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.

On October 20, 2023 Exact Sciences Corp. (NASDAQ: EXAS), a leading provider of cancer screening and diagnostic tests, reported that it will present new data supporting the company’s research in early cancer detection, genomic testing, and treatment guidance at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, October 20-24, in Madrid, Spain (Press release, Exact Sciences, OCT 20, 2023, View Source [SID1234636191]).

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Exact Sciences will feature studies from across its multi-cancer early detection (MCED) and precision oncology portfolios, highlighting:

Two trials evaluating the company’s blood-based, MCED program1,2

OncoExTra data showing the frequency of the detection of actionable fusions, signals of some cancers, in nearly 8,000 people with solid tumors, helping inform treatment decisions by using next-generation sequencing (NGS) to assess a tumor’s RNA and DNA3
"At Exact Sciences, we are driving paradigm shifts in the early detection and treatment of cancer," said Jorge Garces, Ph.D., chief science officer, Exact Sciences. "With continued advances in understanding tumor biology and the precise identification of actionable biomarkers, our screening and diagnostic tools are improving the lives of people living with or at risk for cancer today – and are poised to transform the cancer landscape in the future."

Cancerguard

Exact Sciences is taking a robust and rigorous approach to developing an MCED test, and today unveiled its brand name, Cancerguard. Building upon decades of research, Exact Sciences is designing the Cancerguard test to harness the additive sensitivity of multiple biomarker classes to detect more early-stage cancers. The Cancerguard test will utilize a streamlined and standardized imaging-based diagnostic pathway, resulting in fewer follow-up procedures. The test is being developed to provide high specificity to help minimize false positives, while detecting multiple cancers, including those with the biggest impact on human health. To learn more, visit View Source

The company will host a symposium at the congress titled "Shifting the Paradigm of Cancer Detection: Multi Cancer Early Detection," featuring experts from leading oncology research institutions and Exact Sciences. The session will highlight research ushering in the era of MCED tests, including results from multiple studies that support a vision for the future where MCED testing, added to current recommended cancer screenings, may help identify more cancers in earlier stages and have an impact on public health.

Key Data Presentations at ESMO (Free ESMO Whitepaper) 20231-6

LBA24: Multiparametric prognostic score in early HR+/HER2- breast cancer:
Impact of Recurrence Score (RS), clinical-pathological factors, gene mutations and histology

Data embargoed until 00:05 CEST / 6:05 AM EDT on Thursday, 19 October 2023
Authors: Gluz, O. et al.
Date/Time: October 23, 2023, 11:05 AM CEST
Location: Bilbao Auditorium (Mini-Oral session, Breast Cancer Early Stage)

Key Takeaway: Exploratory analysis of data from Phase III ADAPT trial to determine if expanding use of clinical-pathological factors, including adaptive factors (e.g., Ki67 response), provides additional clinically useful prognostic information when added to the Recurrence Score in multivariable models.4

Abstract #183P: Frequency of actionable fusions in 7,735 patients with solid tumors

Data embargoed until 00:05 CEST / 6:05 PM EDT on Monday, October 16
Authors: McDonnell, K. et al.
Date/Time: October 21, 2023, 7:30 AM CEST
Location: Hall 8

Key Takeaway: Comprehensive genomic profiling approaches that include RNA sequencing can improve fusion detection compared to exome or targeted DNA sequencing alone. This study demonstrates the potential of the OncoExtra test to identify fusions that are relevant for determining therapy, disease prognosis or clinical trial eligibility.3

Abstract #317P: Awareness of genomic testing among patients with breast cancer in Europe

Data embargoed until 00:05 CEST / 6:05 PM EDT on Monday, October 16
Authors: Cardone, A. et al.
Date/Time: October 21, 2023, 7:30 AM CEST
Location: Hall 8

