On April 1, 2019 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, reported an update on its clinical development programs along with financial results for the fourth quarter and year ended December 31, 2018 (Press release, Leap Therapeutics, APR 1, 2019, View Source [SID1234534880]).
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Leap Highlights
· DKN-01 plus Keytruda exceeds benchmarks in gastric cancer
·Predictive biomarker enables patient selection
· DKN-01 plus paclitaxel exceeds benchmarks in esophagogastric cancer
·Two DKN-01 monotherapy responses in endometrial cancer
· DKK1-positive prostate cancer study enrolling 97 patients
· TRX518 has first reported GITR agonist monotherapy confirmed partial response in the industry
· TRX518 combination with Keytruda or Opdivo demonstrating durable complete and partial responses
· TRX518 combination with gemcitabine achieved partial response and meaningful clinical benefit in patients who had previously progressed on gemcitabine therapy
·Raised $13.225 million to support further clinical development
DKN-01 Clinical Update
DKN-01 is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein, a Wnt pathway modulator. DKN-01, as a single agent, has achieved partial responses in three different cancer indications. In combination with immune checkpoint inhibitors and with chemotherapy, DKN-01 has achieved overall response rates and survival data that is greater than the historical benchmarks, particularly in biomarker targeted patient populations.
·DKN-01 plus Keytruda (pembrolizumab) exceeds PD-1 antibody monotherapy benchmarks in gastric and gastroesophageal junction cancer Leap has completed the enrollment of fifty-two patients who have advanced esophagogastric cancer and who were naïve to PD-1/PD-L1 therapy. Thirty-four patients with gastric (GC) or gastroesophageal junction (GEJ) cancer were enrolled, and twenty-five are evaluable for tumor response. Five patients (20%) have had a partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and eight patients (32%) have experienced a best response of stable disease (SD), representing a disease control rate (DCR) of 52%. One patient continuing on therapy for six months has 36.4% tumor reduction, a PR by immune related RECIST (iRECIST), but not considered a PR by RECIST v1.1 due to tumor growth of greater than 20% at the first assessment, likely representing pseudoprogression. All of the patients in the study have tumors that are microsatellite stable or unknown, representing a population in which the benchmark overall response rate (ORR) of PD-1 antibodies is approximately 9%.
·DKK1 biomarker predicts response to DKN-01 plus Keytruda The overall response rate (ORR) and DCR has been higher in patients with higher DKK1 expression as measured by in situ hybridization RNAscope (H-scores). DKK-1 H-scores have been determined for thirty-two evaluable PD-1 therapy naïve patients, including nineteen GC/GEJ patients. Nine GC/GEJ patients had DKK1 H-Scores of greater than 31, including the six PRs (66.7%) by RECIST and iRECIST, two patients (22.2%) experiencing SD, and one patient (11.1%) with progressive disease. In the ten GC/GEJ patients with DKK1 H-Scores of 31 or lower, two patients (20%) had a best response of SD and eight patients (80%) had progressive disease.
·DKN-01 plus paclitaxel exceeds chemotherapy benchmark in esophagogastric cancer patients In total, fifty-eight patients with advanced esophagogastric cancer were treated, with fifty-two evaluable for response. Across all lines of prior therapy and tumor types, DKN-01 plus paclitaxel generated a 25.0% ORR, 13.4 weeks median progression-free survival (PFS), and 27.9 weeks median overall survival (OS). In the fifteen evaluable second-line patients, the combination of DKN-01 plus paclitaxel generated a 46.7% ORR, 19.6 weeks PFS, and 61.1 weeks OS. In a recent benchmark study in second-line esophageal cancer patients, single agent chemotherapy achieved a 6.7% ORR, 3.4 month PFS, and 7.1 month OS.
·Two monotherapy and one combination therapy responses for DKN-01 in advanced gynecological cancers, with seventy-eight patients now enrolled DKN-01, both as a monotherapy and in combination with paclitaxel, generated PRs and durable clinical benefit, including in patients with carcinosarcoma and Wnt pathway alterations. There have now been two DKN-01 monotherapy PRs and one PR in combination with paclitaxel in patients with epithelial endometrial cancer, all of whom have had Wnt pathway alterations. In total, seventy-eight patients have now been enrolled in this study, and many are pending first efficacy evaluation.
