Investor Presentaiton
HLX42 (EGFR ADC) Presented Excellent Preclinical Data in ESMO and Was
Granted Fast Track Designation by FDA
ESMO 2023 FPN: 683P
•
II.
Title
Preclinical evaluation of HLX42, a novel EGFR-targeting ADC, for Cetuximab or TKI
resistant cancer
In vivo efficacy results
III.
IV.
V.
In in vivo studies, HLX42 showed potent tumor suppression in several CDX and PDX
models that were cetuximab or TKIs resistant
As in the HT-29 model, weekly administration of HLX42 at 8 mg/kg for 3 weeks resulted in
90.2% TGI. HLX42 showed better in vivo efficacy and elicited more durable antitumor
responses in a head-to-head comparison with conventional ADC technologies VC-
MMAE
In the NCI-H1993 model, weekly administration of HLX42 at 8 mg/kg for 3 weeks resulted in
91.5% TGI compared to 79.8% TGI when treated with anti-EGFR Ab-GGFG-Dxd
In the EBC-1 model, weekly administration of HLX42 at 8 mg/kg for 3 weeks eradicated all
lesions; all mice remained tumor free three weeks after the last dose, while tumor began to
regrow in the anti-EGFR Ab-VC-MMAE treated group
HLX42, combined with a 3rd generation TKI, showed strong synergy in the LU3075 lung
cancer PDX model while the model poorly responded to Osimertinib monotherapy
In another lung cancer PDX model harboring EGFR exon 19 deletion/T790M/C797S mutations,
which exhibited complete resistance to Osimertinib, a single dose of HLX42 1mg/kg
treatment resulted in significantly complete response compared with the control group
In our pilot toxicity studies conducted in rats and cynomolgus monkeys, HLX42
demonstrated good safety profiles in both species
Regulatory and Clinical Trial Progress
31
On Dec. 27, 2023, the US FDA granted Fast Track Designation (FTD) to HLX42 for the
treatment of patients with advanced or metastatic EGFR-mutated non-small cell lung cancer
whose diseases have progressed on a 3rd-generation EGFR tyrosine kinase inhibitor treatment
IND of HLX42 for the treatment of advance/metastatic solid tumors has been approved by
China NMPA and the US FDA successively during Oct. to Nov., 2023
On Mar. 14, 2023, the phase I clinical trial of HLX42 for the treatment of advance/metastatic
solid tumors has completed the first patient dosing in China
Tumor Volume (mm³)
B
Tumor Volume (mm³)
A
4000-
3000-
2000-
1000-
HT-29 CDX Model
HLX07, 8mpk, QW*3
UI VA 1mink W
HLX42, 8mpk, QW*3
10
20
30
40
Days Post Treatment (d)
NCI-H1993 CDX Model
2000
1500-
1000-
500-
0-
0
5
10
15
20
25
Days Post Treatment (d)
C
EBC-1 CDX Model
2500-
Tumor Volume (mm³)
2000-
1500-
1000-
500-
O 2024 Henlius.
10
20
30
40
50
Days Post Treatment (d))
Tumar Volume (mm)
E
800-
HLX07, 8mpk, QW*3
HLX07-GGFG-Dxd, 3mpk, QW*3
-HLX07-VC-MMAE, 3mpk, QW*3
Payload, 0.24mpk, QW*3
HLX42, 3mpk, QW*3
HLX07-GGFG-Dxd, 8mpk, QW*3
→HLX42, 8mpk, QW*3
HLX07, 8mpk, QW*3
-Payload,024mpk, QW'3
HLX07-GGFG-Dxd, 3mpk, QW*3
HLX07-GGFG-Dxd, 8mpk, QW*3
HLX07-VC-MMAE, 3mpk, QW*3
HLX42, 3mpk, QW*3
HLX42, 8mpk, QW*3
Tumor Volume (mm³)
600-
400-
200-
1200-1
800-
400-
Osimertinib Partial-Response NSCLC PDX model
Vehicle control
HLX07, 8mpk, OW*4
Osimertinib, 20mpk, QD*28
Osimertinib, 20mpk, QD 28+ HLX42, 1mpk, QW*4
HLX42, 1mpk, QW*4
Osimertinib, 20mpk, QD 28+ HLX42, 3mpk, QW*4
HLX42, 3mpk, QW*4
HLX42, 8mpk, QW*4
20
30
40
Days Post Treatment (d)
Osimertinib-resistant NSCLC PDX Model
Vehicle control
Osimertinib, 10mpk, QD*21
0
3
9 12 15 18
21
Days Post Treatment (d)
IgG-Linker-Payload 8mpk, QW*4
HLX42, 1mpk, single dose
HLX423mpk, single dose"
HLX42,8mpk, single dose
2 Henlius
复宏汉霖View entire presentation