Phase 2 Study Evaluating the Efficacy of the Combination of DKN-01 (DKK1 Inhibitor, Leap Therapeutics) and Pembrolizumab in the Treatment of Advanced or Recurrent Endometrial Cancer

To learn if the combination of DKN-01 and pembrolizumab can help to control advanced or recurrent endometrial cancer.

Start Date29 Aug 2023

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+3]

NCT05480306 / RecruitingPhase 2

Randomized Phase 2 Study of DKN-01 Plus FOLFIRI/FOLFOX and Bevacizumab Versus FOLFIRI/FOLFOX and Bevacizumab as Second-line Treatment of Advanced Colorectal Cancer (DeFianCe)

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients.

Start Date30 Aug 2022

Sponsor / Collaborator

Leap Therapeutics, Inc.

NCT04363801 / Active, not recruitingPhase 2

A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients With Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (DisTinGuish)

A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination with Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients with Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Start Date29 Jul 2020

Sponsor / Collaborator

Leap Therapeutics, Inc.

[+1]

100 Clinical Results associated with Sirexatamab

100 Translational Medicine associated with Sirexatamab

100 Patents (Medical) associated with Sirexatamab

Literatures (Medical) associated with Sirexatamab

01 May 2023·Gynecologic oncology

DKK1 is a predictive biomarker for response to DKN-01: Results of a phase 2 basket study in women with recurrent endometrial carcinoma.

Article

Author: LyBarger, Kristopher ; Matulonis, Ursula ; Duska, Linda R. ; Sachdev, Jasgit ; Piper, Diane ; Birrer, Michael ; Kagey, Michael H. ; Hamilton, Erika ; O'Malley, David M. ; ElNaggar, Adam C. ; Goodman, Howard M. ; Barroilhet, Lisa M. ; Sirard, Cynthia A. ; Castro, Cesar ; Arend, Rebecca ; Bradley, William ; Jackson, Camille Gunderson ; Dholakia, Jhalak ; Mahdi, Haider ; Liu, Amy

PURPOSE:

Dickkopf-1 (DKK1) is a Wnt signaling modulator promoting tumor growth, metastasis, angiogenesis, and immunosuppression by regulating innate immunity. DKK1 is over-expressed in gynecologic cancers and is associated with shortened survival. DKN-01 is a humanized monoclonal antibody with DKK1 neutralizing activity that may provide clinical benefit to patients whose tumors have overexpression of DKK1 or Wnt genetic alterations.

METHODS:

We conducted an open-label, Phase 2 basket study with 2-stage design in patients with endometrial carcinoma (EC) and platinum-resistant/refractory epithelial ovarian cancer. DKN-01 was administered either as monotherapy or in combination with weekly paclitaxel at investigator's discretion. All patients underwent NGS testing prior to enrollment; tumor tissue was also tested for DKK1 expression by RNAscope pre-treatment and after cycle 1 if available. At least 50% of patients were required to have a Wnt signaling alteration either directly or tangentially. This publication reports results from the EC population overall and by DKK1-expression.

RESULTS:

DKN-01 monotherapy and in combination with paclitaxel was more effective in patients with high DKK1-expressing tumors compared to low-expressing tumors. DKN-01 monotherapy demonstrated an objective response rate [ORR] of 25.0% vs. 0%; disease control rate [DCR] of 62.5% vs. 6.7%; median progression-free survival [PFS] was 4.3 vs. 1.8 months, and overall survival [OS] was 11.0 vs. 8.2 months in DKK1-high vs DKK1-low patients. Similarly, DKN-01 in combination with paclitaxel demonstrated greater clinical activity in patients with DKK1-high tumors compared to DKK1-low tumors: DCR was 55% vs. 44%; median PFS was 5.4 vs. 1.8 months; and OS was 19.1 vs. 10.1 months. Wnt activating mutations correlated with higher DKK1 expression. DKN-01 was well tolerated as a monotherapy and in combination with paclitaxel.

CONCLUSIONS:

Collectively, data demonstrates promising clinical activity of a well-tolerated drug, DKN-01, in EC patients with high tumoral DKK1 expression which frequently corresponded to the presence of a Wnt activating mutation. Future development will focus on using DKN-01 in DKK1-high EC patients in combination with immunotherapy.

