CCR5 x CXCR4

WOBURN, Mass.--(BUSINESS WIRE)-- Aphios Corporation announced today that it has been granted US Patent No. 11,981,174 for CCR5 and CD4 siRNA-targeted therapeutics for treatment of HIV-1 and other diseases. More than 35 million people have died from AIDS, and 37 million people are living with HIV worldwide. In the United States, an estimated 1.2 million people are currently living with HIV and approximately 40,000 infections occur each year. There is no vaccine against HIV, and current medications have multiple long-term adverse effects such as: (i) rapid emergence of pools of drug-specific resistance HIV mutants that are not responsive to treatment; (ii) drug toxicity; (iii) drug/pill burden that often cause non-adherence; and (iv) high lifetime economic costs. Therefore, the need for alternative therapeutic approaches/strategies remain a critical challenge to global public health. RNA-based therapeutics hold great promise in the progress towards alternative HIV treatment. Specifically, small interfering ribonucleic acid (hereinafter referred to as siRNA) has widely been demonstrated to protect hosts from viruses, making this evolutionary conserved double-stranded RNA an important candidate for therapeutic intervention. But full harnessing of RNA as therapeutics is significantly impeded by the lack of appropriate delivery strategies that ensure RNA stability and potency in humans. In this invention, novel siRNAs were designed to downregulate CCR5, CD4 and CXCR4 genes, based on an analysis of all known alternative transcripts for each gene from both human and monkey (Macaca mulatta) genomes. SuperFluids are used to nanoencapsulate siRNA in phospholipid liposomes and lipid nanoparticles (nanosomes) for the improved delivery of siRNA and other biologics to diseased cells. Elements of the invention also pertain to targeting nanosomes containing specific siRNA sequences to cells expressing those receptors on the cell surface by coating them with specific ligands. Nanosomal formulation of siRNA and small molecules offers a potential avenue to improving the efficacy of siRNA constructs. About Aphios Corporation: Aphios ( ) is an emerging growth, green biotechnology company developing enabling technology platforms to improve drug discovery and manufacturing, nanotechnology drug delivery and pathogenic safety. Based on these platforms, Aphios is developing enhanced therapeutics to improve quality-of-life and treat chronic diseases including cancers, infectious diseases such as HIV/AIDS, and central nervous system disorders in an environmentally sustainable manner.

- Data supporting high expression of activation and tumor targeting markers of NK cells mass cultured without feeder cells - Proved the excellent anti-tumor efficacy in various solid tumor-bearing animal model - Submitted an IND for phase 1 trial for T.O.P. NK to MFDS last September SEONGNAM, South Korea--(BUSINESS WIRE)-- GICELL announced the data from the preclinical studies on T.O.P. NK (Tumor targeting, Optimally Primed NK), an allogeneic NK cell therapy which had been presented at the Society for Immunotherapy of Cancer (SITC) held in Boston, MA, US. The SITC is one of the world's top three cancer societies and has been known as the largest conference in the field of immuno-oncology. This press release features multimedia. View the full release here: The GICELL presents preclinical data of T.O.P. NK at SITC in Boston, MA, USA. (Photo provided by GICELL) The company presented the preclinical study results as a poster titled “Highly potent Tumor-targeting Optimally Primed Natural Killer cells produced under feeder-cell free conditions in a 50L-scale bioreactor with cytokine-fusion proteins elicits robust anti-tumor response in preclinical study.” In general, cancer cell-derived feeder cell culture is a common method for NK cell expansion, but GICELL is harnessing its wholly-owned platform to culture NK cells on a large scale without feeder cells which is a safer and simpler way for NK cell therapy. One of the key features of T.O.P. NK cell is the mass cultivation of NK cells from healthy donors. T.O.P. NK showed high expression rates of activating receptors, cytotoxic proteins, and chemokine receptors that are important for anti-tumor activity. In particular, T.O.P. NK displays a high expression rate of CCR5 and CXCR4 among chemokine receptors. Through this, the company explained that it is expected to have excellent targeting and anti-tumor abilities against solid tumors expressing the chemokine ligands. Cryopreservation technology for long-term storage and distribution is the key to the commercialization of allogeneic NK cell therapy. GICELL also proved its cryopreservation technology with no significant difference expression rate of the functional markers and viability of T.O.P. NK even after freezing and thawing. T.O.P. NK shows excellent anticancer activity in tumor-bearing animal models. According to the data in immunodeficient mice (NOG mice) implanted with human cancer cell lines, the growth of various solid tumors (4 types of colorectal cancer, 1 type of head and neck cancer, 1 type of breast cancer) was significantly inhibited by T.O.P. NK administrated via intravenous route compared to the control. In addition, there were no treatment-related adverse events in the toxicity study performed at a Good Laboratory Practice (GLP) institution. Based on these preclinical data, GICELL submitted an IND for a phase 1 clinical trial for patients with solid tumors and hematologic cancer to the Ministry of Food and Drug Safety (MFDS) in September. Through this clinical trial, GICELL will evaluate the safety, tolerability, and efficacy of T.O.P. NK. Chun Pyo Hong, CEO of GICELL, said, “There are many other companies that are developing off-the-shelf cell therapies but we find there are still unmet needs in cell therapies that can be manufactured on a large scale. We expect to initiate phase 1 clinical trial in earlier 2023 and hope to treat patients with malignant tumors as soon as possible.” GICELL has recently signed the R&D partnership agreements of CAR-NK with HK inno.N Corp. and Cartexell Inc. based on its outstanding immune cell expansion technology.

