On April 13, 2021 Galectin Therapeutics Inc. (NASDAQ:GALT), the leading developer of therapeutics that target galectin proteins, reported that a paper published in the peer-reviewed Journal for ImmunoTherapy of Cancer (JITC), the highest ranked fully open access immunology journal, provides further clinical evidence that using belapectin, a potent galectin-3 inhibitor, in combination with pembrolizumab (KEYTRUDA), a PD-1 inhibitor, significantly enhances tumor response to immunotherapy in patients with advanced metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC) (Press release, Galectin Therapeutics, APR 13, 2021, View Source [SID1234578044]).

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 paper, titled "Enhancing Clinical and Immunological Effects of anti-PD-1 with Belapectin, a Galectin-3 Inhibitor" (doi:10.1136/jitc-2021-002371) describes results from an ongoing Phase 1 clinical study, a collaboration between Galectin Therapeutics and Providence Cancer Institute in Portland, Oregon.

Following the recent publication of positive preclinical results that showed the inhibition of galectin-3 in combination with an agonist anti-OX40 monoclonal antibody reprograms the tumor microenvironment to favor anti-tumor activity, the current study tests the clinical hypothesis that galectin-3 blockade with belapectin in combination with pembrolizumab enhances tumor response for patients with advanced MM or HNSCC.

In the study, as previously disclosed, an objective response was observed in 50% of MM (7/14) and 33% of HNSCC (2/6) patients. This compares favorably to published response rates on pembrolizumab alone. The authors noted that the combination was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab alone. In addition, the analysis of patients’ tumor tissue revealed reduced monocytic myeloid-derived suppressor cells and increased effector memory T-cell activation in responders compared with non-responders. Also, an increased baseline expression of galectin-3 positive tumor cells correlated with clinical response.

"Immunotherapy is a significant breakthrough in the treatment of many cancers, but tumor-induced immune suppression contributes to treatment resistance. Galectin-3 is an important driver of this tumor-induced immunosuppression, and this clinical study constitutes proof-of-concept that the addition of belapectin, a galectin-3 inhibitor, to a PD-1 inhibitor can benefit cancer patients," said Dr. Brendan Curti, M.D., Earle A. Chiles Research Institute, a division of Providence, and the first author of the paper.

"The analysis of patients’ tumor tissues is consistent with previously published pre-clinical data with belapectin and confirms the ability of belapectin to modulate the tumor microenvironment to favor anti-tumor activity. The possibility to improve the tolerance and safety of immunotherapy is also very exciting," commented Pol F. Boudes, M.D., Chief Medical Officer of Galectin Therapeutics. "These proof-of-concept clinical data provide a strong rationale to initiate a randomized placebo-controlled phase 2 clinical trial to evaluate the efficacy and safety of belapectin in combination with a PD-1 inhibitor compared to a PD-1 inhibitor alone in this cancer patient population. We look forward to continuing our work with Providence Cancer Institute, and we anticipate the upcoming release of additional data from the expansion cohort in this study."

About Belapectin (GR-MD-02)

Belapectin (GR-MD-02) is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of NASH and fibrosis. Galectin-3 plays a major role in diseases that involve scarring of organs including fibrotic disorders of the liver, lung, kidney, heart and vascular system. Belapectin binds to galectin-3 and disrupts its function. Preclinical data in animals have shown that belapectin has robust treatment effects in reversing liver fibrosis and cirrhosis. A Phase 2 study showed belapectin may prevent the development of esophageal varices in NASH cirrhosis; these results provide the basis for the conduct of the NAVIGATE trial. The NAVIGATE trial (NAVIGATEnash.com), entitled "A Seamless Adaptive Phase 2b/3, Double-Blind, Randomized, Placebo-controlled Multicenter, International Study Evaluating the Efficacy and Safety of Belapectin (GR-MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis" began enrolling patients in June 2020 and is posted on www.clinicaltrials.gov (NCT04365868). Galectin-3 also has a significant role in cancer, and the Company is supporting a Phase 1 study in combined immunotherapy of belapectin and KEYTRUDA in treatment of advanced melanoma and in head and neck cancer.

On April 13, 2021 BridgeBio Pharma, Inc. (NASDAQ: BBIO) reported a collaboration with Oregon Health & Science University (OHSU) in Portland, Oregon, to advance research and the development of investigational medicines for patients with genetically driven conditions (Press release, BridgeBio, APR 13, 2021, View Source [SID1234577967]).

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!

"We feel privileged to have the opportunity to work with OHSU to focus on developing potential therapies for diseases with clear genetic drivers and severe unmet need," said BridgeBio founder and CEO Neil Kumar, Ph.D. "OHSU was one of the first research institutions we connected with in the early days of BridgeBio, and we look forward to deepening our relationship through close collaboration with their scientists as we strive to help patients together."