01 Jan 2023·Liver international : official journal of the International Association for the Study of the Liver

DKK1 drives immune suppressive phenotypes in intrahepatic cholangiocarcinoma and can be targeted with anti‐DKK1 therapeutic DKN‐01

Article

Author: Tsokkou, Panagiota ; Musialik, Kamila I. ; Horcas‐Lopez, Marta ; Newman, Walter ; Kagey, Michael H. ; Boulter, Luke ; Waddell, Scott H. ; Gournopanos, Konstantinos ; MacMaster, Stephanie ; Soong, Daniel Y. H. ; Ng, Minn‐E ; Cambridge, William A. ; Wilson, David H. ; Jarman, Edward J. ; Pollard, Jeffrey W.

Abstract:

Background and aims:

Dickkopf‐1 (DKK1) is associated with poor prognosis in intrahepatic cholangiocarcinoma (iCCA), but the mechanisms behind this are unclear. Here, we show that DKK1 plays an immune regulatory role in vivo and inhibition reduces tumour growth.

Methods:

Various in vivo GEMM mouse models and patient samples were utilized to assess the effects of tumour specific DKK1 overexpression in iCCA. DKK1‐driven changes to the tumour immune microenvironment were characterized by immunostaining and gene expression analysis. DKK1 overexpressing and damage‐induced models of iCCA were used to demonstrate the therapeutic efficacy of DKK1 inhibition in these contexts using the anti‐DKK1 therapeutic, DKN‐01.

Results:

DKK1 overexpression in mouse models of iCCA drives an increase in chemokine and cytokine signalling, the recruitment of regulatory macrophages, and promotes the formation of a tolerogenic niche with higher numbers of regulatory T cells. We show a similar association of DKK1 with FOXP3 and regulatory T cells in patient tissue and gene expression data, demonstrating these effects are relevant to human iCCA. Finally, we demonstrate that inhibition of DKK1 with the monoclonal antibody mDKN‐01 is effective at reducing tumour burden in two distinct mouse models of the disease.

Conclusion:

DKK1 promotes tumour immune evasion in iCCA through the recruitment of immune suppressive macrophages. Targeting DKK1 with a neutralizing antibody is effective at reducing tumour growth in vivo. As such, DKK1 targeted and immune modulatory therapies may be an effective strategy in iCCA patients with high DKK1 tumour expression or tolerogenic immune phenotypes.

01 Feb 2022·Gynecologic oncology reports

Response to anti-DKK1 therapy in uterine carcinosarcoma: A case report

Author: Scalise, C B ; Arend, R ; Vaena, D ; Kagey, M H ; ElNaggar, A ; Sirard, C ; Zhang, N

Targeted therapies are being increasingly used in clinical practice and trials. However, tumor heterogeneity among sites of metastatic disease can occur creating a conundrum when utilizing biomarker directed therapies. Here we demonstrate a patient with recurrent uterine carcinosarcoma whose local recurrence and metastatic recurrence had a varied response to paclitaxel in combination with DKN-01, a monoclonal antibody against DKK1, a modulator of Wnt/β-catenin and PI3K/AKT signaling pathways. This may be explained by differences in mutational profile found between the two sites. Our findings highlight the importance of analyzing tissue from the primary tumor as well as metastatic lesions, especially if there is a discrepancy in their response to treatment.

News (Medical) associated with Sirexatamab

13 May 2024

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Leap Therapeutics Reports First Quarter 2024 Financial Results

