Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today reported financial results for the third quarter ended September 30, 2022.
- Presented clinical data from Part A of the DisTinGuish study of DKN-01 plus BeiGene’s tislelizumab in gastroesophageal adenocarcinoma (GEA) cancer patients, and the Phase 2 WAKING study of DKN-01 plus Tecentriq® in oesophagogastric adenocarcinoma (OGA), at the European Society for Medical Oncology (ESMO) Congress
- Presented clinical data from Part B of the DisTinGuish study of DKN-01 plus tislelizumab in GEA cancer patients whose tumors express high levels of DKK1 (DKK1-high), and preclinical data supporting further evaluation of DNK-01 in colorectal cancer (CRC), at the Society for Immunotherapy of Cancer (SITC) Annual Meeting
- Enrolled first patient into Part C of the DisTinGuish study, the randomized controlled trial of DKN-01 plus tislelizumab and chemotherapy in first-line G/GEJ patients
- Enrolled first patient into the Phase 2 DeFianCe study of DKN-01 in second-line CRC patients
“This past quarter saw incredible progress across our DKN-01 program as we continue to focus on execution in our clinical, preclinical, biomarker, and manufacturing activities, and advance into the next stages of development,” said Douglas E. Onsi, President and Chief Executive Officer of Leap. “Results from Parts A and B of the DisTinGuish trial have been compelling with updated data presented at both ESMO and SITC. We were also delighted to announce the enrollment of the first patients into both Part C of the DisTinGuish gastric cancer study and the newly-initiated DeFianCe colorectal cancer trial, as we explore the broad therapeutic potential of DKN-01.”
DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways, which play an important role in tumor cell signaling and in mediating an immuno-suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating natural killer (NK) cell ligands on tumor cells.
- Updated Clinical Data from Part A of DisTinGuish Study of DKN-01 Plus Tislelizumab in First-Line Patients with Advanced GEA at the ESMO Congress. The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy in patients with inoperable, locally advanced GEA.
- Overall median progression-free survival (PFS) was 11.3 months, exceeding benchmark results in unselected patients and in all four important biomarker-directed subgroups (DKK1-high, DKK1-low, PD-L1-low, and PD-L-1-high).
- Median overall survival was not yet reached.
- Overall response rate (ORR) was high and durable in unselected and aggressive subgroups (DKK1-high and PD-L1-low); 68% ORR in modified intent-to-treat (mITT) population overall (1 complete response, 14 partial responses).
- DKN-01 and tislelizumab plus CAPOX was well tolerated in first-line treatment for advanced GEA patients, with a safety profile consistent with previous reports.
- New Clinical Data from WAKING Study of DKN-01 Plus Tecentriq® at the ESMO Congress. The WaKING study (NCT04166721) is an investigator-sponsored study of DKN-01 in combination with atezolizumab, Roche’s anti-PD-L1 antibody, in patients with microsatellite stable esophago gastric cancer who have progressed following chemotherapy. This study is being sponsored by The Royal Marsden Hospital in the United Kingdom and being funded by Roche as part of its imCORE network.
- Updated Data from Part B of DisTinGuish Study of DKN-01 Plus Tislelizumab in Second-Line Patients with Advanced GEA Cancer Whose Tumors Exress High Levels of DKK1-High at the SITC Annual Meeting.
- DKN-01 and tislelizumab were well tolerated at both 300mg and 600mg DKN-01 doses with no Grade 5 treatment-emergent AEs (TEAE) and no TEAEs leading to study drug discontinuation or dose reduction
- In evaluable anti-PD-1/PD-L1 naïve mITT population (n=43), 27% ORR and 43% disease control rate (DCR), exceeding the benchmark studies for anti-PD-1 monotherapy
- In DKK1-high/PD-L1-high CPS ≥ 10 patients: 55% ORR, 73% DCR, and 7.7 months PFS
- In DKK1-high/PD-L1-negative CPS < 1 patients: 27% ORR
- New Preclinical Data in Colorectal Cancer (CRC) Models at the SITC Annual Meeting.
- DKN-01 additive activity with 5-fluorouracil (5FU) and can overcome 5FU-resistance in two xenograft models, resulting in tumor regressions. 5FU-resistant models are reflective of a second-line CRC population currently being recruited in the DeFianCe study.
- Treatment with DKN-01 as monotherapy or in combination with anti-PD-1 resulted in tumor regression in a CT26 synergenic CRC model.
- Leap Announced First Patient Enrolled in Part C of Phase 2 DisTinGuish Study of DKN-01 in Combination with Tislelizumab and Chemotherapy Compared to a Tislelizumab and Chemotherapy Control Arm, in Patients with G/GEJ. The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. Part C of the DisTinGuish study will enroll approximately 160 first-line, HER2-negative patients who have had no prior therapy for unresectable locally advanced or metastatic G/GEJ adenocarcinoma.
- Leap Announced First Patient Enrolled in DeFianCe Study of DKN-01 in Combination with Standard of Care Bevacizumab and in Chemotherapy in Second-Line Patients for the Treatment of CRC. The DeFianCe study (NCT05480306) is a Phase 2 study of DKN-01 in combination with bevacizumab and SOC chemotherapy in patients with advanced CRC who have received one prior systemic therapy. The study is designed with an initial 20 patient cohort and to then expand into a 130 patient randomized controlled trial against bevacizumab and SOC chemotherapy.
Net Loss was $15.1 million for the third quarter 2022, compared to $11.1 million for the three months ended September 30, 2021.
Research and development expenses were $12.1 million for the three months ended September 30, 2022, compared to $10.1 million for the three months ended September 30, 2021. The increase of $2.0 million in research and development expenses was due to an increase of $1.4 million in clinical trial costs due to patient enrollment and the duration of patients on study, an increase of $0.4 million in payroll and other related expenses due to increased headcount, and an increase of $0.2 million in stock-based compensation expense.
General and administrative expenses were $3.2 million for the three months ended September 30, 2022, compared to $2.4 million for the three months ended September 30, 2021. The increase of $0.8 million in general and administrative expenses were due to an increase of $0.5 million in professional fees due to higher recruiting costs and an increase of $0.2 million in payroll and other related expenses due to an increase in headcount.
Cash and cash equivalents totaled $78.3 million at September 30, 2022. Additionally, short-term research and development incentive receivable totaled $1.3 million.
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 in clinical trials in patients with esophagogastric, colorectal, and gynecologic cancers. Leap has entered into a strategic collaboration with BeiGene, Ltd. for the rights to develop DKN-01 in Asia (excluding Japan), Australia, and New Zealand. For more information about Leap Therapeutics, visit http://www.leaptx.com or view our public filings with the SEC that are available via EDGAR at http://www.sec.gov or via https://investors.leaptx.com/.