CD47 TO (%)Patient

ALX148, a CD47 Blocker, in Combination with Standard Chemotherapy and Antibody Regimens in Patients with
Gastric/Gastroesophageal Junction (GC) Cancer and Head and Neck Squamous Cell Carcinoma (HNSCC); ASPEN-01
10

ALX148 10 mg/kg + Pembrolizumab (N=12)
ALX148 10 mg/kg + Trastuzumab (N=10)
ALX148 10 mg/kg + Trastuzumab/Pembrolizumab + Chemo (N=6)
ALX148 15 mg/kg + Trastuzumab + Chemo (N=10)

5

0

24

48

72

96

120

Time (hours)

144

PD

100

1

168

0

PR

RBC

120

80

PR

60

120
PD

PR

10

0

20

10

0

20

30

30

2

3

4*

5

6

7

8

9

10

9

9

9

0

9

50

9

100

ALX + Tras + Chemo
Gatric ALX(10) N=3

Partial Response
Partial(PR)Response (PR)80

Progressive Progressive
Disease (PD)Disease (PD)
Patient on Treatment
Patient on Treatment

60
40
20 40

40

0

50

Study Weeks
0
Study Weeks

Keun-Wook Lee , Hyun Cheol Chung , Won Seog Kim , Laura QM Chow , Nehal Lakhani , Wells Messersmith , Yung-Jue Bang , Patricia LoRusso , Philip Fanning , Pierre Squifflet , Feng Jin , Alison Forgie , Hong Wan , Jaume Pons , Sophia Randolph , Time
JustinGainor(day)
1Complete Response
Complete(CR)Response (CR)

100

40

20

CD4

PR

CD47 TO (%)

Cancer Cell

Patient

ALX148 Concentrat

Cancer Cell

50

150

200

11

ALX + Tras + Chemo
Gatric ALX(15) N=10

50

60

50
100

150

60
200

Time (day)ALX + Pembro + Chemo
HNSCC ALX(10) N=3

ALX + Pembro + Chemo

1Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea; 2Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea; 3Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea; 4University of Washington, Seattle, WA, USA; 5START Midwest, Grand Rapids, MI, USA;HNSCC ALX(15) N=2
6University of Colorado Cancer Center, Aurora, CO, USA; 7Seoul National University College of Medicine, Seoul, Korea; 8Yale Cancer Center, New Haven, CT, USA; 9ALX Oncology, Burlingame, CA, USA; 10International Drug Development Institute, Brussels, Belgium; 11Massachusetts General Hospital Cancer Center, Boston, MA, USA

Fc Receptor

Enhances CrossPriming of T Cells
IFN

Fc Receptor

Anti-Cancer
Antibody
Anti-Cancer
Antibody

CD47
Cancer Cell

CD47

TNF
Cytotoxic
GranulesIFN
TNF

T CellM1

Cytotoxic Granules
ALX148

M1

CD86

M1

Dendritic Cell

M2 M2Tumor Antigen

MHC II
Dendritic Cell

CCR7

SIRP

MHC II

M2——

1 (20)

—

—

—

—

—

—

—

—

—

63 (36-83)
10
4

58 (45-79)

PR

PR SD

11 PR
PR
3 PR PR— PR PR
PR
SD
SD
SD

SD

5
9SD

4
1

4
1
—

7
13

Partial Response (PR)19 (95)

Patient on Treatment

N/A

Study Weeks
209 (45)
30 N/A

N/A

40

50

40

Study Weeks

10 (50)17 (85)
1L HNSCC 1 (20)

12 (60)

