On August 12, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that data from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib, a first-in-class menin inhibitor, in adult and pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) have been published in the Journal of Clinical Oncology (Press release, Syndax, AUG 12, 2024, View Source [SID1234645737]).

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"Publication of the pivotal AUGMENT-101 dataset in KMT2Ar acute leukemia allows for a broader dissemination of these important data and highlights revumenib’s impressive and consistent clinical profile that has led to meaningful results for these advanced patients," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "These data serve as the foundation for the NDA filing that is currently being reviewed by the FDA under its RTOR program. As we approach the potential FDA approval of revumenib, we are actively preparing for a successful commercial launch to enable us to deliver this important medicine to patients in need."

"Despite an increased understanding of the mechanisms governing development of KMT2Ar acute leukemia, no available therapies adequately serve this population," said Ghayas C. Issa, M.D., Assistant Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "The high rate of deep, MRD negative responses along with a safety profile that supports prolonged time on therapy and maintained remission post-stem cell transplant gives me confidence that revumenib could serve as a paradigm-changing treatment."

The FDA has granted Priority Review for the New Drug Application (NDA) for revumenib for the treatment of adult and pediatric R/R KMT2Ar acute leukemia. The NDA is being reviewed under the FDA’s Real-Time Oncology Review Program (RTOR) and has a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2024.

In March 2024, the Company announced the completion of enrollment in the final AUGMENT-101 pivotal trial cohort in patients with R/R mutant nucleophosmin (mNPM1) AML. Topline data is expected in the fourth quarter of 2024 and could support a supplemental NDA filing for revumenib in R/R mNPM1 AML in the first half of 2025.

About the data

The publication entitled "Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)" includes positive data from a total of 94 acute leukemia patients with KMT2Ar in the pivotal trial as of the July 2023 data cutoff, 57 of whom had central confirmation of their KMT2Ar status, sufficient follow-up and were in the efficacy analysis.

The AUGMENT-101 trial met its primary endpoint at the protocol-defined interim analysis with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) among the 57 efficacy evaluable patients in the KMT2Ar acute leukemia population. The CR + CRh rate was 23% (10/44; 95% CI: 11.5, 37.8) in adult patients and 23% in pediatric patients (3/13; 95% CI: 5.0, 53.8). The median time to CR + CRh in the overall efficacy-evaluable population was 1.9 months (range: 0.9, 4.6) and the CR + CRh responses were durable with a 6.4-month (95% CI: 3.4, NR) median duration and 46% (6/13) remaining in response at the time of data cutoff. Minimal residual disease (MRD) status was assessed in 10 of the 13 patients who achieved a CR + CRh, 70% (7/10) of whom were MRD negative.

In the efficacy evaluable patients, the overall response rate1 was 63% (36/57; 95% CI: [49.3, 75.6]), and the composite response rate (CRc) was 44% (25/57). MRD status was assessed in 22 of the 25 patients who achieved a CRc, 68% (15/22) of whom were MRD negative. Responses were observed in all major subgroups, including across the number of prior treatments and prior stem cell transplant, and across a broad age range with the youngest responder aged 1 year and oldest aged 75 years. A total of 14 (39%) patients who achieved an overall response underwent HSCT, eight of whom did not achieve a CR or CRh prior to transplant. Half (7/14) of the patients who had an HSCT resumed revumenib treatment post-transplant. Median overall survival at the time of data cutoff was 8.0 months (95% CI: 4.1, 10.9).

Revumenib was well tolerated and the safety profile was consistent with the Company’s previously reported data. In the pivotal AUGMENT-101 trial safety population (n=94), treatment-emergent adverse events (TEAEs) of Grade ≥3 that occurred in ≥10% of patients included febrile neutropenia (37%), neutropenia (29%), thrombocytopenia (21%), anemia (18%), differentiation syndrome (16%), QTc prolongation (14%), sepsis (12%), and hypokalemia (11%). TEAEs leading to dose reduction or discontinuation were low at 9.6% (9/94) and 12.8% (12/94) of patients, respectively. Grade 3 DS was observed in 15% (14/94) of patients while one patient (1%) experienced Grade 4 DS and no patients experienced Grade 5 DS. No Grade 4 or 5 QTc events occurred. There were no discontinuations related to DS, cytopenias or QTc prolongation as of the July 2023 data cutoff.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, and full data have now been published in the Journal of Clinical Oncology. Revumenib was granted Orphan Drug Designation for the treatment of AML and ALL by the FDA and for the treatment of AML by the European Commission, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

On August 12, 2024 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported its financial results for the second quarter ended June 30, 2024 and provided an update on its clinical development pipeline and other corporate developments (Press release, Prelude Therapeutics, AUG 12, 2024, View Source [SID1234645736]).

