patients

0200 mg every three weeks (Q3W)

High Affinity CD47
Binding Domains of SIRPα

0
0

50

100

150

200

A Phase 2 Study of Evorpacept (ALX148) in Combination with Pembrolizumab in Patientswith Advanced Head and Neck Squamous Cell Carcinoma (HNSCC); ASPEN-03≥2L HER2 positive GC

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

PR

PR

PR

Optimized, picomolarbinding affinity

50

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

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

100

150

200

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

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

PR

SD

PR

Patient

PR

80

PR

60

Checkpoint Inhibitor (CPI) NaïvePR
6 PR
CPI Prior Therapy
ORR
DCR
SD
CPI Naïve
40.0% (4/10) 50.0% (5/10)
SD
CPI Prior
0.0% (0/10) 10.0% (1/10)
SD

Change in Baseline (%)

Fc domain mutated toeliminate Fcγ receptor
binding and minimize
associated toxicity

Inactive
Fc Domain0Time (day)Checkpoint Naïve
Prior Therapy

6
6
6
6
6
6
7
Jong Chul Park1, Kevin Harrington2, Bhumsuk Keam3, Jean-Pascal Machiels4, Sjoukje Oosting5, Tim Welliver6, Shanhong Guan
90 , Feng Jin , Alison Forgie , Philip Fanning , Katherine Ruffner *, Jaume Pons , Sophia Randolph , Ezra Cohen
40

20

Partial Response (PR)0Stable Disease (SD)• Fc domain enables

with HNSCC (ASPEN-01 Study)

antibody-like PK.

Response
N=20: recurrent/metastatic HNSCC,
Patients
atEvaluable
least one prior systemic
therapy
Patient

size of typical antibody.

Fc domain mutated toeliminate Fcγ receptor
binding and minimize
associated toxicity0

T cellTumorantigenTreatment:

T cellEndpoints:

N=20: recurrent/metastatic HNSCC,

2

to block the CD47-SIRPα
myeloid checkpoint
leading to enhanced
phagocytosis andactivationof dendritic cells
Response
evaluable patients

N=20: recurrent/metastatic HNSCC,

3

antigens to cytotoxic
T cells

mediated inhibition ofactivated T cells

Treatment:
Evorpacept 10 mg/kg once a• maximum tolerated dose

Stable Disease (SD)
Progressive Disease (PD) Partial Response (PR)
Stable Disease (SD)Patient on Treatment

40

Study Weeks

Progressive Disease (PD)
Patients on Treatment
Deceased Patients

50

60

50

200

300

400

60

500

600

700

15

0

Study Endpoints

30

1L HNSCC

0

2

20

35

0

40

23

CPS

5
5
0 65 80 5
5 25
–
0
1
• ASPEN-03 53(Figure 4) is an ongoing non-comparative, open-label, randomized Phase 2
CR

global study of evorpacept + pembrolizumab or pembrolizumab alone in patients withPR
metastaticor unresectable recurrent, PD-L1-positive (CPS ≥1) HNSCC who have not yet-30Complete Response (CR)
CPI
Naïve
been treated for their advanced
disease. CPI Prior Therapy
PD
Partial Response (PR)• After an initial safety lead-in cohort, ASPEN-03 will randomize ~177 patients 2:1 to receiveDOR

4.3 months (95% CI 1.9, NC)

PR

NA

Progressive Disease (PD)

2.0 months (95% CI 0.9, 3.6)
-60
evorpacept+ pembrolizumab or pembrolizumabalone.
mPFS

4.6 months (95% CI 0.5, 7.5)

Study
25.1 months (95% CI 15.3,
25.6) Weeks
24.4 months (95% CI 1.0, 24.4)

HPV (p16) status.
-90• Patients in the evorpacept + pembrolizumab treatment arm will receive evorpacept
45 mg/kg IV Q3W.

