On June 6, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported it will host an investor webcast on Friday, June 10, 2022 at 8:00am ET (2:00pm CEST) to discuss initial clinical data from its on-going Phase 2 APEX trial evaluating bezuclastinib in patients with Advanced Systemic Mastocytosis being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress (Press release, Cogent Biosciences, JUN 6, 2022, View Source [SID1234615619]).

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The event will be led by Andrew Robbins, Cogent’s President and CEO, and will include a presentation by Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute. The speakers and additional members of Cogent leadership will be available during the Question and Answer session.

The webcast will be accessible through the Investors and Media section of Cogent’s website at www.cogentbio.com. Following the live webcast, an archived replay will also be available.

On June 6, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company targeting diseased macrophages in patients with sepsis and solid tumors, reported that the Israeli Ministry of Health (MOH) authorized the initiation of a company-sponsored Phase I/II clinical trial evaluating Allocetra combined with chemotherapy in patients with peritoneal metastases arising from solid cancer (Press release, Enlivex Therapeutics, JUN 6, 2022, View Source [SID1234615635]).

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Peritoneal cancer, whether originating from a primary tumor within the peritoneum or from a metastatic tumor elsewhere in the body, is a terminal disease with a poor prognosis. Patients with peritoneal metastases are in urgent need of novel treatment options, as standard-of-care (SOC) chemotherapy provides only modest survival benefits. The median survival of patients with peritoneal metastases differs based on the location of the primary tumor but is frequently poor, with survival rates of 2.9 months, 6.5 months, and 6.9 months reported for cancers of pancreatic, gastric, and colorectal origins, respectively.

The planned Phase I/II trial is an open-label dose escalation and expansion trial that is expected to enroll a total of approximately 12 patients across four cohorts. It is designed to evaluate the safety and potential preliminary efficacy of Allocetra combined with SOC chemotherapy in patients with peritoneal metastases arising from solid cancer. The study will begin with two cohorts of intra-patient and intra-cohort dose escalation to determine the maximum feasible dose (MFD) of Allocetra in this population, followed by two additional cohorts comparing administration of Allocetra at the selected dose either before or after administration of SOC via a pressurized intraperitoneal aerosol chemotherapy procedure (PIPAC; a technique applied when patients are not eligible to receive the standard treatment due to a considerable tumor load, or large quantities of persistent ascites and other circumstances).

Intraperitoneally delivered Allocetra and SOC chemotherapy administered via PIPAC will be given to patients every six weeks. Systemic chemotherapy will also be administered per the treating oncologist’s plan. The primary endpoint is the number and severity of Allocetra-related adverse events and serious adverse events during the 16-week period, starting from the first administration of study treatment. Secondary endpoints include efficacy assessments, such as best overall response rate (ORR), progression-free survival, and overall survival. Changes from baseline in macrophage and immune cell characteristics in peritoneal fluid and tissues will also be assessed as an exploratory endpoint.

Currently, the efficacy of many anti-cancer agents is hampered by the body’s tumor defense mechanisms that facilitate the recruitment of macrophages which become "pro-tumor" tumor associated macrophages (TAMs) rather than "anti-tumor" macrophages. The TAMs typically form a physical layer on top of the solid tumor and induce immunosuppression in the solid tumor microenvironment. This in-turn promotes tumor growth and metastasis and contributes to poor clinical outcomes and response to therapy. Previously reported preclinical data from solid tumor models suggest that Allocetra has the potential to reprogram pro-tumor macrophages back to their homeostatic state and may thereby promote disease resolution and provide patients that do not respond well to existing FDA-approved therapies with an effective treatment option.

Einat Galamidi, M.D., Vice President, Medical of Enlivex, stated: "Receiving this authorization from the MOH is an important step toward expanding Allocetra’s potential therapeutic impact into oncology. Our preclinical studies suggest Allocetra may enhance the efficacy of a broad range of therapeutic agents by weakening tumor defense mechanisms through a novel mechanism of action that drives macrophage populations towards a more anti-cancer state. We look forward to beginning the clinical evaluation of this hypothesis through both this chemotherapy combination study and an additional planned solid tumor study that will evaluate Allocetra combined with a checkpoint inhibitor."

Enlivex plans to initiate the Phase I/II trial evaluating Allocetra in combination with chemotherapy in patients with peritoneal metastases arising from solid cancer in Q3 2022. The Company also expects to initiate a Phase I/II trial evaluating Allocetra in combination with an immune checkpoint inhibitor in late 2022.