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"Our team continues to make solid progress towards the Company’s ambitious R&D objectives that we established for 2024 and beyond. We are focused on advancing our two lead clinical programs, including the first-in-class, highly selective SMARCA2 degrader, PRT3789 and a potent and selective CDK9 inhibitor, PRT2527, both on track to report initial clinical results this year," stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude.

Dr. Vaddi continued, "We believe that targeting the SMARCA pathway has the potential to deliver a ‘pipeline in a program.’ We are building on our leadership position by advancing the industry’s first highly selective oral SMARCA2 degrader, PRT7732, into the clinic, and will initiate a study of PRT3789 in combination with KEYTRUDA in collaboration with Merck later this year. Additionally, in collaboration with AbCellera, we are developing precision ADCs with SMARCA payloads to extend the reach of our molecules to an even broader set of cancers without SMARCA4 mutations."

"Regarding our clinical development programs, we are very pleased with the progress of both of our SMARCA2 degraders, PRT3789 and PRT7732," added Jane Huang, M.D., President and Chief Medical Officer of Prelude. "We are looking forward to sharing the initial clinical data from the Phase 1 study of our highly selective SMARCA2 degrader which has been chosen as the subject of an oral presentation at the upcoming ESMO (Free ESMO Whitepaper) Congress in September."

Dr. Huang continued, "Additionally, based on the continued progress of PRT2527, our selective CDK9 inhibitor, we intend to present interim phase 1 clinical data, including a potential best-in-class safety profile in the fourth quarter of this year."

Clinical Program Updates and Upcoming Milestones

PRT3789 – A first-in-class, highly selective, intravenous SMARCA2 Degrader

PRT3789 is a first-in-class SMARCA2 degrader, highly selective for SMARCA2 and designed to treat patients with a SMARCA4 mutation. Cancer patients whose tumors have SMARCA4 mutations have a poor prognosis and as a result, this is an area of high unmet medical need.

PRT3789 is in Phase 1 clinical development in biomarker selected SMARCA4 mutant patients. Enrollment remains on track, and the Company expects to conclude monotherapy dose escalation in 2024 and identify a recommended Phase 2 dose. In addition, enrollment of patients into back-fill cohorts enriched for NSCLC and SMARCA4 loss-of-function mutations is ongoing, as is enrollment of the combination with docetaxel cohort.

Objectives for this first Phase 1 clinical trial are to establish the safety and tolerability profile of PRT3789 as both monotherapy and in combination with docetaxel, evaluate activity, pharmacokinetics and pharmacodynamics and determine a dose and potential indications for advancement into registrational clinical trial(s).

Prelude recently launched an educational video series focused on the science of SMARCA biology, the discovery of first-in-class, highly selective SMARCA2 degraders and the unmet medical need for patients with SMARCA4 mutated cancer. This series can be found on the Company’s website under Highly Selective SMARCA2 Degraders – Prelude Therapeutics (preludetx.com).

Interim Phase 1 data selected for an oral presentation at the ESMO (Free ESMO Whitepaper) Congress 2024

The abstract titled "First Clinical Results from a Phase 1 Trial of PRT3789, a First-in-Class Intravenous SMARCA2 Degrader, in Patients with Advanced Solid Tumors with a SMARCA4 Mutation," will be presented by Robin Guo, M.D. from Memorial Sloan Kettering Cancer Center. The ESMO (Free ESMO Whitepaper) Congress 2024 Scientific Committee selected the abstract as an oral presentation.

The presentation is scheduled for September 13th, 2024, at 4:00 PM CEST (10:00 AM EST) in the Santander Auditorium (Hall 5) as part of the Developmental Therapeutics Session.

