High Affinity CD47
Binding Domains of SIRPα
Optimized, picomolarbinding affinity

Best Relative Change from Baseline
in Myeloblast Values (%)

Abstract ID# CT060

300

Fc domain mutated toeliminate Fcγ receptor
binding and minimize
associated toxicity

Inactive
Fc Domain

250
200

ASPEN-02: A Phase 1 Study of Azacitidine in Combination with Evorpacept forHigher-Risk Myelodysplastic Syndrome (MDS)
Fc domain mutated toeliminate Fcγ receptor
binding and minimize
associated toxicity

Inactive
Fc Domain

150

100

Inactive Fc

Evorpacept

50

Best Relative Change from Ba
in Myeloblast Values (%)

binding affinity

Evorpacept

0

SIRPα

Cancer Cell

CD47

150
100
50
0
-50
-100
-150
1

2

3

4

5

Guillermo Garcia-Manero , Bart L. Scott , Ashwin Kishtagari , Srinivasa R. Sanikommu , Aref Al-Kali , Je-Hwan Lee , Juan Miguel Bergua-Burgues , Maria Diez-Campelo , Harry P. Erba , Carmen Garcia-Hernandez ,
11
12
13
14
15
16
16
16
16
16
16
17
, Jessica K. Altman
Guillermo Sanz Santillana , Casey O’Connell , Jun Ho Jang , Dong-Yeop Shin , Hamid Sayar , Mayank-100Rao , Richard S. Schwartz , Xuebei An , Feng Jin , Alison J. Forgie , Athanasios C. Tsiatis
1800
1

2

3

4

5

Inactive Fc

Evorpacept

6

-50

7

8

Calreticulin

SIRPα

LRP

Evorpacept

Red Blood
Cell

9

10

Azacitidine + ALX148 20 mg/kg Q2W (n=1)

6

7

8

9

Azacitidine + ALX148 60 mg/kg Q4W* (n=12)

FcγR

Azacitidine

Ph 1 Dose Expansion (N~40)

ALX14830 mg/kg
IV Q2W

Figure 1. Evorpacept Potently and Selectively Blocks CD47 Binding to SIRPα• Fc domain enables

IV Q2W

antibody-like PK.
• Molecular weight ishalf the size of typicalantibody.

250 200

200 150Cancer Cell

LRP
Azacitidine

Patient

Macrophage200 150

Median Age, Years (range)
Sex, nRace, nWorking Group (IWG) criteria.3
mCR
On Treatment
SD
mCR*
mCR*
• The Phase 1 will enroll
approximately
up to 18 patients over 3 planned dose levelsin theOff Treatment
PD
mCR expansion
dose escalation part, and approximately 40 patients over 2 dose levels in the doseSD # Proceeded topart (Figure**3). mCR*
stem cell transplantPD# Proceeded to

2

3

4

Months5Months66stem cell transplant

7
7

8

8

9

9

10
10

0

White
Black
0 -50
Asian
-50 -100
Other
Unknown

Cytogenetic
Risk atScreening,n (%)

On Treatment• Response assessments were performedbytheinvestigatorpermodifiedInternational
mCR*
mCR*
Off Treatment

5

M
50
F 100

ALX148 Serum Concentrations (µg/mL)

Patient

Patient

mCR
and adverse events as characterized by type, frequency, severity, timing, seriousness andrelationship to study treatment.
SD**mCR• Key eligibility requirements include patients with R/R or ND HR-MDS (IPSS-R score >3.5) andPD with R/RSD**a baseline ECOG status of 0-2. For patients
MDS, prior exposure to hypomethylating
agents (HMA) is allowed (Dose escalation). Patients with ND HR-MDS must have had no priorPD
mCR
exposure to HMA or cytotoxic chemotherapy
forthe# treatment of MDS (prior use of single
agent lenalidomide for low or intermediate-1 risk MDS with deletion 5q abnormality is#
mCR*mCRfor
allowed) and must be appropriate candidates
single-agent AZA treatment.

