HX-009

P1/2, N=124, Not yet recruiting, Hangzhou Hanx Biopharmaceuticals, Ltd.

We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009's candidacy for its clinical development.

P1/2, N=99, Recruiting, Hangzhou Hanx Biopharmaceuticals, Ltd. | Trial completion date: Aug 2023 --> Dec 2026 | Trial primary completion date: Dec 2022 --> Dec 2025

P1, N=80, Active, not recruiting, Hangzhou Hanx Biopharmaceuticals, Ltd. | N=25 --> 80 | Trial primary completion date: Nov 2023 --> Dec 2024

In the humanized mouse syngeneic A20 B-lymphoma (huCD47-A20) HuGEMM model, which has quadruple knocked-in hPD1xhPD-L1xhCD47xhSIRPα genes and an intact autologous immune-system, a contribution of effect is demonstrated for each targeted biologic (HX008 targeting PD1 and SIRPα-Fc targeting CD47), which is clearly augmented by the dual targeting with HX009. Lastly, the expression of the immune-checkpoints PD-L1/L2 and CD47 seemed co-regulated among a panel of lymphoma-derived-xenografts, where HX009 maybe more effective in those with upregulated CD47. Our data warrants HX009's further clinical development for treating NHLs.

AM7577 model responded significantly better than AM8096, likely due to the significantly higher expression of CD47 and also better than Ara-C standard of care (SOC) treatment at 3mg/kg. In contrast, in the subcutaneous transplanted AML cell line-derived model, MV4-11, there is little anti-tumor activity observed, although there is significant expression of CD47 on the tumor cells. In conclusion, our data seems to suggest that HX009 could be a candidate immunotherapy for CD47hi AML, with CD47 expression being a positive predictive biomarker, warranting further evaluation.

P1, N=25, Active, not recruiting, Hangzhou Hanx Biopharmaceuticals, Ltd.

P2, N=210, Active, not recruiting, Waterstone Hanxbio Pty Ltd | Recruiting --> Active, not recruiting

HX009, on an every 2 weeks dosing schedule, up to 7.5 mg/kg, is well-tolerated, without any DLT to date . Antitumor activity was seen at 1 mg/kg and 5 mg/kg cohorts with objective responses in multiple tumor types; Further investigation in phase Ib/II studies is warranted.