Abstracts are anticipated to be available on the ESMO (Free ESMO Whitepaper) website on September 9th, 2024 at 12:05 AM CEST (6:05 PM EST on September 8th).

Clinical collaboration announced with Merck to evaluate PRT3789 in combination with KEYTRUDA in patients with SMARCA4-mutated cancers

In July 2024, Prelude announced a clinical collaboration with Merck to evaluate PRT3789 in combination with KEYTRUDA in patients with SMARCA4-mutated cancers.

The mechanistic rationale and pre-clinical data to support the SMARCA2 and anti-PD-1 monoclonal antibody (mAb) combination was previously presented by the Company at the 2023 AACR (Free AACR Whitepaper) AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). In pre-clinical models, SMARCA2 degrader combined with an anti-PD-1 mAb in SMARCA4-mutated cancers enhanced anti-tumor immunity and demonstrated tumor regressions. Please see the Company’s website under Publications – Prelude Therapeutics (preludetx.com) for more information.

Under the terms of the Agreement, Merck will provide KEYTRUDA to Prelude. Prelude will be the sponsor of the Phase 2 clinical combination trial, anticipated to initiate in the fourth quarter of 2024. Prelude and Merck each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

PRT7732 – A potent, highly selective and orally bioavailable SMARCA2 Degrader

Prelude has identified a series of highly selective and orally bioavailable SMARCA2 degraders. The lead oral candidate, PRT7732, recently was granted IND authorization from the FDA and is expected to enter Phase 1 clinical development in the second half of 2024.

PRT2527 – A potent and highly selective CDK9 Inhibitor

PRT2527 is a potent and highly selective CDK9 inhibitor that has the potential to avoid off-target toxicities observed with other less selective CDK9 inhibitors. The Company is currently advancing PRT2527 as monotherapy in both lymphoid and myeloid hematological malignancies, and in combination with zanubrutinib in B-cell malignancies.

PRT2527 is expected to complete monotherapy dose escalation in B-cell malignancies this year. Initiation of dose escalation in myeloid malignancies occurred in the first half of 2024. Interim Phase 1 data is on track for presentation in the fourth quarter of 2024.

Second Quarter 2024 Financial Results 

Cash, Cash Equivalents, and Marketable securities:

Cash, cash equivalents and marketable securities as of June 30, 2024 were $179.8 million. The Company anticipates that its existing cash, cash equivalents and marketable securities will fund Prelude’s operations into 2026. 

Research and Development (R&D) Expenses:

For the second quarter of 2024, R&D expense increased to $29.5 million from $25.0 million for the prior year period. Research and development expenses increased primarily due to an increase in our chemistry, manufacturing, and controls (CMC) expense to support our pre-clinical and clinical research programs. We expect our R&D expenses to vary from quarter to quarter, primarily due to the timing of our clinical development activities.  

General and Administrative (G&A) Expenses:

For the second quarter of 2024, G&A expenses increased to $7.7 million from $7.4 million for the prior year period. The increase is primarily due to an increase in professional fees incurred as we expand our operations to support our research and development efforts.

Net Loss:

For the three months ended June 30, 2024, net loss was $34.7 million, or $0.46 per share compared to $30.4 million, or $0.54 per share, for the prior year period. Included in the net loss for the quarter ended June 30, 2024, was $6.1 million of non-cash expenses related to the impact of expensing share-based payments, including employee stock options, as compared to $6.7 million for the same period in 2023.

On August 12, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended June 30, 2024 (Press release, ORIC Pharmaceuticals, AUG 12, 2024, View Source [SID1234645734]).

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"We have made strong progress on advancing the pipeline, deepening strategic relationships, and growing the leadership team to add new functional capabilities," said Jacob M. Chacko, M.D., president and chief executive officer. "We are making good progress on the expansion cohorts for ORIC-114 in three different selected patient populations in NSCLC and have initiated combination dosing for ORIC-944 in prostate cancer. The clinical trial collaboration and supply agreements with Bayer and Johnson & Johnson are pivotal steps in supporting those combination cohorts. Finally, we bolstered our leadership team to add commercial and medical affairs capabilities in advance of the potential initiation of multiple registrational trials in 2025. We look forward to sharing further clinical updates in 2025."

