Stable Disease (SD)
Progressive Disease (PD)
Patients on Treatment
Deceased Patients% ChangPR
PR

Progressive Disease

Patient

Fc domain mutated toeliminate Fcγ receptor
binding and minimize
associated toxicity

InactiveFc Domain

PR

Partial Response-60

PR

Complete Response% Change in Baseline Measurable Lesions

A Phase 2 Study of Evorpacept (ALX148) in Combination with Pembrolizumab and Chemotherapy
in Patients with Advanced Head and Neck Squamous Cell Carcinoma (HNSCC); ASPEN-04-40

Optimized, picomolarbinding affinity

SDPRPRPR

PR

PR

Partial Response (PR)SD

Stable Disease (SD)4030% Change in B
Measurable L

Binding Domains of SIRPα200-20-40-60-800–002+–3+50

100

150

200

250300Time from Initiation of Treatment (days)

103+2+3+2+3+––2+–HER2
Score

-10

Beatriz Cirauqui , Ezra Cohen , Bhumsuk Keam , Jean-Pascal Machiels , Sjoukje Oosting , Tim Welliver , Shanhong Guan , Feng Jin , Alison Forgie , Philip Fanning , Katherine Ruffner *, Jaume Pons , Sophia S. Randolph6, Kevin Harrington7123456666SDSD66Progressive Disease (PD)
Patient on Treatment

PD-20
6-30

1Institut Catala d’Oncologia, Barcelona, Spain; 2University of California San Diego, San Diego, United States; 3Seoul National University Hospital, Seoul, Korea; 4Cliniques
Universitaires
Saint-Luc,Brussels,Belgium;
5University
Medical Center Groningen, Netherlands;
6ALX Oncology Inc., South San Francisco,Partial Response-400102030405060United States; 7The Royal Marsden Hospital, London, United Kingdom
Stable Disease
Study Weeks

3Fc domain mutated toPD-L1•InactiveThrough increased activationof theeliminate
Fcγimmune
receptor system, a combination of evorpacept +bindingmight
and minimize
Fcpembrolizumab
DomainEvorpacept + 5FU/platinum
have more antitumor activity
in R/M HNSCC thanPembrolizumab
SIRPα associated toxicity

T cellT cellFigure
2. Evorpacept, Pembrolizumab,
and Chemotherapy Combine
TcellcellT ceto Activate the Antitumor Immune Response

1Evorpacept(15 mg/kg)

3

100%

TCR

(20.5%, 100%)
T cell66.7%(20.8%, 93.9%)Tumor

1.6 antigen(1.3, 1.9)
5.3
(5.0, 8.8)

200-40-60-80

1 Evorpacept binds to CD47expressed by cancer cells
to0block the CD47-SIRPα–
myeloid checkpoint
leading to enhanced
phagocytosis and60
activationof dendriticcells
Population
Evorpacept-20
Dose
1L HNSCC

2 Activated dendritic cells
cross-present tumor
40
antigens(includingtumor antigens released
in response to treatment
with chemotherapy) tocytotoxic T cellsMedianNORR(95% CI)

Follow-Up*(95% CI)

0T cell

-20

050

100

150

200

250

Time from Initiation of Treatment
binds to(days)
3 Pembrolizumab
PD-1, relieving PD-1/PD-L150 of
mediated inhibition
CPSactivated T cells

6040202030≥2L HER2
Studypositive
Weeks GC
40005010015050250

60050Response (PR)PartialCPS
Stable Disease (SD)
Progressive Disease (PD)
Patients on Treatment
Deceased Patients

PRPRPR

Complete Response PR% Change in Baseline
Measurable Lesions

40000
1010
2030
4040
5050
6060
2030
Study
StudyWeeks
Weeks
Notes: Data Cutoff October 1, 2020; *Intent to treat population:
HNSCC (10 + 15 mg/kg) N=5; HNSCC (15 mg/kg) N=2
Lee KW, et al. SITC Annual Meeting; 2020. Abstract #404.

