On October 20, 2023 Therapeutic Solutions International, Inc. (TSOI), reported the successful first treatment of a patient with FloraStilbene, a patent pending formulation of the abortion pill’s active ingredient, RU486, and pterostilbene (Press release, Therapeutics Solutions International, OCT 20, 2023, View Source [SID1234636197]).

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The Company has been utilizing pterostilbene, a naturally occurring analog of resveratrol, found in blueberries, for the treatment of cancer and immune modulation for several years, including being granted a patent on synergies with conventional immunotherapies1. In May of this year, Res Nova signed a collaborative agreement with compounding pharmacy Cure Stat Rx for developing a compounded formulation of FloraStilbene2.

"I have worked with Dr. Ramesh Chigurupati, President, and CEO of Cure Stat Rx for many years and have always been impressed by the efficiency and excellence in ability to provide compounded drugs and formulations," said Dr. James Veltmeyer, Chief Medical Officer of Res Nova Bio. "We look forward to offering FloraStilbene to all patients taking immunotherapy, chemotherapy, or radiation therapy that can benefit from immune stimulation of NK cells, T cells, and dendritic cells."

FloraStilbene has previously been shown to enhance immunotherapy of various tumors3, as well as chemotherapy efficacy4.

"The strategic objective of Therapeutic Solutions International is to develop intellectual property, use it to seed a subsidiary company, and let the subsidiaries grow and flourish," stated Timothy Dixon, President, and CEO of Therapeutic Solutions International. "I am extremely proud of the leadership role of Ms. Ramos who in the period of less than a year was able to take FloraStilbene from concept to patient. This is literally unheard of in traditional biotechnology development models."

In addition to Res Nova, Therapeutic Solutions International has multiple subsidiaries including a) Campbell Neurosciences, focused on the identification of suicidal propensities using a proprietary test and various interventions5; b) Breath Biologics, which is in discussions with the FDA for its filed Phase I/II trial in COPD6; c) CTE Biologics, which is advancing its clinical stage technology for treating Chronic Traumatic Encephalopathy7; and d) VasoSome Vascular, which is in preclinical development of mesenchymal stem cell derived exosomes for treatment of aortic aneurysms8.

"I am thankful for our translational medicine team that has worked closely with Drs Veltmeyer and Chigurupati for making this first patient treatment a reality," said Famela Ramos, President, and CEO of Res Nova Bio. "Although we plan on performing clinical trials to formally establish a level of efficacy, we believe it is imperative to get this drug into the hands of physicians as soon as possible, and we are thankful for having the opportunity to do this today."

On October 20, 2023 AnHeart Therapeutics ("AnHeart"), a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer, reported positive interim results from its global pivotal Phase 2 clinical trial, TRUST-II. Interim data from the trial showed taletrectinib, AnHeart’s investigational next-generation ROS1 inhibitor, shrank tumors (confirmed objective response rate, cORR, as assessed by an independent review committee, IRC) in 92% of patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) who had not previously been treated with a ROS1 tyrosine kinase inhibitor (TKI naïve) (Press release, AnHeart Therapeutics, OCT 20, 2023, View Source [SID1234636196]). Taletrectinib shrank tumors in 57% of patients who had previously been treated with a ROS1 TKI (TKI pre-treated). Taletrectinib also showed robust intracranial activity in the subgroup of patients with disease that had spread to the brain.

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Median progression-free survival (IRC-assessed) was not reached for TKI naïve patients and was 11.7 months for TKI pre-treated patients, respectively. Taletrectinib was generally well tolerated, and its safety profile was consistent with previous trials. The most common treatment emergent adverse events (TEAEs) were increased liver enzymes and gastrointestinal-related adverse events, the majority of which were Grade 1 or Grade 2. Incidence of neurological TEAEs were low; the most common was dizziness (13%), most of which was Grade 1.

"While people with other types of lung cancer have seen great advances, there has been limited progress for people with ROS1-positive NSCLC, which presents significant treatment challenges," said Maurice Pérol, M.D., TRUST-II trial investigator and Head of Thoracic Oncology at Léon Bérard Cancer Center, Lyon, France. "These interim TRUST-II data represent a significant step forward in the pursuit of better treatment options. Taletrectinib’s overall profile suggests it has the potential to be the medicine people with ROS1-positive NSCLC have been waiting for."

