On December 11, 2024 iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, reported a clinical update on its lead asset, roginolisib. Results from the completed Phase I DIONE-01 study are due to be presented at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) annual congress tomorrow, 12 December at 12:30 CET (presentation 164P) (Press release, iOnctura, DEC 11, 2024, View Source [SID1234649059]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Allosteric modulator of PI3Kδ, roginolisib, has a unique chemical structure and binding mechanism which makes it highly specific for PI3Kδ, giving it an advantageous pharmacology profile and an unprecedented safety profile compared to previous generations of PI3Kδ inhibitors.

Roginolisib is being investigated in solid and hematological malignancies including uveal melanoma (UM), a rare cancer of the eye. Eye melanoma is a rapidly growing market which is projected to be worth USD 9.56B by 2032[1].

The two-part Phase I study DIONE-01, firstly evaluated continuous daily dosing of roginolisib [at 10, 20, 40 and 80 mg] in 24 patients with pretreated solid tumors and follicular lymphoma (FL), and secondly evaluated a dose confirmation cohort in 20 UM patients.

Results from DIONE-01 show:

Study met its primary objective to determine the safety of the anticipated optimal biologically effective dose (BED): Roginolisib was well tolerated at the recommended Phase II dose (RP2D) of 80mg, with <7% Grade 3/4 treatment-emergent adverse events (TEAEs) considered to be related to roginolisib. TEAEs did not result in immune-related toxicity, or dose-limiting toxicity, in either solid tumor or hematological patients. In contrast to prior PI3Kδ inhibitors, roginolisib dosing did not require dose modifications.
Roginolisib is well tolerated over long periods of treatment, up to 4.5 years.
Median overall survival (OS) was 16 months for the 29 patients with UM treated with roginolisib, who had previously received a median of two prior therapies. This exceeds the median OS of 7 months observed in historical controls in patients receiving immunotherapies as second line treatment[2].
Median progression free survival (PFS) was 5 months for patients treated with roginolisib versus less than 3 months for historical controls2.
Clinical findings validate the mechanism of action of roginolisib: roginolisib reduces immune-suppressive immune cells and chemokines, UM-related tumor clones (ctDNA) and PI3K-related signaling indicating a rebalancing of the immune system.
Catherine Pickering, Chief Executive Officer of iOnctura, said: "The Phase I DIONE-01 data highlight the benefits of roginolisib for patients with uveal melanoma and advanced cancers. Roginolisib’s unique allosteric binding mechanism has translated into a differentiated beneficial clinical profile, including a doubling of overall survival compared to historical controls in uveal melanoma. We are delighted to announce these data support progression of roginolisib into a randomized Phase II study."

Professor Michele Maio, University of Siena and Principal Investigator of the roginolisib studies, added: "Being able to continue to investigate roginolisib in a randomized Phase II study is a positive step to understand more about this already well tolerated molecule. Roginolisib has given prolonged disease stabilization to patients with uveal melanoma who have exhausted all other therapeutic options. So far, these patients have maintained a good quality of life without major limitations. I’m looking forward to seeing what the Phase II trial delivers over the coming months."

Activation of trial sites for the Phase II OCULE-01 study (NCT06717126) investigating roginolisib versus investigator’s choice in the second-line+ treatment of uveal melanoma is ongoing.

On December 11, 2024 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical-stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer and other indications, reported a partnership with CareDx, Inc. (NASDAQ: CDNA) The Transplant Company who will perform pharmacokinetic analysis using its AlloCell solution in the ACHIEVE clinical trial (Press release, TC Biopharm, DEC 11, 2024, View Source [SID1234649058]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The ACHIEVE clinical trial is an adaptive, open-label, phase II study designed to evaluate the efficacy and effectiveness of TCB008, an allogeneic gamma delta T cell therapy for patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS).

CareDx is a leading precision medicine company focused on discovering, developing, and commercializing healthcare solutions for transplant patients and caregivers. CareDx’s AlloCell test, a sensitive solution for pharmacokinetic monitoring of allogeneic immune and stem cell therapies, will be used to evaluate the expansion and persistence of TCB008 in patients enrolled in the ACHIEVE trial.