CAMBRIDGE, Mass., May 13, 2024 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today reported financial results for the first quarter ended March 31, 2024. Leap Highlights: Completed $40 million private placement financing with participation from Gilead Sciences, Inc., a life sciences-focused investor, Samsara BioCapital, 683 Capital Partners, LP, Laurion Capital Management, and Rock Springs Capital Presented clinical data from Part A of the Phase 2 DeFianCe study evaluating DKN-01 in combination with standard of care bevacizumab and chemotherapy in second-line patients with advanced colorectal cancer (CRC), at the 2024 ASCO Gastrointestinal Cancers Symposium Expanded the ongoing randomized controlled Part B of the DeFianCe study from 130 patients to 180 patients to enhance the statistical power for patients with left-sided CRC; enrollment now expected to be completed in late Q3 or early Q4 2024 Completed enrollment in the randomized controlled Part C of the Phase 2 DisTinGuish study evaluating DKN-01 in combination with tislelizumab and chemotherapy in patients with advanced gastroesophageal junction (GEJ) and gastric cancer; first randomized controlled data for DKN-01 expected in the second half of 2024 or early 2025 "We appreciate the strong support of Gilead and the new and existing institutional investors who participated in our recent $40 million financing that will enable the expansion and continued execution of the DKN-01 development program," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "The financing provides cash runway into the second quarter of 2026, allowing the expansion of Part B of the DeFianCe CRC study to 180 patients, the full maturation of data in Part C of the DisTinGuish GEJ/gastric cancer study, and the manufacturing of Phase 3 clinical trial material. We are well positioned for continued success and look forward to achieving major clinical milestones in the year ahead." Business Update: Completed a $40 million private placement. In April 2024, Leap entered into a securities purchase agreement with a select group of institutional investors to issue and sell an aggregate of 12,660,993 shares of its common stock ("Common Stock") at a price of $2.82 per share and pre-funded warrants to purchase 1,523,404 shares of Common Stock at a price of $2.819 per share of Common Stock issuable upon exercise of the pre-funded warrants, in a private placement. Gross proceeds from the private placement were approximately $40 million with participation from new and existing investors, including Gilead Sciences, Inc., a life sciences-focused investor, Samsara BioCapital, 683 Capital Partners, LP, Laurion Capital Management, and Rock Springs Capital. The net proceeds from this financing, combined with existing cash, cash equivalents and marketable securities, are expected to fund Leap's operating and capital expenditures into the second quarter of 2026 and enable expansion of the DKN-01 DeFianCe clinical trial and development program. DKN-01 Development Update Presented initial clinical data from Part A of the DeFianCe Study of DKN-01 plus bevacizumab and chemotherapy in colorectal cancer (CRC) patients. The Company presented initial data from Part A of the DeFianCe study (NCT05480306), a Phase 2 study evaluating DKN-01 in combination with standard of care (SOC) bevacizumab and chemotherapy in second-line (2L) patients with advanced microsatellite stable (MSS) CRC patients at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, held in San Francisco on January 18-20, 2024 and during the Company's conference call on January 23, 2024. Key Findings (as of the December 6, 2023 data cutoff) : Across all patients enrolled (n=33): Overall response rate (ORR) among response-evaluable patients (n=27) was 30% and disease control rate (DCR) was 93%, including 8 partial responses (PR) and 17 patients with a best response of stable disease (SD) Median progression-free survival (PFS) was 6.3 months 9 patients remained on therapy and were beyond 8.5 months Enhanced activity in patients with left-sided tumors (n=25), a group that has more frequent activation of the Wnt pathway modulated by DKK1 33% ORR and 100% DCR in response-evaluable population (7 PRs, 14 SDs) Preliminary median PFS of 8.6 months (9 patients continuing therapy within subgroup) Compelling ORR, DCR and PFS in patients with rectal/rectosigmoid carcinomas (n=15), a population with increasing incidence among young people and shown to have the highest DKK1 levels: 46% ORR and 100% DCR in response-evaluable population (6 PRs, 7 SDs) Preliminary median PFS of 9.4 months (6 patients continuing therapy within subgroup) Higher baseline plasma DKK1 levels correlated with improved responses DKN-01 plus bevacizumab and chemotherapy was well-tolerated, with a majority of DKN-01 related events being low grade (Grade 1/2) Part B of the DeFianCe Study of DKN-01 plus bevacizumab and chemotherapy in CRC patients is ongoing, with enrollment expanded to 180 patients and expected to be completed in late Q3/early Q4 2024. The Company expanded the randomized controlled Part B of the DeFianCe study from 130 to 180 patients and included PFS in the subpopulation of patients with left-sided CRC as an additional primary endpoint. The Company expects to complete enrollment in late Q3 or early Q4 2024 with data expected in mid-2025. As of May 8, 2024, 114 patients have enrolled in Part B. Completion of enrollment in the randomized controlled Part C of the DisTinGuish study evaluating DKN-01 in combination with tislelizumab, BeiGene's anti-PD-1 antibody, and chemotherapy in patients with advanced gastroesophageal junction and gastric cancer. Part C of the DisTinGuish study (NCT0436380) is a Phase 2, randomized, open-label, multicenter study of DKN-01 in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal