung cancer phase I trial and a $2 million grant from the Department of Defense that supports a biomarker study in our ENV-105 lung cancer trial as well.
Significant non-dilutive funding for the company now as well as from our preclinical times before we went public of approximately $25 million in non-dilutive NIH funding that supported the research leading up to these phase I and phase II trials. We recently had a term sheet that we reported with an OrbiMed company, Celyn Therapeutics. This is an escape mechanism of EGFR therapies like osimertinib that then use the c-Met pathway in order to have the cells proliferate. What KROS-741 does is it's a pan inhibitor of the c-Met pathway and targets just about all of the mutations that are known in this pathway as compared to previous c-Met inhibitors.
It's also attractive in that it has less toxicity in terms of peripheral edema in dogs that have been treated. The drugs that are on the market, capmatinib, tepotinib, cabozantinib, only impact very limited numbers of mutations of c-Met, whereas our drug, KROS-741, targets just about all of these mutations. All of the escape mutations from EGFR that use c-Met will hopefully be targeted by 741 and also have less of the problem of peripheral edema and skin rashes that are debilitating for patients. If we demonstrate that in our phase I trial, we believe that oncologists will flock to this drug as compared to what's readily available on the market presently.
We've shown with human tumor cells that our drug works much better than previous capmatinib, which only impacts a limited number of mutations. This is a nodal chart of the pathways that 741 targets, and it's really isolated to the c-Met pathway, unlike the other inhibitors that are on the market that impacts RAS, EGFR, VEGF, and other targets that makes it a dirty type of c-Met inhibitor. We will do a phase I trial with lung cancer patients both before and after progression and in esophageal gastric cancer patients that are biomarker positive or have c-Met mutations.
This will hopefully be a trial that we'd bring through our consortium at Cedars-Sinai, the Mayo Clinic, and the Cleveland Clinic. I think this is what OrbiMed saw as a driver for our company being able to move these therapeutics efficiently from a translational research to clinical trials. Again, as the political environment in China becomes more problematic and the FDA no longer accepts data from this country, I think it makes sense to have a pathway in the States. where trials can be done efficiently at low cost. Immune suppression is the other leg of the company, and immunotherapy is a $118 billion market with only a 17% response rate.
One of the biggest problem is that we can generate T- cells only to a limited number as compared to the total number of cancer cells there are. One of our products, KROS-101, targets the GITR ligand, which is a pathway in which we can increase killer T- cells, decrease suppressor T- cells in a fashion to impact all of immuno-oncology. Although immuno-oncology has taken its hits recently, we believe this target of the GITR ligand, which impacts both the antigen-presenting cells and the T- cells, allows us to increase dramatically the number of T- cells and all of the different types of T- cell subsets.
And it decreases T reg cells along with the ratio of our killer cells to the T reg cells, allowing it to kill significantly the tumor cells in animal models and increase survival in animal models. We've also shown that the GITR antagonist will target autoimmune diseases and this has been of great interest to partnering pharma companies that are looking for a novel autoimmune therapeutics that can really impact the number of T- cells. This really works the opposite of KROS-101 in that it decreases the number of effector T- cells and increases the T regs that inhibit the entire immune response.
This should have an impact in autoimmune diseases as well as in organ transplantation, where it's critical to reduce the number of T- cells that are against the targets. Our intellectual property is very strong and extends out to 2040, both for the composition of matter as well as methods of use. Our team is small. They're all investigators at Cedars-Sinai Medical Center. This allows us to really exploit the clinical trial consortium that Cedars is developing with the Mayo Clinic and the Cleveland Clinic. People ask us how we can compete with large pharma companies that have hundreds of scientists each. It's really because we're not competing with them, we're collaborating with them to bring their drugs to allow them to be more effective for a longer period of time.
These are our directors, and we're really relying them to make our connections to large pharma, where they have spent much of their career to enable these partnerships and collaborations that we are developing. In summary, we're a clinical stage company with an antibody that impacts the central mechanism of cancer drug resistance. We have an extensive pipeline that targets immune suppression. We're enrolling in phase I and II trials with interim efficacy data coming out in the next quarter. We have a strategic relationship with Cedars-Sinai Medical Center, where we're all investigators, that enables us to take advantage of the academic consortium that's developing to bring these trials to clinical trials more effectively and efficiently.
We are acquiring a novel small molecule that counters lung cancer EGFR therapy resistance that marries well with our resistance theme in our company and allows us to bring OrbiMed into our cap table, stabilizing our cap table through primary healthcare funds. These are some of our catalysts coming up with partnering advances with a research collaboration with a major pharmaceutical in the second quarter of 2026. Safety data and interim efficacy data from our phase I lung cancer trial in the second quarter of 2026. Phase II trial for prostate cancer with efficacy data and report on the third quarter of 2026. An IND for KROS-741 c-Met inhibitor in the third quarter of 2026.
A research collaboration for KROS-101 GITR ligand checkpoint inhibitor in the third quarter as well. Thank you so much for your attention. Happy to take any question. Yes, sir. About $3.2 million, $3.2 million. It's been about $200,000 per month. Our outstanding shares, approximately 22 million shares. Floats approximately 13 million, no debt, and a pretty clean structure. With our catalysts and our trials, we hope this will be a transformative year for the company. Yes, sir. We're always working on grants and yes. You know, the donor has helped a lot with supporting our trials as well.
We believe with collaborations that we'll report with Pharma and hopefully them coming in and supporting the trials, that will lead to significant non-dilutive funding and partnering potentials as well.
How much do you anticipate in 2026 if you want to name it?
We will need to do another raise at some point. We do have an ATM facility and ELOC, you know, on large volume days. That's a very low cost of capital. At some point, we will need to utilize that or do a financing around these catalysts that we will have over the next couple of quarters. Yes, sir.
It was with a fund, Helena Partners. We recently renegotiated the rate so that it's more favorable to the company. Okay, well, thank you very much for your attention.