It is expected that these expansion and persistence data will provide an understanding of the duration and effect of TCB008 Gamma Delta T-Cells in reconstituting the immune system of acute myeloid leukemia patients enrolled in the ACHIEVE trial.

"Our partnership with CareDx is a significant milestone," said Alison Bracchi, Executive Vice President of Clinical Operations at TC BioPharm. "The collaboration is pivotal to the development and optimization of TCB008 as a therapy for acute myeloid leukemia and other blood cancers."

"We are thrilled to continue to progress the science of allogeneic cell therapy for patients battling acute myeloid leukemia," said Marica Grskovic, PhD, CareDx Chief Strategy Officer. "This partnership builds upon our growth strategy to expand into hematology oncology with pharmacokinetic and monitoring assays for patients undergoing cell therapy."

On December 11, 2024 Accent Therapeutics, a clinical-stage biopharmaceutical company pioneering novel, targeted, small molecule cancer therapeutics, reported that the first patient has been dosed in the Phase 1/2 clinical trial evaluating the safety and tolerability of ATX-559, a first-in-class oral DHX9 inhibitor (Press release, Accent Therapeutics, DEC 11, 2024, View Source [SID1234649057]). The company also announced the retirement of Robert A. Copeland, Ph.D., Co-Founder, President, and Chief Scientific Officer (CSO), and the promotion of Serena Silver, Ph.D., to CSO.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ATX-559 is a first-in-class potent and selective inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase, which is reported to play a critical role in tumors with high levels of replication stress (including breast, ovarian, colorectal, endometrial, gastric, and others), representing large patient populations with significant unmet medical need. The ATX-559 Phase 1/2 study (NCT06625515) is designed to evaluate the molecule’s safety profile at multiple dose levels, assessing tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy. The trial is enrolling solid tumor patients, with a particular focus on patients with BRCA1- or BRCA2-deficient breast cancer and patients with MSI-H and/or dMMR solid tumors (including certain patients with colorectal, endometrial, gastric, and other cancers). The advancement of ATX-559 into the clinic, followed closely by the KIF18A program, which is expected to enter the clinic in 1H 2025, marks a critical milestone for the company to advance potentially transformative therapies for cancer patients.

"We are thrilled to begin evaluating ATX-559 in cancer patients. While PARP inhibitors are useful standard treatments for BRCA1- and BRCA2-deficient breast cancer, the majority of patients with metastatic disease will likely need a different treatment within a year or two. Likewise, about half of patients with MSI-H/dMMR colorectal cancer patients will need additional treatments following PD-(L)1 inhibitors," said Jason Sager, M.D., Chief Medical Officer of Accent Therapeutics. "With ATX-559 entering clinical trials and Accent’s KIF18A inhibitor poised to begin Phase 1 studies, we are well-positioned to translate our rigorous scientific research into the development of multiple new medicines for treating cancer. These programs represent years of the Accent Therapeutics team’s pioneering research and scientific rigor as we seek to identify meaningful new treatment options for patients who face these challenging malignancies."

Effective January 1, 2025, Serena Silver, Ph.D., will be promoted to the position of Chief Scientific Officer. Dr. Silver joined Accent in September 2022 as Vice President of Biology, bringing a breadth of experience across target discovery, drug discovery, and translational research. Prior to joining Accent, Dr. Silver was Vice President of Discovery Biology and Technologies at Fulcrum Therapeutics, where she led scientific teams to develop and deploy new assay modalities and complex cellular models of disease to identify targets and discover therapeutics for rare diseases. Previously, Dr. Silver led the Molecular Pharmacology group at Novartis Oncology, the Target ID and Validation team at Sanofi Oncology, and worked at the forefront of functional genomics screening technology at the Broad Institute. Dr. Silver holds a Ph.D. in Biology from the Massachusetts Institute of Technology and completed a postdoctoral fellowship at Harvard Medical School.

"We are delighted to promote Dr. Silver to the position of Chief Scientific Officer. Her exceptional expertise in cancer biology and strategic vision make her the ideal scientific leader as we continue to advance the science underlying our novel DHX9 and KIF18A programs in our mission to bring innovative treatments to patients," said Shakti Narayan, Ph.D., J.D., Chief Executive Officer of Accent Therapeutics. "Since co-founding Accent in 2017 and serving as President and CSO, Dr. Copeland’s visionary leadership has been instrumental in shaping our scientific direction. We want to thank Bob for his invaluable contributions to Accent and wish him the best for the future."