adenocarcinoma. Part C enrolled 170 first-line, HER2-negative patients randomized 1:1 to evaluate DKN-01 in combination with tislelizumab and SOC chemotherapy, compared to tislelizumab and SOC chemotherapy alone. The primary objective is PFS in DKK1-high and in all patients. Secondary objectives of Part C include OS and ORR as measured by RECIST v1.1 in DKK1-high and in all patients. The Company expects to report initial data from Part C of the DisTinGuish study in the second half of 2024 or early 2025 when the PFS data are mature. Selected First Quarter 2024 Financial Results Net Loss was $13.8 million for the first quarter 2024, compared to $41.9 million for the same period in 2023. The decrease was primarily due to $29.6 million of in-process research and development ("IPR&D") expense associated with the Flame merger in January 2023. Research and development expenses were $11.3 million for the first quarter 2024, compared to $38.9 million for the same period in 2023. The decrease of $27.6 million was primarily due to $29.6 million of IPR&D associated with the Flame merger. In addition, there was a decrease of $0.4 million in manufacturing costs related to clinical trial material manufacturing campaigns and a decrease of $0.1 million in consulting fees associated with R&D activities. These decreases were partially offset by an increase of $2.0 million in clinical trial costs and an increase of $0.5 million in payroll and other related expenses due to an increase in headcount of our R&D full-time employees. General and administrative expenses were $3.5 million for the first quarter 2024, compared to $3.8 million for the same period in 2022. The decrease was due to a decrease of $0.3 million in professional fees associated with our business development activities. Cash and cash equivalents totaled $54.9 million at March 31, 2024, exclusive of the $37.2 million net proceeds of the private placement completed in April 2024. Research and development incentive receivables, current portion, totaled $0.7 million at March 31, 2024. About Leap Therapeutics Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. DKN-01 is being developed in patients with esophagogastric, gynecologic, and colorectal cancers. FL-301, is a humanized monoclonal antibody targeting Claudin18.2, being developed in patients with gastric and pancreatic cancer. Leap also has preclinical antibody programs targeting Claudin18.2/CD137 and GDF15. For more information about Leap Therapeutics, visit or view our public filings with the SEC that are available via EDGAR at or via . FORWARD-LOOKING STATEMENTS This press release contains forward-looking statements within the meaning of the federal securities laws. Such statements are based upon current plans, estimates and expectations of the management of Leap that are subject to various risks and uncertainties that could cause actual results to differ materially from such statements. The inclusion of forward-looking statements should not be regarded as a representation that such plans, estimates and expectations will be achieved. Words such as "anticipate," "expect," "project," "intend," "believe," "may," "will," "should," "plan," "could," "continue," "target," "contemplate," "estimate," "forecast," "guidance," "predict," "possible," "potential," "pursue," "likely," and words and terms of similar substance used in connection with any discussion of future plans, actions or events identify forward-looking statements. All statements, other than historical facts, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates; the anticipated expansion of the DeFianCe study and timing for completion of clinical trials and release of clinical trial data and the expectations surrounding the outcomes thereof; Leap's future clinical or preclinical product development plans for any of Leap's product candidates; Leap's estimations of projected cash runway; the anticipated closing date of the private placement; the amount of proceeds to be received by Leap and Leap's intended use of proceeds from the private placement; and any assumptions underlying any of the foregoing, are forward-looking statements. Important factors that could cause actual results to differ materially from Leap's plans, estimates or expectations could include, but are not limited to: (i) Leap's ability to successfully execute its clinical trials and the timing of enrollment in and cost of such clinical trials; (ii) the results of Leap's clinical trials and pre-clinical studies; (iii) Leap's ability to successfully enter into new strategic partnerships for DKN-01 or any of its other programs and to maintain its ongoing collaborations with BeiGene, NovaRock and Adimab; (iv) whether any Leap clinical trials and products will receive approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies; (v) exposure to inflation, currency rate and interest rate fluctuations, as well as fluctuations in the market price of Leap's traded securities; and (vi) that the initiation, conduct, and completion of clinical trials, laboratory operations, manufacturing campaigns, and other studies may be delayed, adversely affected, or impacted by global conflict, or supply chain related issues. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or Implied) are made about the accuracy of any such forward-looking statements. Leap may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Leap's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither Leap, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Leap's views as of any date subsequent to the date hereof. CONTACT: Douglas E. Onsi President & Chief Executive Officer Leap Therapeutics, Inc. 617-714-0360 [email protected] Matthew DeYoung Investor Relations Argot Partners 212-600-1902 [email protected] SOURCE Leap Therapeutics, Inc.

