Voyager Therapeutics : HER2+ Vectorized Antibody Presentation (SNO 2021)

AAV MEDIATED BRAIN DELIVERY OF AN ADCC-ENHANCED ANTIBODY

OBVIATES XENOGRAFT GROWTH IN MOUSE MODELS

OF HER2+ BREAST CANCER BRAIN METASTASIS

Dan R. Laks, PhD

Scientist II, Voyager Therapeutics

Society for Neuro-Oncology (SNO)

Friday, November 19, 2021

© Voyager Therapeutics

Disclosures

Dan Laks is a full-time employee of Voyager Therapeutics

© Voyager Therapeutics

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Hypothesis: AAV mediated production of anti-HER2 antibodies in the CNS will mitigate prognosis of metastatic HER2+ breast cancer

Suggest bolding subtitles

Systemic αHER2	AAV gene therapy can
antibody therapies are	enter the brain and
limited in their CNS	generate stable
distribution by the	expression of
blood-brain barrier and	therapeutic antibodies
CNS efflux
Addressing an unmet medical need

© Voyager Therapeutics

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Strategy: Employ brain cells as antibody factories through AAV mediated gene therapy

ADCC+	rA	AV targetin	g
	the CNS
(enhanced)

Antibody prevents receptor dimerization & promotes ADCC (antibody dependent cell cytotoxicity).

Vectorized antibodies are a method to generate persistent, high coverage target-engagement in the CNS

© Voyager Therapeutics

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Relative Viability (% of Isotype Control)

Transgene: A vectorized αHER2 mAb with enhanced ADCC (ADCC+) properties

		BT474			Promega ADCC Reporter Bioassay		Promega ADCC Reporter Bioassay
				FcγRIIIa V158 Variant (High Affinity)		FcgRIIIa F158 Variant (Low Affinity)
125						BT-474 target cells					BT-474 target cells
				60							60
				Induction	50						Induction	50
100				40						40
				Fold	30						Fold	30
75				20						20
				10							10
					0							0
					0.0001	0.001	0.01	0.1	1	10		0.0001	0.001	0.01	0.1	1	10
50					vAntibody Concentration (μg/mL)			vAntibody Concentration (μg/mL)
IC50: 0.0502 ug/ml					Isotype Control						Isotype Control
	Emax: 31.72%					vTrastuzumab						vTrastuzumab
					αHER2 mAb ADCC+						αHER2 mAb ADCC+
25
0										Cell/Tumor models
0.001	0.01	0.1	1	10
	vAntibody Concentration (µg/mL)		BT-474-Luc: Primary HER2 ductal carcinoma, breast
	Isotype Control			cancer tumor cells.
	αHER2 mAb ADCC+		MDA-MB-361-Luc: Originated from breast cancer brain
		metastasis tumor cells, of HER2 adenocarcinoma
					(glandular), cultured as tumorspheres.
															© Voyager Therapeutics	| 5 |