ALX148, a CD47 Blocker, in Combination withRituximab in Patients with Relapsed/Refractory (R/R)
Non-Hodgkin Lymphoma; ASPEN-01
Tae Min Kim, MD, PhD1, Nehal Lakhani, MD, PhD2, Justin Gainor, MD3, Manali Kamdar, MD4,
Philip Fanning, PhD5, Pierre Squifflet, MSc6, Feng Jin, PhD5, Alison Forgie, PhD5 , Hong I Wan, PhD5,Jaume Pons, PhD5, Sophia S Randolph, MD, PhD5 and Won Seog Kim, MD, PhD71Seoul National University Hospital, Seoul, South Korea; 2START Midwest, Grand Rapids, MI USA;
3Massachusetts General Hospital Cancer Center, Boston, MA USA; 4University of Colorado Cancer Center, Aurora, CO USA;
5ALX Oncology, Burlingame, CA, USA; 6International Drug Development Institute, Brussels, Belgium;
7Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

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Disclosures

TMKim: AstraZeneca-KHIDI; AstraZeneca; Novartis; Takeda; Sanofi; Roche/Genentech; Voronoi and Boryung.
NLakhani: Alexion; Alpine Immune; ALX Oncology; Apexian; Asana Biosciences; Ascentage Pharma; Beigene; Celgene;
Cerulean; Constellation; Coordination Therapeutics; Cytomx; Formation Biologics; Forty Seven; Ikena Oncology; Incyte; InhibRx; Innovent Bio; Jounce; Livzon; Loxo; Macrogenics; Merck; Mersana; Northern Biologics; Odonate; Pfizer; Regeneron;
Sapience; Shattuck Labs; Symphogen; TaiRx and Tesaro. JGainor: Ironwood; Agios; Amgen; Array; Blueprint Medicines;
Bristol-Myers Squibb; Genentech; Jounce; Gilead; Lilly; Merck; Moderna; Oncorus; Regeneron; Takeda; Theravance;
Adaptimmune; Ariad; AstraZeneca; Novartis and Tesaro. MKamdar: Roche. PFanning: ALX Oncology. PSquifflet: ALX
Oncology and IDDI. FJin: ALX Oncology. AForgie: ALX Oncology. HWan: ALX Oncology and Tallac. JPons: ALX Oncology.
SRandolph: ALX Oncology. WSKim: Roche; Pfizer; Johnson and Johnson; Celltrion; Kyowa Kirin; Dongs and Mundipharma.

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ALX148 Potently and Selectively Binds CD47 to Block SIRP⍺ Interaction• CD47-SIRPα signaling is a myeloid checkpointmechanism that signals the macrophage toignore the cell on which CD47 is expressed.1
Tumors upregulate CD47 to evade the immune
response, and high expression of CD47 in NHL isreported to correlate with a worse OS, while
CD47 blockade in addition to rituximab
augments rituximab-mediated phagocytosis.2,3• ALX148 is an engineered fusion protein
comprised of a high affinity CD47 blocker linked
to an inactive human immunoglobulin Fc region.
It blocks the CD47-SIRPα interaction, thereby
enhancing anti-tumor immunity.3

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High Affinity CD47
Binding Domains of SIRP⍺

Optimized, picomolarbinding affinity
Fc domain mutated to eliminate
Fcγ receptor binding andminimize associated toxicity• Fc domain enables
antibody-like PK.
• Molecular weight half thesize of typical antibody.

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ASPEN-01: A First-in-Human Phase 1 Study of ALX148
ASPEN-01 evaluates ALX148 administered asa single agent (Part 1) and in combination withestablished anticancer antibodies (Part 2)
including in combination with rituximab inpatients with relapsed or refractory B-cell non
Hodgkin lymphoma (NHL).
• Part 1 (single agent): No MTD reached,maximum administered dose 30 mg/kg QOW.4• Part 2 (combination): ALX148 (administered
10 mg/kg or 15 mg/kg QW) combined withstandard regimens of rituximab (administered375 mg/m2 QW x 4 followed by once
monthly x 8).5
– Primary Endpoint: First cycle ALX148 dose limiting
toxicity (DLT) in combination with rituximab.