1L HNSCC

Time (hours)
72

96

120

144

168

Table 1. ALX148 Combination(GC) and HNSCC Tumor Cohorts
TimeGastric/Gastroesophageal(hours)Combination Dose Expansion≥2L HER2-Positive GC (N=14) ALX148 + Trastuzumab + Ramucirumab + Paclitaxel
Progressed on prior trastuzumab, fluoropyrimidine, or platinum≥2L HER2-Positive GC (N=20) ALX148 + Trastuzumab
Progressed on prior fluoropyrimidine(progression on trastuzumab and platinum allowed)
1L HNSCC (N=5) ALX148 + Pembrolizumab + 5FU + Platinum
No prior treatment for advanced disease% Change in Baseline
Measurable Lesions% Change in Baseline
Measurable Lesions
20• Primary Study Objective: Characterize ALX148 safety profile as a single agent (Part 1) and020

in combination
with established anti-cancer-20antibodies
with or without standard
40
0chemotherapy (Part2).
-40
-20
40
• Here30wereport preliminary data from the GC-60 and HNSCC patient cohorts receiving ALX148-40
plus20chemotherapy
combinations, and updated
data from the GC and HNSCC patient
30
-80
50
100
200
250
cohorts receiving ALX148 plus pembrolizumab0 -60and ALX148
plus 150
trastuzumab,
as of 300
Time from Initiation of Treatment (days)-80
October
10 2001, 2020.
0
50
100
150
200
250
300
2+

–

3+

3+

2+

3+

Time from Initiation of Treatment (days)

2+

3+

–

–

–

HER2

—

—

—

—

—

—

—

—

—

—

—

—

—

1 (20)*——

Dysphagia

—

—

—

—

1 (20)———

Pericarditis Constrictive

—

—

—

—

1 (20)*

—

—

—

—

—

—

1 (20)*———

Response

60 5. Clinical Activity
Tableof ALX148
Chemotherapy Combinations in Response Evaluable
Optimized,
picomolarbindingaffinity GC Cancer and 1L HNSCC
Patients with ≥2L HER2
PositiveN

ORR
Median Follow-Up*(95% CI)positive GC(95% CI)≥2L HER2

14

64.3% (38.8; 83.7)

ALX148 (15 mg/kg)

11

63.6% (35.4; 84.8)

PR

4.2 mo (2.4; 6.2)

ALX148 (10 mg/kg)

3

66.7% (20.8; 93.9)

8.9 mo (5.1; 9.6)

Fc domain mutated to
Dose Fcγ receptor
Inactive Population ALX148eliminate
binding and minimize
Fc Domain
associatedtoxicity≥2L Gastric ALX148+ Trastuzumab

144120168144-40 168
-60
-80

50

100

150

200

250

–

0

2+

–

3+

3+

2+

3+

2+

3+

–

–

–

2+

HER2
Score

PR
SD

PR

PR
5.3
mo (2.8; 6.7)

Partial Response
Stable Disease-50

Progressive Disease

60

60

40

40

20
0
-20
-40

20

-20
-30
-40
-50
-60

PR

ALX148

Table 3. ALX148CD47+ Trastuzumab + Ram/Pac
RBC (N=14)100 120

CD4MHC II
CD4

Dendritic Cell

120

SIRP

M2
M2

120

CCR7

100

Tumor Antigen

Patient

CD86

Anti-Cancer

Antibody Events
Treatment Related Adverse
RBC

120

Inactive
Fc Domain• ALX148 (10 mg/kg
QW) + trastuzumab+ chemo, ≥2L GC: N=3 [2 PR confirmed, 1 SD]
Fc domain
mutated toeliminate
receptor• ALX148 (10 mg/kg
QW) +Fcγ
trastuzumab,≥2L GC: N=19 [4 PRconfirmed), 5 SD, 10 PD]
1L (3
HNSCC
binding and minimize

associated toxicity• HNSCC Expansion

0

–

CR
• ALX148 (15 mg/kg QW) + pembrolizumab + chemo, CPI naive 1L HNSCC:
N=1 [1 PR unconfirmed]• ALX148 (10 mg/kg QW) + pembrolizumab + chemo, PRCPI naive 1L HNSCC: N=3 [1 CR unconfirmed,

2+

ALX + Tras + Chemo
Gatric ALX(10) N=3

ALX + Tras + Chemo
Gatric ALX(15) N=10

ALX + Pembro + Chemo
HNSCC ALX(10) N=3

50 0

10050

150100200150

250
200

300
250

PR

PR

-20 80PR
Partial
PR Response (PR)
Stable Disease (SD)PR
Partial Response-40 Partial Response
Progressive Disease (PD)PR on Treatment
Stable Disease
Patients
40
Stable Disease
Patients
PR-50 Progressive
Disease Deceased
Progressive
DiseaseSD-60 20