Key Takeaway: This study demonstrates that awareness of and access to genomic testing for breast cancer in Europe is sub-optimal. Genomic testing, involving expression profiling of tumor tissue removed from patients with breast cancer, is a powerful tool to help choose the most appropriate treatment for individual patients. Researchers surveyed women with HR+/ HER2 – breast cancer, eligible for genomic testing at the time of diagnosis, in five Western Europe countries about their awareness of genomic testing for treatment decision making.5

Abstract #189P: Design and enrollment for a classifier development study for a blood-based multi-cancer early detection (MCED) test

Data embargoed until 09:00 CEST / 3:00 PM EDT on Saturday, October 21
Authors: Douville, C. et al.
Date/Time: October 21, 2023, 09:00 AM CEST
Location: Hall 8

Key Takeaway: The Ascertaining Serial Cancer patients to Enable New Diagnostic 2 (ASCEND 2) study selected cancer types in an incidence-targeted manner, including rare and common cancers and evenly distributed stages. The ASCEND-2 study represents a racially, ethnically, and geographically diverse cohort for MCED test development.1

Abstract #202P: Participant perceptions and mammography adherence from DETECT-A, the first prospective interventional trial of a multi-cancer early detection (MCED) blood test

Data embargoed until 00:05 CEST / 6:05 PM EDT on Monday, October 16
Authors: Papadopoulos, N. et al.
Date/Time: October 21, 2023, from 09:00-17:00 CEST
Location: Hall 8

Key Takeaway: These data suggest that MCED testing did not significantly increase anxiety and depression or negatively impact mammography adherence for respondents with available data.2

Symposium at ESMO (Free ESMO Whitepaper) 2023:

Title: Shifting the Paradigm in Cancer Detection

Co-chairs:
Elizabeth O’Donnell, MD, Dana-Farber Institute & Harvard Medical School
Tomasz Beer, MD, FACP, Co-chair Chief Medical Officer and VP, Multi-cancer Early Detection, Exact Sciences
Faculty:
Nickolas Papadopoulos, PhD, Ludwig Center & The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Catherine Marinac, PhD, Dana Farber Institute & Harvard Medical School
Frank Diehl, PhD SVP Research and Development, Exact Sciences
Date/Time: Monday, October 23, 13:00 CEST
Location: Burgos Auditorium Hall 3, IFEMA MADRID, Madrid, Spain

Summary: Multi-cancer early detection (MCED) testing may help shift the paradigm in cancer screening, enabling detection of more cancers in earlier stages when they are more treatable. Results from multiple studies have demonstrated the potential value of MCED testing, and recent studies combining multiple biomarker classes in MCED test design have demonstrated the ability to enhance test performance for early-stage cancer detection. These results support a vision for the future where MCED testing is a part of routine primary care screening.6

This symposium is intended for healthcare providers and may discuss agents and products in development that have not been cleared or approved in your country or by any other national regulatory authority. The European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) does not endorse any company, or their products/services.

On October 20, 2023 SystImmune, Inc. (SystImmune), a clinical-stage biotechnology company, reported the presentation of pivotal data from its oncology portfolio at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (Press release, SystImmune, OCT 20, 2023, View Source [SID1234636190]). The event is scheduled to take place from October 20th to 24th in Madrid, Spain, where new clinical findings will be unveiled from trials involving BL-B01D1 and BL-M07D1.

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The expanded results from these clinical trials of BL-B01D1 will include data from patients with several solid tumor types in advanced stages and having multiple cycles of prior therapies. The data presented at ESMO (Free ESMO Whitepaper) builds on previously reported clinical data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), and recent recognition for BL-B01D1 conferred by industry experts at the 14th Annual World ADC meeting in San Diego who recognized SystImmune’s BL-B01D1 as a "Runner-Up" in the award category of "Most Promising Clinical Candidate".

"Encouraging signals of efficacy from the Ed-04 payload supported our decision to expand our pharmacopeia of targeting ADCs that deliver this novel and highly potent topoisomerase 1 inhibitor to a wider patient population with diverse diseases, while we expand our understanding of the exceptional properties of this linker-warhead combination," said Martin Olivo, M.D., CMO of SystImmune.