This arrangement builds on five years of informal collaborations between the two organizations. Under the agreement, the BridgeBio team will work closely with OHSU scientists and investigators to advance potential medicines for patients with genetically driven conditions, including cancers.

"BridgeBio’s approach to identifying and developing novel therapies allows them to interact with multiple investigators at OHSU who are studying a wide variety of diseases," said OHSU Chief Research Officer and Executive Vice President Peter Barr-Gillespie, Ph.D. "We believe their expertise and infrastructure will help lead to the rapid development of new drugs. We see this collaboration as an important part of our efforts to bring OHSU innovations to clinical significance."

BridgeBio collaborates with stand-out academic institutions, including OHSU, to support research around genetically driven conditions and is focused on rapidly translating findings into meaningful treatments for patients. Today BridgeBio also announced formal partnerships with Brown University, GlycoNet, The Lundquist Institute, Roswell Park Comprehensive Cancer Center, University of California, Davis and University of California, San Diego – for a total of 20 partnerships between BridgeBio and leading academic and research institutions to date. For a list of some of the institutions BridgeBio partners with, please visit Our Partners page.

With a diverse pipeline encompassing investigational therapies for rare diseases and genetically validated cancers, BridgeBio provides the insights and support needed to rapidly progress therapeutic research from labs to clinical development. BridgeBio intends to develop similar long-term partnerships based on trust, engagement, science and respect to support its mission of developing life-changing medicines for patients with genetically driven conditions as quickly and safely as possible.

On April 13, 2021 Purple Biotech Ltd. ("Purple Biotech" ", or the "Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies by overcoming tumor immune evasion and drug resistance, reported that additional preclinical data supporting the mechanism of action of NT219, a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3, were presented in a poster entitled "Adaptation of colorectal cancer cells to the brain microenvironment: The role of IRS2," at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting (Press release, Purple Biotech, APR 13, 2021, View Source [SID1234577984]). These data update and expand on the results previously reported by the Company from its collaboration with Professor Ido Wolf, Head of the Oncology Division at Tel Aviv Sourasky Medical Center.

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!

Colorectal cancer (CRC) represents the fourth most frequent cause of brain metastasis, which is the most common brain tumor. The study included an analysis of more than 16,000 human CRC local and metastasis samples, and revealed increased amplification of IRS2 in brain metastases.

In an in vitro system mimicking the brain microenvironment, IRS2-overexpressed CRC cells showed prolonged survival. Importantly, transcriptomic analysis demonstrated significant enrichment of the oxidative phosphorylation (OXPHOS) pathway by IRS2. CRC cells expressing IRS2 showed increased mitochondrial activity and glycolysis-independent viability. Inhibition of IRS2 using NT219 dose-dependently inhibited IRS2-expressing cells viability and OXPHOS genes expression.

The Wnt/β-catenin pathway was among the most significantly enriched pathways in the brain metastasis, as IRS2-expressing cells showed increased transcriptional activity of the β-catenin. In addition, NT219 decreased the transcriptional activity of β-catenin in IRS2-expressing CRC cells to a greater extent than AKT and PI3K inhibitors, and most significantly suggested relevance of IRS2 in activating β-catenin. It was further shown that 5-FU, a chemotherapy approved for treating CRC, elevated β-catenin expression, and that NT219 diminished both 5FU-induced and the basal level of the β-catenin expression. Utilizing an intracranial animal model, it was also demonstrated that while 5-FU alone had no significant effect, the combination of 5-FU and NT219 significantly inhibited the formation of brain metastasis and extended survival rates of the study mice.

"We are excited about these highly encouraging study results," said Bertrand Liang, M.D., Ph.D., Chief Medical Officer of Purple Biotech. "These compelling data provide important insights regarding the role of IRS2 in promoting CRC brain metastasis, and suggest that novel agents such as NT219 have the potential to effectively inhibit the development of brain metastasis. Our ongoing Phase 1/2 clinical trial of NT219 as monotherapy for the treatment of solid tumors, followed by a dose escalation of NT219 in combination with cetuximab, an epithelial growth factor receptor (EGFR) blocking monoclonal antibody, for the treatment of recurrent and/or metastatic solid tumors and squamous cell carcinoma of the head and neck cancer, is proceeding with enrollment as planned and we continue to expect the availability of top-line data from the first part of this study in the second half of this year."

The poster presentation is available at View Source

On April 13, 2021 BridgeBio Pharma, Inc. (NASDAQ: BBIO) reported a collaboration with Roswell Park Comprehensive Cancer Center to advance the development of investigational therapeutics for patients with genetically driven cancers (Press release, BridgeBio, APR 13, 2021, View Source [SID1234577968]).

