On May 25, 2023 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported that the Company will be presenting new long-term follow-up data in first-line patients with advanced gastric or gastroesophageal junction adenocarcinoma (GEA) from Part A of the DisTinGuish study, a Phase 2 clinical trial evaluating Leap’s anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with BeiGene’s tislelizumab and chemotherapy, at the upcoming 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL on June 2-6, 2023 (Press release, Leap Therapeutics, MAY 25, 2023, View Source [SID1234632063]).

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"The long-term follow-up data for DKN-01 in combination with tislelizumab and chemotherapy indicates a novel and well-tolerated treatment with the potential for enhanced response rate, survival, and quality of life for advanced GEA patients," said Samuel Klempner, MD, Associate Professor at Harvard Medical School and principal investigator on the DisTinGuish study. "Median overall survival and progression-free survival for patients treated with DKN-01 plus tislelizumab and chemotherapy exceeded current PD-1 combination benchmarks, especially for those patients with low expression of PD-L1. Together with the previously reported data on the encouraging outcomes with DKN-01 for patients with high DKK1 expression, these results provide strong support for the ongoing randomized controlled clinical trial in first-line GEA patients."

"We are excited about the latest data from Part A of the DisTinGuish study which continues to show DKN-01 plus tislelizumab and chemotherapy as a safe and active treatment where tumor reductions can continue to deepen over time. It is extremely encouraging to see an additional patient achieve a partial response, which is ongoing, after 22 months on therapy," said Cynthia Sirard, MD, Chief Medical Officer of Leap Therapeutics. "A 90% overall response rate in DKK1-high patients and 86% overall response rate in PD-L1 low patients, both of which are associated with poor outcomes, along with 11.3 months median progression-free survival and 19.5 months median overall survival in the full population, demonstrates the important potential of DKN-01. We look forward to completing enrollment in the randomized controlled clinical trial late this year and seeing data from our ongoing colorectal cancer trial in the coming months."

Key Findings Part A DisTinGuish

· Median overall survival (OS) of 19.5 months and median progression-free survival (PFS) of 11.3 months exceeds benchmark results in the overall first-line patient population (n=25)

· Compelling OS and PFS results in all four important biomarker subgroups

○ 18.7 months OS and 10.7 months PFS in PD-L1-low (vCPS < 5) patients (n=16)
○ 22.0 months OS and 11.6 months PFS in PD-L1-high (vCPS > 5) patients (n=6)
○ 16.9 months OS and 11.3 months PFS in DKK1-high patients (n=12)
○ 24.4 months OS and 12.0 months PFS in DKK1-low patients (n=9)

· Additional patient with a partial response after 22 months on therapy improves objective response rate (ORR) to 73% in the overall modified intent-to-treat population (n=22), with one (5%) complete response (CR), 15 (68%) partial responses (PR), 5 (23%) best responses of stable disease (SD), and 1 (5%) non-evaluable (NE)

○ 86% ORR in PD-L1-low patients (n=14: 12 PR, 2 SD)
○ 67% ORR in PD-L1-high patients (n-6: 1 CR, 3 PR, 1 SD, 1 NE)
○ 90% ORR in DKK1-high patients (n=10: 9 PR, 1 NE)
○ 67% ORR in DKK1-low patients (n=9: 1 CR, 5 PR, 3 SD)
· Consistent with previous results, combination was well tolerated with manageable toxicity, with most adverse events related to DKN-01 being low-grade (76%)

Leap Poster Details:

Title: A phase 2 study (DisTinGuish) of DKN-01 in combination with tislelizumab + chemotherapy as first-line (1L) therapy in patients with advanced gastric or GEJ adenocarcinoma (GEA).