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PrimaryDisease, nFollicular
Marginal Zone (MZL)
Mantle Cell (MCL)DLBCLMedian Age, Years (range)
Sex, nRace, nECOG, PS, nM
F
AsianWhite01Median Prior Therapy, n (range)

ALX14810 mg/kg QW+ rituximab(n=22)
52411

ALX14815 mg/kg QW+ rituximab(n=11)
311666 (32-80)

64 (53-78)

1751847156592293 (1-7)

3 (1 -5)• As of October 1, 2020, ALX148 in combination with rituximab has
been administered to 33 patients with advanced relapsed andrefractory non-Hodgkin lymphoma.
• The majority of patients enrolled were male (70%), Asian (82%) andhad an ECOG PS score of 1 (73%).
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ASPEN-01: Preliminary Clinical Safety and Anti-Cancer Activity
Clinical Safety of ALX148 in Combination
with Rituximab• Twenty-eight (84.8%) patients experienced
any adverse event. Nineteen (57.6%) patientsexperienced any TRAE.
• No ALX148 dose limiting toxicities were reported, themaximum administered dose was 15 mg/kg QW.

Clinical Activity of ALX148 in Combination withRituximab in Response-Evaluable Patients• ALX148 10 mg/kg + rituximab (N=22)– 4CR ([2] Follicular, [1] Marginal Zone, [1] MCL)
– 5PR ([2] DLBCL, [1] Follicular, [2] Mantle Cell)– 6SD ([2] DLBCL, [2] Follicular, [1] Mantle Cell, [1] Marginal Zone)• ALX148 15 mg/kg + rituximab (N=10)– 3CR ([2] Follicular, [1] Marginal Zone)– 4PR ([2] DLBCL, [1] MCL, [1] Follicular)

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ALX148 + Rituximab (N=33)
Related Adverse Event

Total n (%)≥Grade 3 n (%)

Rash

8 (24.2)—Fatigue

4 (12.1)—

Nausea2 (6.1)—

Neutrophil Count
Decreased

2 (6.1)2 (6.1)

Anemia2 (6.1)1 (3)Myalgia2 (6.1)—

Pruritus

2 (6.1)—

Data Cutoff 01Oct2020.

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Clinical Activity of ALX148 + Rituximab in Response-Evaluable Patients
Population
ALX148 Dose

NORR
(95% CI)

DCR(95% CI)Median DOR(95% CI)Median TTR(range)

Median PFS(95% CI)Median OS(95% CI)NHL(10 mg/kg ALL)

22

40.9%
[20.7; 63.6]

59.1%[36.4; 79.3]

14.9[1.81; 14.9]

1.88[1.51 - 2.07]

7.43[1.88; 13.2]

18.5[7.34; NC]NHL(10 mg/kg aggressive)

15

33.3%
[11.8; 61.6]

46.7%[21.3; 73.4]

5.56[NC; NC]

1.88[1.81 - 1.91]

2.53[0.95; 7.43]

8.95[2.50; NC]NHL(10 mg/kg indolent)

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57.1%
[18.4; 90.1]

85.7%[42.1; 99.6]

NC

1.92
[1.51 - 2.07]

NCNC

1070.0%[34.8; 93.3]

70.0%[34.8; 93.3]

NC

1.88
[1.71 - 5.43]

NC

NC

NHL
(15 mg/kg aggressive)

6

50.0%
[11.8; 88.2]

50.0%[11.8; 88.2]

NC

1.88
[1.71 - 5.43]

NC

NC

NHL(15 mg/kg indolent)

4100%[NC; NC]

100%[NC; NC]NC

1.74[1.71 - 1.88]

NC

NC

NHL
(15 mg/kg ALL)

Aggressive: Relapse/refractory Diffuse Large B Cell Lymphoma and Mantle Cell Lymphoma; Indolent: Follicular Lymphoma and Marginal Zone Lymphoma; ORR: Objective response rate (complete +partial response rate); DCR: Disease control rate (CR+PR+SD≥24 weeks); DOR: Duration of response (months); TTR: Time to response (months); PFS: Progression free survival (months); OS: Overallsurvival (months); CI: Confidence interval; NC: Could not be calculated. Data Cutoff 01Oct2020.

