Jeopardy!

Broad Population

100

What is the indication for Imaavy?

IMAAVY is a neonatal Fc receptor blocker indicated for the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients 12 years of age and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

200

What is the inclusion criteria for Vibrance re: age?

Pediatric participants 2 to less than (<) 18 years of age (globally) and 8 to <18 years of age (for United States sites only).

300

How was seronegative defined in the Vivacity trial vs. ADAPT SERON?

Vivacity: diagnosis of gMG with generalized muscle weakness meeting the clinical criteria as defined by MGFA Clinical Classification Classes IIa/b, IIIa/b, or IV a/b at screening. Participants undetectable for all gMG-implicated autoantibodies were considered as seronegative.

ADAPT SERON: AChR-; abnormal SFEMG or MuSK+, PLUS history of + edrophonium chloride test or positive response to previous MG treatment (AChEI, IVIg/SCIg, PLEX, etc.).

400

What was the QMG change from baseline over weeks 22 and 24 in the MuSK+ group?

Imaavy + SOC: -5.50

Placebo + SOC: -1.73

(between group difference of -3.77)

Sustained Efficacy

100

What population was allowed to enroll into the OLE study?

Patients from phase 2 and phase 3 could enroll. 

Data presented has been from the primary efficacy population (seropositive: anti-AChR+, anti-MuSK+ and/or anti-LRP4+) from Vivacity-MG3.

200

What was the earliest time point that NIPO showed improvement over placebo for MG-ADL? QMG?

Clear separation from placebo was observed at week 1 for MG-ADL (LSM: –0.82; SE: 0.410) and week 2 for QMG (LSM: –3.08; SE: 0.506).

300

What % of participants in the OLE were able to decrease or stop steroids by week 60 and was efficacy maintained?

45% (40/89) of participants receiving steroids at open-label baseline were able to decrease or discontinue steroids at data cutoff of week 60.

Efficacy was maintained in participants who decreased/discontinued steroids.

400

At OLE week 60, what were the changes from baseline in MG-ADL for PBO/NIPO + SOC and NIPO/NIPO + SOC?

At OLE week 60, MG-ADL mean (SE) change from double-blind baseline was −6.01 (0.503) in PBO/NIPO + SOC and −5.64 (0.621) in NIPO/NIPO + SOC.

Safety & IgG Reduction

100

What are the 7 infection categories reported in Imaavy patients listed in the PI?

Upper respiratory tract infection (46%), respiratory tract infection (28%; including pneumonia, bronchitis, COVID-19), urinary tract infection (15%), herpes (8%; including herpes simplex, herpes zoster, herpes zoster oticus), influenza (8%), oral infection (8%; including candidiasis and dental infections), and skin infection (7%; including cellulitis).

200

What were the IgG reductions at the end of the OLE for both groups?

At OLE week 60, mean (SE) % change from baseline of IgG levels were –61.56 (2.297)% in NIPO/NIPO + SOC and −61.96 (2.686)% in PBO/NIPO + SOC groups.

300

How many adjudicated MACE events occurred during the OLE?

Fatal: 2 events, 2 patients

Non-fatal: 7 events, 1 patient

400

Across all NIPO studies, what are the incidence rates per 100 patient-years for herpes zoster for NIPO and PBO arms?

In a pooled analysis of the double-blind, PBO-controlled periods across all indications in which IMAAVY has been studied (i.e., phase 2 and 3 clinical studies in gMG, Sjogren’s disease, rheumatoid arthritis and systemic lupus erythematosus), exposure-adjusted incidence rates per 100 patient-years for herpes zoster were 3.12 and 1.09 in the IMAAVY and PBO arms, respectively.

Pipeline Team

100

Which of our competitors has an oral tablet under investigation for wAIHA and what is that MOA?

1. Rilzabrutinib 400 mg oral daily (Wayrilz label for ITP)
2. Sanofi
3. BTKi blocks the bruton tyrosine kinase (BTK) enzyme crucial for B cell receptor signaling, thereby preventing proliferation, survival, and activation of B cells. 
4. Wayrilz is selective, reversible inhibitor that inhibits B cell activation and interrupts phagocytosis by Fcgamma receptor. It has covalent and noncovalent binding which increases selectivity (LUNA3)

200

Why is wAIHA so heterogeneous and unpredictable? 

Cases can develop gradually or fully compensated to fulminant presentation and rapid onset of life-threatening anemia

Determinants of heterogeneity are: 1) Type of hemolysis (intravascular or extravascular) which is related to autoantibody class; 2) Thermal amplitude and efficiency in activating complement; 3) Efficacy of erythroblastic response 

300

In the ENERGY trial, was NIPO studied in the various types of mechanisms of disease, i.e. primary versus drug-induced, SLE/CLL associated disease, transplants, etc.? 

1. Patients secondary to other autoimmune disease or lymphoproliferative disorders may be eligible if they are stable (no changes in concomitant disease-related medications and severity of disease) for at least 3 months prior to SCREENING. Patients with lymphoproliferative disease must also have a low grade, but stable and be, in the opinion of the Investigator, unlikely to require chemotherapy or monoclonal antibody therapy during double-blind period of the study. Patients requiring change of treatment or new treatment (but not rescue therapy for wAIHA) during the double[1]blind period will be terminated from the study.

400

Who will be eligible for OLE?

Have completed the double-blind period (through Week 24), or

• have required rescue therapy after Week 4 of the double-blind period, or
• failed to demonstrate an increase from baseline in Hgb of at least 1 g/dL at or after Week 16 of the double-blind period