ALX Oncology : ASH Conference Call Presentation

ASH Conference Call

Evorpacept: Targeting CD7 as a Myeloid Checkpoint in MDS

• CD47, a marker of self, is upregulated by tumors to evade the immune system
• CD47-SIRPαsignaling represents a myeloid checkpoint mechanism in cancer
• CD47 engages SIRPα and signals the macrophage to ignore the cell on which it is expressed

High Affinity CD47

Binding Domains of SIRP⍺

Inactive

Fc Domain

Molecular weight half the	Evorpacept increases pro-phagocytic	While sparing normal hematopoietic cells
size of a typical antibody	signal provided by azacitidine	from destruction
2 Kauder, SE. et al. PLoS ONE. 2018 August;13(8): e0201832

Preclinical: Evorpacept increases phagocytosis of leukemia cells in combination with backbone MDS drug azacitidine

Calreticulin levels on HL60 Cells

	2.0
over mediaonly)	1.5
1.0
(fold
Calreticulin	0.5
	0
	0	0.039	0.078	0.156	0.312	0.625	1.25	2.5

Azacitidine (uM)

Phagocytosis of HL60 Cells

	50
	40
Phagocytosis,%CFSE+	30
20
	10
	0
	Media	312 nM	40nM	evorpacept+
	only	azacitidine	evorpacept	Azacitidine

Azacitidine induces calreticulin display

Evorpacept increases phagocytosis in combination with azacitidine

3

Evorpacept (ALX148) + AZA Combination Significantly Increases Efficacy in Disseminated AML Xenograft Model

Total Flux (photons/sec)

				HL60 LUC
10	11
				PBS
10	10			ALX148 (30 mg/kg)
10	9			Azacitidine (5mg/kg)
10	8			Azacitidine + ALX148 (30)
10	7
10	6
10	5
⇑⇑⇑⇑⇑⇑⇑⇑⇑⇑⇑⇑⇑⇑
		50	100
		03
			Day Post Innoculation

		HL60 Survival
Survival	100
80			ALX148 (30 mg/kg)
			PBS
of	60
			Azacitidine (5mg/kg)
Probability
40			Azacitidine + ALX148
	20
	0
	0	50	100	150

Day Post Innoculation

Chen et al., ASH 2020 Abstract #1965

4

ASPEN-02 Study Design

Incorporation of dose optimization in Phase 1 prior to initiation of randomized phase 2 study

Phase 1 3+3 Dose Escalation (N~18)

Rel/ref or previously untreated higher-risk MDS

ALX148 60 mg/kg

IV Q4W

	+AZA 75 mg/m2
ALX148 30 mg/kg	daily x 7d
IV Q2W	28-day cycles

ALX148 20 mg/kg

IV Q2W

Phase 1 Dose Expansion (N~40)

Previously untreated higher-risk

MDS

Expansion Dose 1 (N~20)

ALX148 at 60 mg/kg IV Q4W +AZA 75 mg/m2 daily x 7d

Expansion Dose 2 (N~20)

ALX148 at 40 mg/kg IV Q4W +AZA 75 mg/m2 daily x 7d

Phase 2 (N~155)

Previously untreated higher-risk MDS

		ALX148 at RP2D
randomize		+AZA 75 mg/m2 daily x 7d
2	28-day cycles
	:
	1
	AZA 75 mg/m2 daily x 7d
		28-day cycles