ABOUT ALLOCETRATM

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On June 6, 2022 Cellworks Group, Inc., a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology, reported results from the myCare-004 study, which demonstrate that the Cellworks Singula Therapy Response Index (TRI) is highly predictive of Overall Survival (OS), Disease-Free Survival (DFS) and Mandard-tumor regression grade (TRG) for gastroesophageal adenocarcinoma (GEA) patients (Press release, Cellworks, JUN 6, 2022, View Source [SID1234615652]). In this retrospective study, Singula TRI provided additional predictive information for OS and DFS beyond patient age, patient gender and physician-prescribed treatment.

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The results from the myCare-004 clinical study were featured in a poster session as part of the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting during the Gastrointestinal Cancer – Gastroesophageal Pancreatic and Hepatobiliary Track and available online as Abstract 4064.

"This study confirmed that there are many dysregulated signaling pathways responsible for hallmark behaviors of cancer and variable drug response in gastroesophageal adenocarcinoma patients," said Dr. Elizabeth Smyth, Cambridge University Hospitals NHS Foundation Trust and Co-Principal Investigator of the myCare-004 clinical study. "Cellworks personalized therapy biosimulation enables us to utilize a patient’s comprehensive next generation sequencing (NGS) results and understand the downstream molecular effects of specific drugs on cell signaling to predict how each patient will respond to therapies prior to treatment. The next step is to evaluate whether biosimulation-informed therapy selection can be used prospectively to improve the survival of GEA patients."

"Gaining a better understanding of the molecular determinants of gastroesophageal adenocarcinoma is key to improving therapy response rates for GEA patients," said Dr. Rebecca Fitzgerald, MD, Professor of Cancer Prevention at the University of Cambridge; Director of the CRUK Cambridge Centre Early Detection Institute; and Co-Principal Investigator of the myCare-004 clinical study. "There are limited treatment options for this cancer type and we look forward to testing the Cellworks personalized therapy predictions in a prospective trial."

The Cellworks Biosimulation Platform simulates how a patient’s personalized genomic disease model will respond to therapies prior to treatment and identifies novel drug combinations for treatment-refractory patients. The platform is powered by the groundbreaking Cellworks Computational Omics Biology Model (CBM), a network of 7,000+ human genes, 30,000+ molecular species and 100+ signaling pathways. As part of the biosimulation process, personalized disease models are created for each patient using their cytogenetic and molecular data as input to the Cellworks CBM. The Cellworks platform analyzes the impact of specific therapies on the patient’s personalized disease model and generates a Singula biosimulation report with Therapy Response Index (TRI) scores from 0 to 100 that predict the efficacy of specific chemotherapies.

myCare-004 Clinical Study

Background

In this study, the Cellworks Singula Therapy Response Index (TRI) was used to prospectively predict the Overall Survival (OS), Disease Free Survival (DFS) and Mandard-tumor regression grade (TRG) in a retrospective cohort of gastroesophageal adenocarcinoma patients from the UK OCCAMS consortium. 271 GEA patients were selected who had pre-chemo treated biopsies with 50x whole genome sequencing. 234 patients were male and 30 female with a median age of 65.6 years. Within the study population, there were 35 T2, 215 T3, 70 N0, 126 N1, 62 N2 and 266 M0. Patients were prescribed chemotherapy treatments according to UK clinical guidelines.

Methods

A mechanistic model created for each patient using comprehensive genomic inputs biosimulated downstream molecular effects of cell signaling and drugs for a patient’s personalized in silico disease model. Random sampling stratified by clinical factors was used to split the data into independent training (N=140) and validation (N=131) subsets. Multivariant Cox Proportional Hazard (PH) and Proportional Odds models were used to predict survival and pathological response as a function of the pre-defined Therapy Response Index (TRI) and clinical thresholds compared with standard clinical factors.

Results

Cellworks Personalized Therapy Biosimulation found that 99% of the patients’ tumors had deficiency in DNA repair genes. Other pathways included amplification of multi-drug resistance pumps, TP53 mutations and aberrations of the PI3K/AKT pathway genes. Cellworks Singula Therapy Response Index (TRI) provided additional predictive information for OS and DFS beyond physician prescribed treatment and standard clinical factors. TRI was also predictive of TRG in univariate analysis. TRI scores were generated for 82 alternate therapies for each patient, enabling selection of optimal therapies with estimates of improvements in median OS and DFS compared to standard care (SC).

Conclusions

The study found that Cellworks Singula TRI was predictive of Overall Survival (OS), Disease-Free Survival (DFS) and Mandard-tumor regression grade (TRG) beyond clinical factors in this cohort of gastroesophageal adenocarcinoma (GEA) patients. These positive results suggest the utility of biosimulation-informed therapy selection to improve survival of GEA patients.