Second Quarter 2024 and Other Recent Highlights

ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Announced the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 and the selection of two provisional recommended phase 2 doses.
Announced first patients dosed across three expansion cohorts in the Phase 1b trial of ORIC-114 in patients with mutated non-small cell lung cancer (NSCLC), including EGFR exon 20 insertion (EGFR exon 20 inhibitor naïve), HER2 exon 20 insertion, and EGFR atypical mutations.
Initiated an extension cohort to evaluate ORIC-114 for the treatment of patients with first-line, treatment-naïve EGFR exon 20 insertion NSCLC.
Expect to report updated Phase 1b data in the first half of 2025.
ORIC-944: a potent and selective allosteric inhibitor of PRC2

Initiated dosing of ORIC-944 in combination with NUBEQA (darolutamide) and in combination with ERLEADA (apalutamide) in the ongoing Phase 1b trial for prostate cancer in first half of 2024.
Entered into clinical trial collaboration and supply agreements with Bayer and Johnson & Johnson to support the ongoing Phase 1b trial of ORIC-944 in combinations with AR inhibitors for the treatment of prostate cancer.
Presented preclinical data at the 2024 AACR (Free AACR Whitepaper) Annual Meeting demonstrating superior drug properties and synergy data in prostate cancer models, reinforcing the promise of ORIC-944 as a potential best-in-class treatment for combination with AR inhibitors.
Discovery Pipeline:

Presented at the 2024 AACR (Free AACR Whitepaper) annual meeting the first preclinical data on ORIC-613, a potential first- and best-in-class development candidate selectively inhibiting PLK4.
Corporate Highlights:

Expanded the leadership team with the appointment of industry veteran Keith Lui as Senior Vice President of Commercial and Medical Affairs.
Second Quarter 2024 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $308.5 million as of June 30, 2024, which the company expects will be sufficient to fund its operating plan into late 2026.
R&D Expenses: Research and development (R&D) expenses were $28.9 million for the three months ended June 30, 2024, compared to $18.8 million for the three months ended June 30, 2023, an increase of $10.2 million. For the six months ended June 30, 2024, R&D expenses were $50.9 million, compared to $38.3 million for the six months ended June 30, 2023, an increase of $12.6 million. The increases were due to a net increase in external expenses related to the advancement of product candidates and discovery programs, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.6 million and $1.2 million for the three and six months ended June 30, 2024, respectively.
G&A Expenses: General and administrative (G&A) expenses were $7.1 million for the three months ended June 30, 2024, compared to $6.2 million for the three months ended June 30, 2023, an increase of $0.9 million. For the six months ended June 30, 2024, G&A expenses were $14.1 million, compared to $12.4 million for the six months ended June 30, 2023, an increase of $1.7 million. The increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation of $0.6 million and $1.3 million for the three and six months ended June 30, 2024, respectively.

On August 12, 2024 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that the Company has been awarded a $2 million grant from the National Institutes of Health (NIH) Small Business Innovation Research (SBIR) program to support the clinical investigation of MT-601 in patients with non-Hodgkin’s lymphoma (NHL) who have relapsed following anti-CD19 chimeric antigen receptor (CAR) T cell therapy (Press release, Marker Therapeutics, AUG 12, 2024, View Source [SID1234645733]).

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The SBIR grant has been awarded based in part on Marker’s preliminary clinical data in patients with lymphoma (Press Release, September 11, 2023) as well as non-clinical data demonstrating the anti-tumor activity of MT-601 on anti-CD19 CAR resistant lymphoma cells (Press Release, May 31, 2023). The proceeds of the grant will support the nationwide multi-center Phase 1 APOLLO study (ClinicalTrials.gov identifier: NCT05798897), evaluating the safety and efficacy of MT-601, a multi-tumor associated antigen (multiTAA)-specific T cell product, in patients with relapsed NHL including those previously treated with anti-CD19 CAR-T cell therapy. Including this SBIR grant, the Company has been awarded over $19 million in non-dilutive funding proceeds.

