On January 11, 2023 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing novel synthetic lethality-based cancer therapeutics targeting DNA damage response (DDR) pathways, reported that the first patient was dosed in its Phase 1/2a monotherapy clinical trial of ATRN-119, the Company’s lead ATR inhibitor for the treatment of cancers with DDR mutations (Press release, Aprea, JAN 11, 2023, View Source [SID1234626174]).

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The Phase 1/2a clinical trial is a multi-center, open-label, dose-escalation and expansion study designed to test ATRN-119 monotherapy in patients with advanced solid tumors harboring defined mutations in DDR pathways. The Phase 1 part of the study will assess tolerability, pharmacokinetics, recommended Phase 2 dose and analysis of patient biomarkers. The Phase 2a expansion portion of the trial is designed to further evaluate tolerability and efficacy of ATRN-119 monotherapy. ATRN-119 is structurally differentiated from other ATR inhibitors. In preclinical studies, ATRN-119 has demonstrated potent anti-proliferative activity against a variety of cancer cell lines, inhibited tumor growth in genetically defined ovarian, colon, pancreatic and prostate cancer xenograft models and has shown potential to have lower hematological toxicity than other ATR inhibitors.

"Initiating clinical evaluation of ATRN-119 marks a significant milestone in our efforts to advance the development of our growing pipeline of DDR inhibitors," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea Therapeutics. "We are committed to developing and advancing next-generation, synthetic lethality-based therapies to address the unmet medical needs of patients with genetically defined cancers. We look forward to sharing the preliminary data from this study throughout 2023."

Principal Investigator for the trial, Dr. Fiona Simpkins, M.D. Assistant Professor of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, added: "Mutations in DDR pathways are a hallmark of many aggressive cancers and inhibition of ATR is a promising therapeutic approach to selectively target and exploit the genetic vulnerabilities of tumors with these mutations. The initiation of this Phase 1 trial represents an important step in the clinical evaluation of ATR as a target for cancer therapy."

On January 10, 2023 Atavistik Bio, a biotechnology company focused on revolutionizing the discovery of new allosteric protein-metabolite interactions to develop novel small molecule drugs for cancer, inborn errors of metabolism and other serious diseases, reported that it has entered into a collaboration agreement with Plex Research, a company providing a novel artificial intelligence (AI)-powered drug discovery platform (Press release, Atavistik Bio, JAN 10, 2023, View Source [SID1234647392]). Atavistik Bio’s incorporation of Plex Research’s technology will enrich the informatics capabilities of its Atavistik Metabolite Protein Screening (AMPS) platform and accelerate its drug discovery pipeline.

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Atavistik Bio’s scalable AMPS platform combines an extensive and continually expanding protein-metabolite database map ("the Interactome"), along with advanced informatics tools, deep expertise in chemistry, and computationally rich structure-based design to systematically identify and understand the role of protein-metabolite interactions across important biological and disease-relevant pathways to inform small molecule drug discovery.

Under the collaboration, Atavistik Bio will enhance its proprietary Interactome map with Plex Research’s cloud-based AI-powered drug discovery search engine of large and disparate data sources to reveal hidden connections between related metabolites and ligands, pathways, biomarkers, and disease-relevant biology. The integration of Atavistik Bio’s AMPS data with Plex Research’s platform will create a unique and customizable data analysis engine to rapidly enable novel insights for drug discovery.

"Allosteric interactions, which we know can present novel druggable nodes for intractable targets, historically have been difficult to discover. Using our AMPS platform, we are able to systematically and rapidly interrogate protein-metabolite interactions to reveal new, disease-relevant allosteric binding sites," said Marion Dorsch, Ph.D., Atavistik Bio’s President and Chief Scientific Officer. "Fusing the enterprise-level capability of Plex’s access to large public databases with Atavistik’s proprietary data infrastructure has the potential to significantly augment the power of our AMPS platform and accelerate our efforts to drive the discovery of novel therapeutics for unmet patient needs."

"Atavistik’s platform creates opportunities to drug proteins in new ways by uncovering previously unknown regulatory sites with potentially important roles in disease," said Doug Selinger, President and CEO of Plex Research. "The breadth and depth of the Plex platform will provide important context for Atavistik’s AMPS data, which will enable better characterization of putative protein regulatory sites, ligand binding, and potential impacts on disease processes. The synergies between our technology platforms are compelling, and we’re excited to see where it will take us."

On January 10, 2023 Prestige Biopharma Limited, a Singapore-based biopharmaceutical company specializing in antibody drug development, reported that the company has obtained a patent in Korea for ‘Novel CTHRC1-specific antibodies and the use thereof’ (PBP1710) designed by its Innovative Discovery Centre (IDC) to treat solid cancer including pancreatic cancer (Press release, Prestige BioPharma, JAN 10, 2023, View Source [SID1234626262]).

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Solid tumors including pancreatic cancer, express abnormally high levels of CTHRC1 (collagen triple helix repeat containing 1), a protein that facilitates cancer cell migration and growth. PBP1710 specifically binds to CTHRC1 and exerts anti-metastasis and anti-tumor growth effects.

According to IDC, PBP1710 has shown remarkable research results on a cellular level, reducing cancer cell migration and invasion by approximately 45% in solid cancer such as pancreatic cancer, ovarian cancer, breast cancer and colorectal cancer. In addition, animal testing has shown PBP1710’ effect to inhibit cancer cell proliferation is equivalent to that of current primary cancer treatment in the market.