Presenter: Samuel J. Klempner, Harvard Medical School

Session Type: Poster Discussion Session

Session Title: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Date and Time: Monday, June 5, 2023, at 11:30 a.m. CT

Abstract Number: 4027

Poster Number: 335

About the DisTinGuish Study

The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, with or without chemotherapy as first-line or second-line therapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. The study is being conducted in three parts in the United States, the Republic of Korea, the United Kingdom, and Germany. Part A enrolled 25 first-line HER2- GEA cancer patients to receive DKN-01 in combination with tislelizumab and capecitabine and oxaliplatin. Part B enrolled 52 second-line GEA cancer patients whose tumors expressed high levels of DKK1 to receive DKN-01 in combination with tislelizumab. Part C is enrolling approximately 160 first-line HER2- GEA cancer patients in a randomized controlled trial of DKN-01 in combination with tislelizumab and chemotherapy compared to tislelizumab and chemotherapy. Tislelizumab is provided for the study through a clinical collaboration with BeiGene, Ltd.

On May 25, 2023 ISA reported that it will present the first clinical data of the combination of ISA101b and Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in patients with recurrent metastatic Human Papilloma Virus type 16 (HPV16) induced head and neck cancers who progressed on pembrolizumab or nivolumab (Press release, ISA Pharmaceuticals, MAY 25, 2023, View Source [SID1234632062]).

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Patients with recurrent and/or metastatic HPV16 positive OPC who experienced disease progression during or within 6 months after prior anti-PD1 therapy were to be treated until disease progression or withdrawal. Patients that never responded to prior treatment were also included. Further information can be found on clinicaltrials.gov (NCT04398524). Recruitment in this study is ongoing; results of the complete trial will become available mid-2024.

Presentation Title: Phase 2 study of ISA101b (peltopepimut-S) and cemiplimab in patients with advanced HPV16+ oropharyngeal cancer who failed anti-PD-1 therapy
Presentation Details: Monday 5th June 2023, 1:15-4:15pm CDT
Presenting Author: Dr. Anthony Kong, Principal Investigator
Session (poster): Head and Neck Cancer
ISA101b immunotherapy targets human papillomavirus type 16 (HPV16) positive cancers. It induces strong and specific immune responses to the HPV16 virus, and (re-)establishes a powerful and targeted T-cell immune response against infected and/or cancerous cells and tissues. Re-ignition of an anti-tumor effect of anti-PD1 therapy after failure of checkpoint inhibition by the addition of a therapeutic vaccine is a unique feature.

Head-and-neck cancer can be a severe and life-threatening disease. HPV16 is a major cause of head-and-neck cancer. Recurrent and metastatic HPV16 positive OPC is a form of head-and-neck cancer with a high unmet medical need. In September 2021 the U.S. Food and Drug Administration (FDA) granted Fast Track designation to ISA101b for the treatment of recurrent and metastatic HPV16 positive OPC.

For more information, please contact us at [email protected].

On May 25, 2023 INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported that Dr. Jacqueline Shea, President and CEO, and Dr. Michael Sumner, CMO, will present at the 2023 Jefferies Healthcare Conference (Press release, Inovio, MAY 25, 2023, View Source [SID1234632061]).

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2023 Jefferies Healthcare Conference
Date: Friday, June 9, 2023
Time: 8:00 AM ET
Format: Fireside Chat

During the conference, Dr. Shea and members of INOVIO’s management team will conduct one-on-one meetings with registered investors.

A webcast of the presentation will be available on the INOVIO Investor Relations Events page at View Source A replay of the webcast will be available for 90 days after the date of the presentation.

On May 25, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported acceptance of its IMerge Phase 3 abstract as an oral presentation at the upcoming 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Geron, MAY 25, 2023, View Source [SID1234632060]). This abstract describes statistically significant positive efficacy and safety data from the pivotal IMerge Phase 3 clinical trial evaluating the Company’s first-in-class telomerase inhibitor, imetelstat, in lower risk myelodysplastic syndromes (MDS). These data support the Company’s planned New Drug Application (NDA) submission to the U.S. FDA which is on track for June 2023, to support a potential U.S. commercial launch of imetelstat in lower risk MDS in the first half of 2024.