Phase 2Clinical ResultFinancial StatementASCOPhase 3

18 Mar 2024

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Leap Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results

CAMBRIDGE, Mass., March 18, 2024 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today reported financial results for the fourth quarter and year ended December 31, 2023. Leap Highlights: Presented new clinical data from Part A of the Phase 2 DeFianCe study evaluating DKN-01 in combination with standard of care bevacizumab and chemotherapy in second-line patients with advanced colorectal cancer, at the 2024 ASCO Gastrointestinal Cancers Symposium Completed enrollment in the randomized controlled Part C of the Phase 2 DisTinGuish study evaluating DKN-01 in combination with tislelizumab and chemotherapy in patients with advanced gastroesophageal junction and gastric cancer "As we reflect on the fourth quarter and the achievements of the past year, we are proud of the strides we've made in advancing DKN-01 and integrating our pipeline of earlier stage biomarker-targeted antibody therapies. The data from Part A of the DeFianCe study, demonstrating a 30% overall response rate and a 93% disease control rate in second-line colorectal cancer patients, showcases a strong foundation as we move into the randomized controlled Part B of the study," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "Additionally, the completion of enrollment in Part C of the DisTinGuish study in first-line gastroesophageal junction and gastric cancer patients positions us to deliver the first randomized controlled data for DKN-01 starting in the middle of the year. As we look ahead to a data rich 2024, we remain focused on our mission to deliver new personalized medicines to patients fighting against cancer." DKN-01 Development Update Presented initial clinical data from Part A of the DeFianCe Study of DKN-01 plus bevacizumab and chemotherapy in colorectal cancer (CRC) patients. The Company presented initial data from Part A of the DeFianCe study (NCT05480306), a Phase 2 study evaluating DKN-01 in combination with standard of care (SOC) bevacizumab and chemotherapy in second-line (2L) patients with advanced microsatellite stable (MSS) CRC patients at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, held in San Francisco on January 18-20, 2024 and during the Company's conference call on January 23, 2024. Key Findings: As of the December 6, 2023 data cutoff, across all patients enrolled (n=33): Overall response rate (ORR) among response-evaluable patients (n=27) was 30% and disease control rate (DCR) was 93%, including 8 partial responses (PR) and 17 patients with a best response of stable disease (SD) Median progression-free survival (PFS) was 6.3 months 9 patients remained on therapy and were beyond 8.5 months Enhanced activity in patients with left-sided tumors (n=25), a group that has more frequent activation of the Wnt pathway modulated by DKK1 33% ORR and 100% DCR in response-evaluable population (7 PRs, 14 SDs) Preliminary median PFS of 8.6 months (9 patients continuing therapy within subgroup) Compelling ORR, DCR and PFS in patients with rectal/rectosigmoid carcinomas (n=15), a population with increasing incidence among young people and shown to have the highest DKK1 levels: 46% ORR and 100% DCR in response-evaluable population (6 PRs, 7 SDs) Preliminary median PFS of 9.4 months (6 patients continuing therapy within subgroup) Higher baseline plasma DKK1 levels correlated with improved responses DKN-01 plus bevacizumab and chemotherapy was well-tolerated, with a majority of DKN-01 related events being low grade (Grade 1/2) The Company expects the 130 patient randomized controlled Part B to complete enrollment in mid-2024. As of March 15, 2024, 80 patients have enrolled in Part B. Announced completion of enrollment in the randomized controlled Part C of the DisTinGuish study evaluating DKN-01 in combination with tislelizumab, BeiGene's anti-PD-1 antibody, and chemotherapy in patients with advanced gastroesophageal junction and gastric cancer. Part C of the DisTinGuish study (NCT0436380) is a Phase 2, randomized, open-label, multicenter study of DKN-01 in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal adenocarcinoma. Part C enrolled 170 first-line, HER2-negative patients randomized 1:1 to evaluate DKN-01 in combination with tislelizumab and SOC chemotherapy, compared to tislelizumab and SOC chemotherapy alone. The primary objective is progression-free survival (PFS) in DKK1-high and in all patients. Secondary objectives of Part C include overall survival and objective response rate as measured by RECIST v1.1 in DKK1-high and in all patients. The Company expects to report initial data from Part C of the DisTinGuish study in mid-2024. Selected Year-End and Fourth Quarter 2023 Financial Results Net Loss was $81.4 million for the year ended December 31, 2023, compared to $54.6 million for the year ended December 31, 2022. The increase was due to in-process research and development acquired