"We are pleased to receive the SBIR grant from the NIH to support our clinical Phase 1 study in CAR-relapsed patients with non-Hodgkin’s lymphoma," said Juan Vera, M.D., President and CEO of Marker Therapeutics. "Although anti-CD19 CAR-T cells are rapidly expanding as a treatment option in patients with hematological malignancies, approximately 40-60% of patients will relapse within the first year of therapy with currently no standard of care for patients post CD19-targeting CAR-T cells. The NIH award process is highly competitive, and we believe that the decision the NIH made suggests the potential scientific merit and the capacity of Marker’s APOLLO study to address an unmet medical need."

Dr. Vera continued: "While our results of the APOLLO study are preliminary, as we move through the dose escalation part of the study, we are encouraged by the objective responses observed in all three study participants treated at City of Hope (Press Release, April 8, 2024) and the lack of cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) observed. We will continue to closely monitor all patients for long-term treatment effects and durability of response, and with the non-dilutive funding support from NIH we look forward to treating additional participants in this Phase 1 study."

"This grant award is a testimony of our continued commitment to apply for non-dilutive funding and allows us to leverage our data to drive innovation and growth while maximizing shareholder value. Obtaining non-dilutive funding is an ongoing effort, and we are actively applying for additional opportunities as they become available," concluded Dr. Vera.

About the NIH SBIR Program

The NIH Small Business Innovation Research (SBIR) Program sets aside more than $1.2 billion from its Research & Development Funding to specifically support early-stage small businesses throughout the United States. Many companies leverage the NIH SBIR funding to attract the partners and investors needed to take an innovation to market. The Small Business program focuses on a variety of high-impact technologies including research tools, diagnostics, digital health, drugs, and medical devices, and can provide the seed funding needed to bring scientific innovations from bench to bedside.

About MT-601

The Company’s lead product, MT-601, is a multi-tumor associated antigen (multiTAA)-specific T cell product that utilizes a non-genetically modified approach that specifically targets six different tumor antigens upregulated in lymphoma cells (Survivin, PRAME, WT-1, NY-ESO-1, SSX-2, MAGE-A4). Marker is currently investigating MT-601 in the Company-sponsored Phase 1 APOLLO trial (clinicaltrials.gov identifier: NCT05798897) for the treatment of lymphoma patients who are relapsed after or where CD19 CAR-T cell therapy is not an option.

About APOLLO

The APOLLO trial (clinicaltrials.gov Identifier: NCT05798897) is a Phase 1, multicenter, open-label study designed to evaluate the safety and efficacy of MT-601 in participants with lymphoma who relapsed after anti-CD19 CAR-T cell therapy or where anti-CD19 CAR-T cell therapy is not an option. The primary objective of this exploratory Phase 1 clinical trial is to evaluate the safety and preliminary efficacy of MT-601 in participants with various lymphoma subtypes. Under the APOLLO trial, it is anticipated that nine clinical sites across the United States will cumulatively enroll up to approximately 30 participants during the dose escalation phase.

About multiTAA-specific T cells

The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood capable of recognizing a broad range of tumor antigens. Unlike other T cell therapies, multiTAA-specific T cells allow the recognition of hundreds of different epitopes within up to six tumor-specific antigens, thereby reducing the possibility of tumor escape. Since multiTAA-specific T cells are not genetically engineered, Marker believes that its product candidates will be easier and less expensive to manufacture, with an improved safety profile, compared to current engineered T cell approaches, and may provide patients with meaningful clinical benefits.

On August 12, 2024 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported financial results for the second quarter ended June 30, 2024 (Press release, Leap Therapeutics, AUG 12, 2024, View Source [SID1234645732]).

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Leap Highlights:

· Overall response rate (ORR) increases to 33% across all evaluable patients and 38% across evaluable patients with left-sided CRC in updated data from Part A of the Phase 2 DeFianCe study evaluating DKN-01 in combination with bevacizumab and chemotherapy in second-line patients with advanced colorectal cancer (CRC)
· Expanded the randomized controlled Part B of the DeFianCe study to 180 patients; enrollment expected to be completed by end of September 2024 with data expected in mid-2025
· Patient follow-up continues in the randomized controlled Part C of the Phase 2 DisTinGuish study evaluating DKN-01 in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal junction (GEJ) and gastric cancer; data expected in Q4 2024 or early 2025
· Completed $40 million private placement with new and existing investors, including Gilead Sciences, Inc.

