On July 22, 2019 HAMLET Pharma is reported the successful outcome of the Phase I/II trial, aimed at studying the safety and efficacy of Alpha1H in patients with bladder cancer (Press release, HAMLET Pharma, JUL 22, 2019, View Source [SID1234537656]). The first data analysis has revealed highly significant differences between the Alpha1H treated patients and the placebo group, for several crucial efficacy variables. Treatment was also shown to be safe, as no drug-related side effects were observed.

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Alpha1H triggered significant shedding of cells in all tumor patients, who received the treatment (p< 0.0001).In addition, Alpha1H triggered the excretion of whole tumor fragments into the urine (p<0.0001), illustrating the potent effect compared to the placebo group.

"This is a bench-to-bedside moment and we are grateful to all, who have made this possible. The results inspire us to continue the efforts making Alpha1H available to cancer patients," says Catharina Svanborg, founder, CMO and chairman of the board of Hamlet Pharma Ltd.

"This is a very important milestone for the company. We need more evidence but hopefully this could be the gentle chemotherapy of the future," says Mats Persson, CEO of Hamlet Pharma Ltd.

Alpha1H triggered cell death in the tumor, as shown by cytolysis and apoptosis, a beneficial form of cell death. These findings support the key mechanisms of action of Alpha1H discovered in the laboratory and the successful translation from the laboratory to the clinic.

Carefully selected safety variables were recorded according to safety guidelines. The effects of Alpha1H occurred without drug-related side effects in the patients, consistent with the lack of toxicity observed in animal models of bladder cancer.

The clinical trial of 40 patients (20 placebo and 20 with treatment who received 6 infusions over 22 days) has been a technical success, due to the competence and commitment of the different study teams involved. A team of experts at the Motol University Hospital in Prague handled patient enrolment, clinical care, pathology assessments and treatment. The study was monitored by a highly renowned, clinical trial CRO in Prague. Scientific coordination was from Lund University, where research sample analysis was handled and molecular information obtained. Additional study variables will be communicated as soon as data is available.

Notes to Editors

HAMLET Pharma plans to conduct further studies in bladder cancer and several other cancer indications, such as colon cancer and brain tumors; all hard to cure with current therapies. HAMLET Pharma has 35 patents for the manufacturing and use of HAMLET as well as the second-generation Alpha1H derivative of the HAMLET molecule. HAMLET has been found to kill more than forty types of cancer cells to date in laboratories. The work has been published in leading international journals like The New England Journal of Medicine, GUT commented in Nature Reviews Gastroenterology and PNAS (Proceedings of the National Academy of Science, USA).

On July 22, 2019 Salarius Pharmaceuticals, Inc. (Nasdaq: SLRX), a clinical-stage oncology company targeting the epigenetic causes of cancers, reported it has enrolled the first patient in a Phase 1 clinical study of the company’s lead compound, Seclidemstat, in patients with advanced solid tumors resistant to standard-of-care therapies. Seclidemstat is a differentiated reversible inhibitor of the widely studied epigenetic enzyme lysine-specific demethylase 1 (LSD1) (Press release, Flex Pharma, JUL 22, 2019, View Source [SID1234537641]). This is Salarius’ second Phase 1 clinical study for Seclidemstat, which is also the subject of an ongoing clinical study focused on Ewing sarcoma, a devastating bone and soft tissue cancer for which Seclidemstat has Orphan Drug Designation and Rare Pediatric Disease Designation from the U.S. Food and Drug Administration (FDA). Salarius expects to report early cohort data from both Phase 1 clinical studies in 2020.

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David Arthur, President and CEO of Salarius Pharmaceuticals, stated, "We are excited to expand our clinical pipeline for Seclidemstat to include patients with advanced solid tumors and we believe addressing the epigenetic dysregulation underlying certain cancers represents a potentially powerful approach to providing a therapeutic benefit for patients with limited or no other treatment options. With potential data readouts from both clinical programs expected next year, we hope to further establish Salarius in this exciting and growing field."

Seclidemstat is an oral small molecule inhibitor of LSD1, a validated drug target for clinical development. LSD1 is known to associate with more than 60 different gene regulatory proteins to drive a variety of cancer types. High levels of LSD1 expression are often correlated with poor patient prognosis. The open-label, dose escalation/dose expansion Phase 1 clinical study in advanced solid tumor cancers is designed to evaluate the safety, pharmacokinetics and pharmacodynamics of Seclidemstat, as well as establish a recommended dose for Phase 2 studies. The study is enrolling patients with advanced (non-Ewing’s) solid tumors, with a focus on prostate, breast, ovarian, melanoma, colorectal, non-Ewing’s sarcomas and other cancers where Seclidemstat demonstrated single-agent preclinical activity. The study will also use established and exploratory biomarkers to assess sensitivity and early signs of therapeutic activity in these patients.

