Kodiak Sciences : Clinical Trials at the Summit Annual Meeting

KSI-501:

A Novel Bispecific Antibody Biopolymer Conjugate

Targeting IL-6 and VEGF

Mark Barakat, M.D.

Retinal Consultants of Arizona

Clinical Trials at the Summit 2023

10 June 2023

Disclosures

• Presenter's Financial Disclosures:
• • Kodiak (C, S)
• This presentation will discuss IRB/IEC approved research of an investigational medicine.

(C): Consultant; (S): Stock/shareholder; (R): Grants/Research Support

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Key Points

Unmet need

Conclusions

Multifactorial

etiology

KSI-501 - new

category of retinal medicine inhibiting IL-6 and VEGF

Anti-VEGF therapy has transformed the retinal exudative disease landscape, but response to treatment is heterogenous, and treatment burden remains a substantial challenge

The pathophysiology of retinal vascular and hyperpermeability disorders is multifactorial and multiple cytokines beyond VEGF are thought to be involved

• VEGF and IL-6 are key mediators of inflammation, hyperpermeability and angiogenesis, three major components of pathophysiology in these diseases.

Dual inhibition of IL-6 and VEGF may provide additional clinical benefits in DME, wAMD, uveitic macular edema, and other retinal diseases with an inflammatory component

First-in-human Phase 1 multiple ascending dose study is currently ongoing in the US, initially in DME patients. Additional disease cohorts anticipated later in 2023.

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Substantial patient-to-patient variability is the norm for patients treated with anti-VEGF monotherapy

BCVA change from baseline during year 1 for	OCT CST change from baseline during year 1
individual patients treated with Q8W	for individual patients treated with Q8W
aflibercept	aflibercept
BCVA change from baseline (ETDRS letters)	OCT CST change from baseline (µm)

Individual patient variability underlies the mean BCVA and OCT curves for patients treated with

anti-VEGF monotherapy, suggesting need for additional mechanisms of action

Aflibercept-treated subjects completing Year 1 of Phase 2b/3 study of tarcocimab tedromer in wet AMD, NCT04049266.

BCVA, best corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; OCT, optical coherence tomography; CST, central subfield thickness

The pathophysiology of retinal vascular and hyperpermeability disorders involves multiple cytokines

IL-6 Pathway

gp130 IL-6 Rα

	Endothelial	Vascular	Vascular
	Activation	Hypertrophy	Permeability
	Endothelial	Vascular	Immune Cell
	Dysfunction	Fibrosis	Recruitment
Angiogenesis	BRB	Inflammation
Breakdown

• IL-6is a pro-inflammatory cytokine and immune growth factor implicated in the pathophysiology of multiple retinal diseases and is associated with poor anti-VEGF treatment response
• • Associated with higher incidence of proliferative DR
  • Associated with disease progression in AMD, DR and RVO
  • Implicated in anti-VEGF treatment resistance
  • Upregulates VEGF
  • Stimulates defective angiogenesis independent of
    VEGF

BRB: blood retinal barrier

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