in the Flame merger which was expensed during the year ended December 31, 2023, costs incurred in connection with our research and development programs, and from general and administrative costs associated with our operations. Research and development expenses were $73.2 million for the full year 2023, compared to $45.0 million for the same period in 2022. Research and development expenses were $11.7 million for the fourth quarter ended 2023, compared to $11.0 million for the same period in 2022. The increases for the full year 2023 were primarily due to in-process research and development acquired in the Flame merger, an increase in clinical trial costs, and an increase in payroll and other related expenses due to an increase in headcount of research and development full-time employees. General and administrative expenses were $13.8 million for the full year 2023, compared to $11.8 million for the same period in 2022. General and administrative expenses were $3.1 million for the fourth quarter ended 2023, compared to $2.9 million for the same period in 2022. The increases for the full year 2023 were primarily due to costs associated with our business development activities and an increase in payroll and other related expenses due to an increase in headcount of general and administrative full-time employees. Cash and cash equivalents totaled $70.6 million at December 31, 2023. Research and development incentive receivables totaled $0.8 million at December 31, 2023. About Leap Therapeutics Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. DKN-01 is being developed in patients with esophagogastric, gynecologic, and colorectal cancers. FL-301, is a humanized monoclonal antibody targeting Claudin18.2, being developed in patients with gastric and pancreatic cancer. Leap also has preclinical antibody programs targeting Claudin18.2/CD137 and GDF15. For more information about Leap Therapeutics, visit or view our public filings with the SEC that are available via EDGAR at or via . FORWARD-LOOKING STATEMENTS This press release contains forward-looking statements within the meaning of the federal securities laws. Such statements are based upon current plans, estimates and expectations of the management of Leap that are subject to various risks and uncertainties that could cause actual results to differ materially from such statements. The inclusion of forward-looking statements should not be regarded as a representation that such plans, estimates and expectations will be achieved. Words such as "anticipate," "expect," "project," "intend," "believe," "may," "will," "should," "plan," "could," "continue," "target," "contemplate," "estimate," "forecast," "guidance," "predict," "possible," "potential," "pursue," "likely," and words and terms of similar substance used in connection with any discussion of future plans, actions or events identify forward-looking statements. All statements, other than historical facts, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates; the anticipated timing for completion of clinical trials and release of clinical trial data and the expectations surrounding the outcomes thereof; Leap's future clinical or preclinical product development plans for any of Leap's product candidates; Leap's estimations of projected cash runway; and any assumptions underlying any of the foregoing, are forward-looking statements. Important factors that could cause actual results to differ materially from Leap's plans, estimates or expectations could include, but are not limited to: (i) Leap's ability to successfully execute its clinical trials and the timing of enrollment in and cost of such clinical trials; (ii) the results of Leap's clinical trials and pre-clinical studies; (iii) Leap's ability to successfully enter into new strategic partnerships for DKN-01 or any of its other programs and to maintain its ongoing collaborations with BeiGene, NovaRock and Adimab; (iv) whether any Leap clinical trials and products will receive approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies; (v) exposure to inflation, currency rate and interest rate fluctuations, as well as fluctuations in the market price of Leap's traded securities; and (vi) that the initiation, conduct, and completion of clinical trials, laboratory operations, manufacturing campaigns, and other studies may be delayed, adversely affected, or impacted by global conflict, or supply chain related issues. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or Implied) are made about the accuracy of any such forward-looking statements. Leap may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Leap's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither Leap, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Leap's views as of any date subsequent to the date hereof. CONTACT: Douglas E. Onsi President & Chief Executive Officer Leap Therapeutics, Inc. 617-714-0360 [email protected] Matthew DeYoung Investor Relations Argot Partners 212-600-1902 [email protected] SOURCE Leap Therapeutics, Inc.