Michael Gordon, M.D., Medical Director of Oncology Clinical Trials at the HonorHealth Research Institute and principal investigator of the advanced solid tumor Phase 1 study, commented, "Epigenetics is a rapidly growing field within oncology, and selective yet reversible inhibitors such as Seclidemstat represent the cutting-edge progress being made in this space. We know that epigenetic modulation by LSD1 occurs not only through its enzymatic activity as a demethylase, but also via its scaffolding properties. If clinical studies prove Seclidemstat is able to safely and effectively inhibit both mechanisms of gene regulation by LSD1, which is supported by substantial preclinical work, Seclidemstat will have a highly differentiated profile that could translate into improved outcomes for patients."

On July 22, 2019 Compugen Ltd. (NASDAQ: CGEN), a leader in predictive discovery and development of first-in-class therapeutics for cancer immunotherapy, reported that the Company will release its second quarter 2019 financial results on Monday, August 5, 2019 before the U.S. financial markets open (Press release, Compugen, JUL 22, 2019, View Source [SID1234537657]). Management will host a corresponding conference call and webcast to review the results and provide a corporate update at 8:30 AM ET.

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To access the live conference call by telephone, please dial 1-888-407-2553 from the U.S., or +972-3-918-0644 internationally. The call will also be available via live webcast through Compugen’s website, located at the following link. Following the live audio webcast, a replay will be available on the Company’s website.

On July 21, 2019 PACT Pharma, a leader in the fields of cancer immunology and cell therapy in collaboration with a team at UCLA, reported new data demonstrating for the first time the ability to identify mutation targets unique to each person’s cancer and verify the cancer specificity of multiple cloned T cell receptors (Press release, PACT Pharma, JUL 21, 2019, View Source [SID1234537638]). Each patient’s cancer has a private signature of mutations, creating an opportunity to develop fully personalized immune therapies that have the potential to eradicate tumor cells. Defining these cancer mutation targets for each person, known as neoantigens, enables the company to use its proprietary gene engineering technologies to manufacture an immune cell therapy product for each person with cancer. The presentation was at the AACR (Free AACR Whitepaper)’s Special Conference on Immune Cell Therapies for Cancer. The company has begun enrolling patients with advanced solid tumors in its Phase 1 dose escalation study of NeoTCR-P1, an autologous gene-edited TCR T cell product that targets personalized neoantigens (View Source).

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"These exciting results open a bold new frontier for directing a person’s own immune system to treat patients with solid cancers, an area that hasn’t yet seen the successes of immune cell therapies that we have seen for blood cancers," said PACT’s Chief Executive Officer Alex Franzusoff, Ph.D. "While it is early, the results demonstrate the possibility for PACT’s approach to ignite a patient’s immune response directly against their unique tumor mutation signature, within a clinically relevant timeframe, with potential applicability to most cancers and all ethnicities across the globe."

Today’s data is relevant because they show that mutations that build up in tumors, creating the unique tumor mutation "signature" that drives each patient’s cancer, have already triggered each person’s immune system to target those unique mutations, but at a very low level. Now those low-level targeted immune responses can be analyzed with greater accuracy, used to manufacture a truly personalized treatment that is tailored for each patient with cancer, and evaluated in clinical trials.

The company’s approach is designed to select and confirm tumor-exclusive mutations to empower a patient’s immune system to target their specific cancer. PACT utilizes bioinformatics to identify the mutation blueprint of each person’s tumor, and then uses its barcoded snare technologies to capture pre-existing T cells from the blood that already recognize and target the unique mutations. From that group, a proprietary selection platform is used to identify the ideal T cell receptors for specific mutations. Once the target is authenticated, the company uses non-viral gene editing to engineer the ideal mutation-targeted T cell receptors into T cells from the same patient. When reinfused back to the patient, these T cells have the potential to eliminate tumor cells that express these unique mutations.

"The results presented today show that PACT’s approach of neoantigen-specific T cell capture and non-viral precision genome engineering is indeed groundbreaking and promising for a new chapter in personalized immune cell therapies for patients with solid cancers," said Antoni Ribas, a professor of medicine at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who is a co-author of the study and also a co-founder of PACT. "The demonstration that T cell receptor-engineered T cells using the PACT approach can specifically kill that same person’s cancer cells is based on the analysis of immune cells captured from the blood of a patient with a long-lasting response to anti-PD-1 therapy."