1

–

–

–

–

–

3

100 –

–

–

–

3
SIRPα

–

–

1

1

–

Cancer Cell

Cancer Cell

Decreased
LRP

–

7

ND HR-MDS
N=52
70.5 (24-88)

8
5

31
21

10
2
0
0
1

41
3
6
1
1

8

FcγR
SIRPα

2
–
Macrophage
–

3

1

1
FcγR

–

5

–

9 (13.8%)–

8 (12.3%)

Evorpacept Red Blood
–
5
–
Cell

SF3B1
10
SRSF2
RUNX1

2 (15.4%)
01 (7.7%)1

Very Good01 3 6
1
Good
01 3 624
Intermediate
Poor
Very Poor
Not Evaluable
Missing

24

48

150
200

3
–
2

–
3
–

3
Red Blood
Cell

–
1

Macrophage

1

1 48

–
–
–

-150

8 (12.3%)

1800

8 (12.3%)
5 ( 7.7%)

Expansion– Ph 1 Dose3–
– (N~40)1

5 ( 7.7%) **–4 ( 6.2%)

Previously
168
3– untreated– 336 –
higher-risk
MDSTime (hour)0Expansion
1 Ph 1 Dose
– Dose2Group 1 (N~40)–
4 ( 6.2%)
Previously untreated
Azacitidine + Expansion
ALX148 20 mg/kg
Q2W1–(Dose~20)Escalation (n=3)
Dose

–

1

–

3

–

3 (5.8%)8 (15.4%)
8 (15.4%)

4 ( 6.2%)

higher-risk
MDS
Azacitidine + ALX148
30 mg/kg Q2W– Dose Escalation (n=3)
ALX148
Azacitidine + ALX148 60 mg/kg Q4W – Escalation + Expansion (n=38)–– 60 mg/kg
3 IV Q4W
1–
4 ( 6.2%)
Azacitidine + ALX148 40 mg/kg Q4W – Dose Expansion (n=20)

Expansion Dose
1 (~20)
+
–
–
–
3
–
–
3 ( 4.6%)
Azacitidine
ALX148+ Azacitidine
2
Azacitidine+ ALX148 40
mg/kg Q4W**(n=23)
9
10
Daily
x–7d
75
mg/m
60
mg/kg
IV Q4W
Neutropenia
–
–
–
–
–
1
2
3 ( 4.6%)
2
ALX148 IV Q4W
75 mg/mAzacitidine + ALX148 60 mg/kg Q4W** (n=29)
30* Data
mg/kg
Cutoff 03January 2024; Safety population(n=65); Table includes evorpacept related+adverse events in ≥5% of patients andDaily x 7d
all Grade 3 and Grade 4 evorpacept-related adverse events occurring in ≥2 subjects.
Azacitidine
IV Q2W~20)+ Azacitidine
ExpansionDose
2x (7d228-DayCycles
Daily
75
mg/m
ALX14875 mg/m2
Total
ALX148
30
mg/kg
N=65
Daily x 7d
40 mg/kg IV Q4W
ALX148 IV Q2W
Expansion Dose2 (~20)+28-Day Cycles
70.0 (24-88)
20 mg/kg• Among subjects evaluable for response:
Azacitidine
ALX1482
Daily
x 7d 8 with CR,
mg/m
IV Q2W • 21 out of 52 (40.4%) subjects with ND HR-MDS achieved75
40
mg/kg
IVincluding
Q4W
a response,
39
ALX148+
1 with PR, 10 marrow CR, 2 with HI-E and HI-P, 21 SD and 3 PD.
26 20 mg/kg
Azacitidine• 2 out of 13 (15.4%) subjects with R/R MDS achieved a response,
including 2 marrow CR, 8 SD
75 mg/m2 Daily x 7d
and 2 PD.
IV Q2W
51• The median duration of treatment is 4.6 months (range: 0.9-22.1 months) for ND HR-MDS
5
and 3.7 months (range:
0.9-17.1 months) for R/RMDS
MDS. The median duration of treatment
6
Relapsed/Refractory
for all patients is 4.4 months (range: 0.9-22.1).
1
2• Decrease in bone marrow blasts was observed in subjects with both ND HR-MDS andInitial Activity of EVO + AZA

SD**

168

5 (7.7%)8 (12.3%)
9 (13.8%)0 **336 1 (1.5%)

with HI-E
1 with HI-P
2
with HI-N

SD
672 2
1
PD

3

4

05

Months8 (61.5%)
4 2 (15.4%)
5

6

2 (3.8%)2 (3.1%)PD
210(3.1%)
7 2 (3.8%) 8 # Proceeded
9 tostem cell transplant 1 (1.5%)
1 (1.9%)21 (40.4%)
7 3 (5.8%) 8

