On April 22, 2024 ReNAgade Therapeutics, a company unlocking the limitless potential for RNA medicines, reported an oral and poster presentation highlighting preclinical data supporting its comprehensive RNA technology platform at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting being held May 7-11, 2024, in Baltimore, Maryland (Press release, ReNAgade Therapeutics, APR 22, 2024, View Source [SID1234642225]).

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"We are excited to highlight foundational research and development advancements at ASGCT (Free ASGCT Whitepaper) supported by our poster presentation illuminating ReNAgade’s continued work in validating our immune tropic LNP-based delivery systems in NHPs with broad potential applications in oncology and autoimmune diseases," said Pete Smith, Ph.D., Chief Scientific Officer of ReNAgade. "Additionally, our oral presentation demonstrates a non-viral, all-RNA gene editing system enabling in vivo, exon-sized insertion and probable re-dosing with the goal of higher specificity and a better safety profile when used in the clinical setting. Together, these promising data are another important step in our efforts to innovate beyond the current limitations of RNA medicine."

Key Highlights from the Abstracts:

Employed a systematic barcoding screening approach to evaluate and identify engineered lipid nanoparticles (LNP) from a library of 200+ LNPs across multiple structural and chemically distinct classes of ionizable, helper, structural, and hydrophilic lipids. Lead LNP candidate demonstrated ~60% delivery efficiency in total splenic T cells and ~80% delivery efficiency in peripheral blood T cells in non-human primate models.
Improved retron-mediated target insertion through a combination of retron reverse transcriptase (RT) engineering, non-coding RNA (ncRNA) minimization, chemical modification, and homology-dependent repair manipulation. Combination of retron system optimization and ncRNA engineering led to 2-fold higher 305 base pair insertion and ~40% editing efficiency in hematopoietic stem cells.
ASGCT Annual Meeting Presentation Details:

TITLE: "Retron Mediated Exon-Sized Genome Insertion Using an All-RNA System"
SESSION TITLE: New Technologies for Gene Targeting and Gene Correction
PRESENTATION TYPE: Oral
ABSTRACT NUMBER: 14
PRESENTER: Inna Shcherbakova, Ph.D., Senior Director, Platform, ReNAgade Therapeutics
DATE AND TIME: Tuesday, May 7, 2024, from 2:15 p.m. – 3:30 p.m. ET

TITLE: "Novel Immune Tropic LNP-Based mRNA Delivery in Non-Human Primates"
SESSION TITLE: Wednesday Posters: Other Nonviral Delivery
PRESENTATION TYPE: Poster
ABSTRACT NUMBER: 749
PRESENTER: Juliet Crabtree, Ph.D., Associate Principal Scientist, ReNAgade Therapeutics
DATE AND TIME: Wednesday, May 8, 2024, at 12:00 p.m. ET

On April 22, 2024 Immunovia (NASDAQ Stockholm: IMMNOV), the diagnostics company with the mission to increase pancreatic cancer survival through early detection, today announced its next-generation pancreatic cancer test achieved both the primary and secondary endpoints in a model-development study (Press release, Immunovia, APR 22, 2024, View Source [SID1234642224]).

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In the study, Immunovia’s next-generation test demonstrated specificity of 98 percent and sensitivity of 75 percent in detecting early stage (1 and 2) pancreatic ductal adenocarcinoma (PDAC), a very aggressive and the most common form of pancreatic cancer. The Immunovia test was also significantly more accurate than CA19-9, the biomarker commonly used to detect pancreatic cancer.

Importantly, these results confirm the technical advancement of the next-generation test over Immunovia’s first-generation test, IMMray PanCan-d. The next-generation test includes high-performing protein biomarkers, making the test less reliant on CA19-9. This is a major achievement as around 10 percent of patients, including many patients of African ancestry, do not produce CA19-9, so the IMMray PanCan-d test could not be used in those patients. The results with the new test were achieved including PDAC patients with low CA19-9 values.

Furthermore, the new test does not provide indeterminate or "borderline" results; all patients are classified as positive or negative for pancreatic cancer. With the first-generation Immunovia test, IMMray PanCan-d, about 10 percent of patients received a test result of "borderline", creating indecision for clinicians.

The next-generation test is now established on a broadly used ELISA platform, resulting in more precise protein measurement, faster testing, and lower cost of goods sold.

"Pancreatic cancer is a brutal and lethal cancer. People at risk for pancreatic cancer need a simple, fast, and easy blood test to detect cancer early. We are very excited about the potential of our test to meet this need and increase survival rates for these patients," says Jeff Borcherding, CEO and President of Immunovia.

The model development study was designed to select the highest performing biomarkers to include in the next-generation test, to define the algorithm to produce a diagnostic result, and to provide an initial assessment of the test’s clinical performance. The study included 481 blood samples from the U.S. and Europe. Of these, 133 were samples from patients with stage 1 or 2 PDAC. The 348 control samples represented a wide range of subjects, including people at high-risk for hereditary and familial pancreatic cancer, diabetics, patients with benign pancreatic lesions worrisome for PDAC, and healthy individuals.