"We now have consistent results from two Phase 2 trials with taletrectinib. In both trials, taletrectinib shrank tumors in almost every ROS1 TKI naïve person and more than half of people previously treated with a ROS1 TKI, and the responses were durable. Taletrectinib was well tolerated, which is extremely important as we work to extend the time people with advanced ROS1-positive NSCLC live without their disease getting worse," said Jerry Wang, PhD, Chief Executive Officer of AnHeart. "We anticipate reporting final data from TRUST-II next year, and look forward to making continued progress in our efforts to positively impact the lives of people living with lung cancer."

Results will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 by Maurice Pérol, M.D., TRUST-II trial investigator and Head of Thoracic Oncology at Léon Bérard Cancer Center, Lyon, France on October 23, 2023 (abstract #1373P).

Taletrectinib has been granted Breakthrough Therapy Designations for the treatment of advanced or metastatic ROS1-positive NSCLC by both the U.S. Food and Drug Administration and the China National Medical Products Administration (NMPA).

About the TRUST-II Trial

TRUST-II (NCT04919811) is a global pivotal, multicenter, single-arm, open-label, Phase 2 clinical trial evaluating taletrectinib as a monotherapy in approximately 154 patients with ROS1-positive NSCLC and other solid tumors. Patients received 600 mg of taletrectinib once-a-day. Cohorts 1 and 2 of the trial are intended to be registrational and are evaluating taletrectinib in ROS1-positive NSCLC patients who have either not previously been treated with a ROS1 TKI (TKI naïve, n=53), or who have previously been treated with one approved ROS1 TKI (crizotinib or entrectinib, n=46), respectively. Cohorts 3 and 4 are exploratory and are evaluating taletrectinib in ROS1-positive NSCLC patients who have previously been treated with two or more ROS1 TKIs (n=35), or patients with ROS1-positive NSCLC or other ROS1-positive solid tumors who are ineligible for Cohorts 1 to 3 (n=20), respectively. Patients are being enrolled at sites in the United States, Canada, Europe and Asia.

Interim efficacy data for Cohorts 1 and 2 were reported from 46 patients who had approximately six months of follow-up at the data cut-off date of July 12, 2023.

In ROS1 TKI naïve patients (n=25), 16% of whom had also previously received chemotherapy:
92.0% of patients’ tumors shrank in response to taletrectinib treatment (cORR as assessed by IRC)
Median duration of response and median progression-free survival were not reached
At 12 months, 89.5% of patients who responded to taletrectinib treatment were still responding
Taletrectinib shrank brain tumors in 80.0% of people whose cancer had spread to the brain (n=5; intracranial cORR as assessed by IRC)
In patients previously treated with one ROS1 TKI (n=21), 52% of whom had also previously received chemotherapy:
57.1% of patients’ tumors shrank in response to taletrectinib treatment (cORR as assessed by IRC)
Median duration of response was not reached
At 12 months, 81.5% of patients who responded to taletrectinib were still responding
Median progression-free survival was 11.7 months
Taletrectinib shrank brain tumors in 62.5% of people whose cancer had spread to the brain (n=8; intracranial cORR as assessed by IRC)
Interim safety data from TRUST-II (n=107) showed the majority of TEAEs were Grade 1 or Grade 2. The most common TEAEs were increased liver enzymes (increased alanine aminotransferase: 64%; increased aspartate aminotransferase: 63%), diarrhea (43%), and nausea (43%), the majority of which were Grade 1 or Grade 2. Incidence of neurological TEAEs were low; the most common was dizziness (13%), most of which was Grade 1. Dose reductions and treatment discontinuations due to TEAEs were 34% and 2%, respectively. There were no treatment-related deaths.

More detailed results from today’s presentation can be found on AnHeart’s website at View Source

For additional information about TRUST-II visit View Source

About Taletrectinib

Taletrectinib is an oral, potent, brain penetrant, selective, next-generation potential best-in-class ROS1 inhibitor being evaluated for the treatment of ROS1-positive NSCLC.

AnHeart previously reported data from the Phase 2 TRUST-I trial (NCT04395677) evaluating taletrectinib in ROS1-positive NSCLC patients in China, which showed a cORR of 92.5% in ROS1 TKI naïve patients (n=67) and 52.6% in crizotinib pre-treated patients (n=38), respectively, as assessed by IRC. The majority of TEAEs were Grade 1 or Grade 2. A pooled analysis of TRUST-I and Phase 1 trials with taletrectinib showed median progression-free survival of 33.2 months and 11.8 months in ROS1 TKI naïve and crizotinib pre-treated patients, respectively.

