Please tell us about your clinical experience. How many patients with solid tumors do you see on a yearly basis? What is the standard of care, and how do you think Leap’s DKN-01 will fit in the space?

How hard is it to achieve meaningful efficacy in the solid tumor indications that Leap Therapeutics is pursuing (endometrial, pancreatic, esophageal, prostate) ?

How significant are the recent results in in patients with inoperable, locally advanced, G/GEJ adenocarcinoma, where:-for patients who received a full cycle of DKN-01 therapy, ORR was 68.2% and 90% ORR in DKK1-high patients/ 56% in DKK1-low patients-Response independent of PD-L1 expression, and particularly strong in the less favorable to checkpoint inhibitor therapy, PD-L1 low (vCPS < 5)-for patients with PD-L1-low expression (vCPS < 5), the ORR was 79%, with 100% in DKK1-high patients and 57% in DKK1-low patients-for patients with PD-L1-high expression (vCPS ≥ 5), the ORR was 67%, with 75% ORR in DKK1-high patients and 50% in DKK1-low patients

Can you tell us about the standard of care for first-line patients with gastric or gastroesophageal junction cancer, and how the results posted by Leap Therapeutics compare?

1. In endometrial cancer, the company reported that:

• DKN-01 has enhanced activity in patients whose tumors express high levels of DKK1: In the group of 22 EEC patients treated with DKN-01 monotherapy for whom DKK1 expression data was available, patients with DKK1-high tumors (n=7) had greater ORR (14% vs. 0%), DCR (57% vs. 7%), and median PFS (3.0 months vs. 1.8 months [HR 0.39; 95% CI: 0.14, 1.1]) compared to patients with DKK1-low tumors (n=15). Additionally, seven patients did not have DKK1 expression results available, of whom one had a complete response (14%) and five (72%) had a best response of stable disease, including three patients with Wnt activating mutations.

• Within EEC, DKN-01 activity strongest in endometrioid histology: In the pooled group of 27 patients with endometrioid histology for whom DKK1 expression data was available, patients with DKK1-high tumors (n=14) had greater DCR (57% vs. 15%) and median PFS (4.1 months vs. 1.8 months [HR 0.34; 95% CI: 0.14, 0.81]) than patients with DKK1-low tumors (n=13). Additionally, seven patients with endometrioid histology did not have DKK1 expression results available, of whom one (14%) had a complete response and five (72%) had a best response of stable disease, including two patients with Wnt activating mutations.

How likely would you be to use DKN-01 in the future?

Principal question is whether a KOL believes the drug is truly synergistic with checkpoint inhibitors and/or chemo since LPTX’s drug has shown little to no activity as a monotherapy.

Why there aren’t more drug companies pursuing the inhibition of DKK1.