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!

"We are honored to begin collaborating with Roswell Park, which is renowned for its excellence in cancer research and its mission to set the gold standard for treating patients with genetically driven cancers," said BridgeBio CEO and founder Neil Kumar, Ph.D.

Under the partnership, BridgeBio will work with scientists at Roswell Park Comprehensive Cancer Center to evaluate new research and development opportunities in oncology that have promise to advance and potentially provide clinical benefit for patients. Select therapeutic programs may be pursued by BridgeBio, in close collaboration with Roswell Park Comprehensive Cancer Center scientists, who would remain deeply involved in the ongoing development of these investigational therapies.

"Collaborating with BridgeBio opens up a platform of new resources to support the incredible Roswell Park innovators working on new ways to care for cancer patients with dire unmet need," said Roswell Park Comprehensive Cancer Center President and CEO Candace S. Johnson, Ph.D. "The ability to tap into this network of expertise means greater visibility for our teams and enables a quicker path to the clinic for our most promising ideas and inventions in areas like genetics, bioinformatics and molecular biology."

BridgeBio partners with stand-out academic institutions, including Roswell Park Comprehensive Cancer Center, to support research around genetically driven conditions and is focused on rapidly translating findings into meaningful treatments for patients. Today BridgeBio also announced formal partnerships with Brown University, GlycoNet, The Lundquist Institute, Oregon Health & Science University, University of California, Davis and University of California, San Diego – for a total of 20 partnerships between BridgeBio and leading academic and research institutions to date. For a list of some of the institutions BridgeBio is partnered with, please visit Our Partners page.

With a diverse pipeline encompassing investigational therapies for both rare diseases and genetically validated cancers, BridgeBio provides the insights and support needed to rapidly progress therapeutic research from labs to clinical development. BridgeBio intends to develop similar long-term partnerships based on trust, engagement, science and respect to support its mission of developing life-changing medicines for patients with genetically driven conditions as quickly and safely as possible.

On April 13, 2021 Genetron Holdings Limited ("Genetron Health" or the "Company", NASDAQ:GTH), a leading precision oncology platform company in China that specializes in molecular profiling tests, early cancer screening products and companion diagnostics development, reported the release of 22 research results at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (AACR 2021) (Press release, Genetron Health Technologies, APR 13, 2021, View Source [SID1234577985]).

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 results were from a series of studies that Genetron Health conducted with 13 leading hospitals in China. The Company leveraged original research and innovative technologies such as integrated DNA and RNA sequencing in gene fusion detection, a new MSI (microsatellite instability) detection algorithm model, its "One-Step Seq" method, and core products such as Onco Panscan and comprehensive sarcoma gene detection tests.

These studies analyzed the spread of various types of cancers throughout the Chinese population, covering lung cancer, intestinal cancer, pancreatic cancer, nervous system tumors, thymic carcinoma, and other types of cancers. More specifically, the studies focused on these cancers’ inheritance, mutation, and fusion characteristics. They paid particular attention to the validity of immunotherapy markers for various types of cancers, as well as rare cancer cases and new therapeutic treatments. These studies provided important insights that can enable the accurate diagnosis and treatment of cancer, facilitating the design of effective products in the future.

Dr. Yunfu Hu, Genetron Health’s Chief Medical Officer, said, "Genetron Health is committed to building a strong bridge between scientific research and clinical applications. The studies’ results show that the Company’s innovative technologies and products can help to further analyze the characteristics of cancer genomics for different types of cancer, optimize conventional technologies, and provide ideas for new product design, so as to promote the healthy development of translational medicine. For example, for soft tissue sarcoma (STS), the use of integrated DNA and RNA sequencing in gene fusion detection can greatly improve the detection rate of STS gene fusion, which may benefit more STS patients.

"For hereditary cancers, the screening method used to detect Li-Fraumeni syndrome will also improve cancer detection rates in these patients and provide more intervention opportunities for them; for colorectal cancer, our analysis of KMT2C/2D inactivation mutations is also pointing to more possibilities for immunotherapy patients. And lastly, our work on rare cancer cases and the experimentation of new treatments is furthering the development of diagnosis and treatment research for these various types of patients," Hu added.

Exploring Ways to Optimize Conventional Technologies

To overcome the DNA-sequencing limitations involved with detecting gene fusion, Genetron Health optimized the use of conventional technologies in Study #2288. During this study, more accurate, efficient, and low-cost detection of gene fusion mutations was achieved at the RNA sequencing level. This was evaluated and verified in a STS cohort of 142 Chinese patients. Compared with DNA detection alone, integrated DNA and RNA sequencing improved the detection rate of STS fusion by 177%, which could provide clinical benefits for more STS patients.

