Announcement • Jun 17
SynAct Pharma AB Reports Positive Results from Phase 2B Advance Study of Resomelagon in Rheumatoid Arthritis SynAct Pharma AB reported that resomelagon in combination with methotrexate showed promising clinical effects on par with previous findings with ACR20 reaching 76.4% in the most effective dose compared to 60.8% in the placebo treated control group (p=0.06, per protocol data set) reaching statistical significance in the subset of patients entering the study with ACR/EULAR class II-III disease, (76.9% vs. 56.5%, p=0.03). The treatment potential was further supported by a significant reduction of CRP (p=0.0037) which was not present in the placebo treated control group. In addition, resomelagon induced a larger reduction in the Simplified Disease Activity Index (SDAI) (p=0.03 vs placebo). Overall, the safety profile of the compound was very good, and the compound was well tolerated. No signs of immune suppression were observed. The ADVANCE (SynAct-CS008) study was a multicenter, randomized, double-blind, placebo-controlled, 12-week study in newly diagnosed, treatment naïve patients with highly active Rheumatoid Arthritis (RA) (Clinical Disease Activity Index (CDAI) > 22; DAS28-CRP >5.1 and hsCRP > 3 mg/L) conducted at sites in Europe and USA. 246 patients were randomized with the aim of confirming the potential of the compound as a novel safe treatment option in RA and identify feasible doses for further (phase 3) clinical development. The study identified 40 mg given once daily as the most effective dose showing reduction in all clinical parameters on par with what has been seen in previous studies. The study confirmed the hypothesis of non-linear dose-response for resomelagon. Per protocol, 42 out of 55 (76.4%) (p=0.06) treated with 40 mg resomelagon reached ACR20 response compared to 31 out of 51 (60.8%) of those treated with Placebo. ACR50 response was reached in 21 of the 55 (38.9%) vs 18 out of 51 (35.3%) in the placebo group. Deeper clinical response like ACR50 continues to improve after ACR20 saturation, indicating that the ACR50 response will continue to increase with treatment beyond 12 weeks of treatment with resomelagon. In patients entering the study with disease classification ACR/EULAR class II and III further substantiated the potential of resomelagon as ACR20 response reached statistical significance in these patients with 40 out of 52 (76.9%) in the 40 mg resomelagon group versus 26 out 46 (56.5%), (p=0.03) in the placebo treated group. Resomelagon in all dose-groups induced a statistically significant reductions in CRP. The resomelagon 40 mg group, CRP (mean values) went from 23.0 to 9.5 mg/L (p=0.0037), compared to 17.7 to 12.0 mg/L (not significant) in the placebo treated group. The mean reduction in the clinical relevant Simplified Disease Activity Index (SDAI) was 35.9 in the resomelagon 40 mg group versus 28.5 (p=0.03) in the placebo group. As per FDA guidance, DAS28-CRP and SDAI are interchangeable measures to be used for dose response studies. Whereas the response to resomelagon was on par with what has been reported previously (BEGIN and subgroup analysis in EXPAND) the least square mean of reduction in DAS28-CRP (primary endpoint) in the per protocol subjects was 1.98 (SE 0.14) vs 1.79 (SE 0.14) in the placebo treated group (p=0.168). The reduction in the placebo treated group was around 50% larger than what was seen in previous studies which made the primary endpoint inadequate to reach significance within the limits of the study design. Overall, the safety profile of the compound was very good and the compound was well tolerated, no signs of immune suppression were observed, no serious adverse event was reported in the resomelagon treated groups, and reduction in the background treatment with methotrexate due to lack of tolerance was only reported in the placebo treated control group. The results from the ADVANCE study are expected to further fuel partnering and licensing discussions. The ADVANCE study was a 12-week randomized, double-blind, multicenter, placebo-controlled Phase 2b study with repeated doses of 40mg, 70mg, and 100mg of AP1189 and placebo. The study includes 246 newly diagnosed patients with Rheumatoid Arthritis (RA), with elevated inflammation levels (CRP levels above 3mg/l), severe disease symptoms, and ready to initiate 1st line methotrexate therapy. Resomelagon in addition to 1st line methotrexate therapy may be a safe and effective way to reduce disease symptoms and may prolong or prevent the need for additional therapy typically adding glucocorticoids and biologic DMARDS. New Risk • Jun 01
New minor risk - Share price stability The company's share price has been volatile over the past 3 months. It is more volatile than 75% of Swedish stocks, typically moving 9.1% a week. This is considered a minor risk. Share price volatility indicates the stock is highly sensitive to market conditions or economic conditions rather than being sensitive to its own business performance, which may also be inconsistent. It also increases the risk of potential losses in the short term as the stock tends to have larger drops in price more frequently than other stocks. Currently, the following risks have been identified for the company: Major Risks Less than 1 year of cash runway based on free cash flow trend (-kr101m free cash flow). Revenue is less than US$1m. Minor Risks Share price has been volatile over the past 3 months (9.1% average weekly change). Market cap is less than US$100m (kr845.6m market cap, or US$90.9m). 
