Guard Therapeutics (public) ("Guard" or "the Company") today provides an assessment of the full results from the Phase 2b POINTER study evaluating RMC-035 in patients undergoing open-heart surgery. As previously communicated, the study did not meet its primary or key secondary efficacy endpoints, although promising signals were observed with the 30 mg dose level, particularly in reducing acute kidney injury. Given the overall negative outcome of the study, the Company has decided to discontinue all further development of RMC-035.
"While POINTER did not deliver the efficacy needed to advance RMC-035, the study provides valuable insights and supportive signals-particularly at the 30 mg dose-that strengthen our confidence in its mechanism of action and in the second-generation GTX-peptide platform for development in chronic kidney disease. We will now focus on the most promising opportunities and continue to explore strategic options that best support long-term value for patients and shareholders," said Tobias Agervald, CEO of Guard Therapeutics.
Primary and Key Secondary Endpoints Not Met
Consistent with earlier topline disclosures, the POINTER study did not meet the primary endpoint of change in estimated glomerular filtration rate (eGFR) at Day 90, nor the key secondary endpoint of major adverse kidney events at Day 90 (MAKE90). The Company also observed that overall study outcomes were largely influenced by the 60 mg dose group, which did not replicate the efficacy previously seen in the Phase 2a AKITA study, despite achieving similar target plasma drug concentrations.
Secondary Endpoint AKI Within 72 Hours
Across the total study population, there was a general trend toward reduced acute kidney injury (AKI) within 72 hours following surgery for RMC-035 vs placebo: 27.8 vs 37.5% (relative risk [RR] 0.75, p=0.17).
Supportive Efficacy Signals in the 30 mg Dose Group
Analyses of dose cohorts showed a consistently more favorable efficacy trend for the 30 mg dose across key endpoints:
- Day 90 eGFR: Net benefit of 0.42 ml/min/1.73m2 vs placebo (p=0.86)
- MAKE90: 8.5% vs 15.1% (RR=0.56, p=0.29)
- AKI (based on serum creatinine): 23.4% vs 37.5% (RR=0.63, p=0.103)
- AKI (based on cystatin C): 4.3% vs 15.3% (RR=0.28, p=0.061)
Subgroup Analyses
Prespecified subgroup analyses demonstrated favorable trends with RMC-035 in patients with diabetes and chronic kidney disease (CKD):
- Diabetic patients (pooled RMC-035 vs placebo): MAKE90 5.1% vs 20% (RR=0.26, p=0.059)
- 30 mg dose - diabetic patients: MAKE90 0% vs 20% (p=0.036)
- 30 mg dose - CKD patients: MAKE90 0% vs 13.6% (p=0.15)
These findings reinforce that the 30 mg dose performed more consistently across multiple clinically relevant kidney-related endpoints.
Safety Profile
RMC-035 was generally well tolerated across all dose levels, and no safety concerns were identified.
Interpretation of 60 mg Dose Performance
The overall negative study results were primarily influenced by the 60 mg cohort, which failed to replicate the previously observed efficacy. The Company notes that differences in baseline characteristics-such as higher age, elevated body mass index, and reduced eGFR-along with intercurrent clinical events during follow-up, may have contributed to these outcomes.
Implications for Development Strategy
Despite encouraging signals from the 30 mg dose level, Guard Therapeutics' assessment is that the POINTER results are not sufficiently strong to justify further development of RMC-035. Accordingly, the Company has decided to discontinue the program entirely, with no plans to pursue RMC-035 in open-heart surgery or any other indication.
However, the Company believes that the results support continued development of GTX peptides for chronic indications, such as within selected patient groups with CKD where the mechanism of action remains highly relevant. Since GTX peptides share the same mechanism of action as RMC-035, clinical insights from acute treatment with RMC-035 can be transferred to chronic treatment settings with GTX peptides. The combined data from the AKITA and POINTER studies indicate that optimal dosing of RMC-035 provides a notable effect during the active treatment phase-reduction of kidney injury markers and decreased incidence of AKI-which strengthens the hypothesis that continuous treatment in these patient groups may both enhance efficacy and improve the ability to demonstrate it clearly based on regulatory-accepted endpoints.
The company will communicate shortly about next steps and the strategic path forward.
For further information, please contact:
Tobias Agervald, CEO
Telephone: +46 8 670 65 51
E-mail: info@guardtherapeutics.com
About Guard Therapeutics
Guard Therapeutics is a Swedish clinical-stage biotechnology company that identifies and develops new therapies for diseases with a large unmet medical need, focusing on different forms of kidney disease. The company's candidate drugs are based on the endogenous protein alpha-1-microglobulin. Guard Therapeutics is listed on Nasdaq First North Growth Market Stockholm (ticker: GUARD).
Certified Adviser is Svensk Kapitalmarknadsgranskning AB, www.skmg.se.