Kairos Pharma Reports Encouraging Phase 1 Safety Results for ENV-105 Combined with Osimertinib in EGFR-Mutated Lung Cancer
Kairos Pharma, Ltd., a clinical-stage biopharmaceutical company focused on developing therapies to overcome drug resistance in cancer, has announced encouraging interim safety results from its ongoing Phase 1 clinical trial evaluating ENV-105 (carotuximab) in combination with osimertinib (Tagrisso®) for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).
The interim analysis demonstrated a favorable safety profile among the first 13 patients treated with the investigational combination. According to the company, no Grade 3 or higher treatment-related serious adverse events associated with ENV-105 have been observed to date, supporting continued dose evaluation and progression toward future efficacy assessments.
The findings represent an important milestone for Kairos Pharma’s lead oncology program, which is designed to restore sensitivity to osimertinib after tumors develop resistance to the widely used targeted therapy. Because resistance to osimertinib remains one of the greatest challenges in treating EGFR-mutated lung cancer, the company believes ENV-105 could potentially address a significant unmet medical need if future clinical studies confirm its therapeutic benefit.
Drug Resistance Remains a Major Challenge in Lung Cancer
Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all lung cancer diagnoses.
Among patients with NSCLC, mutations involving the epidermal growth factor receptor (EGFR) define one of the most important molecular subgroups. Advances in precision medicine have transformed treatment for these patients through the development of EGFR-targeted therapies that selectively inhibit cancer-driving signaling pathways.
The introduction of third-generation EGFR inhibitors, particularly osimertinib, has significantly improved clinical outcomes by extending progression-free survival and delaying disease progression compared with earlier treatments.
However, despite impressive initial responses, virtually all patients eventually develop acquired resistance, allowing cancer cells to resume growth despite continued therapy.
Overcoming this resistance has become one of the highest priorities in EGFR-targeted oncology research.
A Multi-Billion-Dollar Therapeutic Market
The commercial significance of EGFR-mutated NSCLC reflects both the prevalence of the disease and the widespread adoption of targeted therapies.
The global market for EGFR-directed treatments is currently estimated at approximately US$10 billion across major healthcare markets and is projected to exceed US$13 billion by 2030, driven by continued growth in precision oncology and molecular testing.
Osimertinib, marketed as Tagrisso®, has become the worldwide standard first-line treatment for patients with EGFR-mutated NSCLC.
Annual global sales of the therapy have reached approximately US$6 billion, reflecting its central role in current treatment guidelines.
Despite its success, the inevitable development of resistance limits the long-term clinical benefit patients receive from therapy.
Limited Options After Resistance Develops
When patients experience disease progression while receiving osimertinib, treatment options become considerably more limited.
Although chemotherapy and other targeted therapies may be considered depending on the specific resistance mechanisms involved, outcomes after progression generally remain less favorable than during initial treatment.
Currently, there is no FDA-approved therapy specifically designed to restore tumor sensitivity to osimertinib after resistance has developed.
As a result, many patients experience disease progression with relatively few effective treatment alternatives.
Kairos Pharma is pursuing a different strategy aimed not at replacing osimertinib but at restoring its effectiveness.
A Strategy Focused on Resensitization
Rather than developing another competing EGFR inhibitor, Kairos Pharma has built its clinical program around the concept of tumor resensitization.
The company’s approach seeks to identify biological mechanisms responsible for drug resistance and selectively disrupt those pathways, allowing previously effective therapies to regain activity.
This strategy could potentially:
- Extend progression-free survival
- Delay treatment failure
- Preserve quality of life
- Increase the overall clinical utility of existing targeted therapies
- Delay the need for alternative treatments
If successful, ENV-105 may complement rather than replace osimertinib, expanding treatment possibilities for patients who would otherwise face limited options after progression.
Targeting CD105
ENV-105 (carotuximab) is a first-in-class monoclonal antibody directed against CD105, also known as endoglin.
CD105 plays an important role in tumor angiogenesis and has increasingly been recognized as a contributor to treatment resistance across multiple cancers.
According to Kairos Pharma, scientific evidence indicates that CD105 expression becomes elevated in many patients who develop resistance to osimertinib.
Overexpression of CD105 is believed to activate signaling pathways that enable tumor cells to survive despite continued EGFR inhibition.
By blocking CD105 activity, ENV-105 aims to dismantle these resistance mechanisms and restore sensitivity to EGFR-targeted therapy.
Mechanism Designed to Restore Treatment Response
Kairos believes ENV-105 acts upstream of several resistance pathways.
Instead of directly attacking EGFR, the antibody targets biological processes supporting resistance development.
Blocking CD105 signaling may create conditions allowing cancer cells to once again respond to osimertinib.
This mechanism represents a different therapeutic philosophy from developing increasingly potent EGFR inhibitors.
Rather than continually replacing one targeted therapy with another as resistance evolves, Kairos hopes to preserve the effectiveness of existing treatment through biologic resensitization.
If validated clinically, this strategy could potentially extend the useful treatment duration of one of oncology’s most widely prescribed targeted therapies.