The evolution of personalized immune-oncology treatments
Recently, a new generation of personalized cellular therapies for cancer has emerged. Rapid sequencing technologies, bioinformatics, and genetic/cellular engineering — in addition to a deeper understanding of clinical immunology and a renaissance in immunotherapy — have made these advancements possible. Designer immune-oncology treatments have been developed, including CAR-T cell therapies, cancer vaccines and tumor-infiltrating lymphocyte therapies.

While transformative, these therapeutic approaches face limitations. CAR-T cells only recognize shared cancer targets expressed on the cell surface, which, while effective for blood cancers, have not been applied successfully to patients with solid cancers, and cancer vaccines are often too slow to address a rapidly growing tumor burden. Further, tumor-infiltrating lymphocytes can be impractical—and at times even impossible—to generate for every patient due to the difficulty of isolating limited numbers of specific tumor-targeting immune cells and then needing to greatly expand their numbers for patient dosing. In the case of expanded immune cells in particular, they often become exhausted before reinfusion, which may limit their value for eliminating the cancer throughout the body.

In order to truly tailor cancer treatments to individuals, the therapy must target each patient’s unique cancer signature–including different tissue compatibility receptors of the immune system, or HLA, in each person. These HLA receptors are key to immune recognition, which is what limits organ sharing between people. PACT’s approach captures this nuance. Custom tailored, yet for a global population, PACT’s approach is designed to select and authenticate tumor-exclusive mutations to empower the patient’s immune system to target their specific cancer for a lasting effect. PACT plans to further investigate the safety and effectiveness of this technology in a series of clinical trials, starting with a first-in-human Phase 1 clinical trial at clinical sites in California.

On July 21, 2019 Ascentage Pharma, a globally-focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, hepatitis B virus and age-related diseases, reported that the company was notified by the U.S. Food & Drug Administration (FDA) on the clearance of the Investigational New Drug (IND) application which allows the company to initiate its Phase Ib clinical trial of HQP1351, a novel drug candidate developed by Ascentage Pharma, for the treatment of patients with tyrosine kinase inhibitors (TKI)-resistant chronic myeloid leukemia (CML) in the United States (Press release, Ascentage Pharma, JUL 21, 2019, View Source;resistant-chronic-myeloid-leukemia-patients-in-the-us-300888373.html [SID1234537658]).

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HQP1351 is the sixth molecule to receive clearance of IND from the FDA for Ascentage Pharma. The Company submitted data generated from over 100 subjects in the Phase I clinical trial in China to the FDA to support the IND application.

This clinical study is a bridging Phase Ib clinical trial with three dose cohorts (30mg, 40mg and 50mg), which is more efficient than the traditional 3+3 dose-escalation study and is expected to accelerate the progress of this clinical trial. It is designed to evaluate the safety, tolerability, and pharmacokinetic (PK) of HQP1351 in CML patients who are resistant or intolerant to at least second-line TKIs and to confirm the recommended Phase II dose (RP2D). This clinical study will be led by Hagop Kantarjian, M.D., Chair of Department of Leukemia at MD Anderson Cancer Center, and other prominent US research centers and hospitals will also participate.

HQP1351 is designed to address the acquired drug resistance from the treatment using Imatinib. Such resistance is developed in 20-30% of patients treated with the drug develop acquired drug resistance, thus representing a major challenge to the treatment of CML. HQP1351 is an oral, third-generation BCR-ABL TKI targeting a broad spectrum of BCR-ABL mutants, including those with the T315I mutation, to treat drug-resistant CML patients. The agent is currently in pivotal Phase II clinical trial and is the first third-generation BCR-ABL inhibitor targeting drug-resistant CML in China. A New Drug Application (NDA) submission is planned upon the successful completion of the pivotal Phase II clinical studies in China.

As previously announced, the updated data from HQP1351 Phase I study in China was accepted as an oral presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting last December. The preliminary data showed that HQP1351 was effective in the treatment of first and second generation TKI-resistant CML, especially the highly resistant CML with T315I mutation, with improved safety profile compared to other agents in the same class. This result demonstrates HQP1351’s best-in-class potential for treating TKI-resistant CML.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented: "Ascentage Pharma used the clinical data from its HQP1351 Phase1 clinical trial in China to support the US IND application. This FDA agreed Phase Ib clinical trial design could significantly accelerate HQP1351’s global clinical development program. Drug-resistant CML represents significant unmet clinical need and we hope that HQP1351 will soon benefit patients worldwide."

About HQP1351
HQP1351 is a novel kinase inhibitor developed by Ascentage Pharma. It is an oral third-generation BCR-ABL inhibitor targeting a broad spectrum of BCR-ABL mutants, including those with the T315I mutation, to treat drug-resistant CML patients. A Phase I clinical trial for patients with TKI-resistant CML has been completed and a pivotal Phase II clinical trial was initiated in China. It also entered a Phase I trial in patients with GIST in China.