Immunovia will now move to a second phase of the model development study, expected to be completed in 6 – 8 weeks, in which it will conduct additional statistical analyses to refine and assess the robustness of the test model. In addition, test performance will be evaluated in a more selective cohort of patients at high risk for pancreatic cancer.

In the second and third quarters of 2024, Immunovia will perform several analytical validation steps to verify the accuracy and reproducibility of the protein biomarker measurements. In the fourth quarter of 2024, the company will conduct a large clinical validation study to confirm the performance of the next-generation test, setting the stage for a U.S. launch in 2025.

Immunovia estimates that there are at least 600,000 individuals in the U.S. at high risk of pancreatic cancer due to family history and genetic mutations. Many more are at risk due to other factors. The current standard of care for surveillance is annual imaging using magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS). High-risk individuals and clinicians at leading high-risk pancreatic cancer surveillance centers have expressed a very strong desire for a simple blood test to make surveillance faster, more convenient, and less invasive.

On April 22, 2024 Hyundai Bioscience (KOSDAQ 048410) reported the positive results from its preclinical study on triple-negative breast cancer, investigating combination therapy of ‘Niclosamide-based oral anti-cancer drug’ jointly developed with CNPharm and Docetaxel, one of widely-used chemical anticancer agents (Press release, Hyundai Bioscience, APR 22, 2024, View Source [SID1234642222]). As a result, the combination therapy was found to be more effective than Docetaxel alone. The anti-cancer efficacy of the combination therapy group was 67% better than the Docetaxel-treated group.

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This preclinical study results will be published through an SCI-level paper.

Hyundai Bioscience has succeeded in repurposing Niclosamide as an oral anticancer drug. Niclosamide had been found effective in treating various cancers by acting on the metabolic process of cancer cells, evidenced by decades of in vitro studies.

Metabolic anticancer drugs inhibit the growth and survival of cancer cells by disrupting the unique metabolic mechanisms of cancer cells as well as blocking the cell signaling pathways. Metabolic anticancer agents exhibit higher antitumor activity when treated with the existing anticancer drugs as a combination therapy.

From the in vitro test, Niclosamide successfully inhibited the proliferation and survival of cancer cells by disrupting their metabolism, preventing the anticancer drug-resistance by blocking the cell signaling pathways of tumor cells and recurrence and metastasis of cancer by inhibiting cancer stem cells. Niclosamide is found to be an antitumor agent that blocks metabolism, and Niclosamide-based anticancer drugs can solve the resistance and metastasis problems simultaneously.

Due to its anticancer mechanism, Niclosamide is effective against multiple cancers, including lung cancer, breast cancer, prostate cancer, colon cancer, liver cancer, kidney cancer, and head and neck cancer. It has also been found to be highly effective against cancers that are resistant to current anticancer treatments such as triple-negative breast cancer, lung cancer, prostate cancer, ovarian cancer, colon cancer, pancreatic cancer, and head and neck cancer.

Although Niclosamide was known for excellent anticancer efficacy, it has not been clinically used on humans for over 60 years because of its ‘low bioavailability’ and ‘short half-life to maintain effective drug concentration in the blood.’

Through its proprietary ‘drug delivery technology’ technology, Hyundai Bioscience, in collaboration with CNPharm, has developed a niclosamide-based oral anticancer drug formulation that enables a drug concentration at IC50 level or higher to inhibit the proliferation of cancer cells even with a non-toxic Niclosamide dose. Their 3-month-long in vivo toxicity tests demonstrated that the Niclosamide blood concentration level of no-observed-adverse-effect level (NOAEL) dose was 7,888 ng/mL. Considering the IC50 of various cancer cells is mostly 65~654 ng/mL, Niclosamide can effectively inhibit cancer cell proliferation even when administered at a dose less than one-tenth of the NOAEL.

Hyundai Bioscience’s in vivo efficacy study on combination therapy of a niclosamide-based anticancer agent with Docetaxel was conducted on animals implanted with triple-negative breast cancer cells. The results confirmed that Niclosamide significantly increased the anticancer efficacy.

Dr. Jin Geun-Woo, leading Hyundai Bioscience R&D, highlighted the significance of these preclinical results, stating, "This is the first case that is statistically proven in vivo that the oral Niclosamide-based anticancer treatment has a remarkable effect on triple-negative breast cancer, a type of cancer that is challenging to treat. Niclosamide-based metabolic anticancer drugs could potentially address the problems of drug resistance and metastasis that make cancer treatment difficult." He added, "Clinical phase 1/2a trials will be conducted in Korea for various difficult-to-treat cancers, including triple-negative breast cancer, pancreatic cancer, ovarian cancer, non-small cell lung cancer (NSCLC), and metastatic prostate cancer."