On June 6, 2022 SOPHiA GENETICS (Nasdaq: SOPH), the creator of a global data pooling and knowledge sharing platform that advances data-driven medicine, reported an update on its multimodal DEEP-Lung-IV clinical study (NCT04994795) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Sophia Genetics, JUN 6, 2022, View Source [SID1234615668]). This will be discussed during the company’s joint Innovation Symposium with GE Healthcare Monday, June 6th from 6:30 – 8:00 pm CDT.

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Immunotherapy has revolutionized the management of metastatic non-small cell lung cancer. Despite its promise, the majority of patients fail to respond to the therapy while being exposed to potentially severe side effects. Existing biomarkers are suboptimal as they do not allow to predict which patients will benefit from the therapy. There is an urgent need to identify biomarkers that are predictive of response to immunotherapy at the individual patient level.

New agreement signed with GE Healthcare to utilize Imaging Fabric to further accelerate radiomics analysis workflows

SOPHiA GENETICS launched the DEEP-Lung-IV clinical study to leverage its multimodal machine learning-powered analytics capabilities to identify multimodal predictive signatures of response to immunotherapy for patients with advanced lung cancer. Through its global footprint, the study is intended to maximize exposure of the machine learning algorithms to a wide range of diverse, real-world data. Insights from the DEEP-Lung-IV study will power one of the applications of the CarePath module of the SOPHiA DDMTM platform, offering advanced data visualization, cohorting, and predictive capabilities in a single solution.

To date, 19 sites across seven countries have signed up for participation in the study, including Roswell Park Comprehensive Cancer Center in New York. "I am personally very excited to join the DEEP-Lung-IV study. I see tremendous value in the multimodal machine learning-powered approach to real-world data analytics and look forward to potentially applying it to other clinical questions of high relevance in lung cancer", said Dr. Prantesh Jain, Assistant Professor of Oncology at Roswell Park Comprehensive Cancer Center. Together, these sites have already recruited over 500 patients.

Early findings are promising and conceptually validate the potential for multimodal signatures to predict response to immuno-chemotherapy at the individual patient level. First results will be discussed during SOPHiA GENETICS’ joint Innovation Symposium with GE Healthcare on Monday, June 6, at 6:30 pm CDT.

"We are very excited by the strong operational traction in recruiting patients to the study, as well as the promising early findings. With its unique machine learning-powered multimodal study design and its focus on collecting very diverse real-world data from lung cancer patients around the world, we feel that the DEEP-Lung-IV study has the potential to usher a new era of precision medicine that would enable predictions at the individual patient level. We look forward to further validating our vision of building a multimodal decentralized collective intelligence, leveraging on real-world data to generate novel insights at the individual patient level," said Dr. Philippe Menu, SVP & Chief Medical Officer, SOPHiA GENETICS.

SOPHiA GENETICS has also entered into an agreement with GE Healthcare to utilize their Imaging Fabric Core and Imaging Fabric Annotation Template, as part of the Edison Digital Health Platform. In the context of the DEEP-Lung-IV clinical study, Imaging Fabric services will be used to visualize, segment, and annotate lung lesions for medical imaging visualization and annotation purposes. This allows SOPHiA GENETICS to further accelerate proprietary radiomics analytics workflows in the context of the study, in particular to move towards automatic whole-body tumor identification, segmentation, and quantification.

"We’re eager to further strengthen our collaboration with SOPHiA GENETICS. The use of Imaging Fabric and the SOPHiA DDMTM Platform are key to create the world of tomorrow, in which we aim to jointly break data silos across data modalities to deliver insights to physicians to help them optimize patient treatment workflows. We look forward to seeing how the DEEP-Lung-IV study results can help improve outcomes for those diagnosed with lung cancer," said Ben Newton, MD, General Manager, GE Healthcare Oncology Solutions.

SOPHiA GENETICS’ DEEP-Lung-IV clinical study aims to predict immunotherapy treatment response upon first evaluation at the individual patient level using data across multiple modalities including genomics, radiomics, clinical, and biological data. The study also aims to validate an algorithm that will allow the prediction of outcomes of the individual patient such as progression-free survival (PFS) and overall survival (OS). This predictive model will help identify patients that are likely to benefit from immunotherapy versus those that are not. It will stratify patients according to risk, helping clinicians make more informed therapeutic decisions for their patients, supporting biopharma to ensure the right patients are selected for clinical trials.

On June 6, 2022 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported an update to its strategic priorities and the streamlining and realignment of resources to support its key value-generating indications and programs and extend its estimated cash runway into late 2024 (Press release, Vincerx Pharma, JUN 6, 2022, View Source [SID1234615685]).