• All patients will receive pembrolizumab 200 mg IV Q3W (for a maximum of 35 cycles).
Figure 4. ASPEN-03 Study Schema
RBC

120

Primary Analysis
Population

CD4

120

100

100

80

40
Recurrentor
20
Metastatic
0
HNSCC
0
50

80

60
Safety Lead-In
Cohort4060

20

0Evorpacept
200
0+
50
Time (day)Pembrolizumab
ALX + Tras + Chemo
ALX + Tras + Chemo
ALX + Pembro + Chemo• ≥18 Years Old
Gatric ALX(10) N=3
Gatric ALX(15) N=10 (N≥6)
HNSCC ALX(10) N=3• ECOG 0-1• PD-L1 CPS ≥1
100

150

80

PR

PD

20PD

10

100

Evorpacept +Pembrolizumab(N≈118)150200Time (day)ALX + Pembro + Chemo
HNSCC ALX(15) N=2

Pembrolizumab(N≈59)

30

Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)

0

0

53

-80

0

5

0

• Patients with metastatic or unresectable, recurrent HNSCC that is PD-L1-positive (CPS ≥1)Complete Response (CR)

40
100

200

50Partial Response (PR)60300
400 500
600
Progressive Disease (PD)and who have not received prior systemic therapy for their advanced disease.

700

Time from Initiation of Treatment (days)• Prior systemic therapy for the treatment of locoregionally advanced disease is allowed if it

Patient on Treatment

10
5

20
65

80

5

30

1L HNSCC
Study Weeks
5

25– CR 0

40
2

50

20

35

0

was completed more than 6 months prior to enrollment.

60

40

23

15

1

0

CPS

PR

DOR

-60

mPFS
120mOS

0

-90

PR

10

100mFollow Up

CPI NaïvePD

CPI Prior Therapy

Complete Response (CR)

4.3 months (95% CI 1.9, NC)

NA

Progressive Disease (PD)

4.6 months (95% CI 0.5, 7.5)

2.0 months (95% CI 0.9, 3.6)

RBC

22.1 months (95% CI 3.1, NC)

20

30

Patient on Treatment

40

Study
100 (95% CI 1.0, 24.4)
25.1 months (95% CI 15.3,
25.6) Weeks
24.4 months

80
60
40
20

ALX + Tras + Chemo
ALX + Tras + Chemo
Lee KW, et al. SITC Annual Meeting;2020.
Abstract
Gatric ALX(10)N=3Gatric #404.
ALX(15) N=10

RBC

CD4
50

60

40

20

20
0
-20
-40
-60
-80

0

50

100

150

200

250

Time from Initiation of Treatment (days)
Exploratory endpoints will characterize
pharmacodynamic
properties.
CPS
40
0
50

0

300

–

Sample Size Determination-20-40

Complete Response
Partial Response
Progressive Disease-60• Statistical assumptions
used for the sample size determination:• 1-sided α = 2.5% and 80% power.
Complete Response (CR)
Partial Response (PR)• 12-month OS rate of 51% for the Pembrolizumab arm2.
Stable Disease (SD)1000
Progressive
Disease (PD)• To500detect 12-month OS rate of 63.7% for the Evorpacept + Pembrolizumabarm.
Patient on Treatment

100• Testingstrategy: Fixed sequence procedure will be used for the testing of

100
80
60

Key Exclusion Criteria

treatment of locoregionallyadvanced HNSCC.
60

40
20

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

CD4

Primary Analysis
Population

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)

1

0
24
72
96
120
144
168
1. Keun-Wook
Lee,48Hyun
Cheol
Time
(hours)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.

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

200• Nasopharyngeal carcinoma (NPC).
40• Prior treatment with any anti-CD47 or anti-SIRPα agent.
20• Prior treatment with a PD-1, PD-L1, or PD-L2 agent, or withagentof Treatment
directed
Time anfrom Initiation(days) to
-20
-40

-60
-80

0

50

100

150

200

250

0
50
another stimulatory or0 co-inhibitory 40
T cell receptor(e.g.,CTLA-4, OX40, CD137).
CPS

–

-20

5

Abstract #439.

