Further analysis of the Phase 2b ADVANCE study reinforces Phase 2b EXPAND results and supports Phase 3 development - FDA discussions on trial design planned for Q4 2026

The analysis was conducted to investigate the higher-than-expected clinical response in the control group receiving placebo in combination with methotrexate and to inform the design of a confirmatory Phase 3 program. The findings provide further insight into the ADVANCE topline results reported in June 2026, including how patients’ disease activity at baseline contributed to regression to the mean (“RTM”).

Treatment-naïve patients with RA may enter clinical studies during a temporary increase in disease activity. Worsening pain or swelling may prompt medical attention or referral to a rheumatologist, with assessments showing high disease activity and signs of systemic inflammation, including elevated C-reactive protein (“CRP”). Baseline measurements may therefore reflect a temporary peak rather than the patient’s typical disease activity. Assessing treatment effects should consequently account for natural fluctuations in disease activity and the potential contribution of RTM.

Approximately one in five patients in the ADVANCE study were identified as experiencing a flare-up at enrollment, reflecting a temporary peak in inflammation. The post-hoc analysis showed that this subgroup accounted for the vast majority of the response variability in the placebo arm.

Among the approximately four in five ADVANCE patients with more stable baseline high-sensitivity CRP (“hsCRP”) levels, ACR20 response rates were 79% with resomelagon 40 mg and 55% with placebo (p < 0.05).

The ACR50 response rate was 38% in the resomelagon 40 mg group, compared with 30% in the placebo group.

DAS28-CRP decreased from baseline by 2.0 points in the resomelagon 40 mg group, compared with 1.5 points in the placebo group.

These results confirm the positive results observed in the EXPAND study in patients with hsCRP levels above the normal range and support the potential clinical benefit of resomelagon.

The post-hoc analysis supports a clinically meaningful treatment effect of resomelagon and its continued development at a dose of 40 mg once daily in a Phase 3 trial. The proposed trial will be designed to reduce the impact of baseline instability and prospectively power ACR20 and ACR50 comparisons. SynAct plans to submit the proposed trial design and supporting toxicology program to the FDA in early Q4 2026 for discussion at an FDA Type C meeting with feedback expected end of the year or early 2027.

“These results help explain an important source of variability in ADVANCE and give us a clearer basis for designing our Phase 3 trial. We aim to establish more stable inflammatory activity before randomization while maintaining our focus on patients with early RA. By extending treatment to 26 weeks, we can assess whether the strong ACR20 response observed at week 12 translates into a more pronounced ACR50 response,” said Thomas Jonassen, Chief Scientific Officer of SynAct.

SynAct plans to submit the findings for publication in scientific journals and for presentation at rheumatology congresses.

Analysis results support SynAct’s development and strategic opportunities
The results support SynAct’s evaluation of strategic partnerships and transactions to maximize shareholder value, including global or regional licensing agreements for resomelagon in RA and other autoimmune diseases, an outright sale of resomelagon or a potential sale of SynAct. These strategic alternatives remain a priority for the company. Resomelagon’s potential to enable early intervention and help limit the long-term consequences of disease progression could represent a multi-billion-dollar opportunity.

In parallel, SynAct is pursuing development and partnering opportunities for host-directed therapies in infectious diseases, including dengue, where effective treatments could improve outcomes for millions of patients worldwide. The company is expanding its preclinical datasets to explore broader applications in inflammatory diseases, including potential combinations with antiviral and anti-inflammatory treatments.

SynAct intends to advance these programs in parallel and expand its development and partnering activities. Milestones over the coming months are expected to provide greater clarity on the programs’ development paths and commercial potential.

“Our priority is to define a clear path to market for resomelagon in RA while advancing its broader potential in host-directed therapies. Strategic partnerships and transactions are central to this strategy. We are evaluating global and regional licensing opportunities as well as other strategic alternatives that can help bring resomelagon to patients and realize its full value,” said Jeppe Øvlesen, Chief Executive Officer of SynAct.

Expected clinical and commercial milestones

• Feedback from the FDA Type C meeting on the proposed Phase 3 trial design and supporting evidence.
• First commercial agreement in Brazil for the dengue program.
• Data from Part 1 of the Phase 2 RESOVIR-2 study in dengue, subject to local authority approval of the protocol amendment.
• Evaluation of strategic partnerships and transactions to maximize shareholder value, including global or regional licensing agreements, an outright sale of resomelagon or a potential sale of SynAct.
• Completion and reporting of full Phase 2 data from the RESOVIR-2 study in dengue.
• Completion and reporting of Phase 2 data from the RESPIRE study in patients with respiratory viral infections.

The upcoming clinical data, regulatory feedback and strategic activities are expected to guide the next stage of resomelagon’s development and strengthen the basis for strategic partnerships and transactions. Advancing the RA program toward Phase 3 remains SynAct’s priority, alongside continued efforts to realize resomelagon’s broader clinical and commercial potential in host-directed therapies for infectious diseases.