HER2
Score

PR

500

Figure 3. ALX148
Concentration-Time
Profiles by Dose Level
and Combination Partner

100
50

10

ALX148 10 mg/kg + Pembrolizumab (N=12)
ALX148 10 mg/kg + Trastuzumab (N=10)
ALX148 10 mg/kg + Trastuzumab/Pembrolizumab + Chemo (N=6)
ALX148 15 mg/kg + Trastuzumab + Chemo (N=10)

5

1
0

24

48

72

96

Time (hours)

120

144

168

100

50 ALX148

Anti-Cancer
Antibody

Population
ALX148CD47
10 mg/kg + Pembrolizumab (N=12)(10 ALX148
mg/kg
QW)
N
ALX148 10 mg/kg + Trastuzumab (N=10)

10
5

SIRP
ORR
M2
(95% CI)

M2

Tumor Antigen

ALX148 10 mg/kg + Trastuzumab/Pembrolizumab + Chemo (N=6)

21.1%(8.5; 43.3)

Cancer Cell
≥2LALX148
Gastric
ALX148+ + Chemo (N=10)15 mg/kg+ Trastuzumab
19
Trastuzumab

1
0

48
72
96
≥2L24HNSCC
No
Time (hours)
Prior CPI ALX148 +Pembrolizumab 120

120

100
≥2L HNSCC Progressedon Prior CPI ALX148+
80
Pembrolizumab
60*Intent to treat population: Gastric N=20.
40

20

10

10

144

168

40%
(16.8;
68.7)
RBC
0%(0; 27.8)

Median
DORCCR7(95% CI)MedianMedianMHC II
PFS
OS*(95% CI)(95% CI)MedianFollow-Up*(95% CI)

8.7 mo(5.6; 9.4)

2.2 mo(1.9; 5.5)

8.1 mo(3.4; 12.6)

19.8 mo(11.7; 19.8)

4.3 mo(1.9; NC)

4.6 mo(0.5; 7.5)

22.1 mo(3.1; NC)

25.1 mo(15.3; 25.6)
CD4

N/A

Dendritic Cell

120

100

2.0 mo(0.9; 80
3.6)
60
40
20

7.4 mo(3.1; 15.4)

24.4 mo(1.0; 24.4)

200
150

• Near complete CD47 target occupancy is maintained throughout ALX148 dosing interval

PD
PR

20

PR

-80

PR
PR 0

40

-20
-40
-60

PR

10 SD

20

50

100

150

Stable Disease (SD)
200

250

60

Complete Response (CR)-60

Partial Response (PR)
10050

150100200150Progressive Disease (PD)
250

300

200
250
Patient
on Treatment
Time from Initiationof Initiation
Treatment
Time fromof(days)
Treatment (days)

CPS
50

300

CPS

30

SD

40

Partial Response (PR)50

60

Stable Disease (SD)CompleteComplete
ResponseResponse
Progressive Disease (PD)Partial Response
PartialResponse
Patient
on Treatment
Progressive
Disease Disease
Progressive

PD

10

20

30

Study Weeks

40

1L HNSCC

RBC

120

50

60

60
40

PD

20
0
50

PR

150

200

60
40

Complete Response (CR)20

Partial Response (PR)50

Patient on Treatment
100
150

200

Time (day)ALX + Tras + Chemo
GatricALX(15) N=10
20

CD163

Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)
PatientsResponseon Treatment
Complete
Complete(CR)Response (CR)
Deceased Patients

