On June 24, 2024 Sustained therapeutics reported that the first patient has entered the Phase II/III trial of ST-02, innovative cancer medication targeting Upper Tract Urethral Carcinoma (UTUC) (Press release, Sustained Therapeutics, JUN 24, 2024, View Source [SID1234644520]).

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A rare form of cancer, UTUC affects over 7,000 individuals annually across North America. UTUC is a cancer of the inside lining of the kidney (the "collecting system" – where urine starts to drain after it is made by the kidney) and the ureter (the tube that carries urine from the kidney to the bladder). Its location in the upper collecting system makes it challenging to access and completely remove with traditional laser resection.

"This is a new opportunity in the treatment of UTUC," says Dr. Peter Black, lead investigator of the clinical trial and a Senior Research Scientist with the Vancouver Prostate Centre. "Currently we have limited treatment options for this uncommon and challenging cancer, and this approach may allow better disease control without having to remove a kidney."

The first patient in the clinical trial has been enrolled at the Vancouver Prostate Centre, and it is anticipated that 5 other sites will take part in the study. The company plans on enrolling approximately 75 patients in the combined Phase II/III trial and believes that ST-02 may be designated an orphan drug. Orphan drug designation can qualify the company for incentives such as tax credits, exemption from user fees, and seven years of market exclusivity after approval.

Sustained Therapeutics’ ST-02 product for UTUC is a sustained release formulation that enables direct delivery of chemotherapy to the site of the carcinoma via a catheter. Using the company’s proprietary platform technology, the medication releases slowly over about 24 hours exactly where the cancer is located, coating the tissue and delivering chemotherapy at higher concentrations and for longer than the current standard of care. The company believes that this direct sustained delivery may be more effective and result in fewer side effects than other forms of chemotherapy that are a current standard of care.

"ST-02 is Sustained Therapeutic’s second product to reach Phase II trials, and demonstrates our potential to develop multiple products using our novel drug delivery platforms. As such, it is a very important development in our portfolio," says Dr. Martin Gleave, Founder and Chief Medical Office of Sustained Therapeutics and Distinguished Professor in the UBC Department of Urologic Sciences and Director of the Vancouver Prostate Centre (VPC). "This new therapeutic, designed specifically for UTUC, could address an important unmet need for patients. It’s an exciting time to be a part of this work."

On June 24, 2024 SOPHiA GENETICS (Nasdaq: SOPH), a cloud-native healthcare technology company and a global leader in data-driven medicine, reported its new Residual Acute Myeloid (RAM) Application (Press release, Sophia Genetics, JUN 24, 2024, View Source [SID1234644519]). The new offering expands the company’s comprehensive oncology portfolio to support measurable residual disease (MRD) capabilities and will be available to customers worldwide this summer.

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Acute Myeloid Leukemia (AML) represents about one percent of all cancers worldwide, yet is one of the most common forms of leukemia in adults1. Over 50 percent of AML patients relapse within 3 years after achieving complete remission2, therefore post-treatment monitoring is imperative for AML patients, particularly within the first two years, to help quickly detect any signs of relapse3. MRD solutions can help inform post-remission therapy and identify early relapse, and serve as a primary endpoint in clinical trials, helping researchers detect even the smallest trace of cancer and support better patient outcomes.

"AML unfortunately still remains an area of high unmet medical need today, with associated suboptimal patient outcomes. MRD measurement and monitoring has a critical role to play, for example by enabling research into the most optimal sequencing of therapies," said Philippe Menu, M.D., PhD., Chief Medical Officer and Chief Product Officer, SOPHiA GENETICS. "We are proud to contribute to the fight against AML through our SOPHiA DDM RAM Solution. In particular we feel that the capability to seamlessly track longitudinally the evolution of individual mutations over time through a dedicated add-on module of our SOPHiA DDM Platform has the potential to be a game-changer for clinical researchers."

