Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2023 Or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-37990 LEAP THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware State or other jurisd ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2023 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-37990 LEAP THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware State or other ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2023 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-37990 LEAP THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware State or other juris ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2023 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-37990 LEAP THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) 27-4412575 (I.R.S. Employer ...

Table of Contents Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).Yes ☐ No ☒ UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 Or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file num ...

DKN-01 Clinical Development - DKN-01 exhibits single-agent activity in three indications and is being explored in combinations with checkpoint inhibitors and chemotherapy[4, 13] - In first-line GEJ/GC, DKN-01 combined with tislelizumab and chemotherapy showed a 68% overall response rate (ORR) in the mITT population[21, 64] - In DKK1-high patients within the first-line GEJ/GC study, the ORR reached 90% with DKN-01, tislelizumab, and chemotherapy, and a median PFS of 113 months was observed[21, 23, 29, 64] - In second-line GEJ/GC, DKN-01 plus tislelizumab demonstrated a 27% ORR and 43% disease control rate (DCR) in anti-PD-1/PD-L1-naïve mITT patients[32] - In second-line GEJ/GC DKK1-high/PD-L1 vCPS ≥ 10 patients, DKN-01 plus tislelizumab achieved a 55% ORR and 73% DCR[32, 36] - DKN-01 monotherapy in 2L+ EEC showed a 25% ORR and 63% clinical benefit in DKK1-high patients, with a median PFS of 43 months compared to 18 months in DKK1-low patients[78, 82] Strategic Partnership with BeiGene - Leap Therapeutics has a strategic partnership with BeiGene, including a potential $10 million option exercise fee based on data from DKN-01 plus tislelizumab combination studies in gastric cancer[15] - The total potential option exercise, clinical, regulatory, and commercial milestones could reach $132 million[15] - Total payments to date from BeiGene amount to $1525 million, comprising a $3 million option fee and a $1225 million equity investment[15] Colorectal Cancer Development - Preclinical data suggests DKN-01 has additive activity with 5-FU chemotherapy and can overcome 5-FU resistance in colorectal cancer models[65, 68, 70] - DKN-01 also shows additive activity with anti-PD-1 antibodies in colorectal cancer models[65, 72]

For the transition period from to Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2022 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Commission file number: 001-37990 LEAP THERAPEUTICS, INC. 27-4412575 (I.R.S. Employer Identification No.) 47 Thorndike St, Suite B1-1, Ca ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2022 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-37990 LEAP THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware State or other juris ...

FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 For the transition period from to Commission file number: 001-37990 LEAP THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware State or other juri ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2021 Or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-37990 LEAP THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware State or other jurisd ...