ALX + Pembro + Chemo

30HNSCC ALX(10) N=3 40

Study Weeks

ALX + Pembro + Chemo
HNSCC ALX(15)50 N=2

ALX148, a high affinity CD47 myeloid checkpoint inhibitor with an inactive
Fcγ domain and favorable toxicity profile demonstrates objective response incombination with trastuzumab, pembrolizumab and multi-agent chemotherapies
in patients with GC and HNSCC.
• Preliminary data suggests that ALX148 can be safely combined with the multiagent chemotherapy regimens studied with no maximum tolerated dose reached.
Partial Response (PR)The maximum
administered dose of ALX148 in combination was 15 mg/kg QW.
Stable Disease (SD)
Disease (PD) promising initial ORR of 64% in patients with ≥2L HER2
• ALX148Progressive
demonstrates
Patients on Treatment
positive
GC in combination with trastuzumab and ramucirumab + paclitaxel that
Deceased Patientscompares favorably with the historical data.
• ALX148 demonstrates initial promising anti-cancer activity including complete andpartial objective responses in combination with pembrolizumab + 5FU + platinumin patients who have not received prior treatment for their advanced HNSCC, andwhose tumor may be immunologically hot or cold.
• Updated data from patients with ≥2L HER2 positive GC receiving ALX148 +trastuzumab suggests promising clinical activity after their tumors have progressed
upon prior trastuzumab therapy.
• Updated data from patients who have never been treated with a CPI for their≥2L HNSCC and who received ALX148 +pembrolizumab suggests clinical activity
beyond that expected from pembrolizumab monotherapy.
• Preliminary pharmacokinetics and pharmacodynamic analysis demonstrates noimpact of the combination partners upon ALX148 exposure levels with full CD47
receptor occupancy.

Acknowledgments

Progressive Disease (PD)0Time (day)ALX + Tras + Chemo
Gatric ALX(10)10 N=3CD8

1. Weiskopf, K., Eur J Cancer. 2017 May;76:100-109.
2. Kauder, S.E. et al., PLoS ONE. 2018 August;13(8): e0201832.
3. Lakhani, N. Journal of Clinical Oncology 2018 36:15_suppl, 3068-3068.
4. Chow et al. Journal of Clinical Oncology 2020 38:15_suppl, 3056-3056.

80

0
100

CD163

References

100 CR

100
PR

CD8

Patients in combination cohorts continue to be followed (NCT03013218).

CD4

120

80

CD68

Conclusions

300

Progressive Disease (PD)Time from Initiation of Treatment (days)
Patient on Treatment

Study Weeks

SD

PD-L1

Partial Response (PR)
0

-80
50 0

0

0 50

40

–

-60

CD68

Progressive Progressive
Disease (PD)Disease (PD)

SD

PR

PD-L1

Stable Disease(SD)Disease (SD)
Stable0-80

40Patient 2 Best Overall Response: PR
Immunologically “Cold” Tumor

infiltratingPatient
T lymphocytes(CD8) and tumor associated macrophages and myeloid cells
on Treatment
Patient on Treatment(CD68 and CD163).
• Patient 2: HNSCC (CPS 0) characterized as immunologically “cold” where immune cells are
excluded from the tumor core while present at lower density in the peri-tumoral regions.

Figure 7. Best Overall and Duration of Response in Patients While Receiving ALX148 +Pembrolizumab + 5FU + Platinum

0

150
100

Time (day)Time (day)Partial Response
Partial(PR)Response (PR)

20

SD

0

0

050

ALX + Tras + Chemo
ALX + Tras + Chemo
ALX + PembroALX+ Chemo
ALX + PembroALX+ Chemo
ALX + Tras + Chemo
ALX + Tras + Chemo+ Pembro + Chemo+ Pembro + Chemo
Gatric ALX(10)Gatric
N=3 ALX(10) N=3
Gatric ALX(15)Gatric
N=10 ALX(15) N=10
HNSCC ALX(10)N=3 ALX(10) N=3HNSCC ALX(15)N=2 ALX(15) N=2
HNSCC
HNSCC

• Patient 1: HNSCC (CPS 50) characterized as immunologically “hot” with a high density of40SD-30 60300

ALX148

CD47
Study
Weeks
Table 6. Updated Clinical Activity in Response
Evaluable
Patients
Receiving ALX148 +M1
ALX148Trastuzumab and Pembrolizumab in ≥2L HER2M1Positive
GC and ≥2L HNSCC
CD86

