ASPEN-01: A Phase 1 Study of ALX148, a CD47 Blocker, in Combination with Trastuzumab, Ramucirumab,
ndand Paclitaxel in Patients with 2 Line HER2-Positive Advanced Gastric or Gastroesophageal Cancer
Hyun Cheol Chung,1* Keun-Wook Lee,2* Won Seog Kim,3 Justin Gainor,4 Nehal Lakhani,5 Laura QM Chow,6** Wells Messersmith,7 Philip Fanning,8 Pierre Squifflet,9 Feng Jin,8 Alison Forgie,8 Hong Wan,8 Jaume Pons,8 Sophia Randolph,8 Patricia LoRusso101Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; 2Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea; 3Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea; 4Massachusetts General Hospital, Boston, MA;
5START Midwest, Grand Rapids, MI; 6University of Washington, Seattle, WA; 7University of Colorado Cancer Center, Aurora, CO; 8ALX Oncology Inc, Burlingame, CA, USA, 9International Drug Development Institute, Brussels, Belgium, 10Yale Cancer Center, New Haven, CTBackground• CD47, a myeloid checkpoint and marker of self, signals the macrophage toignore the cell on which CD47 is expressed by binding its receptor, SIRPα.1
Tumors upregulate CD47 to evade the immune response.
• ALX148 is a high affinity CD47 blocking fusion protein with an inactive humanimmunoglobulin Fc region (Figure 1) designed to enhance the activity ofanti-cancer targeted antibodies and checkpoint inhibitors with minimal
hematologic toxicity2.
• ASPEN-01 (AT148001), a first-in-human phase 1 study evaluates ALX148
administered as a single agent (Part 1) and in combination with establishedanti-cancer antibodies (Part 2).

Figure 1. ALX148 Potently
and Selectively Binds CD47
to Block SIRPα Interaction• Fc domain enables antibodylike PK.
• Molecular weight half the sizeof typical antibody.
•• Primary Study Objective: Characterize ALX148 safety profile as a single agent(Part 1) and in combination with established anti-cancer antibodies with or without
standard chemotherapy (Part 2).
• Tolerability of ALX + trastuzumab has been reported previously4.

Table 3. ≥ Grade 3 Adverse Events• Here we report tolerability data from fully enrolled GC patient cohorts receiving
ALX148 + trastuzumab + ramucirumab + paclitaxel as well as updated clinicalactivity of all GC cohorts as of May 03, 2021.

Adverse EventMethods
Study Design• Part 1 (single agent): Patients were administered escalating doses of
intravenous ALX148 (0.3 to 10 mg/kg QW; or 30 mg/kg Q2W)3.
• Part 2 (combination): A subgroup of patients with HER2 positive Gastric/GEJ
cancer were administered ALX148 10 or 15 mg/kg QW in combination withtrastuzumab (8 mg/kg IV→6 mg/kg Q3W) with or without ramucirumab(8 mg/kg Days 1, 15 Q4W) and paclitaxel (80 mg/m2 Days 1, 8, 15 Q4W).
- Adequate organ function and hemoglobin ≥9 g/dL.
- No prior treatment with an anti-CD47 or anti-SIRPα agent.
- HER2-positive-status for study eligibility as locally assessed by sites using an
FDA approved test for gastric cancer.

progressed on prior fluoropyrimidine(progression on trastuzumab and platinum allowed)

Dose Escalation ALX148
10 mg/kg QW (n=3)
15 mg/kg QW (n=15)≥2L HER2-Positive GC
ALX148 + Trastuzumab + Ramucirumab + Paclitaxel
progressed on prior trastuzumab and fluoropyrimidine, or platinum34410mg/kg

15mg/kg

10mg/kg

15mg/kg

Neutrophil Count
Decreased

1 (5.6) 4 (22.2) 1 (5.6)

1 (5.6)––––

Patient Baseline Characteristics

Hypertension

2 (11.1) 4 (22.2)

–––

–

–

–

Anemia–3 (16.7)

–––

––

–

• 38 patients have been enrolled into Part 2 GC combination cohorts.