Phase 2Clinical ResultFinancial StatementASCO

30 Jan 2024

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Florida Cancer Specialists & Research Institute Contributing to Global Advancements for Treatment of Gastrointestinal and Genitourinary Cancers

FCS Experts Share Clinical Research and Case Presentations at Clinical Symposiums FORT MYERS, Fla., Jan. 30, 2024 /PRNewswire/ -- Florida Cancer Specialists & Research Institute, LLC (FCS) continues to advance the treatment of gastrointestinal and genitourinary cancers, as evidenced by participation at two global gatherings held this month and sponsored by the American Society of Clinical Oncology (ASCO®). FCS medical oncologists and hematologists are co-authors of four FCS studies of advanced treatments featured at the ASCO® 2024 Gastrointestinal (GI) Cancers Symposium: Continue Reading FCS medical oncologists and hematologists are co-authors of four FCS studies of advanced treatments featured at the ASCO® 2024 Gastrointestinal (GI) Cancers Symposium. Elizabeth Guancial, MD, FCS medical oncologist and hematologist, served as a member of the program committee for the ASCO® 2024 Genitourinary (GU) Cancers Symposium, and participated as a co-chair and featured speaker on drug shortages. Phase 1/1b study investigating a novel monoclonal antibody therapy targeting sialyl Lewis A: Phase 1 monotherapy and combination with mFOLFIRINOX in patients with advanced pancreatic cancer, coauthored by Manish Patel, MD, FCS director of drug development, and Judy Wang, MD, FCS associate director of drug development. Phase 1b/2 study of ADG126 a masked antibody therapy for the treatment of metastatic colorectal cancer, coauthored by Manish Patel, MD. Phase 2 study to evaluate the efficacy and safety of DKN-01 plus bevacizumab and chemotherapy for the treatment of advanced colorectal cancer, coauthored by Liliana Bustamante, MD and Jeffrey Alan Bubis, DO, FACOI, FACP. Phase 1 study of EO-3021, an antibody drug, in adult patients with solid tumors, coauthored by Cesar Augusto Perez, MD, FCS director of drug development, Lake Nona DDU. Elizabeth Guancial, MD, FCS medical oncologist and hematologist, served as a member of the program committee for the ASCO® 2024 Genitourinary (GU) Cancers Symposium, and participated as: Co-chair of a general session featuring a panel of experts discussing available and evolving treatment options for patients with metastatic hormone sensitive prostate cancer after upfront treatment intensification. Featured speaker for a session reviewing the shortage of drugs for urothelial carcinoma. Her presentation was titled, "The Platinum Shortage from a Community Oncologist Perspective." Case presenter for a Phase 3, pivotal trial of PNT2002 radioligand therapy for metastatic prostate cancer. Also featured was a first in-human Phase 1 study of CC-94676, a first in-class androgen receptor ligand-directed degrader in patients with metastatic castration-resistant prostate cancer, co-authored by Manish Patel, MD. "The scientific research conducted daily in clinical trials across our statewide practice has an immediate and lasting impact on treatment decisions that are improving outcomes for cancer patients worldwide," said Bradley Monk, MD, who joined the practice earlier this year to serve as medical director of the FCS late-phase clinical research program. Manish Patel, MD, added, "Our studies and presentations demonstrate our focus and growing understanding of emerging and promising treatment modalities, including targeted immunotherapies and molecular-based treatments, which are improving survivorship for many forms of cancer once considered incurable. We are excited to share our findings and join with our colleagues to enhance and advance patient care." Dr. Patel oversees FCS' three early phase Drug Development Units in Sarasota, Lake Mary and Lake Nona. More than 300 active clinical trials are underway at FCS at any point in time. Gastrointestinal cancers affect the digestive tract organs, such as the stomach, large and small intestine, pancreas, colon, liver, rectum, anus and biliary system. Genitourinary cancers, including kidney and bladder cancers, occur in the urinary system of men and women and in the reproductive organs in men, such as prostate and testicular cancers. About Florida Cancer Specialists & Research Institute, LLC: (FLCancer.com) Florida Cancer Specialists & Research Institute (FCS) offers patients access to more clinical trials than any private oncology practice in Florida. The majority of new cancer drugs recently approved for use in the U.S. were studied in clinical trials with FCS participation.* Recognized for our research, FCS is a recipient of the national Clinical Trials Participation Award presented by the American Society of Clinical Oncology (ASCO). FCS physicians, trained in prestigious medical schools and research institutes, are consistently ranked nationally as Top Doctors by U.S. News & World Report. Celebrating its 40th year in 2024, FCS has built a national reputation for excellence that is reflected in exceptional and compassionate patient care, driven by innovative clinical research, cutting-edge technologies and advanced treatments, including targeted therapies genomic-based treatment and immunotherapy. Our highest values are embodied by our outstanding team of highly trained and dedicated physicians, clinicians and staff. *Prior to approval SOURCE Florida Cancer Specialists & Research Institute

ASCOImmunotherapyPhase 1Phase 2Phase 3

100 Deals associated with Sirexatamab

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of large intestine	Phase 2	US	Leap Therapeutics, Inc.	30 Aug 2022
Adenocarcinoma of large intestine	Phase 2	DE	Leap Therapeutics, Inc.	30 Aug 2022
Adenocarcinoma of large intestine	Phase 2	KR	Leap Therapeutics, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	US	Leap Therapeutics, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	DE	Leap Therapeutics, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	KR	Leap Therapeutics, Inc.	30 Aug 2022
Gastroesophageal junction adenocarcinoma	Phase 2	US	Leap Therapeutics, Inc.	29 Jul 2020
Gastroesophageal junction adenocarcinoma	Phase 2	DE	Leap Therapeutics, Inc.	29 Jul 2020
Gastroesophageal junction adenocarcinoma	Phase 2	KR	Leap Therapeutics, Inc.	29 Jul 2020
Gastrooesophageal junction cancer	Phase 2	US	Leap Therapeutics, Inc.	29 Jul 2020

