Conducting a global, two-trial program in GA will be expensive and time consuming, and even if favorable, the FDA and comparable foreign regulatory authorities may not accept data from one or both of our trials in our global Phase 3 clinical program for ANX007.
The ARCHER II Phase 3 trial is designed to be a global sham-controlled trial and the ARROW trial is expected to be an injection-controlled head-to-head trial against SYFOVRE®. The FDA has recommended the use of an injection comparator instead of a sham control in ophthalmic trials. As a result, the data from the ARCHER II study, even if positive, may be insufficient for regulatory approval in the United States. The Company is planning to conduct the ARROW study to demonstrate ANX007’s significant protection against vision loss over SYFOVRE®. However, the FDA may not agree that the data from the ARROW trial is sufficient to warrant approval of ANX007, even if the results are sufficiently positive. In such an event, we may be required to conduct one or more additional clinical trials before seeking FDA approval of ANX007, which would increase our expenses and could delay or prevent commercialization of ANX007 in GA. Moreover, there are no currently approved therapies for GA in Europe, and the results of the ARROW study may not be acceptable to the EMA or any other comparable foreign regulatory authorities.
Conducting two large Phase 3 trials in multiple jurisdictions is expensive and can take many years to complete, and we cannot guarantee that clinical trials will be conducted as planned or completed timely, if at all. In addition, there are two FDA-approved therapies for GA in the United States, which may adversely impact our ability to recruit patients into our clinical trials. We may need additional capital to complete both the ARCHER II and ARROW clinical trials and may not be able to raise sufficient capital in a timely manner. The occurrence of any such events could delay either trial, prevent us from completing one or more of our clinical trials, seeking FDA approval of ANX007 for GA, if ever, and could delay or prevent commercialization of ANX007.
In addition, none of the FDA-approved therapeutics in GA have been assessed using vision preservation as the primary endpoint. Due to the lack of BCVA ≥15-letter loss results for SYFOVRE®, we may experience difficulties in conducting the ARROW trial, including powering for statistical significance, potential delays in enrollment, emerging safety data for SYFOVRE®, and potential inability to timely obtain SYFOVRE®, which may result in substantial delays in the development of ANX007. There is no assurance that in a head-to-head study, ANX007 will result in statistically significant clinical superiority over SYFOVRE® or that he overall results will be sufficient to support marketing approval.
ANX1502
On December 20, 2023, the Company also reported results from the Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) healthy volunteer study of ANX1502, an oral, selective small molecule inhibitor that targets the active form of C1s responsible for classical pathway activation. ANX1502 was generally well-tolerated and achieved target serum levels and demonstrated pharmacokinetic (PK) measures that support advancement into a proof-of-concept clinical study to assess pharmacodynamic (PD) effect and efficacy in patients with Cold Agglutinin Disease (CAD). Based on these data, the Company intends to advance a tablet formulation of ANX1502 into a proof-of-concept study in patients with CAD, expected to initiate in 2024.
Dose-proportional PK and targeted levels of active drug were observed across both SAD and MAD cohorts of the healthy volunteer study. Single doses of 525 mg to 1025 mg of ANX1502 demonstrated suppressed C4d serum levels in healthy volunteers with higher than median baseline C4d, a biomarker of complement activation. Furthermore, across all doses evaluated, ANX1502 was observed to be generally well-tolerated with mild to moderate treatment-emergent adverse events (TEAEs), none of which exceeded Grade 2. The most frequent TEAEs were gastro-intestinal, which included nausea, emesis, and diarrhea. No serious adverse events were reported, and there were no significant clinical or lab findings.