Dr. Copeland has served as Co-Founder, President, and Chief Scientific Officer at Accent since the company’s founding in 2017. He was formerly President of Research and CSO of Epizyme, Inc. and before that, Vice President of Cancer Biology in the Oncology Center of Excellence in Drug Discovery at GlaxoSmithKline. He has contributed to drug discovery and development efforts leading to 20 investigational new drugs entering human clinical trials. He is a member of the editorial boards of Molecular Cancer Therapeutics (AACR) (Free AACR Whitepaper) and ACS Medicinal Chemistry Letters. He also serves on multiple biotechnology scientific advisory boards. Dr. Copeland received his doctorate in chemistry from Princeton University and was the Chaim Weizmann Fellow at the California Institute of Technology. He was elected a Fellow of the American Association for the Advancement of Science (AAAS) and of the Royal Society of Chemistry.

"I am honored to step into the role of CSO at Accent," said Dr. Silver. "Our team has made significant strides towards advancing transformative medicines for cancer patients, and I am excited to lead our scientific efforts as we enter the clinic. I look forward to leveraging our exceptional talent and rigorous scientific foundation to continue translating our discoveries into impactful therapies for patients."

In addition to ATX-559, Accent anticipates initiating a Phase 1 trial in 1H 2025 for its second program targeting KIF18A in chromosomally instable tumors. The transition to a clinical-stage company marks a meaningful inflection point as Accent continues to advance its pipeline of innovative cancer therapies.

About ATX-559

ATX-559 is a first-in-class potent and selective inhibitor of DHX9, a novel and previously undrugged RNA and DNA/RNA helicase, which is reported to play a critical role in tumors with high levels of replication stress (including breast, ovarian, colorectal, endometrial, gastric, and others), representing large patient populations with significant unmet medical need. DHX9 has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability. In addition to exploiting key tumor vulnerabilities in DNA repair deficient backgrounds (e.g., BRCA) and hyper-mutated states (e.g., MSI-H/dMMR), Accent is exploring the sensitivity of other tumor types to DHX9 inhibition, and the potential to combine DHX9 inhibitors with other cancer treatments to maximize its full potential for helping patients. Therefore, this enzyme represents a compelling novel oncology target. Accent retains full worldwide rights to ATX-559, currently being evaluated in a Phase 1/2 clinical trial (NCT06625515), and the DHX9 program.

About KIF18A

Accent’s second lead program is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability, but not in healthy cells. KIF18A inhibitor treatment results in rapid cell death for cancers with an abnormal number of chromosomes (aneuploid) in vitro and in vivo, while cells with normal numbers of chromosomes (euploid) are unaffected. Accent retains full worldwide rights to the KIF18A program, which is anticipated to enter the clinic in 1H 2025.

On December 11, 2024 Florida Cancer Specialists & Research Institute, LLC (FCS) medical oncologists and hematologists reported groundbreaking breast cancer research studies being presented this week at the San Antonio Breast Cancer Symposium (Press release, Florida Cancer Specialists & Research Institute, DEC 11, 2024, View Source;research-institute-advancing-breast-cancer-research-302328323.html [SID1234649056]). Abstracts that detail first in-human Phase 1 and Phase 2 clinical trials conducted with FCS participation were selected to be highlighted at the prestigious international symposium attended by oncology experts from 100 countries.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

FCS Assistant Managing Physician David Wenk, MD said, "It is gratifying to share significant findings that are transforming and expanding treatment options for patients around the world diagnosed with breast cancer and other breast diseases." In the U.S., breast cancer is the most common cancer among women, after melanoma skin cancer. It affects men as well. Survival rates have increased dramatically in recent years thanks to ongoing advances in clinical research.