100150200250300CPS50

Complete Response
Partial Response

Progressive Disease• Patients with-40metastatic or unresectable, recurrent HNSCC
who have not received priorsystemic therapy for their advanced disease.
-60• Prior systemic therapy for the treatment of locoregionally advanced disease is allowed if
it was completed more than 6 months prior to enrollment.
40300-20

0050

100

150

200

250

300

–

3+3+2+3+2+3+–

–

2+–

HER2
Score

200-20-40

Patient on Treatment

Primary• After an initial20safety lead-in cohort, ASPEN-04 will randomize ~162 patients
2:1Analysis
to receive-60

Population
evorpacept+ pembrolizumab+ chemotherapy
orTimepembrolizumab+(days)
chemotherapy.
0102030405060from Initiation of Treatment-800Study
Weeks
05050

100

150200250• Prior treatment with a PD-1, PD-L1, or PD-L2 agent, or with an agent directed to anotherstimulatory or co-inhibitory T cell receptor (e.g., CTLA-4, OX40, CD137).

40

20060-204020RBC

CD412010060
402008010060
40
20150200050

Time (day)ALX + Tras + Chemo
Gatric ALX(10) N=3CD47 TO (%)

CD47 TO (%)

ALX + Pembro + Chemo
HNSCC ALX(10) N=3150

200

ALX + Pembro + Chemo
HNSCC ALX(15) N=2500

1005010

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• Statisticalassumptions used for the sample size determination:
1
Complete Response (CR)
Partial Response (PR)0244872

96120

144

168

Time (hours)• 1-sided α = 2.5% and
80% power.
Progressive Disease (PD)
Patient on Treatment• 12-month OS rate of 53% for the Pembrolizumab + Chemo arm2.
• To detect 12-month OS rate of 66.3% for the Evorpacept + Pembrolizumab +Stable Disease (SD)co-primary endpoints.

References
1. Keun-Wook Lee, Hyun Cheol Chung, Won Seog Kim, et al. ALX148, a CD47 blocker, in combination withstandard chemotherapy and antibody regimens in patients with gastric/gastroesophageal junction (GC)cancer and head and neck squamous cell carcinoma (HNSCC); ASPEN-01. Poster presented at: Society for
Immunotherapy of Cancer (SITC) Annual Meeting; November 11-14, 2020. Abstract #404.
2. Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab Alone or With Chemotherapy Versus Cetuximab
With Chemotherapy for Recurrent or Metastatic Squamous Cell Carcinoma Of The Head And Neck
(Keynote-048): A Randomised, Open-Label, Phase 3 Study. The Lancet. 2019 Nov 23; 394 (10212): 1915-1928.

100150Time (day)ALX + Tras + Chemo
Gatric ALX(15) N=10

• We would like to thank all the participating patients and their families as well as site research staff.
• This study is being conducted in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck &Co., Inc., Kenilworth, NJ, USA.

*Dr. Ruffner was employed by ALX Oncology Inc during the reporting period.

050

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

Abstract #433.

10080

0100Time (day)• Contact email: info@alxoncology.com• Trial Registration: ClinicalTrials.gov identifier, NCT04675333• Presented at the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting; November 10-14, 2021.

CPS6050

Acknowledgments• Prior treatment with any anti-CD47 or anti-SIRPα agent.

1200

Progressive Disease

300

Safety Lead-In
positive score, and HPV (p16) status.
Complete Response
Pembrolizumab +-20
CohortPartial Response
Recurrent
Chemotherapy• Patientsin theorevorpacept treatment arm will receive evorpacept
45 mg/kg
IV Q3W.
Progressive Disease
Metastatic-40(N≈108)• All patients
receive pembrolizumab
200 mg
Evorpacept+ IV Q3W (maximum of 35 cycles), 5FU
HNSCCwill2(1000 mg/m-60/day continuous infusion
Days 1, 2, 3,+ 4 Q3W x 6 cycles) and either carboplatin
Pembrolizumab
80
5 mg/ml/min
Day 1 Q3W x 6 cycles) or cisplatin (100 mg/m2 as a•(AUC≥18 Years
Old as a 60 min infusion
Chemotherapy
Checkpoint Naïve60mininfusionDay
1Q3Wx6cycles).
•PriorECOG(N≥6)
Therapy 0-1
60• PD-L1Pembrolizumab +Unselected
Chemotherapy
40(N≈54)-60-50• Nasopharyngeal carcinoma(NPC).
-600 factors used to randomize patients include geography, PD-L1 combined• Key minimization–Evorpacept +-40

-30

of locoregionally advanced HNSCC.
Stable DiseaseCR0-60Time from Initiation of Treatment (days)

Key Exclusion-10 Criteria

200-40102+ALX + Tras + Chemo
Gatric ALX(10) N=3150• Testing Strategy: Fixed sequence procedure will be used for the testing of20-80

0100

Chemotherapy arm.