Presentations at the ESMO (Free ESMO Whitepaper) congress include:

Molecule Name

Title 

Abstract Number/
Presentation Details  

BL-B01D1

BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate,
in patients with non-small cell lung cancer: Updated results from first-
in-human phase I study

Abstract #1316MO

Oral Presentation: Saturday,
October 21st, 9:40 a.m. –
9:45 a.m. CEST

BL-M07D1

BL-M07D1, a HER2 antibody-drug conjugate in subjects with locally
advanced or metastatic HER2 expressing breast cancer and other solid
tumors.

Abstract #2017

Poster Available:
Monday, October 23rd

About BL-B01D1

The company is developing BL-B01D1, a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3. These proteins are highly expressed in most epithelial tumors. The tetravalent BL-B01D1 has two binding domains for distinct Growth Factor Receptors that drive cancer cell proliferation and survival. Inheriting the SI-B001 mechanisms of action, BL-B01D1 blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. Upon antibody mediated internalization, BL-B01D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death.

About BL-M07D1

The company is developing BL-M07D1, a HER2 specific IgG-based ADC carrying DAR8 of the Ed-04 payload technology. The Ed-04 payload technology is composed of a potent topoisomerase 1 inhibitor and a serum-stable linker that is cleavable by cathepsin-B. By targeting proliferating cancer cells that express HER2, the BL-M07D1 has the potential to treat multiple epithelial cancer types, including breast and colorectal cancer types.

On October 20, 2023 Astrazeneca reported Positive results from a planned interim analysis of the MATTERHORN Phase III trial showed treatment with Imfinzi (durvalumab) in combination with standard-of-care FLOT neoadjuvant chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel given before surgery) demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of pathologic complete response (pCR) versus neoadjuvant chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers (Press release, AstraZeneca, OCT 20, 2023, View Source [SID1234636186]).

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These results will be presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain (abstract #LBA73).

Treatment with Imfinzi plus neoadjuvant FLOT chemotherapy resulted in a pCR rate of 19% versus 7% for patients treated with neoadjuvant chemotherapy alone as assessed by blinded independent central review (BICR) (difference in pCR rate 12%; odds ratio [OR] 3.08; p<0.00001). The rate of either complete or near-complete responses was 27% with the Imfinzi combination and 14% with neoadjuvant chemotherapy alone.

The trial, which is assessing Imfinzi in combination with FLOT chemotherapy as a perioperative treatment (before and after surgery), will continue as planned to assess the primary endpoint of event-free survival (EFS) and the key secondary endpoint of overall survival (OS) to which the trial team, investigators and participants remain blinded.

Yelena Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York and principal investigator in the trial said: "Disease recurrence after curative-intent surgery is far too common for patients with resectable gastric and gastroesophageal junction cancers. These early MATTERHORN results showing encouraging pathologic complete responses give hope that adding durvalumab to FLOT chemotherapy in the future will offer a much-needed new treatment approach in the perioperative setting."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The results from MATTERHORN highlight the potential of early treatment for patients with gastric and gastroesophageal junction cancers using an immunotherapy and chemotherapy combination. These findings reinforce our commitment to improving outcomes in gastrointestinal cancers, where unmet need is high and treatment options are limited."

Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant setting. Further, the safety and tolerability of adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination. Grade 3 or higher adverse events from all causes were similar between the two arms, occurring in 69% of patients treated with the Imfinzi-based regimen versus 68% for neoadjuvant chemotherapy alone.