Study #2080 optimized the algorithm that detects MSI through next generation sequencing (NGS). The study was conducted on a large cohort of 2,523 samples with various types of cancers. According to the study results, the optimized algorithm was 99.9% consistent with PCR (polymerase chain reaction) testing – the industry’s current gold standard. The positive predictive value of MSI-H was 98.73%, and the negative predictive value of MSS was 99.92%.

Focusing on Hereditary Cancers

Two studies (#1464, #2557) provided screening methods for Li-Fraumeni syndrome, an inherited condition that is characterized by an increased risk for certain types of cancer. These methods utilized in-depth analysis of germline mutations and investigated the distribution of genetic characteristics for pancreatic cancer in the Chinese population, providing evidence and additional ideas for the diagnosis and treatment of hereditary cancers.

Investigating Gene Mutation and Fusion Characteristics

Nine studies (#2217, #2163, #2223, #2216, #2215, #2313, #2252, #2183, #2182) examined the mutation and fusion characteristics of soft tissue sarcoma, melanoma, neuroendocrine tumors, non-small cell lung cancer, thymic carcinoma, small bowel adenocarcinoma, ampullary carcinoma, etc. The studies focused on finding potential targets for precise therapeutic treatment, drug-resistant targets and effective countermeasures.

Probing Immunotherapy Markers

Four studies (#1639, #1640, #1641, #1681) investigated the predictive effects of KMT2C/D loss-of-function mutations, DDR signaling pathway-related gene mutations, ARID1A mutations, and BRCA1/2 mutations on immunotherapy treatments for a wide range of cancer types, providing further insights.

Spotlight on Rare Cancer Cases and New Treatment Therapies

Five studies (#0803, #0422, #1209, #1199, #0625) detected special molecular abnormalities in patients with Lynch syndrome-related lung cancer, metastatic melanoma, anaplastic thyroid carcinoma, papillary thyroid carcinoma and liposarcoma, respectively. In these studies, scientists used molecular detection to diagnose and classify such cancers, and new, targeted therapy and immunotherapy schemes were adopted for these patients, benefiting them in the long run.

Abstract#

Title

1464

Enrichment and screening of LFS patients by analyzing TP53 germline mutations of a Chinese cancer cohort

2252

Genome profiling of thymic carcinoma identifies putative driver mutations in the NF-κB signaling pathway

2557

Germline mutation landscape in a large cohort of Chinese pancreatic cancer patients

0803

Molecular diagnosis and immunotherapy of a rare lung carcinoma patient associated with PMS2 c.1144+1G>A mutation-driven Lynch syndrome

0422

Sequential targeted therapy and immunotherapy of a BRAF positive metastatic melanoma patient with BRAF inhibitor vemurafenib, MEK inhibitor cobimetnib and a novel PD-1 antibody Sintilimab

2183

Genomic profiling of small bowel adenocarcinoma reveals targetable mutations in multiple signaling pathways

2217

More somatic mutations can be detected in cerebrospinal fluid ctDNA of NSCLC patients with brain metastases

2182

Evaluation of somatic and germline mutations in ampullary carcinoma reveals actionable targets in multiple signaling pathways

1209

An effective treatment for recurrent and inoperable anaplastic thyroid carcinoma using sintilimab and anlotinib: a case report

1681

Correlation of BRCA1/2 mutations with response to immune checkpoint inhibitors in colorectal cancer

1641

The predictive values of ARID1A mutations for response to immune checkpoint inhibitors are varied in different types of solid tumors

1639

Correlation of KMT2C/D loss-of-function mutations with PD-L1 expression and response to immune checkpoint inhibitors in solid tumors

1640

Correlations of DNA damage response gene alterations with response to immune checkpoint inhibitors are different in solid tumors

2288

Identification of gene fusions in soft tissue sarcoma improved by integrative DNA and RNA sequencing

2163

Molecular characteristics of CDK4 and/or MDM2 amplification in Chinese soft tissue sarcoma (STS) patients

0625

Co-amplification of CDK4 and MDM2 plus HMGA2 fusion in a patient with myogenic differentiation dedifferentiated liposarcoma

2223

Distinct genomic features of cutaneous, acral and mucosal melanomas in a Chinese retrospective cohort

2216

Exploration of the genomic features of pan-neuroendocrine tumors in a Chinese retrospective analysis

2215

Landscape of RET fusion identified by next‑generation sequencing in a Chinese multi-cancer retrospective analysis

1199

Mosaic KRAS G12S mutation associates with poor outcome in papillary thyroid carcinoma: A case report

2080

Tumor microsatellite instability detection method using paired tumor-normal sequence data

2313

The characteristics of ERBB2 exon 20 insertion in a large cohort of Chinese NSCLC patients