• HNSCC suitable for local therapy.
• Progressive disease80within 6 months of completion of systemic therapy for the
40

60

10

• Contact email: info@alxoncology.com• Trial Registration: ClinicalTrials.gov identifier, NCT04675294• Presented at the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting; November 10-14, 2021.

60

80

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

120

100

60

60

• Duration of response80• Progression-free survival
60• Overall survival
40• Safety

Co., Inc., Kenilworth, NJ, USA.

• ECOG performance status 0 or 1.

Partial Response (PR)

7.4 months
120(95% CI 3.1, 15.4)• Measurable disease per RECIST v1.1.
• Adequate bone marrow, renal, and liver function.
• Age ≥18 years, except in regions in which the minimum age for subject participationis >18 years.

Notes: Data Cutoff October 1, 2020; Patients who received at least one dose of ALX148 in the expansion phase,00
had a baseline assessment,
and50at least one
post-baseline
diseaseassessment;
ORR– OverallResponse
Rate;200
0
100
150
200
0
50
100
150
DCR – Disease Control Rate; CPS – Combined
Time (day) Positive Score.
Time (day)80

Key Secondary Endpoints

References

Key Inclusion Criteria

Patient on Treatment

-60

-100

Study Weeks

Eligibility Criteria

Checkpoint Naïve
Prior TherapyPR30• 12-month overall survival rate
• Objective response rate

Patient on TreatmentmOS
22.1 months (95% CI 3.1, NC)
7.4 months (95% CI 3.1, 15.4)
0
1030
40 include geography,
50
60• Key minimization
factorsused20to randomize
patients
CPS, andmFollow Up

Co-Primary Endpoints

50
co-primary
endpoints.

Change in Baseline (%)

Patient

0120

Endpoints:

30

CD47 TO (%)

TCR

60

CD47 TO (%)

Response
evaluable patients

PD-1

2

• maximum tolerated dose
Evorpacept 10 mg/kg once a• anti-cancer activity
week (QW)
at least one prior systemic therapy+
dendritic cells
N=10: binds
checkpoint
inhibitor naïveActivatedPembrolizumab
Pembrolizumab binds to
Evorpacept
to CD47
cross-present
tumor
PD-1, relieving PD-1/PD-L1expressedby cancer cells
patients
200 mgevery three weeks (Q3W)

T cellce

1

Pembrolizumab

SIRPα

20

PR

-30

Dendritic cell

T cell

1

3 PD-L1

Dendritic cell

Evorpacept

T cellCancer cell

Dendritic cell

Pembrolizumab

Dendritic cell

Dendritic cell

CD47

Dendritic cell

T cellT cell
ce

Tumor
Tumor
antigenantigen

PR•

60
Checkpoint Inhibitor(CPI) NaïvePR
1L HNSCC40CPI Prior TherapyPR
20
DCR
SD ORR
CR0
CPI Naïve
40.0% (4/10) 50.0% (5/10)
SD-20
CPI Prior
0.0% (0/10) 10.0% (1/10)
SD-40

Patient

1 with pembrolizumab has the potential to augment both
• Evorpacept used in combination% Change in Baseline Measurable Lesions

3 PD-L1

TCR
Cancer cell
T cell

10

PR

PR

90

metastatic (R/M) HNSCC
CD47 with PD-L1-positive tumors (combined positive score (CPS) ≥1).

Cancer cell

PR

Study Methods

100

Time from Initiation of Treatment (days)

PR

Patient

Fcγ receptor lymphocytes. Pembrolizumab as a single
Inactive
efficacy throughactivationeliminateof tumor-infiltrating
Cancer cell
Cancer cell
Cancer cellTumorbinding
and minimize
Fcagent
Domainis a standard treatment
optionfor patients with antigen
previously untreated recurrent or
associated toxicity

PD-1
Figure 2. The Combination of Evorpacept and Pembrolizumab
Can Bridge2
the Innate and Adaptive Immune Responses