ALX + Pembro + Chemo
HNSCC ALX(15) N=2

0

-40

60

0
Adverse Event80 Cancer Cell
Total N (%)
80 100–100
0Diarrhea
3 (21)
1 PR confirmed, 1 PD]
60 80
60
80
-20
-20
RASH
3 (21)• ALX148 (10 mg/kg QW) + pembrolizumab, CPI naive ≥2L HNSCC: N=10 [4PR (2 confirmed),
40 60
40Complete Response (CR)60
PD
2 SD, 4 PD]
Urticaria
3 (21)
Partial Response (PR)
20 40
20
40
-40
• ALX148 (10 mg/kg QW) + pembrolizumab, progressed on prior CPI ≥2L HNSCC: N=10 [3Progressive
SD, 7 PD]
Disease (PD)-40
Fatigue
2 (14)
0 20
0PR
20
Patient on Treatment
0
50
100
150
200
0
50
150
200 * Based upon investigator assessed response using RECIST v1.1. All objective responses are unconfirmed as of the cut off datePruritus
2 (14)100000Time (day)unless specified.
-60-60
Lymphocyte Count Decreased
1Time(7) (day)
IFN
0
50
100
150
200
0
50
100
150
200
TNF
M1
1000
Macrophage
ALX + Tras + Chemo
ALX + Tras + Chemo
ALX + Pembro + Chemo
ALX + Pembro + Chemo
T CellTime(day)
Cytotoxic Granules
Abdominal Pain
1 (7)
0
10
20
30
40
50
60
Gatric ALX(10) N=3 Time (day)Gatric ALX(15) N=10
HNSCC ALX(10) N=3
HNSCC
ALX(15)
N=2
SIRP
Fc Receptor
500
RASH – rash and dermatitis

0
200 0

-20

0 – 2+ 0 – 2+ 3+ – 3+ 3+ 2+ 3+ 3+ 2+ 2+ 3+ 3+ 2+ – PR
3+ – – – – HER2
–
Score

-10

20

100
50

40
20

0

from Initiationof Initiation
Treatment
Time GCfromof(days)
Treatment (days)≥2L HER2Time
positive

10

2+

200
150

Patient 1 Best Overall Response: CR
Immunologically “Hot” Tumor

Figure305. Best Overall and Duration of-60Response
in Patients While Receiving ALX148 +-60+ Ramucirumab + Paclitaxel-80
20Trastuzumab
-80
20

-10

150
100

40
20

80
60

Stable Disease (SD)

-60
40

0

100
50

Time (day)Time (day)

60

CD4

ProgressiveIHC
Disease(PD)
Figure 9. Pre-Treatment
Results
from HNSCC Patient 1 (PD-L1 positive) andPatient on Treatment
Patient 2 (PD-L1 negative)

-40

0

050

100

80

CD4

Complete Response (CR)

-30

10

0

120

when combined Partial
withResponse
chemotherapy-containing
regimens.
(PR)

-10

30

40
20

0

300

Time from Initiation of Treatment (days)