Mr. Oh Sang-gi, the CEO of Hyundai Bioscience, announced, "The Niclosamide-based oral anticancer drug project will be carried out by a new subsidiary of Hyundai Bioscience, ADM KOREA," and added, "Hyundai Bioscience therefore plans to transfer its Niclosamide-based oral anticancer technology to its new subsidiary."

On April 22, 2024 ImmPACT Bio USA Inc. (ImmPACT Bio), a clinical-stage biopharmaceutical company developing a new generation of cellular therapies that have the potential to bring transformational benefits to patients, reported that it will present new ex vivo preclinical data for ImmPACT Bio’s bispecific Claudin 18.2 (CLDN18.2)/TGF-β chimeric antigen receptor (CAR) T program for the treatment of solid tumors that express CLDN18.2, including gastric and gastroesophageal junction cancer, as part of a poster presentation at the upcoming American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting, taking place in Baltimore, MD from May 7-11, 2024 and virtually (Press release, ImmPACT-Bio, APR 22, 2024, View Source;car-t-program-at-the-american-society-of-gene–cell-therapy-27th-annual-meeting-302123539.html [SID1234642221]).

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"There is a significant unmet medical need in patients with gastric cancer, which is among the top three deadliest cancers globally. CLDN18.2 has emerged as a promising target due to its elevated expression in tumor cells but not healthy cells. Previous CAR T-cell therapies targeting CLDN18.2 have demonstrated promise but lacked durability, likely due to poor T-cell persistence and function in solid tumors," said Sumant Ramachandra, M.D., Ph.D., chief executive officer of ImmPACT Bio. "We are using a novel bispecific approach designed to enhance CAR T-cell activity in solid tumors by overcoming immune suppression in the tumor microenvironment. We will present new ex vivo preclinical data at ASGCT (Free ASGCT Whitepaper) which demonstrated the ability of our bispecific CAR targeting CLDN18.2 and TGF-β to convert the immunosuppressive TGF-β signal into a T-cell activation signal to ultimately enhance T-cell fitness, reduce regulatory T-cell conversion, and decrease phenotypic exhaustion."

Details for the presentation are as follows:

Title: Engineering a Bispecific Claudin 18.2/TGF-β CAR to Target Claudin 18.2 Positive Tumors and Overcome the Tumor Microenvironment
Abstract Number: 832
Presenter: Jessica Reyes, ImmPACT Bio
Poster Session Date/Time: Wednesday, May 8, 2024 at 12:00 – 7:00 PM ET
Author Reception Date/Time: Wednesday, May 8, 2024 at 5:30 – 7:00 PM ET
Poster Session: Immune Targeting and Approaches with Genetically Modified Cells and Cell Therapies

Abstracts and additional details can be found at the ASGCT (Free ASGCT Whitepaper) 27th Annual Meeting website.

On April 22, 2024 SalioGen Therapeutics, a biotechnology company developing next-generation genetic medicines based on its novel Gene Coding technology, reported that four abstracts, including one oral presentation, will be presented at the upcoming annual meetings of the Association for Research in Vision and Ophthalmology (ARVO) and the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) (Press release, SalioGen Therapeutics, APR 22, 2024, View Source;cell-therapy-asgct-302123770.html [SID1234642220]).

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The presented findings will highlight preclinical data supporting the tolerability and in vivo efficacy of SGT-1001, a development candidate for the one-time treatment of Stargardt disease, a genetic condition that causes progressive vision loss. A separate program under development for cystic fibrosis will show success in targeting integration of the CFTR gene into the native CFTR intron 1, a major step forward in targeted delivery of a large genetic cargo. SalioGen will also share genomic profiling data on its novel Gene Coding technology, which uses transposition to integrate large DNA constructs (up to 100kb) into the genome and promises to overcome key safety risks and limitations of other approaches to genetic medicine.

ARVO will take place in Seattle, Washington, from May 5 to 9, 2024, and ASGCT (Free ASGCT Whitepaper) will take place in Baltimore, Maryland, from May 7 to 11, 2024.

ARVO Presentation Details
Title: ABCA4 gene replacement in a mouse model of Stargardt disease using a mammalian transposon system
Format: Poster Presentation (#A0065)
Location: Exhibit Hall
Date/ Time: Monday, May 6 at 4:00-5:45 MDT

ASGCT Presentation Details
Title: Efficacy and Integration of a Non-Viral ABCA4 Transposon in Treating Stargardt Disease: Evidence from Mice and Primate Studies
Format: Oral presentation (abstract #11)
Location: Ballroom 1
Date/Time: Tuesday, May 7 at 1:30 PM – 1:45 EST

Title: Comprehensive Genomic Profiling of Human CD19 CAR T-cells Engineered with a Mammalian Transposon
Format: Poster presentation (#1212)
Location: Exhibit Hall
Date/Time: Thursday, May 9 at 12:00 EST

Title: A Programmable Mammalian Transposon Achieves Accurate Integration of a CFTR2-27 Superexon in Human Bronchial Epithelial Cells
Format: Poster presentation #1677
Session Room: Exhibit Hall
Date/Time: Friday, May 10, 2024 at 12:00 EST