Among the total patient population, the confirmed ORR was 30% (95% CI, 11.9, 54.3), the median PFS was 7.3 months (95% CI, 3.7, NE). The disease control rate (DCR) was 80%. Among the 11 patients with specific biomarker alterations (PIK3CA/AKT1/PTEN), the confirmed objective response rate was 45.4% (95% CI, 16.7, 76.6), the disease control rate was 82%, and the median PFS was 7.3 months (95% CI, 3.6, 8.2). Investigators concluded that the combination therapy of afuresertib and fulvestrant has shown promising efficacy with a well-tolerated safety profile, supporting further evaluation in the upcoming Phase III part of the study.

LAE 111 is a novel and potent bispecific antibody targeting LILRB1 and LILRB2. It has exhibited superior potency compared to dual antibody NGM707 against LILRB1/2 and other anti-LILRB1, anti-LILRB2 antibodies currently in clinical development. It has also demonstrated exceptional stability and developability in preclinical setting.

Furthermore, the combination of LAE111 with an anti-PD-1/PD-L1 antibody markedly activated T cell response, giving it the potential to become a novel cancer therapy to overcome PD-1/PD-L1 resistance.

LAE113 is an exceptionally potent TIGIT and PVRIG signaling blocker, outperforming existing competitors in the modulation of T cell and NK cell functions. The preclinical profile highlights its outstanding potential as a best-in-class candidate with favorable drug like properties for development.

Furthermore, LAE113 has demonstrated a synergistic effect when combined with LAE005, an anti-PD-L1 monoclonal antibody, in enhancing IFN-γ secretion from CD8+T cells. Additionally, it is a universal ADCC enhancer when combined with monoclonal antibodies and NK cell engagers. These findings make it a highly promising candidate for cancer immunotherapy.

As of September 1, 2023, 40 patients who progressed on 1-3 lines of standard treatments, including at least 1 line of abiraterone, or the second generation of AR antagonists, had been enrolled in the recommended phase 2 dose group. The median rPFS was 7.9 months, 95% CI: (5.7m, NE). This is a significant improvement compared to the median rPFS of 2 to 4 months of mCRPC patients under the standard treatments historically. The investigators support moving forward to the registration phase.

Under the RP2D cohort (50mg BID of LAE001) , 73% patients had a >50% best PSA decline from baseline, among whom 40% had >90% PSA decline from baseline. The preliminary antitumor activity of LAE001 monotherapy at RP2D level supports the potential clinical benefit of treating patients with mCRPC.

The preliminary antitumor activity under the RP2D(LAE001 75mg BID/prednisone 5mg BID and LAE002(afuresertib) 125mg QD) supports the potential clinical benefit for treating drug-resistant mCRPC and moves forward this study to phase II stage.