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 115

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