0

40

40
20

60

0
0

CPS
40
0
50
eliminate(N=5)
Fcγ receptor
Inactiveand pembrolizumab+ 5FU + platinum
was well tolerated, with most treatment
Partial Response (PR)
0 PD
Complete Response (CR) 1L HNSCC ALX148 +
4 PR
75% (30.0; 95.0)
5.0 mo (1.3; 8.8)
binding andPD
Fc Domain
Disease–relatedadverse events (TRAE) reported
ofminimize
low grade and frequency. Safety ofProgressive
ALX148in (PD)(PR) Pembrolizumab + 5FU + Platinum
Partial Response
associated toxicity
PR
PR
Patient on4Treatment
combination with pembrolizumab and trastuzumab has been described elsewhere.
Progressive Disease (PD)
Complete50
Response
0 -20
10
20
30
40
ALX148 (15 mg/kg)
1 PR
100% (20.5; 100)
1.6 mo (1.3; 1.9)
PR
Study Weeks• There were no dose limiting toxicities
reported in patients treated with ALX148 + Patient on Treatment
Partial Response
IFN
PR
TNF
M1
Macrophage
Partial Response (PR)T
Cell
(10 mg/kg)
3
66.7% (20.8; 93.9)Cytotoxic Granules5.3 mo (5.0; 8.8)
trastuzumab 0+ ram/pac or 10
ALX148 + pembrolizumab+ 30
5FU + platinum.
Progressive Disease
20
40
50
60 ALX148SD
SIRP
Fc Receptor
Stable Disease (SD)
ALX148
-40
CD47
Weeks
• All patients in chemo-containing
least
event. Eight (57%)
SD N=5; HNSCC (15 mg/kg) N=2.
Progressive Disease (PD)*Intent+ 15 mg/kg)
0
10 cohorts experienced
20 Study at
30 1 adverse 40
50
60to treat population: HNSCC (10Figure 6. ALX148 + Pembrolizumab + 5FU/Platinum in 1L HNSCC CPI Naïve Patients
M1
ALX148
Patient on Treatment
patients administered ALX148 + trastuzumab + ram/pac
andWeeksno (0%) patient administered
M1
SD
CD86
Study
Response-60Evaluable (n=4)
60Anti-Cancer
High Affinity CD47
ALX148 + pembrolizumab + 5FU + platinum experienced a TRAE.
60 positive GC
PD
≥2L
HER2
Antibody
ALX148
1L HNSCC
Binding
Domainsof SIRPα
ALX148Combination
Expansion Cohorts – Clinical
Activity in
Dendritic Cell
40
40
• The most common TRAEs of ALX148 in combination with trastuzumab + ram/pac (N=14) were Response Evaluable
80
MHC
II
*
80
SIRP
PR
0
10M2
20
30
40
50
60
Patients
CD47
20
CCR7
low grade diarrhea, rash, urticaria (each 21%; Table 3). TRAEs ≥Grade 3 severity were of low
20
CR
M2
PR
Study
Weeks
IFN
TNF
Optimized,
picomolar
Tumor
AntigenM1
frequency(Table 4).
Macrophage
00
T Cell60
PR• HER2
GC
Expansion
60
Cytotoxic Granules
Cancer PositiveCellbindingaffinity
SIRP
Fc Receptor
ALX148-20• There were no treatment
related SAEs reported
in patientstreated with ALX148 trastuzumab
PR
CD47
-20
PR
•
ALX148 (15 mg/kg QW) + trastuzumab + chemo, ≥2L GC: N=11 [7 PR (5 confirmed), 3 SD, 1 PD]
M1
ALX148+ ram/pac or ALX148 + pembrolizumab + 5FU + platinum.
-40
SD
-40
40

1000

40

—

—

Complete Response (CR)• ALX148 (10 and 15 mg/kg QW) + pembrolizumab + 5FU + platinum: N=5.

60

—

—

—

12096

-20

—

PR

No TRAEs were reported in patients receiving:≥2L HNSCC (N=20) ALX148 + Pembrolizumab
40
60Progressed onprior
platinum

1 (7)

96 72

10

—

Patient

50
measuredby flow cytometry.
10
ALX148 10 mg/kg + Pembrolizumab (N=12)• HER2,
CD8,
CD68
and (N=10)
CD163 expression on formalin fixed, paraffin embedded tumor
ALX14810 mg/kg+ Trastuzumab
5 PD-L1,
10
ALX14810 mg/kg+ Trastuzumab/Pembrolizumab
ALX14810 mg/kg
Pembrolizumab (N=12) + Chemo (N=6)
tissue wasmeasuredby ++immunohistochemistry(IHC) assays. HER2 levels were determined
ALX14815 mg/kg+ Trastuzumab+ Chemo(N=10)
ALX14810 mg/kg
Trastuzumab(N=10)
5by HercepTest™.
PD-L1(Clone22C3) Combined
Positive Score (CPS) was determined by
ALX14810 mg/kg+ Trastuzumab/Pembrolizumab+ Chemo (N=6)
1
ALX148 15 mg/kg + Trastuzumab + Chemo (N=10)
pathologist
scoring.
0
24
48
72
96
120
144
168

—

Cardiac Tamponade

CR

PD

—

—

+ Ramucirumab + Paclitaxel

PR

—

60

CR

M1

50
100
• CD47target occupancy (TO) in peripheral blood T lymphocytes and erythrocytes was—High Affinity CD47
Binding Domains of SIRPα

N/A 500 (0)Optimized, picomolarbinding affinity

1 (7)Progressive
StableDisease(PD)(SD)
13 Disease
PatientProgressiveon Treatment
Disease (PD)*Events occurred in a single patient with malignant pericardial effusion.