29 (44.6%)510(7.7%)0
1 (1.9%)
0
3
6
9
Time
(hour)
Months4 (30.8%)
17 (32.7%)
21 (32.3%)Not
0
3 (5.8%)3 (4.6%)48336
672 Evaluable
4 (30.8%)168
10(19.2%)
14 (21.5%)
Dose
Group
Time 20(hour)No Post-Baseline
1Azacitidine(7.7%) + ALX148
6 mg/kg(11.5%)Q2W – Dose Escalation
7 (10.8%)(n=3)
1 (7.7%)4 (7.7%)5 (7.7%)
Assessment
4 Azacitidine(30.8%) + ALX148(28.8%)(29.2%)
30
mg/kg Q2W – Dose 19
Escalation(n=3)
Dose15Group
Azacitidine+ ALX148
60
Escalation+ Expansion (n=38) Note: Only Best Overall Responses lasting at least 4 weeks for CR, PR, mCR, CyR and at least 8 weeks for HI are included; The
0 + ALX148
2 mg/kg(3.8%)
2 (3.1%)
Azacitidine
20 mg/kg
Q2W –Q4W
Dose– Escalation(n=3)
Azacitidine+ ALX148
401 mg/kg
Dose Expansion
Azacitidine
30 mg/kg
Q2W –Q4W
Dose– Escalation(n=3) (n=20)
0 + ALX148(1.9%)
1 (1.5%)best overall response is determined over the first 6 cycles of treatment; Data are pooled between dose escalation and expansion.

Azacitidine + ALX148 60 mg/kg Q4W – Escalation + Expansion (n=38)
Azacitidine + ALX148 40 mg/kg Q4W – Dose Expansion (n=20)
Azacitidine + ALX148 40 mg/kg Q4W** (n=23)
Azacitidine + ALX148 60 mg/kg Q4W** (n=29)

Azacitidine + ALX148 40 mg/kg Q4W** (n=23)
Azacitidine + ALX148 60 mg/kg Q4W** (n=29)

-150
-100

8 (12.3%)

R/R MDS (Figure 4). Relapsed/Refractory MDSECOG PS, n
0
3
24
27
-150
mCR (95% CI 5.8 months, NA) and• Median duration of response (DOR) was 8.5 months
1
10 40 mg/kg Q4W** (n=23)
21
31 60 mg/kg Q4W** (n=29)
Azacitidine + ALX148
Azacitidine + ALX148
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
41 months (95% CI NA, NA) for ND HR-MDS, and
3.5
R/R MDS, respectively.
SD**
2
0
7
7
SD** (95% CI 12.6, 17.9 months) and 11.9 months•
Medianoverallsurvival
(OS)
was
16.6
monthsAzacitidine+
ALX148
40
mg/kg
Q4W**
(n=23)
Azacitidine+
ALX148
60
mg/kg
Q4W**
(n=29)
10000
mCR(95% CI 5.7, 19.4 months) for ND HR-MDS and R/R
MDS, respectively.
Therapy Related
3 (23.1%)
9 (17.3%)
12 (18.5%)
MDS Status,
PDn (%)
Prior HMA Treatment
13 (100%)0
13 (20.0%)
10000
SD**
#
mCR by Modified IWG Criteria3
Table 3: Best Overall Response
IPSS-R Score<4 1000
2 (15.4%)
1 ( 1.9%)
3 ( 4.6%)
PD
at Initial
4-4.5
2 (15.4%)
16 (30.8%)
18 (27.7%)mCR*R/R MDS (N=13)
ND HR-MDS (N=52)
Total (N=65)
Diagnosis,>4.5-65 (38.5%)
14 (26.9%)
19 (29.2%)
1000
#
mCR
ORR
2 (15.4%)
21 (40.4%) On Treatment 23 (35.4%)n (%)>64 (30.8%)
21 (40.4%)
25 (38.5%)
mCR*
Off Treatment
100CR
0
8 (15.4%)
8 (12.3%)
mCR
mCR*
Mutation
TP53
5 (38.5%)
17 (32.7%)
22 (33.8%)SD
PR mCR*0
1 (1.9%)1 (1.5%)On
Treatment
100
PD
Status, n (%)
ASXL1
5 (38.5%)
11 (21.2%)
16 (24.6%)
mCR*
Treatment
2 (15.4%)
10 (19.2%) # Off
12 (18.5%)
Proceeded to
TET2
5 (38.5%)
6 (11.5%)
11 (16.9%)** Marrow CR
mCR
stem cell transplant
10
DNMT3A
2 (15.4%)
10 (19.2%)
12 (18.5%)
HI mCR*
2 (3.8%)2 (3.1%)SD• The primary Phase 1 endpoint is the frequency of first cycleSD**
dose-limiting toxicities (DLTs)0–

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41• The primary Phase 1 objective is to characterize the safety and tolerability of EVO
MDSSD**
administered in combination withRelapsed/RefractoryAZA.