Endpoints• maximum tolerated dose
• anti-cancer activity• Maximum

Evorpacept 10 mg/kg once aweek (QW) 10 mg/kg
Evorpacept+
once
a week (QW) +tolerated dose
Pembrolizumab
Pembrolizumab
200 mg every three weeks (Q3W) PartialAnti-cancer
activity
Response (PR)PRSD

• Anti-PD-1 immune checkpoint
inhibitor
pembrolizumabhas demonstrated antitumor
Fc domain
mutatedto

SIRPαTreatment

PR

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

Endpoints:

Treatment:SD

TO (%)

Evorpacept and Pembrolizumab
Have Complementary
Optimized, picomolarbinding affinity
Mechanisms of Action

innate andEvorpacept
adaptive antitumor immune responses (Figure 2).

PRcheckpoint inhibitor naïve PR
N=10:Recurrent/metastatic
N=20:
PR
patients at least one prior
HNSCC,
SD
200 mgeveryGCthreesystemic therapy≥2L HER2
positiveSDweeks (Q3W)
PR➔ N=10: Checkpoint SD
PR
inhibitor naïve PDpatientsTO (%)High Affinity CD47
Binding Domains of SIRPαPR
PRResponse
evaluable patients• Molecular weight half thePR0% Change in Baseline
Measurable Lesions≥2L HER2 positive
GC
Figure 3. Initial Activity of Evorpacept+ Pembrolizumabin Patients40% Change in Baseline
Measurable Lesions

safety of evorpacept in combination with pembrolizumab in previously untreated patientswith metastatic or unresectable recurrent PD-L1-positive HNSCC.

-80

-100

ALX148 Concentration (µg/mL)

T cell the ASPEN-03 study will assess the efficacy and•TTBasedon these encouraging results,
cell
cell
ce

Figure 1. Evorpacept Potently and Selectively Binds CD47 to Block
Interaction with SIRPαInactive
Fc Domain

antigenDendritic cell

Dendritic cell

(Figure 1) designed to be safely combined with and to enhance the efficacy of standard
anticancer therapeutics.

Optimized, picomolarbinding affinity

2

Dendritic cell

platinum-based therapy (n=10) were treated with evorpacept +PD-1
pembrolizumab andexperienced a 40% ORR and 4.6 months median PFS, comparing favorably with historicalcontrols (Figure 3).
TCR
T cellTumor

Study Weeks

Patient on Treatment-60

Randomized 2:1• PD-L1-unselected immune checkpoint naïve patients whose disease progressed on• Evorpacept is a high affinity CD47-blocking fusion protein with an inactive Fc region

High Affinity CD47
Binding Domains of SIRPαPembrolizumab

SIRPα

30

% Change in Baseline
Measurable Lesions

function. CD47 is upregulated by tumors to evade immune responses and its expression
is associated with poor prognosis in hematologic and solid tumors including HNSCC.

20

CD47 TO (%)• CD47 is a marker of self that interacts with SIRPα on myeloid immune cells, inhibiting their3

1

and acceptable tolerability in patients with ≥2nd line advanced HNSCC in the ongoing
Phase Evorpacept
1 ASPEN-01 study1.

10% Change in Baseline
Measurable Lesions•

anticancer immunity.

The combinationCD47
of evorpacept + pembrolizumab has shown preliminary antitumor activity
PD-L1

0

Progressive Disease (PD)-40

Patient• Both innate and adaptive immune responses are important components ofPD

CD47 TO (%)

Background

Evorpacept + Pembrolizumab Has Demonstrated Initial
CancerCancer cell Activity from
Cancer cell
Antitumor
thecell ASPEN-01
Study
Tumor
antigen% Change in Baseline Measurable Lesions

1Massachusetts General Hospital Cancer Center, Boston, MA; 2The Royal Marsden Hospital, London, United Kingdom; 3Seoul National University Hospital, Seoul, Korea; 4Cliniques Universitaires Saint-Luc, Brussels, Belgium; 5University Medical Center Groningen, Netherlands;
6ALX Oncology Inc., South San Francisco, United States; 7University of California San Diego, San Diego, United States
60-20

Complete Response
Partial Response300