The following FCS medical oncologists and hematologists are co-authors of five abstracts that include first-in-human Phase 1 and Phase 2 clinical trials and will be presented in poster and/or oral presentations:

Lowell Hart, MD, FACP, as first author, and Stacey Garofalo, RN: P4-09-20: Extended Endocrine Adjuvant therapy for Early HR+ Breast Cancer, Comparisons Between Molecular Expression Profiles (Abstract SESS-1965)
Manish Patel, MD, FCS director of drug development, — P4-10-28: Efficacy, safety and biomarker results of AC699, a chimeric estrogen receptor degrader, in patients with advanced or metastatic breast cancer. (Abstract SESS-1394)
Alexander Philipovskiy, MD, PhD: P4-08-20: Trial in progress: A first-in-human phase 1a/b, dose escalation/expansion study of BG-68501/ETX-197 (CDK2 inhibitor) as monotherapy or in combination with fulvestrant for patients with HR+/HER2- breast cancer and other advanced solid tumors; and P2-10-27: An Open Label Study of BTX-A51 in Patients with ER+/HER2- GATA3 Mutant and Wild Type Metastatic Breast Cancer. (Abstract SESS-1333)
Judy Wang, MD, FCS associate director of drug development: P2-10-27: An Open Label Study of BTX-A51 in Patients with ER+/HER2- GATA3 Mutant and Wild Type Metastatic Breast Cancer. (Abstract SESS-1333) and P4-08-24: AKTive-001: A Phase 1/1b Multiple Cohort Trial of ALTA2618 in Patients with Advanced Solid Tumors with AKT1 E17K Mutation (Trial in Progress) (Abstract SESS-614)
Dr. Manish Patel oversees the statewide practice’s three drug development units, which, at any given time, are providing patients with the most advanced treatment options with access to over 130 clinical trials. He said, "Clinical trials lay the foundation for the future of cancer care, showcasing groundbreaking advancements in targeted therapies and innovative treatment strategies."

On December 11, 2024 A2A Pharmaceuticals, Inc. ("A2A or "the company"), a clinical-stage pioneering biopharmaceutical company focused on developing innovative cancer therapies, reported significant progress in its clinical studies exploring TACC3 (Transforming Acidic Coiled-Coil 3) inhibition in patients with ovarian cancer, triple-negative breast cancer (TNBC), and endometrial cancer, as well as other malignancies (Press release, A2A Pharmaceuticals, DEC 11, 2024, View Source [SID1234649055]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A2A Pharmaceuticals has progressed into cohort 4, an important inflection point in its Phase 1 clinical trial to assess the safety and efficacy of its lead TACC3 inhibitor, A0-252. Early results have shown strong safety and efficacy profiles with the potential for a wide therapeutic index in these patient populations.

"We are excited about the advancements in our TACC3 program and its potential for patients with challenging cancer diagnoses. The company is continually exploring collaborations and partnerships to accelerate development timelines and enhance patient access to cutting-edge treatments," said Sotirios Stergiopoulos, M.D. President, CEO and Founder, A2A Pharmaceuticals, Inc. "Our focus on understanding the biology of cancer and leveraging innovative targeted therapies underscores our commitment to transforming cancer care and improving outcomes for patients."

"While our current focus with AO-252 is on addressing the unmet needs in ovarian, TNBC, and endometrial cancers, we are equally excited about its potential to benefit patients in other indications in the future," said Robbin Frnka, vice president of Clinical Operations. "This is just the beginning of our journey, and we look forward to exploring broader applications of this promising treatment option to make an even greater impact across multiple indications of need."

"This trial represents a promising step forward in delivering therapies that could impact the standard of care for patients," said Alex Spira, Principal Investigator of Next Oncology Virginia. "A2A Pharmaceuticals is committed to supporting the cancer community by advancing novel therapies that target the underlying biology of tumors."

Key Highlights of the TACC3 Program:

The selected cancers are characterized by limited treatment options and high rates of recurrence in patients. A2A’s TACC3 inhibitor is designed to disrupt critical cellular mechanisms involved in cancer cell proliferation, providing a much-needed new avenue of treatment for patients battling these aggressive malignancies.

Beyond these indications, pre-clinical studies suggest A2A’s TACC3 PPI inhibitor may also show efficacy in other solid tumors, including gastric and prostate cancers, sarcomas and certain hematologic malignancies. Ongoing research efforts are focused on expanding the indication spectrum and optimizing treatment regimens for diverse cancer types.