4

150 100

50

670.0 (62-81)-100 -150(20 mg/kg Q2W, 30 mg/kg Q2W, or 60 mg/kg Q4W) combined with AZA (75 mg/m2 IV/SC x7d) in a 28‑day treatment cycle. Subsequently patients with ND HR-MDS were randomized
to receive EVO 40mg/kg Q4W or 60 mg/kg Q4W in combination with standard AZA in
expansion cohorts.
Relapsed/Refractory MDS

3

R/R MDS
N=13

250 200

ASPEN-02 Phase 1 Design

2

SIRPα
CD47
Neutrophil

01750 1700
0
1
2300
3
4
5
Months1700
Table 1. Patient Baseline Characteristics
300 250

Methods

1

Calreticulin

Vomiting–

Calreticulin
Azacitidine
Infusion Relatedwith R/R MDS (EVO 0doses
of
20
mg/kg
Q2W
[n=1]
or
60
mg/kg
Q4W
[n=12]),
and52
subjects
10 –Macrophage-50
Reaction

Previously
untreatedor previously
untreated• TreatmentRel/refwith azacitidine
inducescell-surface expression of calreticulin,
a pro-phagocytic
higher-risk MDS
signal. Concurrenthigher-risk
blockadeMDSof the CD47 myeloid checkpoint with EVO
may augment
theExpansion
Dose
1
(~20)
ALX1482
phagocytosis of leukemia cells by macrophages, in preclinical models.
ALX14860 mg/kg~Q4W
Expansion
Doseon1IV(normal20)• Toxicity from CD47-targeted
antibody
dependent
cellularphagocytosis(ADCP)
60
mg/kg
ALX148
IV Q4W
hematopoietic cells
is spared due to evorpacept’s inactivated Fc region.ALX148 +60 mg/kg
60 mg/kg
IV Q4W
Azacitidine
IV Q4W+ Azacitidine
2+
Daily x 7d
75
mg/m
2
ALX14875 mg/mAzacitidine
30 mg/kg
Daily x 7d
+ Azacitidine
2
Daily x 7d
75
mg/m
2
ALX1487528-Day
mg/m Cycles
IV Q2W
Expansion Dose 2 (~20)
30 mg/kg
Daily x 7d
ALX148
IV Q2W
Expansion
20)
40 Dosemg/kg2IV(~Q4W
28-Day Cycles
ALX148
ALX148 +20 mg/kg
40 mg/kg
IV Q4W
Azacitidine
ALX148+ 2 Daily x 7d
75 mg/mIV Q2W• Usinga 3+3 dose escalation, subjects with relapsed/refractory (R/R) or Azacitidinewith higher risk (HR)20 mg/kg
2
andof intravenous
Daily x 7dEVO
75 mg/mIVnewly
Q2W diagnosed (ND) MDS were administered escalating doses

0

Nausea• As of January 3, 2024, 65 subjects were treated inSD**
the phase 1 portion, including 13 subjects

Ph 1 Dose Expansion (N~40)
Ph 1 3+3 Dose Escalation (N~18)• In vitro modelsRel/ref
suggestthat evorpacept
enhances phagocytosis in combination
Previously untreatedor previously
untreatedhigher-risk MDS
MDS
Ph 1 Dose Expansion(N~40)
Ph 1 3+3 Dosehigher-risk
Escalation(N~18)
with azacitidine.

**

CD47

–

Patient Patient

Macrophage

SIRPα

mCR
Patient Baseline
Characteristics
50

ALX148 Serum Concentrations (µg/mL)

Cancer Cell

Azacitidine

Diarrhea
Evorpacept

SD**

100 50Best Relative Change from Baseline
in Myeloblast Values (%)
Best Relative Change from Baseline
in Myeloblast Values (%)