30

9 (45)1 (7)Supraventricular
Tachycardia

7 Response
Stable Disease(SD)
Partial
(PR)

—

72 48

Time (hours)
Time (hours)

20

Deceased Patients

Urinary Tract Infection

6
12
2

4
1

1 (7)

Platelet Count
Decreased

15
5

PR

PR

20

62.5 (35-81)

PR

PR

13
6
1

PR

SD
Progressed Upon PriorPD
13 (93)Anti-HER2 Therapy, n (%) PD
010Progressed Upon
10
≥2 Prior anti-HER20
1 (7.1)
Therapies n (%)
Progressed Upon Prior
1 (7.1)CPI Therapy, n (%)

PR

PR

15
5

PR
SD

61 (45-63) PR

Partial Response (PR)
Stable Disease(SD)
Partial Response(PR)
Progressive
Disease(PD)(SD)
StableDiseasePatients Progressiveon TreatmentDisease (PD)
DeceasedPatients
Patients
on Treatment

Lymphocyte
Count Decreased

48 24

30

% Change in Baseline
Measurable Lesions≥2L HER2 positive GC≥2L HER2 positive GC

24 0

60

80

120
100

CD47 TO (%)

—
—

0

80

CD47 TO (%)

1 (7)
1 (7)

4

RBC

100

CD47 TO (%)

AnemiaHypophosphatemia

3

CD47 TO (%)—

4% Change in Baseline
Measurable Lesions—

CD47 TO (%)

ALX148 Concentration (µg/mL)

1000• Adequateorgan function and hemoglobin ≥9 g/dL.
500• No
100 prior treatment with an anti-CD47 or anti-SIRPα agent.

asurable Lesions
able Lesions—

CD47 TO (%)

ALX148 Concentration (µg/mL)(0.3 to 10 mg/kg QW; or 30 mg/kg QOW).3• Part 2 (combination): Patients were administered ALX148 10 or 15 mg/kg QW in combination
with pembrolizumab (200 mg IV Q3W), trastuzumab (8 mg/kg IV → 6 mg/kg Q3W), ramucirumab(8 mg/kg Days 1, 15 Q4W), paclitaxel (80 mg/m2 Days 1, 8, 15 Q4W), cisplatin (100 mg/m2
Q3W
x 6), carboplatin (AUC 5 mg/ml/min Day 1 Q3W x 6), and 5FU: 1,000 mg/m2/day Days 1,
1000
2, 3,
5004 Q3W x 6)

0—

ALX148 Concentration (µg/mL)• Part 1 (single agent): Patients were administered escalating doses of intravenous ALX148–—

Patient
Patient

Study Design

48—• ALX148 in combination with trastuzumab+ ramucirumab+ paclitaxel (ram/pac) (N=14),
Fc domain mutatedto

Methods

24—

SafetyCCR7Tumor Antigen

0

5 (36)

N/A – not applicable; CPI – checkpoint inhibitor; Ram/Pac – ramucirumab + paclitaxel

Cancer Cell

1Hypertension

ALX148
ALX148+ Trastuzumab
ALX148+ Pembrolizumab
ALX148+ Ram/Pac + Trastuzumab + 5FU/Platinum + Pembrolizumab≥2L GC≥2L GC
1L HNSCC≥2L HNSCC(N=14)(N=20)(N=5)(N=20)

Visceral DistantHigh Affinity CD47
13 (93)
Binding Domains of SIRPαMetastasis, n (%)

ALX148
CD86

SIRP

M2

CD47

—

CD47 TO (%)

ALX148—

CD47 TO (%)

ALX148

M1
CD47

ALX148

M1—

ALX148 Concentration (µg/mL)

SIRP

T Cell

ALX148

1 (20)

3-20

CD47 TO (%)