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"We believe that imetelstat has the potential to be practice-changing in lower risk MDS based on the unprecedented durability of transfusion independence, as well as broad activity across a range of disease subtypes in IMerge Phase 3," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "We are thrilled that these data will be featured in an oral presentation at ASCO (Free ASCO Whitepaper), where we will have a significant medical affairs presence to bring more awareness to the continuing unmet need in lower risk MDS and very much look forward to meaningful engagement with the medical community."

Details for the oral presentation are as follows:

Abstract #:7004

Title:IMerge: "Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Imetelstat in Patients (pts) With Heavily Transfusion Dependent (TD) Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESA)."

Date/Time:June 2, 2023 at 2:12 p.m. CT

Session:"Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant"

Presenter:Amer Methqal Zeidan, Yale School of Medicine

The abstract recaps top-line results from IMerge Phase 3 with a data cut-off of October 2022. As reported in January 2023, the primary endpoint of 8-week transfusion independence (TI) was met with high statistical significance (P<0.001) for imetelstat-treated patients (39.8%) vs. placebo (15.0%). Key secondary endpoint of 24-week TI and hematologic improvement erythroid (HI-E) under 2018 IWG criteria were also met with high statistical significance (P<0.001 for each) for imetelstat-treated patients vs. placebo.

In addition, the rate of 8-week TI was significantly higher with imetelstat vs. placebo across subgroups, including ring sideroblast (RS) negative patients. Median TI duration was significantly longer for imetelstat-treated patients vs. those on placebo (51.6 vs 13.3 weeks, P< 0.001). Patients receiving imetelstat had significantly higher mean hemoglobin (P < 0.001) and fewer transfusions (P = 0.042) over time than those on placebo.

In three of four genes frequently mutated in MDS, variant allele frequency (VAF) reduction was significantly greater in patients treated with imetelstat than placebo: SF3B1 (P< 0.001), TET2 (P= 0.032), DNMT3A (P= 0.019) and ASXL1 (P= NS). SF3B1 VAF reduction correlated with longer TI duration (P< 0.001).

No new safety signals were identified. The most common Grade 3/4 adverse events (AEs) were thrombocytopenia and neutropenia, with similar rates of Grade ≥3 bleeding and infections on imetelstat and placebo. In patients treated with imetelstat, cytopenias were manageable, of short duration, and > 80% were reversible to Grade ≤2 within 4 weeks.

The abstract concludes that for this lower risk MDS patient population: imetelstat demonstrated statistically significant and clinically meaningful efficacy with high 8- and 24-week TI rates, prolonged TI duration and increased hemoglobin. Also, VAF reduction and its correlation to clinical endpoints support imetelstat’s disease-modifying potential, and safety results were consistent with prior reported experience.

Full text of the abstract is available at www.asco.org.

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Geron plans to submit a New Drug Application (NDA) in the U.S. in June 2023 and a Marketing Authorization Application (MAA) in the EU in the second half of 2023 in the lower risk MDS indication.

On May 25, 2023 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that positive data from the Phase 1 portion of its Acclaim-1 clinical trial evaluating REQORSA Immunogene Therapy in combination with Tagrisso in late-stage non-small cell lung cancer (NSCLC) were published in an abstract at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6, 2023 in Chicago, IL and online (Press release, Genprex, MAY 25, 2023, View Source [SID1234632059]).

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"We are thrilled to have our abstract, which reports positive results from the Phase 1 portion of our Acclaim-1 clinical trial, published at the ASCO (Free ASCO Whitepaper) Annual meeting," said Mark Berger, MD, Chief Medical Officer at Genprex. "We are encouraged by the favorable safety profile of REQORSA, as well as the preliminary efficacy data we have observed, and we believe this data will support our advancement to the Phase 2 portion of the clinical trial."