Evorpacept

Macrophage
LRP

Relapsed/Refractory MDS

Evorpacept
InactiveFc–
63

with ND HR-MDS (EVO doses of 40
PDmg/kg Q4W [n=23] and 60 mg/kg Q4W [n=29]).
LRP
Inactive Fc
PlateletCount• For all 65 patients,-50
medianage
was70(range24–
88)years,
andbaseline
ECOG
scores––-100#
Azacitidine
Decreased
mCR
were
0
(n=27,
41.5%),
1(n=31,
47.7%),
or2(n=7,
10.8%).
Macrophage
Inactive Fc
1 –(N~18)–
Evorpacept
Ph 1Fatigue
3+3 Dose Escalation-100• 3/13 (23.1%) R/R MDS and
ND HR-MDS patients, 12/65 (18.5%) patients overall,-150 9/52 (17.3%)
mCR*
Rel/refor previously untreated
01 3 6 – 24Constipation–
had therapy-related MDS.
Evorpacept
1
2
3
4
5
6 On Treatment
7
8
9 higher-risk MDS
-150
White
BloodEscalation
Cell
ND
mCR* in 5/13 (38.5%) R/R MDS and 17/52 (32.7%)
Off Treatment
Ph
1
3+3
Dose
Red Blood • TP53 mutations were present at baseline–(N~18)–
Azacitidine+
ALX148
20
mg/kg
Q2W
(n=1)
Azacitidine+
ALX148
60
mg/kg
Q4W*
(n=12)SIRPαCount Decreased
Cell
HR-MDS patients, 22/65 (33.8%)
overall.
mCR7
1
2
3
4
5
6
8
9
Rel/refor previously untreatedSD
ALX148 MDS –mCR* risk (Complex: >3 abnormalities) was present in 4/13 (30.8%)
Chillshigher-risk–
Red Blood
•
Very
poor
cytogenetic
R/R
MDS
Azacitidine+
ALX148
20
mg/kg
Q2W
(n=1)
Azacitidine+
ALX148
60
mg/kg
Q4W*
(n=12)
SIRPα
1800
PD
60 mg/kg
Cell
and
in
15/52
(28.8%)ND
HR-MDS,
19/65(29.2%)
overall.
Febrile# Proceeded to
FcγR
**
–
–
IV
Q4W
Neutropenia
stem
cell
transplant• 13/13 (100%) R/R MDS
patients had received prior hypomethylating agents (HMA) or
1800 1750
Macrophage
ALX148
Anemia––cytotoxic chemotherapy.
FcγR
60 mg/kg

Evorpacept

Calreticulin

300 250150 100

200
250

ORR – Objective response rate = CR + PR + mCR + HI; CR – Complete remission; PR – Partial remission; SD – Stable disease;
HI – Hematologic improvement; E – Erythroid; P – Platelet; N – Neutrophil.

Figure-150
5. Evorpacept Concentration-Time Profiles Following IV Infusion
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41
at 20 mg/kg Q2W, 30 mg/kg Q2W, 40 mg/kg Q4W, and 60 mg/kg Q4W(Cycle 1, Day 1) Azacitidine + ALX148 40 mg/kg Q4W** (n=23) Azacitidine + ALX148 60 mg/kg Q4W** (n=29)

mCR
SD**
2

3

4

5

6

Azacitidine + ALX148
20# mg/kg Q2W (n=1)
mCR

1

2
mCR*

3

4

5

6

8

9

7

8

9

10000

1000

100

10

1
01 3 6

24

1800
1700
mCR*
300
1750

# Proceeded tostem cell transplant

Months

6

7

8

9

672

Azacitidine + ALX148 20 mg/kg Q2W – Dose Escalation (n=3)
Azacitidine + ALX148 30 mg/kg Q2W – Dose Escalation (n=3)
Azacitidine + ALX148 60 mg/kg Q4W – Escalation + Expansion (n=38)
Azacitidine + ALX148 40 mg/kg Q4W – Dose Expansion (n=20)PD5Time (hour)

336

Dose Group

SD

4

168

Off Treatment
mCR

3

48

Azacitidine + ALX148
60 mg/kg Q4W* (n=12)
On Treatment

mCR*

1750

7

Azacitidine + ALX148 60 mg/kg Q4W* (n=12)

Azacitidine + ALX148 20 mg/kg Q2W (n=1)
Figure 4b. ND HR-MDS

250
1700
672
300
200
1
2
250
150

-100

SD**

1

150

-50 the dosing interval, including at both peak and trough concentrations ofthroughout
evorpacept, across the four dose levels evaluated.

Relapsed/Refractory MDS

PD

200

• Overall, 0evorpacept exhibited dose-proportional PK, consistent with results from prior studies.
• Full CD47 target occupancy (TO) was observed on peripheral blood RBCs and CD4+ T cells