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Strategic Update Summary:

Prioritizing VIP152 clinical studies to focus on:
Monotherapy in patients with high grade B-cell lymphoma characterized by translocations of MYC and BCL-2 or BCL-6 (aka double-hit diffuse large B-cell lymphoma [DLBCL])
Monotherapy in patients with high-risk chronic lymphocytic leukemia (CLL)
Combination with Bruton tyrosine kinase (BTK) inhibitor in patients with high-risk CLL
Continuing to prioritize advancement of first-in-class and potentially best-in-class bioconjugation assets
Streamlining and realigning resources to support prioritized VIP152 indications and advancement of the bioconjugation programs
Reducing full-time employees by 33%
Implementing additional cost reduction measures
Extending estimated cash runway into late 2024
Positioning company to continue executing on important clinical and preclinical milestones
"Given the unprecedented market conditions, we are making a strategic decision to focus our resources on our ongoing double-hit DLBCL and CLL clinical trials and our next-generation bioconjugation platform to deliver the greatest benefit in these patients as well as maximize value for our shareholders," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx.

"The VIP152 program was designed as a signal-seeking program," added Dr. Hamdy. "Nineteen (19) patients with various MYC+ cancers have been treated. We saw stable disease in 3 patients with ovarian cancer (with one of the three patients completing cycle 6). Despite this preliminary signal in ovarian cancer, the combination of challenging market conditions and the promising VIP152 preclinical and clinical data we have seen in double-hit DLBCL and CLL patients create a compelling rationale for us to focus our efforts on these two indications."

"We continue to be excited about our preclinical bioconjugation platform—a diverse, modular platform of linkers and payloads that can be conjugated with antibodies and small molecules to create novel targeted therapeutics for a broad range of solid tumors and hematologic malignancies and remain on track to file an IND in the second half of this year for VIP236. We also remain on track to file an IND in the second half of 2023 for our initial antibody drug conjugate (ADC), VIP943. We believe our ADCs represent a paradigm-shifting technology with a proprietary and highly differentiated linker and warhead. These innovations are expected to improve efficacy and safety versus current ADCs," continued Dr. Hamdy.

To support this strategy, Vincerx also announced the streamlining and realignment of resources and the implementation of certain cost reduction measures, including a 33% reduction of full-time employees. "Reducing our staff was not an easy decision. It was the tremendous effort of our Vincerx colleagues that allowed us to execute efficiently, despite the extreme pressures of the pandemic. I want to sincerely thank every Vincerx colleague who has been impacted by this realignment. Their contributions have, without a doubt, brought us closer to achieving our goals. The realignment announced today will allow us to focus on and invest in the indications and programs we believe will generate the greatest value while reducing our operating expenses—all with the goal of achieving our anticipated key milestones for VIP152 and our bioconjugation platform," concluded Dr. Hamdy.

CLINICAL UPDATES

VIP152 (as of April 19, 2022):

VNC-152-101 study enrollment (Patients with MYC+ cancer, which included overexpression, translocation, deletion, or amplification):
High-grade lymphoma arm (n=4)
Histologies: triple-hit, double-hit, double expressor and primary mediastinal (n=1 each)
Gynecologic malignancies (n=5)
Includes 1 patient with endometrial cancer who received combination therapy of VIP152 + pembrolizumab
Triple negative breast cancer (n=2)
Tumor agnostic group (n=7)
Consists of various types of gastrointestinal cancer (n=6) and melanoma (n=1)
VNC-152-102 study enrollment:
CLL that has failed BTK inhibitor therapy, as well as venetoclax therapy (n=1)
Clinical outcomes from VNC-152-101 and VNC-152-102:
No new safety signals were identified; manageable treatment-related adverse events included neutropenia and gastrointestinal toxicity (i.e., nausea, vomiting and diarrhea); only 1 patient discontinued due to an adverse event (i.e., Grade 1 nausea)
Progressive disease was observed in 16 patients, despite evidence of tumor shrinkage in some patients including the patient with CLL who had failed BTK inhibitor and venetoclax therapy. Best response in all 19 patients has been stable disease in 3 patients with ovarian cancer as reported at the AACR (Free AACR Whitepaper) Annual Meeting in 2022.
Abstract accepted for poster presentation at the upcoming European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting, titled "VIP152 is a novel CDK9 inhibitor with improved selectivity, target modulation, and cardiac safety in patients with lymphoma."
Presenting author: Melanie Frigault, PhD
Abstract number: P1269
Session date and time: Friday, June 10, 2022; 16:30-17:45 CEST

Bioconjugation Platform:

Continue to advance next-generation modular bioconjugation platform, comprised of a first-in-class SMDC for solid tumors (VIP236) and two potentially best-in-class assets for hematologic malignancies (VIP943 and VIP924)
VIP236: IND filing in solid tumors expected in 2H 2022
VIP943 (anti-CD123) and VIP924 (anti-CXCR5): Manufacturing is underway and IND filing for VIP943 expected in 2H 2023 and VIP924 in 2024