About ROS1-positive NSCLC

More than one million people are anticipated to be diagnosed with NSCLC, the most common form of lung cancer, in the United States, Europe, China and Japan in 2023. It is estimated that approximately 1-2% of people with NSCLC in western countries and approximately 3% in China are ROS1-positive, meaning more than 22,000 people will be diagnosed with ROS1-positive NSCLC in these regions in 2023. There are two FDA approved first-generation TKIs for people with newly diagnosed advanced or metastatic ROS1-positive NSCLC and no FDA approved therapies for people whose ROS1-positive NSCLC has progressed following treatment with these medicines. Up to 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain (brain metastases), increasing up to 55% for those whose cancer has progressed following initial treatment.

On October 20, 2023 Riboscience, LLC, reported the first presentation of data from the ongoing Phase 1 clinical trial of the ENPP1 inhibitor RBS2418 that will be delivered by Dr. Thomas U. Marron, MD, PhD, from Mount Sinai, New York at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 on October 21, 2023 (Press release, Riboscience, OCT 20, 2023, View Source [SID1234636194]). RBS2418 is the first ENPP1 inhibitor in clinical development.

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Clinical study RBS2418-1001 (NCT05270213) is a Phase 1, open-label, non-randomized study in adult patients with advanced, unresectable, recurrent or metastatic solid tumors, who have progressed on, or are ineligible for standard therapies. The dose escalation phase of the study follows a 3+3 design with increasing doses of RBS2418 given orally as monotherapy or in combination with Pembrolizumab.

Riboscience presents data from an ongoing Phase 1 trial of a new immunotherapy in patients with advanced cancers

The ESMO (Free ESMO Whitepaper) presentation #1025MO summarizes the safety, PK and PD results and clinical outcomes of treatment with RBS2418 from the first 19 patients in the dose escalation phase of the study. There are 11 different cancer types represented and 84% of patients had failed 3 or more lines of prior treatment. The concentration of RBS2418 in plasma and in tumor samples exceeded the human serum EC90 of ENPP1 inhibition in all patients at all dose levels (100, 200, 400 mg) and at all time points tested. Median plasma Cmax and Ctrough levels of RBS2418 increased dose proportionally. No DLTs, no treatment-related SAEs or treatment-related AEs above grade 2 were observed for treatment durations up to 1 year. Immune activation and tumor infiltration of CD4 and CD8 cells was observed in patients who expressed ENPP1 and cGAS protein in baseline tumor samples, EG(+) phenotype. The EG(+) phenotype was present in 53% of the patients at baseline.

This phenotype predicted outcome with RBS2418 treatment, as 60% of treated EG(+) patients experienced stable disease as compared to 0% of patients who did not express ENPP1 or cGAS in the baseline tumor sample, EG(-) phenotype. Progression-free survival (PFS) was significantly increased in EG(+) vs EG(-) phenotypes (p=0.0013). Clinical benefit from RBS2418 was dependent on the presence of the drug target (ENPP1), indicating target-inhibition dependent clinical benefit with RBS2418 treatment, consistent with the PK/PD results that demonstrated full ENPP1 inhibition and cGAMP stabilization at all dose levels.

These results show a target-inhibition-dependent immune activation and significant clinical benefit of a well-tolerated oral RBS2418 treatment and support further clinical development of this novel first-in-class immunotherapy agent. The clinical study is proceeding into a dose-expansion phase.

On October 20, 2023 GC Genome Corporation, a leading diagnostics company, reported that it will present data showcasing deep learning algorithm utilizing methylation markers that can identify lung cancer at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 Congress, taking place from October 20-24 in Madrid, Spain (Press release, GC Genome, OCT 20, 2023, View Source [SID1234636193]). The new data showcases GC Genome’s ongoing dedication to assisting individuals battling cancer.

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The poster highlights a combination of methylation markers and deep learning model that can distinguish between lung cancer patients and healthy individuals using methylation and size information. Using a targeted EM-seq panel, the lung cancer detection performance achieved an accuracy of 81.5% and an AUC of 0.87. Moreover, the serial dilution experiments have demonstrated the capability to detect lung cancer with a sensitivity of 80% down to a tumor fraction of 0.1%, offering a highly sensitive and accurate diagnostic tool for lung cancer.

"We are thrilled to introduce our latest findings on the methylation-based deep learning platform which has the potential use in lung cancer diagnostics," said Eun-Hae Cho, Chief Technology Officer at GC Genome Research Center. "The poster we’ll be unveiling at this year’s ESMO (Free ESMO Whitepaper) Congress demonstrates a significant advancement in our research and offers an opportunity for enhanced accuracy through the integration of methylation data and genomics, ultimately leading to the improvement of treatment for lung cancer patients."