A source from Prestige Biopharma stated: "This patent registration is significant in that we are preoccupying the technological advantage on the anti-CTHRC1 antibodies that can be used as a wide range of solid cancer treatments. Considering that CTHRC1 is highly distributed in many different types of cancer, the successful development of PBP1710 as a next-generation antibody drug is expected to greatly contribute to the improvement of cancer patient treatment and survival, particularly in combination with other cancer treatments."

PBP1710 is currently under review for patent registration in 21 other countries and regions including the US, Europe, Japan, and China. Meanwhile, Prestige Biopharma’s first-in-class antibody pipeline for includes PBP1710 (Anti-CTHRC1) and PBP1510 (Anti-PAUF) for pancreatic cancer treatment which is currently in phase 1/2a clinical trial.

CTHRC1 promotes cancer cell migration through activation of the Wnt5 signaling pathway by forming CTHRC1-Wnt5-Fzd2/Ror2 complexes on cancer cells.

CTHRC1 stimulates formation of blood vessels (angiogenesis) in tumor tissues by upregulating the secretion of Ang-2, a Tie2 ligand, from endothelial cells. Activation of Ang-2/Tie2 axis in monocytes is critical in tumor angiogenesis. PBP1710 specifically binds to CTHRC1 and exerts anti-metastasis and anti-tumor growth effects.

On January 10, 2023 Defence Therapeutics Inc. ("Defence" or the "Company"), a Canadian biopharmaceutical company specialized in the development of immune-oncology vaccines and drug delivery technologies, is pleased to reported the advancement in the development of its AccumTM-mRNA vaccine program (Press release, Defence Therapeutics, JAN 10, 2023, View Source [SID1234626260]). This R&D program will not only impact the field of cancer immunotherapy, but it can also be directly applied to the development of new vaccines targeting infectious diseases.

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The mRNA vaccination approach offers tremendous advantages over the use of peptide-or protein-based vaccines. mRNA like any other biomolecule, is extremely sensitive to harsh conditions such as high acidity and enzymatic reactions, which would directly impede their therapeutic potency. In addition, mRNA molecules need to reach the cytoplasm where they can be efficiently translated into full proteins, this is where AccumTM may add stability and potency.

Defence is working with a private European company to synthesize mRNA vaccine coupled with its AccumTM. Defence’s has now completed the first phase of its AccumTM-mRNA vaccine development by achieving the synthesis and the Quality Control of the amino-modified polyA tail Ova mRNA. Defence is advancing on the second step, which consists of coupling AccumTM variants to amino-modified mRNA as well as testing and analyzing: i) the effect of AccumTM and linkers on mRNA stability, ii) the linker coupling onto amino-modified mRNA, iii) the AccumTM coupling onto linker-amino modified mRNA, and finally iv) the purification and analysis of the AccumTM-linker-amino-modified mRNA.

The third and final step of this Accum-mRNA vaccine development, scheduled at the end of January 2023, will be the production of a small vaccine batch to conduct in vivo studies in animals as a head-to-head comparison between AccumTM-linked and "naked" mRNA vaccines for their potential to generate an immune response capable of eradicating and controlling established tumors.

"The development of our AccumTM-mRNA vaccine is on track, our in vivo study on animals with pre-established solid tumors is planned for this quarter with the objective to demonstrate that AccumTM can significantly enhance the therapeutic potency of a given mRNA vaccine", says Mr. Plouffe, CEO of Defence Therapeutics.

The mRNA therapeutics market size is projected to surpass around USD 128.14 billion by 2030 and growing at a registered CAGR of 13.03% from 2022 to 2030 according to Precedence Research.

On January 10 ,2023 Bio4t2 reported that it dosed the first patient with T cells bearing a chimeric antigen receptor (CAR) that targets overexpression of BT-001 antigen present on various types of solid tumors (Press release, Bio4T2, JAN 10, 2023, View Source [SID1234626211]). The CAR-T (B4t2-001) was developed from Bio4t2’s PrismCore platform.

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"This first-in-human study marks the initial therapeutic to be evaluated from Bio4t2’s technology," said Dr. Laurence Cooper MD-PhD, Executive Chairman of the board. "PrismCore is capable of rapidly generating CAR-T to safely target self-antigens, opening a new frontier to delivering CAR-T to treat many types of solid tumors. This clinical trial is at the cutting edge of CAR-T biology and provides a path to treating the enormous numbers of patients who suffer from invasive cancers worldwide," added Dr. Cooper.

"We are excited to have started the clinical trial for our first CAR-T therapy targeting BT-001, which is a novel antigen for such therapies," said Farzad Haerizadeh, PhD, Chief Scientific Officer, and co-founder. "Our CAR-T is calibrated through PrismCore to discriminate between levels of BT-001 on tumors versus healthy cells. Indeed, B4t2-001 in preclinical studies in rodents and non-human primates, safely exhibited potent antitumor activity with long-term protective capacity. This trial helps validate the platform enabling the development of safe and effective CAR-T therapies against multiple types of solid tumors," said Haerizadeh.

About the clinical trial

The phase 1 investigator-initiated study (clinicaltrials.gov NCT05621486) evaluates ascending doses of B4t2-001 targeting BT-001 in patients with solid tumors. This trial assesses the safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary efficacy of autologous CAR-T as a single agent after lymphodepletion in adult subjects at Shanghai East and Shanghai Artemed hospitals in China.