Expansion Dose 2 (~20)
ALX14840 mg/kg IV Q4W+
Azacitidine
75 mg/m2 Daily x 7d

28-Day Cycles

Expansion Dose 2 (~20)
Inactive
100
ALX148binding and minimize
Fc Domain
150-150
40 mg/kg IV Q4W
associatedtoxicityFcdomainmutated
to50
Table 2: Most Common1 Evorpacept
2 3 4 5 6 7 8 9Related
10 11 12 13 14Adverse
15 16 17 18 19 Events*
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41+
eliminate Fcγ receptor
Inactive
100
Azacitidine
binding and minimize
Fc Domain
Azacitidine + ALX148 40 mg/kg Q4W** (n=23)
Azacitidine + ALX148 60 mg/kg Q4W** (n=29)
2
AZA
+
EVO
0
75 mg/m Daily x 7d
associated toxicity
50
R/R MDSND HR-MDS
10000-50
20 mg/kg
60 mg/kg
40 mg/kg
60 mg/kg
0(N=65)
Q2W (N=1)
Q4W (N=12)
Q4W(N=23)
Q4W (N=29)
Inactive
Fc
Evorpacept-100
Grade Grade Grade Grade Grade Grade Grade Grade All Grades-50
Adverse Event, n1000 1/2
n (%)
3/4
1/2
3/4
1/2
3/4
1/2
3/4

300

Results• 40/65 (61.5%) subjects
experienced a serious adverse event (SAE), however, only 8/65 IV Q2W-50
Optimized, picomolar(12.3%) and 7/65 (10.8%)
subjects
experienced an SAE related to AZA and EVO respectively.
Fc domain
mutated tobindingaffinity-100
eliminateFcγ
receptor• There were no EVO-related
deathson study.

28-Day Cycles

Best Relative Change from Baseline
in Myeloblast Values (%)
Best Relative Change from Baseline
in Myeloblast Values (%)

ALX14820 mg/kg

Figure 2. Evorpacept Blocks the CD47 Myeloid Checkpoint While Sparing
Normal Hematopoietic Cells from Destruction

SIRPα+ Azacitidine
75 mg/m2
Daily x 7d

ALX14820 mg/kg

Best Relative
Best Relative
ChangeChange
from Baselinefrom Baseline
in Myeloblast
Values Values(%)
in Myeloblast(%)

the safety and initial activity of evorpacept (EVO) in combination with azacitidine (AZA) in thetreatment of patients with higher-risk myelodysplastic syndrome (MDS).

bindingaffinity
0 experienced• 19/65 (29.2%) subjects
any TEAE ≥Grade 3 in severity related to EVO.

10

200
100

Azacitidine + ALX148 40 mg/kg Q4W** (n=23)
Table 4: Evorpacept
PK Parameters Following IV Infusion at 20 mg/kg Q2W,
Azacitidine + ALX148 60 mg/kg Q4W** (n=29)
30 mg/kg Q2W, 40 mg/kg Q4W and 60 mg/kg Q4W (Cycle 1, Day 1)

150
50

Parameters

20 mg/kg Q2W
(N=3)

100
0

Cmax (µg/mL)

730 ± 389

1911 ± 2113

888 ± 378

1255 ± 283

AUCinf (µg*h/mL)

66833 ± 15312

90633 ±10553

151156 ± 39955

209628 ± 63867

CL (mL/h/kg)

0.309 ± 0.062

0.334 ± 0.041

0.282 ± 0.072

0.322 ± 0.145

Vss (mL/kg)

76.6 ± 19.0

86.7 ± 11.0

95.4 ± 23.0

104 ± 25.2

50
-50
0
-100
-50
-150
-100
-150

ALX148ALX148
Serum Concentrations
Serum Concentrations(µg/mL)(µg/mL)• Final results are presented from the Phase 1 part of the ASPEN-02 study which is assessing

75 mg/m2
Daily x 7d

IV Q2W
250
300

Best Relative
Best Relative
ChangeChange
from Baselinefrom Baseline
in Myeloblast(%)
in Myeloblast
Values Values(%)

IV Q4W

ALX14830 mg/kg300

Patient

immunoglobulin Fc region (Figure 1) that has the potential to enhance the anti-neoplastic
activity of azacitidine with minimal additional toxicity (Figure 2).
1

Calreticulin
CD47

Best Relative Change from Baseline
in Myeloblast Values (%)

ALX14860 mg/kg• Evorpacept (EVO) is a high affinity CD47-blocking fusion protein with an inactivated humanHigh Affinity CD47
Binding Domains of SIRPαHigh Affinity CD47
Binding Domains of SIRPα
Optimized, picomolarbinding affinity
Optimized, picomolarbinding affinity
Fc domain mutated toeliminate Fcγ receptor
Inactivebinding
and minimize
Fc Domain
Fc domain
mutatedtoassociatedtoxicity
eliminateFcγ receptor
Inactivebinding and minimize
Fc Domain
associated toxicity