"With the momentum provided by our $40 million private placement, we are positioned to achieve our critical company milestones," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "We have executed well on our two DKN-01 randomized controlled trials and on preparatory activities for registrational studies. We look forward to sharing initial data from both randomized controlled studies over the next 12 months as we strive to deliver new treatments for patients fighting against cancer."

DKN-01 Development Update

· ORR increases in updated data from Part A of the DeFianCe Study. The DeFianCe study (NCT05480306) is a Phase 2 study evaluating DKN-01 in combination with bevacizumab and chemotherapy in second-line patients with advanced microsatellite stable CRC. Preliminary results from Part A of the study were previously reported at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2024. In April 2024, a ninth Part A patient was identified as having a partial response (PR). This patient, who has left-sided Consensus Molecular Subtype 4 CRC with APC and TP53 mutations and KRAS wildtype genetics, had been previously treated with cetuximab and chemotherapy. The patient enrolled in Part A in March 2023 and had a best response of stable disease (SD) for over a year before the tumor reduction deepened into a PR. The patient remains on study with a confirmed PR.

· Key Updated Part A Findings (as of June 7, 2024 data cut-off):

o Across all patients enrolled (n=33):

§ ORR among response-evaluable patients (n=27) was 33% and disease control rate (DCR) was 93%, including 9 PRs and 16 patients with a best response of SD
§ Median progression-free survival (PFS) was unchanged at 6.3 months

o Enhanced activity in patients with left-sided tumors (n=25), a group that has more frequent activation of the Wnt pathway modulated by DKK1

§ 38% ORR and 100% DCR in response-evaluable population (8 PRs, 13 SDs)
§ Median PFS was unchanged at 8.6 months

o DKN-01 plus bevacizumab and chemotherapy was well-tolerated, with a majority of DKN-01 related events being low grade (Grade 1/2)

· Enrollment in Part B of the DeFianCe Study in CRC patients is ongoing and expected to be completed by the end of September 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. As of August 9, 2024, 161 patients have enrolled in Part B. The Company expects to complete enrollment by the end of September 2024, with data expected mid-2025.

· Randomized controlled Part C of the DisTinGuish study in patients with GEJ and gastric cancer is ongoing, with initial data expected in Q4 2024 or early 2025. 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, HER-2 negative patients with GEJ and gastric cancer. Part C enrolled 170 patients randomized 1:1 to evaluate DKN-01 in combination with tislelizumab and chemotherapy, compared to tislelizumab and chemotherapy alone. The Company expects to report initial data from Part C of the DisTinGuish study in Q4 2024 or early 2025.

Business Update:

· Completed a $40 million private placement. In April 2024, Leap entered into a securities purchase agreement with a select group of new and existing investors including Gilead Sciences, Inc., a life sciences-focused investor, Samsara BioCapital, LP, 683 Capital Partners, LP, Laurion Capital Management LP, and Rock Springs Capital Management LP. Gross proceeds from the private placement were approximately $40 million. 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.

Selected Second Quarter 2024 Financial Results

Net Loss was $20.4 million for the second quarter 2024, compared to $13.4 million for the same period in 2023. The increase was primarily due to an increase in research and development expenses.

Research and development expenses were $17.9 million for the second quarter 2024, compared to $11.1 million for the same period in 2023. The increase of $6.8 million was primarily due to an increase of $5.7 million in clinical trial costs due to patient enrollment, the duration of patients on study, the enhancement of correlative studies, increase in site activity associated with Part C of the DisTinGuish study, and the expansion of the size of Part B of the DeFianCe study. There was also an increase of $0.6 million in manufacturing costs related to clinical trial material and manufacturing campaigns 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 $3.4 million for the second quarter 2024, compared to $3.6 million for the same period in 2023. The decrease was due to a decrease of $0.3 million in professional fees associated with our business development activities, partially offset by a $0.1 million increase in payroll and other related expenses.

Cash and cash equivalents totaled $78.5 million at June 30, 2024.