Clinical Result

Indication

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04057365 (CTgov)	Phase 2	Advanced Bile Duct Carcinoma	15	Nivolumab+DKN-01 (DKN 01 and Nivolumab Safety Run in)	jbdjedhggv(vizcbqxvdh) = uxmjpcmniu kqiionwqqp (febjgwksuk, lcxrpgfhgr - ouwhiuoiha) View more	-	10 Apr 2024
				Nivolumab+DKN-01 (DKN 01 and Nivolumab)	zjgjssllyn(atxvrevmhw) = pspxbtjlva htfmzukgfp (tpmahdkprp, ojmonvagbz - faytghwojz) View more
NCT05480306 (DeFianCe, ASCO_GI2024) Manual	Phase 2	Microsatellite Stable Colorectal Carcinoma Second line Microsatellite Stable (MSS)	33	DKN-01 + FOLFIRI/FOLFOX + bevacizumab	mebqkbpnde(xnjukjaoyy) = iyimvmvcbk tjyxvlcmnl (cuwjbwgfbx ) View more	Positive	18 Jan 2024
NCT03837353 (CTgov)	Phase 1/2	Advanced Prostate Carcinoma	18	DKN-01+Docetaxel (Cohort 1A.1 (DKN-01 300mg, Docetaxel 75 mg/m2))	qxlbbujdfi(waefewymkt) = yxypkupbzb idbypfkpko (fmljzzgrfu, kuptxsomgk - vawkydwxhh) View more	-	18 Dec 2023
				DKN-01+Docetaxel (Cohort 1A.2 (DKN-01 600mg, Docetaxel 75 mg/m2))	qxlbbujdfi(waefewymkt) = vqvmdsvvai idbypfkpko (fmljzzgrfu, lzqjvjbalm - ohvjfgbvoy) View more
NCT04363801 (DisTinGuish, ASCO2023) Manual	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma First line	22	CAPOX+Tislelizumab+DKN 01 (ITT population)	zfqkporqvx(xzynnopbee) = mxzagzgdhl tsakrqktah (ksxntjmojv ) View more	Positive	26 May 2023
				CAPOX+Tislelizumab+DKN 01 (low tumor PD-L1 expression)	zfqkporqvx(xzynnopbee) = vbawxthdmo tsakrqktah (ksxntjmojv ) View more
Pubmed	Phase 2	Recurrent Endometrial Cancer	-	DKN-01 monotherapy	xgjbfrzius(orqzpvzjpm) = wcubfzbpgh ydyogzhnon (jczrzktcdn ) View more	-	29 Mar 2023
				DKN-01 in combination with paclitaxel	xgjbfrzius(orqzpvzjpm) = hkkwqkutig ydyogzhnon (jczrzktcdn ) View more
NCT04363801 (DisTinGuish, SITC2022) Manual	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma Second line DKK1 Overexpression	52	Tislelizumab+DKN 01	ejyipdxmix(cqubnsthto) = lflmfsuqth dlirrotkcb (ndiwciywdo ) View more	Positive	01 Nov 2022
NCT04363801 (DisTinGuish, ESMO2022) Manual	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma First line DKK1 expression	25	DKN-01+tislelizumab+CAPOX (DKK1 high)	aenctojixd(aftjagbgiw) = maaosxebpq fbnwozppbf (kdoppclovr ) View more	Positive	10 Sep 2022
				DKN-01+tislelizumab+CAPOX (DKK1 low)	aenctojixd(aftjagbgiw) = sibkrzrfju fbnwozppbf (kdoppclovr ) View more
NCT04363801 (DisTinGuish, ASCO_GI2022) Manual	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma First line \| Second line	49	CAPOX+tislelizumab+DKN-01 (HER2- regardless of DKK1 status)	oqqdstkjxc(yelgbbbmmb) = Nine pts had D-related ≥G3 toxicities, elevated AST/ALT, elevated alkaline phosphatase, hypophosphatemia, hyponatremia, lymphopenia, neutropenia, diarrhea, vomiting, fatigue all occurring in 1 pt and pulmonary embolism in 2 pts (one G5 event) javnodriei (xdghdxxazj ) View more	Positive	19 Jan 2022
				CAPOX+tislelizumab+DKN-01 (HER2-；DKK1-high)
NCT04363801 (DisTinGuish, ESMO2021) Manual	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma First line DKK1 Overexpression	25	tislelizumab+CAPOX+DKN-01	vewftunlbk(qslevzdeip) = omxinqofgk xjsorqjwtn (onzdeqchlz ) View more	Positive	16 Sep 2021
				tislelizumab+CAPOX+DKN-01 (DKK1-high [5 GEJ, 4 GC])	kcodolyvjj(bofhthjpvu) = udmawgxktk rykhbufxbp (wtouljsqbc )
NCT02375880 (Pubmed \| Clin Cancer Res)	Phase 1	Biliary Tract Neoplasms	51	DKN-01 150 mg	wytchswjqq(pqmdfckpnb) = wiiannpmqe ummpuvahnn (vjgynabwix ) View more	-	01 Dec 2020

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