Activates
3 ALX148
Dendritic Cells and

M1

SIRP
Macrophage

—

4

40
1

% Change in Baseline
Measurable Lesions

Suppressive M2 in Tumor
Microenvironment

Macrophage

—

3

1

RBC

120

100

20
ALX148 10 mg/kg+ Trastuzumab
ALX14810 mg/kg +(N=10)
Trastuzumab (N=10)
5
ALX14810 mg/kg+ Trastuzumab/Pembrolizumab+ Chemo (N=6)+ Chemo (N=6)
ALX14810 mg/kg + Trastuzumab/Pembrolizumab
0
ALX148 15 mg/kg+ Trastuzumab
Chemo (N=10)
ALX14815 mg/kg ++Trastuzumab+ Chemo (N=10)5% Change in Baseline
Measurable Lesions

Increases Ratio
2 ALX148
of Inflammatory M1 toPhagocytosis ofCancer Cells

1 (7)

4

120

40

ALX148 10 mg/kg+ Pembrolizumab(N=12)
10
ALX14810 mg/kg + Pembrolizumab(N=12)% Change in Baseline
Measurable Lesions

Figure 2. ALX148 Bridges Innate and Adaptive Immunity2
Designed to
1 ALX148
Safely Maximize

5 (36)

3

10

Figure 8. CD47 Target Occupancy in Chemotherapy Combination Cohorts

60% Change in Baseline
Measurable Lesions

Inactive
Fc Domain
Inactive
Fc Domain

Table 2. Baseline Characteristics

Neutrophil
Count Decreased

Patient
Patient

Fc domain mutated toeliminateFcγ receptor
Fc domain
mutated tobinding
and minimize
eliminateFcγ receptor
associatedbinding toxicity
and minimize
associated toxicity

Gradecohorts (Table 2).

% Change in %Baseline
ChangePatient
in Baseline Measurable Lesions % Change in Baseline Measurable LesionsALX148 Concentration (µg/mL)
Measurable Lesions

antibody-like PK.
• Molecular weight half thesize of typical antibody.

Relatedn (%)• 59 solid tumor patients have been enrolled into Part 2 GC and HNSCC combination

Median Age
Years (range)
Sex, nM
FRace, n
Asian
White
Other
ECOG PS, n01• Fc domain enables

Optimized, picomolarbindingaffinity picomolar
Optimized,
binding affinity

All Causalityn(%)

Relatedn (%)

50% Change in
Baseline
Patient
Patient
Measurable Lesions

BindingHigh
Domainsof CD47
SIRPα
Affinity
Binding Domains of SIRPαAll Causalityn(%)

Adverse Event50

CD47 TO (%)
Patient

Figure 1. ALX148
PotentlyHigh Affinity
CD47 and Selectively Binds CD47 to Block SIRPα Interaction

Patient Baseline Characteristics

ALX148 + Pembrolizumab +5FU + Platinum (N=5)

500

100 Figure
100 4. ALX148 + Trastuzumab + Ram/Pac ≥2L HER2 Positive GC Response Evaluable (n=14)% Change in Baseline
Measurable Lesions

which CD47 is expressed by binding its receptor, SIRPα.1 Tumors upregulate CD47 to evadethe immune response.
• ALX148 is a high affinity CD47 blocker fusion protein with an inactive human immunoglobulin
Fc region (Figure 1) designed to enhance the activity of anti-cancer targeted antibodies andcheckpoint inhibitors with minimal hematologic toxicity.2• ASPEN-01 (AT148001), a first-in-human Phase 1 study evaluates ALX148 administered as asingle agent (Part 1) and in combination with established anti-cancer antibodies (Part 2).

ALX148 + Trastuzumab +Ramucirumab + Paclitaxel (N=14)

CD47 TO (%)• CD47, a myeloid checkpoint and marker of self, signals the macrophage to ignore the cell on

Table 4. ≥Grade 3 Adverse Events

1000

500

% Change in Baseline Measurable Lesions

Results

CD47 TO (%)

Background

ALX148 Concentration (µg/mL)

1000

60

• We would like to thank all of the participating patients and their families as well as site research staff.
• Contact email: info@alxoncology.com• Presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting November 11-14, 2020
Abstract #404.

*Dr. L Chow currently at University of Texas at Austin, TX.

200