Expansion Dose 1 (~20)
ALX14860 mg/kg IV Q4W+
Azacitidine
75 mg/m2 Daily x 7d

Figure 4a. R/R HR-MDS+ Azacitidine

250

Preliminary
Phase
1
Pharmacokinetic
(PK)
and
100
Pharmodynamic(PD)
Results
50

Expansion Dose 1 (~20)
ALX14860 mg/kg IV Q4W+
Azacitidine
75 mg/m2 Daily x 7d

ALX14860 mg/kg

observed, and a maximum tolerated dose (MTD) was not reached.2
200AEs (TEAEs) were reported in 65/65 (100%) subjects. TEAEs• Treatment-emergent
considered possibly related to EVO were reported in 36/65 (55.4%) subjects and were150(Table 2).
High
Affinity CD47
generally
low grade
Binding Domains of SIRPα• Discontinuation of100
EVO was infrequent, with 3/52 (5.8%) ND-HR, and 0/13 (0%) R/R MDS
subjects discontinuing EVO due to a regimen-related TEAE.
High Affinity CD47
50•
No
subjects
discontinued
EVO
due to an EVO-related TEAE.
Binding Domains of SIRPα
Optimized,
picomolar

Previously untreatedhigher-risk MDS

Rel/ref or previously untreatedhigher-risk MDS

Change in Bone Marrow Blast Percentage
fromIV Q4W
Baseline

1700
300• EVO in combination
with azacitidine was well tolerated. No dose-limiting toxicity was
250

Ph 1 Dose Expansion (N~40)

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

macrophages to ignore the cell on which CD47 is expressed.1 Tumors upregulate CD47 toevade immunologic attack.

CD47

SafetyFigure 3. Phase 1 Study Schema• CD47, a marker of self, engages signal regulatory protein alpha (SIRPα) and signals

SIRPα

1750

Macrophage

ALX148 Serum Concentrations (µg/mL)

Macrophage

Background

FcγR

Azacitidine

Previously untreatedhigher-risk MDS

Rel/ref or previously untreatedhigher-risk MDS

1800

ALX148 Serum Concentrations (µg/mL)

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

LRP

Best Relative Change from Baseline
in Myeloblast Values (%)

1750
3
5
6
Macrophage-150 Medical Center, Nashville, TN, USA; 4Levine CancerMacrophage
The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Fred
Hutchinson
CancerResearchCenter,Seattle,WA,
USA;
Vanderbilt
University
Institute,
AtriumHealth,Charlotte,
NC,
USA;
Mayo
Clinic,Rochester,
MN,
USA;
Universityof
Ulsan
CollegeofMedicine,
Seoul,
Korea,
Cancer Cell
SIRPα
CD47
7
8
1 10Hospital2
3
4 Universitario
5
6
8
9
1700
Republic of (South); Hospital San Pedro de Alcántara, Caceres, Spain; Hospital Universitario de Salamanca, Salamanca, Spain; 9Duke University, Durham, NC, USA;
Generalde 7Alicante,
Alicante,
Spain; 11Hospital Universitario y Politécnico La Fe, Valencia, Spain; 12Universityof Southern California - Keck School of Medicine,
Calreticulin
300
Red Blood
13
14
15
16
17
Azacitidine+
ALX148
20
mg/kg
Q2W
(n=1)
Azacitidine+
ALX148
60
mg/kg
Q4W*
(n=12)SIRPα Seoul, Korea,
Los Angeles, CA, USA; Samsung Medical Center, Seoul, Korea, Republic of (South); Seoul National University Hospital,
Republic of (South); Indiana University Cancer Center, Indianapolis, IN, USA; ALX Oncology Inc., South San Francisco, CA, USA; Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Cell
1

10000

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41

Azacitidine + ALX148 40 mg/kg Q4W** (n=23)

Azacitidine + ALX148 60 mg/kg Q4W** (n=29)

30 mg/kg Q2W(N=3)

40 mg/kg Q4W(N=19)

60 mg/kg Q4W(N=36)

Data Cutoff 05Feb2024; Parameters presented as mean ± SD.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41

Azacitidine + ALX148 40 mg/kg Q4W** (n=23)

Azacitidine + ALX148 60 mg/kg Q4W** (n=29)*AZA10000+ EVO 60 mg/kg Q4W group includes subjects treated with 30 mg/kg Q2W and 60 mg/kg Q4W in the dose escalation
Phase 1;**AZA + EVO 40 mg/kg Q4W group includes previously untreated subjects in the Phase 1 treated with 20 mg/kg Q2W
1000(dose escalation) and 40 mg/kg Q4W (dose expansion). AZA + EVO 60 mg/kg Q4W group includes previously untreated subjects
in the Phase 1 treated with 30 mg/kg Q2W and 60 mg/kg Q4W in both dose escalation and dose expansion; Note: Only subjects
who had bone marrow blasts at both baseline and post-baseline assessed with the same sample collection method and a non-zerobone marrow blast count at baseline are included.