Align with this dedication, GC Genome commercially launched ‘ai-CANCERCH,’ a liquid biopsy test designed for the multi-cancer early detection (MCED) this September. This achievement comes after validating its performance through an assessment involving over 3,000 patients who participated in the Early Access Programme (EAP) during 2022 and 2023. ai-CANCERCH has the capability to predict the presence and specific type of six cancers – lung, liver, colorectal, pancreatic, esophageal, and ovarian cancers – using only a single blood draw. This groundbreaking test relies on a proprietary artificial intelligence algorithm developed by GC Genome. GC Genome’s innovative approach brings hope for improved healthcare outcomes and underscores their commitment to advancing the field of cancer detection and treatment for patients worldwide.

Poster Presentation:

Title: Development of a Deep Learning Algorithm for Lung Cancer Diagnosis Using Methylation and Fragment Size Profiles of cfDNA
Date and Time: Sunday, 22 October 2023, 9:00 AM – 5:00 PM CET
Location: Hall 8 Poster Session 14
Presentation Number: 1251P

On October 20, 2023 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies addressing emerging targets in oncology, reported that it entered into a Clinical Trial Financial Support agreement for an investigator initiated clinical trial (IIT) with the European EMSCO network (Press release, Ryvu Therapeutics, OCT 20, 2023, View Source [SID1234636192]).

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EMSCO was founded in 2012 by Prof. Uwe Platzbecker from the University Hospital Leipzig and head of the German MDS study group, and Prof. Pierre Fenaux from Hôpital Saint Louis in Paris and head of the French MDS study network GFM. Since then, the EMSCO network has been extended to other European countries and has carried out 9 common trials in MDS, of which 3 are ongoing.

The so-called REMARK study is a Phase II RVU120 study in Low-Risk Myelodysplastic Syndromes (LR-MDS) and it will be conducted through the EMSCO network, in cooperation with GCP-Service International West.

The REMARK study aims at the development of RVU120 as a monotherapy for the treatment of patients with LR-MDS.
Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, will take on the role of Coordinating Principal Investigator (CPI).
The study is an essential element of implementing Ryvu’s Development Plans for 2022-2024.
Ryvu will host a virtual webinar on further RVU120 development plans on Monday, October 23 at 9.00 am CEST.
Prof. Uwe Platzbecker, Coordinating Principal Investigator of the REMARK study, said:

– I am very pleased to conduct this study investigating RVU120 in patients with LR-MDS. This approach is supported by a strong preclinical rationale, and the currently available clinical data from the AML and HR-MDS study demonstrating hematologic improvement in many patients. I am confident that RVU120 offers potential to treat this chronic disease, and once its effectiveness is clinically validated, we will have the opportunity to greatly improve the quality of life and survival of patients in need.

– We plan to initiate the study in the first half of 2024. With our extensive expertise and the support of our broader scientific and clinical network, we are well-prepared to efficiently conduct this project.

Hendrik Nogai, MD, Chief Medical Officer at Ryvu Therapeutics, said:

– We are delighted that Professor Uwe Platzbecker is aiming to validate the effectiveness of RVU120 in the treatment of LR-MDS. We strongly believe in the concept of this study and in the potential of RVU120 to address the existing unmet medical need. Considering Professor Platzbecker’s experience as a leading expert in the field and his successful track record in designing and executing clinical programs leading to the approval of new drugs for the treatment of myelodysplastic syndromes, we expect smooth progress and generation of high-quality clinical data, which will bring us another step closer in helping patients.

– The study will be conducted as an investigator-initiated trial designed to provide clinical validation of RVU120’s efficacy in treating LR-MDS, while maintaining a high level of cost-effectiveness. The study results will inform decisions about the future development of RVU120 for this indication.

As an IIT, REMARK will be a study with scientific and medical merit, developed and coordinated by the Investigator. The Clinical Trial Financial Support agreement for the REMARK study is a tripartite arrangement involving Professor Uwe Platzbecker as the Coordinating Principal Investigator, GCP-Service International West (a German Contract Research Organization sponsoring and conducting the study on behalf of the EMSCO network), and Ryvu as the financier. Ryvu will also be responsible for providing the study drug. The estimated Ryvu’s financial contribution to the study is approx. EUR 4 million.

The REMARK study is planned to take place at approximately 25 clinical sites in the EU, with the primary goal of enrolling about 40 patients to generate exploratory clinical data. Start-up activities for the study are scheduled to commence later this year, and patient enrollment is planned to start in the first half of 2024.