·Investigator-Initiated Study in DKK1-positive prostate cancer underway DKK1 is upregulated in a large number of patients whose advanced prostate cancer tumors do not express the androgen receptor. A study led by NYU Langone Medical Center and funded by Leap is enrolling metastatic DKK1-positive castration-resistant prostate cancer patients who have progressed on one or more androgen receptor therapies to be treated with either DKN-01 monotherapy or DKN-01 in combination with docetaxel.
TRX518 Clinical Update
TRX518 is unique among Glucocorticoid-Induced TNF Receptor (GITR) agonist antibodies for its aglycosyl design, permitting activation of GITR signaling without depleting CD8-positive T-effector cells. TRX518 has been shown to increase CD8-positive T-effector cell infiltrate and the expression of granzyme B, as well as decrease CD4-positive T-regulatory cell infiltrate. TRX518 is the first GITR agonist antibody in the industry to have reported partial responses as a monotherapy, in combination with PD-1 antibodies, and in combination with gemcitabine chemotherapy.
·Monotherapy patient with partial response A non-virally mediated hepatocellular cancer patient, who has been treated with single agent TRX518 for nearly two years, has achieved a PR with 47% tumor reduction and continues on study. TRX518 has demonstrated safety, tolerability, and clinical benefit as a monotherapy in patients with heavily pretreated solid tumors.
· Combination with Keytruda or Opdivo (nivolumab) achieved durable, confirmed complete and partial responses in patients not expected to respond to anti-PD-1 therapy An esophageal squamous cell carcinoma patient has a confirmed complete response. The patient has been treated for ten months and continues on study. A patient with uveal melanoma achieved 23% tumor reduction and six months of SD. A patient with urothelial carcinoma who had failed prior Keytruda had a confirmed PR and remained on therapy for six months. Twelve patients have recently enrolled in the expansion cohort for the Keytruda combination.
·Combination with gemcitabine achieved partial response and meaningful clinical benefit in patients who had progressed on gemcitabine therapy A pancreatic cancer patient, who had previously progressed on gemcitabine therapy and two other prior lines of therapy, has now achieved a confirmed PR with 58% tumor reduction. The patient has been treated for nine months and continues on study.
Selected Year-End and Fourth Quarter 2018 Financial Results
Net loss was $23.1 million for the year ended December 31, 2018, compared to $29.7 million for the year ended December 31, 2017. This decrease was primarily due to a noncash charge to decrease the fair value of the warrant liability. Net income was $1.5 million for the fourth quarter of 2018, compared to a net loss of $6.6 million for the same period in 2017. The 2018 increase was due to the decrease in the fair value of the warrant liability in the fourth quarter, leading to a $11 million non-cash gain. The requirement to revalue the warrant liability each quarter has resulted in the Company’s net income or net loss being highly variable.
Research and development expenses were $21.8 million for the full year 2018, compared to $22.5 million for the same period in 2017. This decrease was primarily due to reduced manufacturing expenses of our clinical product candidates and a decrease in stock based compensation expense offset by increased clinical trial costs due to increased patient enrollment. Research and development expenses were $6.9 million for the fourth quarter of 2018, compared to $4.4 million for the same period in 2017. This increase was due to increased clinical development expense associated with the start-up operations and enrollment of our ongoing clinical trials.
General and administrative expenses were $8.9 million for the full year 2018, compared to $9.8 million for the same period in 2017. This decrease was due to a decrease in stock based compensation expense. General and administrative expenses were $2.1 million for the fourth quarter of 2017, compared to $2.1 million for the same period in 2017.
Cash, cash equivalents and marketable securities totaled $16.3 million at December 31, 2018. Research and development incentive receivables totaled $0.8 million. Subsequent to the financial year end, Leap completed a public offering of $13.225 million of common stock and warrants, resulting in net cash proceeds of $12.1 million. Leap believes that its current cash and the expected receipt of research and development tax incentives will be sufficient to fund its operating expenses into the second quarter of 2020.