ALPN-101 (Acazicolcept) in Systemic Lupus Erythematosus

The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from the SLE Disease Activity Index 2000 (SLEDAI-2K), the British Isles Lupus Assessment Group (BILAG) 2004 Index, and the Physician's Global Assessment (PGA). Participants classified as responder if they met all of the following criteria: 1) ≥ 4-point reduction in the SLEDAI-2K total score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B) compared with baseline; and 3) No worsening from baseline in participants' lupus disease activity (i.e., increase of ≥0.3 0 on a 3-point scale) in PGA. The SLEDAI-2K total score falls between 0 and 105, with higher scores representing increased disease activity. SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG: assesses disease extent, severity (range: A[severe] to E[no disease]). PGA: assesses worsening in participant's general health.

The BICLA is a responder index developed to measure response to therapy, and it includes scores from the BILAG, SLEDAI-2K, and Physician's Global Assessment (PGA). BICLA response is defined as: 1) at least 1 gradation of improvement in baseline BILAG 2004 scores in all body systems with moderate disease activity at entry (eg, all B [mild disease] scores falling to C [Stable and mild], or D [no activity]); 2) no new BILAG A or more than 1 new BILAG B scores; 3) no worsening of total SLEDAI-2K score from baseline; 4) ≤ 10% deterioration in PGA score. The PGA is measured on a 0 to 100 mm scale with score 0 indicates No Disease Activity and score 100 indicates the most Severe Disease Activity.

The BILAG-2004 index covers 86 questions item assessed across 9 organ systems. Each question is answered as 0-not present, 1-improving, 2- same, 3-worse, to 4-new.

The BILAG-2004 index categorizes disease activity in each organ system into five different levels from A to E. Grade A represents requires disease-modifying treatment, Grade B represents mild, reversible problems requiring symptomatic therapy, Grade C indicates mild stable disease, and grade D implies no disease activity, but suggests the organ system had previously been affected. Grade E indicates no current or previous disease activity. Higher scores indicate more severe disease activity. Annualized flare rate is defined as the number of flares observed during the treatment period divided by the flare exposure time in days multiplied by 365.25.

Time-to-first SLE flare is defined as the number of days from the administration of first dose to the first occurrence of flare. A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment. The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.

The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. LLDAS was defined as SLE disease activity index (SLEDAI-2k <=4, with no activity in major organ systems (CNS, vascular, renal, cardiorespiratory and constitutional); where "no activity" is defined as all items of SLEDAI-2K within these major organ systems equal to 0; No new features of lupus disease activity compared to previous occurred visit, where the "new feature" is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; PGA (scale 0-3 higher scores = higher severity), <=1; current prednisolone (or equivalent) dose <=7.5 mg daily; and allowance for maintenance doses of immunosuppressive drugs and approved biological agents.

SLEDAI-2K score is a disease activity score used to identify patients with more active disease at enrolment in study. Total score is defined as the sum of the weighted scores of each individual item within each organ system class. For each system organ with baseline score >0, improvement in SLEDAI-2K improvement is achieved by meeting all the following criteria:

• Reduction in system organ scores among participants with baseline SLEDAI-2K scores greater than 0
• No early discontinuation of study drug
• No use of restricted medications beyond the protocol-allowed threshold before assessment

SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).

CLASI is an validated measurement instrument for lupus erythematosus developed for use in clinical studies that consists of separate scores for the activity of the disease. CLASI Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and nonscarring alopecia. The total CLASI activity score ranges from 0-70, with higher scores indicating more severe skin disease.