Details of the abtract are below:

Abstract Number: e15081

Title: ACCLAIM-1 dose escalation: Determination of quaratusugene ozeplasmid and osimertinib recommended phase 2 dose (RP2D)

Session Title: Publication Only: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

The abstract reports preliminary results from eight patients in Genprex’s Phase 1 portion of its Acclaim-1 clinical trial evaluating REQORSA Immunogene Therapy (quaratusugene ozeplasmid) with Tagrisso (osimertinib) in patients with advanced, EGFR mutant NSCLC whose disease progressed after Tagrisso. REQORSA was generally well tolerated, as there were no dose limiting toxicities. Full safety and efficacy data on the Phase 1 portion of the study will be presented at an upcoming medical meeting.

While the Phase 1 portion of the clinical trial is designed primarily to assess safety, promising efficacy results were also observed. One patient at the 0.06 mg/kg dose level, previously treated with carboplatin, pemetrexed, and osimertinib, had a partial remission (PR) by investigator evaluation and treatment is ongoing after 16 cycles, which is approximately 10.5 months. Another patient at the 0.09 mg/kg dose level, previously treated with osimertinib, has stable disease and treatment is ongoing after 14 cycles, or approximately 9 months. The extended and ongoing progression free survival (PFS) of each of these patients is significantly greater than the median PFS observed from treatment with osimertinib alone in this treatment setting in several prior clinical trials1 and is consistent with long-term PFS seen in prior clinical trials of REQORSA. PFS is the primary endpoint of both the Phase 2 expansion portion and the Phase 2 randomized portion of the Acclaim-1 trial.

"Demonstrating a favorable safety profile substantially de-risks the REQORSA development program and is a major accomplishment for Genprex," said Rodney Varner, Chairman, President and Chief Executve Officer of Genprex. "It is encouraging that several patients who were progressing on their previous therapy are now having long periods of response and stable disease in the Phase 1 portion of the study. We wish to thank the patients and investigators participating in our clinical trials and our investors who make it possible to move our drug candidates forward toward availability for patients in need."

1. CHRYSALIS-2 NSCLC clinical trial data reported at ASCO (Free ASCO Whitepaper) 2022

About Acclaim-1

The Acclaim-1 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA, in combination with Tagrisso in patients with late-stage NSCLC with activating epidermal growth factor receptor ("EGFR") mutations whose disease progressed after treatment with Tagrisso.

The enrollment of the dose escalation Phase 1 portion of the Acclaim-1 trial has been completed. The Phase 2 expansion portion of the study is expected to enroll approximately 66 patients, half of whom will have received only Tagrisso treatment and the other half will have received Tagrisso treatment and chemotherapy, to determine toxicity profiles of patients with different eligibility criteria, as well as efficacy and other endpoints. There will be an interim analysis following the treatment of 19 patients in each cohort. The Phase 2 randomized portion of the study is expected to enroll approximately 74 patients to be randomized 1:1 to receive either REQORSA and Tagrisso combination therapy or platinum-based chemotherapy. The primary endpoint of the Phase 2 portion of the trial is progression-free survival, which is defined as time from randomization to progression or death. An interim analysis will be performed at 25 events.

About REQORSA Immunogene Therapy

REQORSA Immunogene Therapy (quaratusugene ozeplasmid) for non-small cell lung cancer (NSCLC) uses Genprex’s unique, proprietary ONCOPREX Nanoparticle Delivery System, which is the first systemic gene therapy delivery platform used for cancer in human clinical trials. The active agent in REQORSA is a plasmid that expresses the TUSC2 tumor suppressor gene. REQORSA consists of the TUSC2 gene expressing plasmid encapsulated in non-viral lipid nanoparticles made from lipid molecules with a positive electrical charge. REQORSA is injected intravenously and specifically targets cancer cells. Once REQORSA is taken up into a cancer cell, the TUSC2 gene is expressed, and the TUSC2 protein is capable of restoring certain defective functions arising in the cancer cell. REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, and modulates the immune response against cancer cells.

Tagrisso is a registered trademark of AstraZeneca plc and is its top-selling drug with 2022 sales of more than $5 billion.