Next-generation sequencing (NGS)-based MRD testing is among the most advanced in cancer screening and monitoring, and can be found only with highly sensitive methods. The SOPHiA DDM RAM Solution provides users with the confidence that MRD will detect even one cancer cell among 10,000 cells. This application will allow users to stay ahead of disease response with the analytical capabilities of the SOPHiA DDM Platform, enabling sensitive variant detection down to 0.01% VAF and covering guideline-recommended genes to deliver robust insights for residual acute myeloid.

Customers using the SOPHiA DDM RAM Solution will have access to longitudinal variant monitoring, allowing them to visualize the mutational landscape for each patient and its evolution over time. The solution also provides users with the most up-to-date databases and customizable reporting features to generate graphical representations and comprehensive MRD reports.

Additionally, the SOPHiA DDM RAM Solution will continually hone its machine learning algorithms to provide the most accurate MRD results in just four days.

Representatives from SOPHiA GENETICS are available at AMP (Association for Molecular Pathology) Europe June 24-27 to discuss AML monitoring with this new application.

For more information on SOPHiA GENETICS, visit SOPHiAGENETICS.com and connect on LinkedIn.

On June 24, 2024 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported clinical program updates for IDE397, a potential first-in-class Phase 2 MAT2A inhibitor targeting MTAP-deletion solid tumors (Press release, Ideaya Biosciences, JUN 24, 2024, View Source [SID1234644518]).

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"We are excited about activating over 35 clinical trial sites globally and the broad advancement of the IDE397 Phase 2 program, including multiple potential first-in-class clinical combinations and Phase 2 monotherapy expansion in priority MTAP-deletion solid tumor types of lung and bladder cancer. We are delighted to provide updated corporate guidance for the IDE397 clinical program, including a clinical date update for the IDE397 Phase 2 monotherapy expansion dose in the second half of 2024," said Yujiro S. Hata, Chief Executive Officer, IDEAYA Biosciences.

The Company is now targeting an IDE397 clinical data update for the IDE397 Phase 2 monotherapy expansion dose in MTAP-deletion bladder and lung cancer in over approximately 15 evaluable patients in the second half of 2024. The clinical data update is anticipated to include a clinical efficacy summary, including a RECIST 1.1 clinical efficacy waterfall, swim-lane plot, and ctDNA molecular response analysis. In addition, at this update the Company also anticipates providing an adverse event, pharmacokinetics and pharmacodynamics summary at the IDE397 Phase 2 monotherapy expansion dose. Next, the Company is initiating an IDE397 Phase 2 monotherapy expansion in MTAP-deletion bladder cancer, in addition to the earlier reported Phase 2 expansion in MTAP-deletion squamous lung cancer. The Company has activated over 35 clinical trial sites globally in the U.S., Canada, Europe, and Asia Pacific to enable potential rapid enrollment for the IDE397 Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer, and for the IDEAYA sponsored clinical combination(s).

IDE397 is a potential first-in-class potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion.

There is an ongoing Phase 2 expansion of IDE397 monotherapy in MTAP-deletion solid tumors (NCT04794699), and an Amgen-sponsored Phase 1/2 trial of IDE397 and AMG 193 combination in MTAP-Deletion NSCLC (NCT05975073) for which the companies intend to develop a joint publication strategy in 2024. Next, there is a Phase 1 clinical trial that will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with Trodelvy (NCT04794699). IDEAYA is also advancing multiple preclinical stage MTAP-deletion programs to enable wholly-owned combinations with IDE397, including a program targeting a Development Candidate nomination in the second half of 2024.

On June 24, 2024 Biond Biologics Ltd. ("Biond" or the "Company"), a private clinical-stage biopharmaceutical company developing novel immunotherapies for cancer and a platform for the intracellular delivery of biologics, reported that the first patient has been dosed in a first-in-human clinical trial testing BND-35, a humanized ILT3/LILRB4 antagonist antibody (Press release, Biond Biologics, JUN 24, 2024, View Source [SID1234644517]).