Fatigue–

2 (11.1)

–––

––

–

Table 1. Baseline Characteristics

Hypophosphatemia–

1 (5.6)––––––

Lymphocyte
Count Decreased–

1 (5.6)–––1 (5.6)––

Platelet CountDecreased–

1 (5.6)––––––Urinary Tract
Infection–

1 (5.6)––––––

Aspartate
Aminotransferase
Increased–

1 (5.6)––––––

Asthenia–

1 (5.6)––––––

Results

15mg/kg

315mg/kg

ALX148+ Trastuzumab+ Ramucirumab+ Paclitaxel≥2L GC (N=18)

ALX148+ Trastuzumab≥2L GC (N=20)

63 (36-83)

58 (45-79)

M

1315

F

55Asian

1513White

36

Other

–

1Diverticulitis–

1 (5.6)––––––

087

Dysphagia–

1 (5.6)––––––11013

Progressed Upon Prior
Anti-HER2 Therapy, n ( %)–1 (5.6)––––––

17 (94)19 (95)

Non-Cardiac
Chest Pain

Progressed Upon ≥2 Prior Anti-HER2Therapy n (%)

1 (6)9 (45)

Progressed Upon Prior CPI Therapy, n (%)

2 (11)

9 (45)

Visceral Distant Metastasis, n (%)

17 (94)17 (85)Median Age, Years (range)

Race, n• Near complete CD47 target occupancy is maintained throughout ALX148 dosinginterval over Cycles 1-3 when combined with chemotherapy-containing regimens.
(For a subset of patients, target occupancy was measured up to or beyond 300days with similar results being observed.)# Centrally assessed, retrospectively, on archival or fresh baseline tissue samples;

Population(EVAL)≥2L
Gastric/GEJ(ALX148
10 mg/kg or
15 mg/kg +TRP)

18

72.2
[49.1%; 87.5%]

NR

SafetyGastric/GEJ(ALX148
10 mg/kg +TRP)

3

66.7[20.8%; 93.9%]

NRNR• ALX148 in combination with trastuzumab + ramucirumab + paclitaxel (N=18) waswell tolerated, with most treatment related adverse events (TRAE) reported of lowgrade and frequency. Safety of ALX148 in combination with trastuzumab has been
described elsewhere4.

Gastric/GEJ(ALX148
15 mg/kg +TRP)

1573.3[48.1%; 89.1%]

NRNR

≥2L
Gastric/GEJ(ALX148
10 mg/kg +Trastuzumab)

19*

21.1
[8.5%; 43.3%]• There were no dose limiting toxicities reported in patients treated with ALX148 +trastuzumab + ramucirumab + paclitaxel.
• All patients in the chemo-containing cohort experienced at least 1 adverse event.
Eight (44.4%) patients administered ALX148 + trastuzumab + ramucirumab +paclitaxel experienced a TRAE.
• The most common TRAEs of ALX148 in combination with trastuzumab +ramucirumab + paclitaxel (N=18) were low grade diarrhea, rash, urticaria (each16.7%; Table 2). TRAEs ≥Grade 3 severity were of low frequency (Table 3).
• There were no treatment related SAEs reported in patients treated with ALX148 +trastuzumab + ramucirumab + paclitaxel.
• Four unrelated SAEs in combination with trastuzumab + ramucirumab + paclitaxel
were reported (1 urinary tract infection; 1 diverticulitis; 1 non-cardiac chest pain;
and 1 fatigue).

Adverse Event Profile in Patients with GC by Dose Level
Table 2. Treatment Related Adverse Events• ALX148 PK following combination therapies with trastuzumab is comparable withand without chemotherapy (ramucirumab + paclitaxel).

Response
ALX148 Combination Expansion Cohorts – Confirmed Objective
Responses in Evaluable Patients

ALX148 + Trastuzumab + Ramucirumab + Paclitaxel(N=18)
Total n (%)
ALX14810 mg/kg

ALX14815 mg/kg

Diarrhea–3 (16.7)

Rash–

3 (16.7)

Urticaria–3 (16.7)

Pruritus–

2 (11.1)

Fatigue

1 (5.6)1 (5.6)

Lymphocyte Count Decreased–

1 (5.6)

Abdominal Pain–

1 (5.6)

Anemia–1 (5.6)

Back Pain–

1 (5.6)

Dermatitis Acneiform–

1 (5.6)

Stomatitis–

1 (5.6)

Vision Blurred–

1 (5.6)• There were no dose limiting toxicities, on study deaths, or ALX148-related SAEs.

• HER2 positive GC Expansion- ALX148 (15 mg/kg QW) + trastuzumab + ramucirumab + paclitaxel, ≥2L GC:
N=15 [1 CR*, 10 PR, 2 SD, 2 PD].
- ALX148 (10 mg/kg QW) + trastuzumab + ramucirumab + paclitaxel, ≥2L GC:
N=3 [2 PR, 1 SD].
- ALX148 (10 mg/kg QW) + trastuzumab, ≥2L GC:
N=19 [4 PR (1 unconfirmed), 5 SD, 10 PD].
* Objective response confirmed after data cut off date.

