Clearside Biomedical : CLS-AX OASIS Cohort 1 Clinical Data

CLS-AX

(axitinib injectable suspension) for Suprachoroidal Injection

OASIS Cohort 1 Clinical Data

CLS-AX Phase 1/2a Clinical Trial in Wet AMD

Trial Design and Objectives

• Open-labelstudy to evaluate safety and tolerability of escalating single doses of CLS-AX administered through suprachoroidal injection following IVT aflibercept
• 3 Cohorts of 5 patients each: n=15
• Dose-escalationof CLS-AX(in mg): Cohort 1 at 0.03; Cohort 2 at 0.10; Cohort 3 currently planned at 0.30
• Evaluate visual function, ocular anatomy, and need for additional treatment
• Assessment for additional treatment: loss from best measurement of >10 letters in BCVA with exudation; increase in CST >75 microns; a vision-threatening hemorrhage

Cohort Enrollment and Treatment
Screening	Baseline	Week 4	Week 8	Week 12
2 mg aflibercept	CLS-AX dosed at baseline	Assessment for	Assessment for	Assessment for
dosed at screening	(30 days post screening)	additional treatment	additional treatment	additional treatment

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Note: aflibercept is dosed via intravitreal injection (IVT); CLS-AX is dosed via suprachoroidal injection | clinicaltrials.gov NCT# 04626128

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Cohort 1: Encouraging Results Support Progression to Cohort 2

• Cohort 1 Objective: To establish a floor of safety in this first-in-human trial with low dose CLS-AX (0.03 mg dose)
• Highly treatment-experienced (at screening prior to aflibercept administration)
• • Total number prior anti-VEGF treatments: mean = 25.8, median = 28.0
  • Total number prior anti-VEGF treatments within the last 12 months: mean = 9.0, median = 11.0
• Demographics & disease characteristics (at baseline prior to CLS-AX administration)
• • Average age: 82 years
  • Mean central subfield thickness (CST) of the macula was 231 µm (range 208 - 294 µm)
  • Mean best corrected visual acuity (BCVA) score was 59.0 (range 29 - 74)
• Conclusion
• • Cohort 1 supports progression to Cohort 2

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Source: Clearside data on file.

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Cohort 1: Summary of Primary and Secondary Measures

SAFETY: CLS-AX WELL TOLERATED

• No study suspension or stopping rules were met
• No SAEs have been reported
• No signs of inflammation, vitreous haze, IOP safety signals, vasculitis, or intravitreal dispersion of investigational product
• 2 TEAEs assessed as unrelated to CLS-AX by the investigators

• Source: Clearside data on file. |. *Post hoc, unadjusted

BCVA AND ANATOMIC RESULTS

• 1-monthvisual acuity improvement of 1 line post CLS-AXvs no change for aflibercept, at this initial low dose
• • Aflibercept: 1-month BCVA change -0.2 ETDRS letters (p=0.862*)
  • CLS-AX0.03 mg: 1-month BCVA change +4.7 ETDRS letters (p=0.029*) with 5/6 patients improving by 4 or more letters
• Mean CST stable within 50 µm at one month post 2 mg aflibercept and at one month post 0.03 mg CLS-AX
• • In these treatment-experienced patients, the normal screening baseline CST imposes a floor effect, limiting improvement in CST

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Best Corrected Visual Acuity

One Month Response Following Aflibercept 2 mg vs CLS-AX 0.03 mg

1 Mo Change after Aflibercept : -0.2 letters, P=0.862*

		9
ScoreLetterBCVAinChange	BaselineandScreeningBetween	8
7
		6
		5
		4					+3
		3
		2			+1	+1
		1	-2			-0.2
		-1
		-3
		0
		-1
		-2
		-3
		1	2	3	4	5	6	Mean
					Subject Number

Mean BCVA at screening (prior to aflibercept) = 59.2

1 Mo Change after CLS-AX : +4.7 letters, P=0.029*

		9			+9
		8					+7
Change in BCVA Letter Score	Between Baseline and Week 4	7
			+6
6
5	+4	+4					+4.7
4
3
2
1						-2
0
-1
		-2
		-3	1	2	3	4	5	6	Mean

Subject Number

Mean BCVA at baseline (prior to CLS-AX ) = 59.0

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Source: Clearside data on file. |. *Post hoc, unadjusted

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