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The first patient was administered BND-35 as a monotherapy at the Institute of Oncology, Davidoff Center, Rabin Medical Center, Israel, one of the six Israel and US trial study sites. The phase 1, open-label, dose escalation study aims to explore the safety, tolerability, anti-tumor activity, pharmacokinetics and exploratory biomarkers for BND-35 as a monotherapy and in combination with two approved drugs, a PD-1/PD-L1 inhibitor or the anti-EGFR drug, cetuximab. The decision to test the combination of BND-35 with cetuximab was driven by supportive pre-clinical data and a deep understanding of the BND-35 mechanism of action. BND-35 augments antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity, which are mediated by binding of Fc receptors (FcR) on immune cells to antibodies as cetuximab and additional tumor targeting antibodies. Each arm of the trial includes the patient populations most likely to benefit from ILT3/LILRB4 blockade based on translational research findings.

"The BND-35 trial design introduces a novel combination therapy that targets the immunosuppressive cell milieu within the tumor microenvironment (TME)," commented Professor Salomon Stemmer, M.D., Head of Research, Development and Innovation and Deputy Director of Davidoff Center at the Rabin Medical Center, and a clinical investigator in the trial. "There’s a pressing need for innovative treatments for cancers that are resistant to existing therapies. Given its promising preclinical efficacy, we’re eager to assess BND-35’s potential in overcoming ILT3/LILRB4-mediated immunosuppression."

"ILT3 is a unique receptor expressed on various suppressive myeloid cells within the TME and the binding of various ligands to ILT3 maintains the TME in an immunosuppressive state. BND-35 has been demonstrated to effectively block the interaction between ILT3 and its various ligands, thereby enhancing the immune system’s ability to fight tumors, resulting in increased physiological anti-tumor responses and enhanced tumor cell destruction by immune cells," stated Tsuri Peretz, project manager for the BND-35 program.

About ILT3/LILRB4/LILRB4

BND-35 is a novel anti-ILT3/LILRB4 antagonist antibody developed for the treatment of solid tumors. BND-35 binds ILT3/LILRB4 with high affinity and blocks its interaction with ligands present in the TME In vitro and ex vivo studies have demonstrated that BND-35 as monotherapy or in combination with anti-PD-1/PD-L1 pathway inhibitors as well as with anti-EGFR agents, enhances the pro-inflammatory activity of various myeloid cells and inhibits the immunosuppressive activity of suppressive myeloid cells, thereby restoring T cell and NK cell activity.

BND-35-induced immune activity enhancement was demonstrated in a unique system of patient-derived tumoroids. In vivo, blocking ILT3/LILRB4 activity with BND-35, as monotherapy or in combination therapy, resulted in decreased tumor growth and induced a pro-inflammatory phenotype in tumor-resident T cells and myeloid cell populations. Further information about the trial is available in View Source;rank=1 (Trial Identifier: NCT06274437).

On June 24, 2024 Daiichi Sankyo reported that (TSE: 4568) EZHARMIA (valemetostat tosilate) has been approved in Japan for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) (Press release, Daiichi Sankyo, JUN 24, 2024, View Source [SID1234644516]). EZHARMIA is now the first dual inhibitor of EZH1 and EZH2 to be approved for PTCL after receiving SAKIGAKE designation for this indication.

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PTCL is a group of rare and often aggressive blood cancers, which represent about 10 to 15% of all nonHodgkin lymphomas (NHL).1 PTCL is more common in Asia, including in Japan, compared to other parts of the world. 2 A majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen and median overall survival following relapse is approximately 5.8 months.

The approval of EZHARMIA by the Japan Ministry of Health, Labour and Welfare (MHLW) is based on results of the VALENTINE-PTCL01 phase 2 trial, which were presented at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. In VALENTINE-PTCL01, an objective response rate (ORR) of 43.7% (n=52, 95% CI: 34.6-53.1) was observed for EZHARMIA in 119 efficacy evaluable patients with relapsed or refractory PTCL as assessed by CT-based blinded independent central review (BICR). Seventeen complete responses (CRs) and 35 partial responses (PRs) were observed. Responses were seen across a variety of PTCL subtypes including angioimmunoblastic T-cell lymphoma (AITL), PTCL not otherwise specified (PTCL-NOS) and other PTCL subtypes.