60

20–50

40
20Sample Size Determination

Time from Initiation of Treatment (days)0• Progressive disease-40within 6 Partialmonthsof completion of systemic therapy for the treatment
Response

global study of evorpacept + pembrolizumab + chemotherapy (5FU + either carboplatin or60
Complete Response (CR)cisplatin) or pembrolizumabPD+ chemotherapy in patients with
PD-L1-unselected metastatic or
Partial Response (PR)Progressive
Disease(PD) advanced disease.
unresectable 40
recurrent HNSCC who have not yet been treatedfortheir4050• HNSCC suitable for -20
local therapy.

4080
ASPEN-04 (Figure4) is an ongoing non-comparative, open-label, randomized Phase 2PR0–

PD

40

20

80
60

Exploratory
endpoints will characterize pharmacodynamic properties.
1000-40-60• ECOG performance status 0 or 1.

Progressive
Disease(PD)
Progressive
Disease(PD)
Patientonon
Treatment
PatientTreatmentPR0-80

is >18 years.

PartialResponse(PR) (CR)Complete
Response
StableDisease(SD) (PR)PartialResponse

PDSD
ProgressiveDisease
PRSD

Checkpoint NaïvePrior Therapy

Pembrolizumab +Chemotherapy(N≈54)

40• Age ≥18 years, except
in regions in which the minimum age for subject participation

PRPR

2010060

Time (day)• Duration of response• Progression-free survival• Overall survival• SafetyCD4120-20• Adequate bone marrow, renal, and liver function.

CRPRPR

40

120020• Measurable disease per RECIST v1.1.

1L HNSCCSDSD
Partial Response

200

Time from Initiation of Treatment (days)

PR–PR

60RBC

• 12-monthoverall survival rate
10080
• Objective response rate
04080
Checkpoint Naïve
Prior Therapy

Co-Primary Endpoints

Key Secondary Endpoints

60

Key Inclusion
Criteria-20

Progressive Disease (PD)-60
Patient on Treatment

40

40

Progressive Disease-60

Study Endpoints

ALX148 Concentration (µg/mL)

5.3(5.0, 8.8)

Change in Baseline (%)

66.7%(20.8%, 93.9%)-20
Partial Response (PR)-40Stable Disease (SD)

-80

10

Patient5.0(1.3, 8.8)

23

PD0-60•PD-1Evorpacept+Study Weeks
Pembrolizumab +Chemotherapy
(N≥6)
30

Eligibility Criteria0

Randomized 2:1

Evorpacept(15 mg/kg)

75%(30.0%, 95.0%)40

1.6(1.3, 1.9)

selinesions

4MedianFollow-Up*(95% CI)100%(20.5%, 100%)% Change in Baseline
Measurable Lesions

1L HNSCC
Evorpacept +Keytruda +5FU + Platinum

ORR(95% CI)

1% Change in Baseline
Measurable Lesions

20N

Dendritic cell

T cellT cecellPopulation
SIRPα
Evorpacept
Dose

5.0
(1.3, 8.8)60

Pembrolizumab60

ne (%)

40

Evorpacept

Dendritic cellin Baseline Measurable Lesions

601(15 mg/kg)

475%(30.0%, 95.0%)

4020

1L HNSCC

3 PD-L1
Change in Baseline (%)

CD4720• ≥18 Years Old• ECOG 0-1• PD-L1Unselected

60MedianFollow-Up*(95% CI)

ORR(95% CI)

Study Methods

Cancer cellTumor
antigen

Evorpacept PR(15 SDmg/kg)
SD% Change in Baseline
Measurable Lesions

Cancer cell

Dendritic cell

Cancer cell

1L HNSCC PR
Evorpacept PR+
Keytruda +PR
5FU + PlatinumSD
Evorpacept

20elineions

Tumor
antigenDendritic cell

Dendritic cell

Dendritic cellTCR

Population SD
Evorpacept
PR N
Dose-20PD-1

HNSCC, where anti-PD-(L)1 therapy historically has diminished efficacy.