Summary of results: MATTERHORN

BICR

Investigator-assessed

Imfinzi plus chemo
(n=474)

Chemo alone
(n=474)

Imfinzi plus chemo
(n=474)

Chemo alone
(n=474)

pCRa

Patients who achieved pCR %

19

7

22

8

Odds ratio (95% confidence interval [CI])

3.08 (2.03-4.67)

3.03 (2.05-4.48)

p-value

<0.00001

N/A

Combined complete and near-complete responsea

Patients who achieved a complete or near-complete response %

27

14

N/A

N/A

Odds ratio (95% CI)

2.19 (1.58-3.04)

N/A

a. BICR review was scored using Modified Ryan criteria

For patients treated with the Imfinzi-based regimen, 87% completed surgery compared to 84% of patients treated with neoadjuvant chemotherapy alone. In patients who had surgery, including patients with surgery attempted but not completed, the rate of R0 resection (patients having no macroscopic or microscopic residual tumour following surgery) was 86% across both arms. The rate of T0 resection (patients with no evidence of their primary tumour) was 23% for the Imfinzi-based regimen compared to 11% for neoadjuvant chemotherapy alone. The rate of N0 resection (patients with no lymph nodes containing cancer cells) was 52% for the Imfinzi-based regimen compared to 36%.

Notes

Gastric and GEJ cancers
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fourth highest leading cause of cancer mortality.2 Approximately one million new patients were diagnosed with gastric cancer in 2020, with 768,000 deaths reported globally.2

GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach.3

By 2030, approximately 70,000 patients in the US, EU and Japan will be newly diagnosed with Stage II-III gastric or GEJ cancers.4 Disease recurrence is common in patients with resectable gastric cancer.1 Approximately one in four patients with gastric cancer who undergo surgery with curative intent develop recurrent disease within one year, reflecting a high unmet medical need.1 Additionally, the five-year survival rate remains poor, with only up to a third of patients alive at five years.5,6

MATTERHORN
MATTERHORN is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, patients were randomised to receive 1500mg fixed dose of Imfinzi plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery, followed by Imfinzi or placebo every four weeks for up to 12 cycles after surgery (including two cycles of Imfinzi or placebo plus FLOT chemotherapy and 10 additional cycles of Imfinzi or placebo monotherapy).

In the MATTERHORN trial, the primary endpoint is EFS, defined as the time from randomisation until progression that precludes surgery or requires non-protocol therapy, local or distant recurrence or progression of disease, or death due to any cause as assessed by BIRC according to RECIST 1.1 and/or local pathology testing. Key secondary endpoints include pCR rate, defined as the proportion of patients who have no detectable cancer cells in resected tumour tissue following neoadjuvant therapy, and OS. The trial randomised 948 participants at sites in the US, Canada, Europe, South America and Asia.

Imfinzi 
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer (BTC) and in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC) in the US, EU, Japan and several other countries based on the TOPAZ-1 and HIMALAYA Phase III trials, respectively.

In addition to its indications in gastrointestinal (GI) cancers, Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small-cell lung cancer (SCLC) based on the CASPIAN Phase III trial. Additionally, Imfinzi is approved in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial. Imfinzi is approved in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 200,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers and other solid tumours. In GI cancers specifically, AstraZeneca has several ongoing registrational trials investigating Imfinzi across multiple liver cancer settings (EMERALD-1, EMERALD-2 and EMERALD-3) and in locally advanced oesophageal cancer (KUNLUN).

On October 20, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for rare and ultrarare diseases, reported the grant of 18,865 restricted stock units of the company’s common stock to 10 newly hired non-executive officers of the company (Press release, Ultragenyx Pharmaceutical, OCT 20, 2023, View Source [SID1234636185]). The awards were approved by the compensation committee of the company’s board of directors and granted under the Ultragenyx Employment Inducement Plan, with a grant date of October 16, 2023, as an inducement material to the new employees entering into employment with Ultragenyx in accordance with Nasdaq Listing Rule 5635(c)(4).

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The restricted stock units vest over four years, with 25% of the underlying shares vesting on each anniversary of the grant date, subject to the employee being continuously employed by the company as of such vesting dates.