"This second indication for EZHARMIA in Japan is an important advance for the treatment of relapsed or refractory peripheral T-cell lymphoma, as new and effective treatment options are needed to improve patient outcomes," said Toshinori Agatsuma, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo.

"EZHARMIA exemplifies the innovative research being conducted by Daiichi Sankyo aimed at creating new medicines with potential to change the standard of care for patients with cancer." 2 The safety profile of EZHARMIA in VALENTINE-PTCL01 was consistent with previous clinical trials. Treatment-related adverse events occurred in 106 of 133 patients (79.7%) with the most common including platelet count decrease (44.4%), anemia (27.1%), dysgeusia (24.8%) and neutrophil count decrease (21.1%).

About VALENTINE-PTCL01 Trial

VALENTINE-PTCL01 is a global, open-label, single-arm, two-cohort phase 2 study evaluating the efficacy and safety of EZHARMIA in patients with relapsed or refractory PTCL and adult T-cell leukemia/lymphoma (ATLL) who received at least one systemic therapy and were ineligible for hematopoietic stem cell transplant at the time of screening. One cohort enrolled patients with PTCL and a second cohort enrolled patients with ATLL.

The primary endpoint of VALENTINE-PTCL01 is ORR assessed by CT-based BICR. Secondary endpoints include duration of response, CR, PR, duration of CR and progression-free survival – all assessed by both BICR and investigator assessment – as well as ORR assessed by investigator, overall survival, safety and pharmacokinetics. Exploratory endpoints include PET-CT-based BICR and biomarker mutational status. Responses were evaluated based on Lugano 2014 response criteria. VALENTINE-PTCL01 enrolled 133 patients at multiple sites in Asia, Europe, North America and Oceania. For more information about this study, visit ClinicalTrials.gov.

About Peripheral T-Cell Lymphoma

PTCL is a group of rare and often aggressive blood cancers, which represent 10 to 15% of all NHLs.1 Approximately 553,000 new cases of NHL were diagnosed worldwide in 2022.3 There are at least 29 recognized subtypes of PTCL, which occur with significant geographic variation.4 PTCL is more common in Asia, including in Japan, compared to other parts of the world.

Prognosis of PTCL is generally poor, with a five-year overall survival rate of 32% in AITL and PTCLNOS, and 7% or lower in certain subtypes. A majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen and median overall survival following relapse is approximately 5.8 months.1 Development of more effective medicines for PTCL continues to be an unmet clinical need, particularly in the relapsed or refractory setting.
About EZH1 and EZH2

The EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes help regulate the expression of genes involved in maintaining healthy hematopoietic stem cells (immature blood cells).6 Both enzymes are recurrently mutated or overexpressed in hematologic malignancies, including T-cell lymphomas, and research shows they contribute to the silencing of tumor suppressor genes and drive oncogenic growth.

About EZHARMIA

EZHARMIA (valemetostat tosilate) is first-in-class dual inhibitor of EZH1 and EZH2 that was discovered by Daiichi Sankyo. EZHARMIA is approved in Japan for the treatment of patients with relapsed or refractory PTCL and for the treatment of patients with relapsed or refractory ATLL. It is an investigational medicine in all countries outside of Japan.

About EZHARMIA Clinical Development Program

A global clinical development program is underway for EZHARMIA in hematologic and solid cancers. In addition to VALENTINE-PTCL01, EZHARMIA is being evaluated in the VALYM phase 2 trial in patients with relapsed or refractory B-cell lymphomas, which is being conducted under a strategic research collaboration with the LYSA-LYSARC-CALYM group in Europe, and a phase 1b study in combination with DXd antibody drug conjugates ENHERTU (trastuzumab deruxtecan) and datopotamab deruxtecan (Dato-DXd) in patients with solid cancers.