40-40

current standard therapeutic approaches (Figure 2).

10% Change in Baseline
Measurable Lesions

standard
optionfor patientswith affinity
previously
recurrent/metastatic
Cancer celluntreated
Cancercell
Cancer cell(R/M) HNSCC,bindingTumor
antigendisease and in combination withboth as a monotherapy for patients with PD-L1-positive
CD47
5FU + platinum fora PD-L1-unselected population.

Recurrent or
Metastatic0HNSCCEvorpacept +Progressive Disease (PD)
Pembrolizumab +Patient on Treatment
Chemotherapy(N≈108)
5060
Partial Response (PR)

Safety Lead-In
Cohort

PRCD47 TO (%)• Pembrolizumab, a T cell checkpoint
inhibitor that activates cytotoxic lymphocytes, is a
Optimized, picomolar

Complete Response (CR)PD

% Change in Baseline Measurable Lesions

Evorpacept,
Pembrolizumab, and Chemotherapy HaveHigh Affinity CD47
Binding
Domainsof SIRPαComplementary
Mechanisms of Action

PR60
Patient

typical antibody.

Progressive Disease (PD)
Patients on Treatment
Deceased Patients

PRPrimary Analysis
Population

PR

Partial Response (PR)
Stable Disease (SD)PatientPatient• Fc domain enables antibody-like PK.
• Molecular weight half the size of≥2L HER2 positive
Figure 3. Evorpacept + Pembrolizumab+ GC
5FU + Platinum Preliminary
PR
Activity in Patients with First-Line HNSCC(ASPEN-01Study)
PR% Change in Baseline Measurable Lesions

Figure 1. Evorpacept Potently
and Selectively Binds CD47 toBlock Interaction with SIRPα• This combination approach could be particularly
beneficial to patients with PD-L1-low2

Dendritic cell

Dendritic cellR/M HNSCC.

(Figure 1) designed to safely enhance standard anticancer therapeutics.

1T cell

T cell in previously untreated patients with PD-L1-unselectedpembrolizumaband chemotherapy
TcellcellT ce• Evorpacept is a high affinity CD47-blocking fusion protein with an inactive Fc region

InactiveFc Domain

TCR• The ASPEN-04 study will assess the efficacy and Tumor
safety of evorpacept in combination withantigen

upregulated by tumors to evade immune responses.

Fc domain mutated toeliminate Fcγ receptor
binding and minimize
associated toxicity

2

Dendritic cell

Pembrolizumab
initial clinicalpreliminary testing inSIRPαthe ongoing Phase 1 ASPEN-01 study1, demonstrating
response and tolerability. In initial data from patients with previously untreated, PD-L1PD-1
unselected R/M HNSCC treated with evorpacept + pembrolizumab+ 5FU/platinum,
patients experienced objective responses including complete response (Figure 3).

• CD47 is a marker of self that interacts with SIRPα on myeloid immune cells and is

Optimized, picomolarbinding affinity

PD-L1

Randomized 2:1

Evorpaceptof the innate and adaptive immune systems. After cytotoxic chemotherapy induces
neoantigen release, myeloid checkpoint inhibitors can help potentiate innate immune
cell activity including antigen presentation by dendritic cells.

High Affinity CD47
Binding Domains of SIRPα1• The combination of evorpacept + pembrolizumab + 5FU/platinum has undergone

CR% Change in Baseline
Measurable Lesions• Anticancer immunity relies on the release of tumor antigens and subsequent activation

Figure 4. ASPEN-04 Study Schema
1L HNSCC
PatientCancer cell
Cancer cell
Cancer cellTumor Chemotherapy
Evorpacept,
Pembrolizumab,andHave
antigenShown Initial
CD47 Antitumor Activity in the ASPEN-01 Study
3CD47 TO (%)

Background-50

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

ALX + Pembro + Chemo
HNSCC ALX(15) N=2200