Pharma Update
Antisense oligonucleotide Factor B in IgAN
IONIS Roche
Positive Ph II UPCR results at 6 months; Ph III (IMAGINATION) initiated in Q2 2023
Antisense oligonucleotide Factor B
(ASO FB)
Alternative complement pathway
ASO FB
C34,0
C3
Clinical development program in IgA nephropathy
Early Ph II results³
Ph III (IMAGINATION) trial design
Experimental
Primary endpoint: Change
in UPCR
arm
C5a
C5
AP C5
Convertase
Factor
D
Factor
AP C3
Convertase
cau
Bb
Amplification
Loop
Factor
D
CBb Bb C36
C3b
Factor
Factor H
C5b
C6-C9
C3
iC3b
CR1
Factor
MAC
C3dg
Opsonization
Inflammation
Cell Lysis
C3a
Inflammation
Change from baseline (%)
-100
09-
-20 0 20 40
Change in UPCR at week 29 (n=10)
Estimated
Enrollment R
N=428
OLE
Q4W dosing until week
105
I
Placebo
arm
D D D
1 15 29
W
Wk
37
105
➡ASO FB subcutaneous
➡Placebo subcutaneous
•
·
Globally, IgAN is the most common primary GN
that can progress to renal failure
High levels of CFB are associated with IgAN 1,2
• ASO FB downregulates CFB production by
inhibiting mRNA translation
⚫ Ph II study met its primary endpoint of change in 24-hour urinary protein, with 44% mean reduction in
proteinuria from baseline to week 293,4
• Achieved secondary endpoint of change in UPCR from baseline to week 29; kidney function stable during
the study³; updated Ph II data to be shared at medical conference in Q4 2023
.
Ph III (IMAGINATION) of ASO FB in IgAN initiated in Q2 2023
Figure adapted from: Barbour et al. ASN Annual Meeting 2022; 1. Chiu et al. Front Immunol. 2021; 12: 638309; 2. Yeo et al. Pediatr Nephrol 2018: 33:763-777; 3. Barbour et al. An Exploratory Trial of an Investigational RNA Therapeutic, IONIS-FB-LRx, for
Treatment of IgA Nephropathy. ASN 2022 Abstract SA-PO714; 4. IONIS press release 2022: https://ir.ionispharma.com/news-releases/news-release-details/ionis-presents-positive-phase-2-data-patients-iga-nephropathy; ASO-Antisense oligonucleotide;
FB-Factor B; IgAN=IgA Nephropathy; CFB-Complement factor B; mRNA-messenger RNA; MoA-Mode of action; UPCR=Urine protein/creatinine ratio; SC-Subcutaneous; Q4W-every 4 weeks; GN=Glomerulonephritis; Ph II trial: NCT04014335; Ph III
(IMAGINATION): NCT05797610; ASO Factor B in partnership with IONIS Pharmaceuticals
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