Encouraging Interim Safety Findings
The ongoing Phase 1 study is primarily designed to evaluate:
- Safety
- Tolerability
- Dose escalation
- Recommended Phase 2 dose
The current interim analysis includes 13 patients treated with the combination of ENV-105 and osimertinib.
According to the company, investigators observed:
- No Grade 3 or higher treatment-related adverse events attributed to ENV-105
- No unexpected safety signals
- Manageable side effects
- Continued treatment feasibility
The favorable early safety profile supports continued patient enrollment and advancement toward future efficacy analyses.
Standard Safety Monitoring
Adverse events within the study are being assessed according to the internationally recognized Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Investigators are also monitoring for dose-limiting toxicities during the initial treatment cycles to determine the appropriate dosing regimen for later-stage clinical development.
Thus far, reported side effects have been manageable using standard supportive care measures.
Although efficacy conclusions cannot yet be drawn from the current analysis, demonstrating acceptable safety remains an essential milestone during early clinical development.
Company Perspective
Dr. John Yu, Chief Executive Officer of Kairos Pharma, emphasized that the company’s objective extends beyond successfully completing a Phase 1 study.
According to Dr. Yu, Kairos aims to develop a therapy capable of fundamentally changing treatment after patients develop resistance to osimertinib.
He explained that the favorable safety profile observed across the first 13 treated patients strengthens confidence in the company’s resensitization strategy and positions ENV-105 as a potential complement to EGFR-targeted therapy rather than a competing treatment.
The company believes this approach could ultimately help preserve the clinical value of osimertinib across the broader EGFR-mutated lung cancer population.
Scientific Foundation Extends Beyond Lung Cancer
Although the current trial focuses on EGFR-mutated NSCLC, Kairos views CD105 as a therapeutic target with broader applications.
Research suggests CD105 contributes to treatment resistance and disease recurrence across multiple forms of cancer.
Preclinical studies have demonstrated that ENV-105 may enhance tumor sensitivity not only to targeted therapies but also to:
- Radiation therapy
- Hormone therapy
These findings suggest the antibody’s mechanism may be applicable across several treatment settings involving acquired therapeutic resistance.
Clinical Development Beyond NSCLC
Kairos is also evaluating ENV-105 in castration-resistant prostate cancer, providing an additional opportunity to validate the CD105-targeting strategy.
According to the company, an ongoing Phase 2 study has demonstrated median progression-free survival exceeding 13 months, representing encouraging preliminary findings relative to current standards of care.
Although further clinical investigation remains necessary, these results suggest suppression of CD105 may produce meaningful clinical benefit across different tumor types.
The company believes this cross-indication activity strengthens confidence in the broader therapeutic potential of the platform.
Scientific Leadership Commentary
Dr. Neil Bhowmick, Chief Science Officer of Kairos Pharma, noted that ENV-105 has continued to demonstrate favorable tolerability across multiple oncology indications.
He stated that the latest safety findings represent another important milestone as the company seeks to establish CD105 inhibition as a strategy for overcoming treatment resistance.
According to Dr. Bhowmick, Kairos remains focused on developing therapies capable of extending treatment benefit while ultimately improving long-term outcomes for patients facing difficult-to-treat cancers.
Next Steps for Clinical Development
The Phase 1 combination study continues to enroll and evaluate patients.
Future analyses will focus on determining:
- Recommended Phase 2 dose
- Preliminary anti-tumor activity
- Objective response rates
- Duration of response
- Progression-free survival
- Biomarker analyses
If safety continues to remain favorable and early efficacy signals emerge, Kairos expects the program to progress into later-stage clinical evaluation.
Such studies will be necessary to determine whether the biological rationale underlying CD105 inhibition translates into meaningful clinical improvements for patients with osimertinib-resistant disease.
The interim Phase 1 safety results represent an encouraging early step in Kairos Pharma’s effort to address one of the most significant unmet needs in EGFR-mutated non-small cell lung cancer: overcoming acquired resistance to osimertinib. With no Grade 3 or higher treatment-related adverse events observed among the first 13 patients receiving the combination therapy, the study supports continued clinical development of ENV-105 and progression toward future efficacy evaluations.
If subsequent trials demonstrate that CD105 inhibition can successfully restore sensitivity to EGFR-targeted therapy, ENV-105 could introduce a novel treatment paradigm centered on resensitization rather than replacement of existing therapies. Such an approach has the potential to extend the clinical benefit of osimertinib, improve outcomes for patients with advanced lung cancer, and contribute to a growing field of precision oncology strategies aimed at overcoming drug resistance.
About Kairos Pharma Ltd.
Based in Los Angeles, California, Kairos Pharma Ltd. (NYSE American: KAPA) is at the forefront of oncology therapeutics, utilizing structural biology to overcome drug resistance and immune suppression in cancer. Kairos Pharma’s lead candidate, ENV-105 (carotuximab), is an antibody targeting CD105 — a protein identified as a key driver of resistance and disease relapse in response to standard cancer therapy. ENV-105 aims to reverse drug resistance by targeting CD105 and restore the effectiveness of standard therapies across multiple cancer types.