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Clinical Activity of ALX148 + Rituximab by Patient with NHL
ALX148 (10 mg/kg QW)* + Rituximab^ ^ ^ ^% Change from Measurable
Baseline Lesion

60
40

50
080

-5060

-100

20100

Aggressive NHLIndolent NHL

400100200

300

400500Time from Initiation of Treatment (Days)

2000-20-20-40-40-60-80^^

Change from Baseline (%)

80

Change from Baseline (%)

100

ALX148 (15 mg/kg QW) + Rituximab
Aggressive NHLIndolent NHL50
0-50-100050

100150 200

250 300 350 400

Time from Initiation of Treatment (Days)-60
1 patient with metabolic CR
not represented in plots-80-100-100
Complete Response

Partial Response

Stable Disease

Progressive Disease

Data Cutoff 01Oct2020; Response evaluable patients; Responses include metabolic response per Lugano Response Criteria.
^ more than 80% increase from baseline. * 1 patient with rapid fatal progressive disease not represented in plot
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ALX148 Clinical Pharmacokinetics and Exposure-Response Analysis• ALX148 concentration-time profiles
following first IV infusion at Cycle 1
Day 1 as single agent or in
combination with rituximab.

• A significant improvement in patients with clinical response (PR,CR) withincreased ALX148 exposure (AUC; p = 0.023) was observed across theexposure range evaluated (10 mg/kg QW - 15 mg/kg QW).

Data Cutoff 01Oct2020.
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Biomarker Analyses of ALX148 + Rituximab• No correlation was observed for baseline
intratumoral CD8 and CD68 expression
and percent change from measurable
baseline lesions• A moderate correlation was seen forbaseline intratumoral CD163 expression
with poorer response (r= 0.4737;p=0.0405; Spearman nonparametriccorrelation)

Percentage• Immunohistochemistry for CD8 (tumorinfiltrating lymphocytes) and CD68 andCD163 (tumor associated macrophages
and myeloid cells) was conducted on
available baseline biopsies

Days

Days

Baseline IntratumoralCD8CD68

CD163% CD8 + Cells% CD68 + Cells% CD163 + Cells

CR (N=4)

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TBNK 15 mg/kg ALX148 + Rituximab (N=11)

Percentage• An expected, reduction in circulating
B cells was seen

TBNK 10 mg/kg ALX148 + Rituximab (N=10)% Change from Measurable
Baseline Lesion• In general, no changes in circulating
T and NK cells were observed following
ALX148 + Rituximab

PR (N=4)

SD (N=6)

PD (N=5)

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Conclusions
ASPEN-01: ALX148 in combination with rituximab maximizes the innate and adaptive immune response
to NHL while avoiding the dose-limiting hematologic toxicities associated with other CD47-targeted
approaches in the clinic.
• ALX148 in combination with standard regimens of rituximab is welltolerated with a favorable hematologic safety profile and no maximum
tolerated dose reached. The maximum administered dose is 15 mg/kg QW.
• ALX148 in combination with rituximab demonstrates linear PK at 10 mg/kg
and 15 mg/kg QW with no impact upon circulating T or NK cells.
• ALX148 demonstrates encouraging anti-cancer activity with 70% ORR at15 mg/kg QW and durable responses in combination with rituximab inpatients with relapsed/refractory NHL (median of 3 prior therapies) thatcompare favorably to historic controls.

We thank all of the participating
patients and their families as wellas the site research staff• Presented at the American Society ofHematology (ASH) Annual Meeting.
• December 5-8, 2020. Abstract #3016;
Contact email: info@alxoncology.com• Initial data suggests ALX148 is well tolerated and demonstrates significant
improvement in clinical response with increased exposure across theexposure range evaluated.

1 Weiskopf, K., Eur J Cancer. 2017 May;76:100; 2Bouwstra, R. et al., Cancer Immuno Research 2019 Oct;7(10):1663; 3Kauder, S.E. et al., PLoS ONE. 2018 August;13(8); 4Lakhani N. et al, #P335, SITC 2018;
5Kim et al., #EP1247, EHA 2020.

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