ND: Not done

PFS
DOR (m) PFS (m) Rate
[95% CI] [95% CI] at 6 m

ORR (%)

Figure 4. ALX148 Concentration-Time Profiles by Dose Level andCombination Partner

Figure 8. Baseline Tumor Infiltrating Immune Cells in Responders andNon-Responders Receiving ALX148 (10 or 15 mg/kg) + TRPTable 4. Clinical Activity of ALX148 Combinations in Response
Evaluable Patients

NAdverse Event≥2L HER2-Positive GC
ALX148 + Trastuzumab

GradeFigure 7. CD47 Target Occupancy from Chemotherapy Combination
Cohorts

Total n(%)
Related10mg/kg

Figure 3. ASPEN-01 – Gastric/Gastroesophageal (GC) Combination
Cohorts
Dose Expansion ALX148
10 mg/kg QW (n=20)

Total n(%)
All Causality
10mg/kg

ECOG PS, n

ALX148 is designed to safely maximize antibody dependent
phagocytosis (ADCP) of cancer cells by targeting CD47 as a myeloidcheckpoint inhibitor2

ALX148 + Trastuzumab + Ramucirumab + Paclitaxel(N=18)

ALX148 Dose QW

Sex, nFigure 2. ALX148 is a Myeloid Checkpoint Inhibitor

Figure 5. Clinical Activity of ALX148 + Trastuzumab + Ramucirumab +Paclitaxel in Patients with GC*HCC and KWL contributed equally to this abstract; **LQMC currently at University of Texas at Austin, TX.

[95% CI]OS (m)[95% CI]

OSRateat 12 m

NR

75.8%

10.5
[4.8; 12.5]

100%NR

66.7%

14.3[12.0; NR]

68.3%

NR

80.8%

9.4
[4.2; 12.5]9.1
74.5%[3.8; NR]

8.7
2.2
8.1
16.7%
38.2%
[5.6; NR] [1.9; 5.5]
[3.4; 12.6]

Follow
Up (m)[95% CI]• Responder: CR+PR (N=7)• Non-Responder: SD+PD (N=4)• Plots represent mean and standard deviation.

27.0
[NR]

TRP: trastuzumab + ramucirumab + paclitaxel; NR: Not reached.
*One patient discontinued prior to first imaging assessment with symptoms consistent with progression and was not evaluable forresponse, per protocol.

Conclusions

Figure 6. Best Overall and Duration of Response in Patients WhileReceiving ALX148 + Trastuzumab + Ramucirumab + Paclitaxel (n=18)

Intended for combination, ALX148 exhibits favorable tolerability
in combination with trastuzumab + ramucirumab + paclitaxel
and demonstrates objective response in patients with GC• Preliminary data suggest that ALX148 can be combined with trastuzumab,ramucirumab and paclitaxel with no maximum tolerated dose reached.
The maximum administered dose of ALX148 in combination was
15 mg/kg QW.
• Preliminary PK/PD analysis demonstrates no impact of the combination
partners upon ALX148 exposure levels with full CD47 receptor occupancy
achieved and numeric increases demonstrated in % baseline tumor
infiltrating immune cells in responding patients.
• ALX148 in combination with trastuzumab, ramucirumab and paclitaxel
demonstrates an initial ORR of 72% and estimated OS at 12 months of
76% in patients with GCs that have progressed on or after a prior
trastuzumab-containing regimen. This compares favorably with both
RAINBOW5 and DESTINY-016 randomized historical controls.
• Updated data from patients receiving ALX148 + trastuzumab after
their tumors have progressed upon prior trastuzumab therapy suggests
clinical activity beyond that expected from either trastuzumab or
chemotherapy alone.

References: 1. Weiskopf, K., Eur J Cancer. 2017 May;76:100-109; 2. Kauder, SE. 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;
5. Wilke et al, Lancet October 2014; 6. Shitara et al, NEJM June 18, 2020 and Enhertu Package InsertAcknowledgments: We would like to thank all of the participating patients and their families as well as site research staff; Presented at the 2021 European Society of Medical Oncology World Congress in Gastrointestinal Cancer (ESMO-GI) Annual Meeting July 03, 2021
Abstract SO-31/#109; Contact email: info@alxoncology.com