1000
100

Summary
of
Red
Blood
Cell
(RBC)
Transfusion
100
10
Dependence
RBC Transfusions
10
1• At baseline,
RBC transfusion-dependent,
01 26
3 6 of 52
24 (50.0%)
48 subjects with
168ND HR-MDS were336
672

Conclusion
Evorpacept was well tolerated in combination with azacitidine, for treatment ofpatients with R/R and ND HR-MDS.

• The combination displays a favorable safety profile across the evaluated exposure

range and is similar to azacitidine monotherapy.
• No maximum tolerated dose was reached, and there were no treatment-related
deaths on study. The maximum administered dose was 60 mg/kg Q4W.
• Overall, Evorpacept demonstrated dose-proportional PK consistent with prior data.
• Evorpacept + azacitidine demonstrates initial activity with 40.4% ORR in ND HR-MDS.

10 (38.5%) of whom achieved RBC transfusion-independence,starting at median 14.6 (range
Time (hour)
8.0-43.0)
1 weeks after commencing treatment with AZA + EVO.
Dose Group• The medianlongest48
RBC transfusion
independence interval
01 3of
6 the24168
336 is 22.4 (range 8.1-48.3) weeks.
672

Azacitidine + ALX148 20 mg/kg Q2W – Dose Escalation (n=3)
Time(hour)
ALX14830 HR-MDS
mg/kg
Q2W were– Dose RBC
Escalation(n=3)• At baseline, 26 of 52 (50.0%) Azacitidine
subjects+with
ND
transfusion-independent,
Azacitidine+ ALX148 60
mg/kg
Q4W – Escalation+ Expansion(n=38)
17 (65.4%) of whom maintained
RBC transfusion-independence,and
9 (34.6%)of whom
Dose
Group
Azacitidine + ALX148 40 mg/kg Q4W – Dose Expansion (n=20)
became RBC transfusion-dependent
study.
Azacitidineon+ ALX148
20 mg/kg Q2W – Dose Escalation (n=3)
Azacitidine + ALX148 30 mg/kg Q2W – Dose Escalation (n=3)• At baseline, 9 of 13 (69.2%) subjects
with R/R HR-MDS were RBC transfusion-dependent,
Azacitidine+ ALX14860
mg/kg Q4W – Escalation + Expansion (n=38)
Azacitidine+
ALX148
40
mg/kg
Q4W**
(n=23)
1 (11.1%) of whom achieved RBC
transfusion-independence,starting
at 14.6
weeks after
Azacitidine+
ALX148
40
mg/kg
Q4W
–
Dose
Expansion(n=20)
Azacitidine + ALX148 60 mg/kg Q4W** (n=29)

commencing treatment with AZA + EVO.

• The longest RBC transfusion independence interval is 15.0 weeks.

Azacitidine + ALX148 40 mg/kg Q4W** (n=23)+ ALX148who
60 mg/kg
Q4W**(n=29)• Of 4 subjects withAzacitidine
R/R HR-MDS
were
RBC
transfusion-independent at baseline,

2 (50%) maintained RBC transfusion-independence, and 2 (50.0%) became RBC transfusiondependent on study.

Note: Transfusion dependence at baseline – Any RBC transfusion in 8 weeks prior to starting treatment; Transfusion
independence – No transfusion over an 8-week period on study; The time to achieving RBC transfusion independence is the timefrom first dose to the first time that an 8-week transfusion-free interval is achieved.

References

1. Kauder, Steven E et al. ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with afavorable safety profile.” PloS one vol. 13,8 22 Aug. 2018
2. Garcia-Manero G et al. Evorpacept (ALX148), a CD47-Blocking Myeloid Checkpoint Inhibitor, in Combination
with Azacitidine: A Phase 1/2 Study in Patients with Myelodysplastic Syndrome (ASPEN-02), Blood 2021; 138(Supplement 1); 2601.
3. Cheson BD et al. Clinical application and proposal for modification of the International Working Group (IWG)
response criteria in myelodysplasia. Blood 2006; 108 (2): 419–425.

Acknowledgments

We would like to thank all of the participating patients and their families as well as site research staff.

Contact Emailinfo@alxoncology.com
Presented at AACR 2024 Annual Meeting.