ROCKVILLE, Md.--(BUSINESS WIRE)-- Creative Bio-Peptides, Inc, a preclinical-stage biotechnology company developing novel therapies to balance the innate immune system and promote regeneration of damaged neurons, today announced the publication of findings from a preclinical study showing that treatment with the multi-chemokine receptor antagonist oral peptide RAP-103 substantially reduced heroin self-administration and motivation to consume heroin. RAP-103 also reduced the severity of naloxone-precipitated withdrawal responses in morphine dependence, as well as morphine-induced respiratory depression. In addition, RAP-103 normalized the components of addiction chemistry in the brain that are altered by opioid abuse. These data were published online ahead of print in the September 2022 issue of the peer-reviewed scientific journal Drug and Alcohol Dependence. “In collaboration with The Center for Substance Abuse Research at Temple University, the team at Creative Bio-Peptides has uncovered a potential non-opioid treatment to reduce the desire to consume opioids and to limit opioid withdrawal and respiratory depression,” said Michael Ruff, PhD, President and CEO of Creative Bio-Peptides. The results identify chemokine receptor antagonist RAP-103 as a potential treatment to enhance opioid analgesia and inhibit opioid-derived dependence, withdrawal and respiratory depression. Chemokines are small peptide hormones of the innate immune system that regulate inflammation, pain and substance abuse. In recent years, research has demonstrated that chemokine-opioid crosstalk is a physiological crossroads for influencing therapeutic and adverse effects of opioids. Activated chemokine receptors, especially CCR2, CCR5 and CXCR4, can control the body’s opioid receptors to increase pain states by reducing opioid-induced analgesia via desensitization of OPRM1 receptors. In studies funded by the National Institutes of Health’s (NIH) HEAL Initiative and the National Institute on Drug Abuse, conducted at The Center for Substance Abuse Research at the Lewis Katz School of Medicine at Temple University, the possible therapeutic use of RAP-103, an orally active small molecule that blocks these multiple chemokine receptors active in pain, was evaluated for its effects to reduce opioid administration, motivation to consume opioids, opioid withdrawal symptoms and opioid respiratory depression. “Chemokine receptor antagonism, with compounds such as RAP-103, has high potential as a pharmacotherapy because blocking specific cell surface receptors with small molecules (called antagonists) is a cornerstone goal of the biopharmaceutical industry,” said Scott Rawls, PhD, the study’s principal investigator, and Professor, Department of Neural Sciences, Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University. About the Study The study was designed to examine the potential medically assisted treatment (MAT) capabilities for opioid use disorder (OUD) with RAP-103, a small orally stable chemokine receptor antagonist peptide that blocks opioid acquisition, maintenance, and withdrawal. In the study, researchers conducted tests of animal self-administration, the gold standard for evaluating abuse liability of drugs. In self-administration experiments, RAP-103 reduced heroin intake and reinforced strength. Daily administration of RAP-103 delayed the onset, and reduced the magnitude, of heroin self-administration. In other experiments, RAP-103 greatly reduced the motivation to maintain opioid use. Other adverse effects of opioids blocked by RAP-103 included the severity of morphine physical dependence and respiratory depression. The behavioral effects of RAP-103 were associated with changes in mesolimbic brain regions known to play a role in dopamine transmission and substance abuse. In additional current studies, the objective is to further demonstrate the feasibility of RAP-103 as a MAT agent and to achieve results to support progressing to clinical trials. The goal is to identify the optimized lowest dose at which RAP-103 mitigates opioid self-administration in progressive-ratio experiments. In view of the unique mechanism of RAP-103 action via chemokine receptor antagonism, researchers will identify chemokine and cytokine changes in mesolimbic (ventral tegmental area and nucleus accumbens) brain reward areas to provide a mechanism for how RAP-103 may mitigate the rewarding effects of opioids and other drugs of abuse. About Creative Bio-Peptides (CBP) CBP was started in late 2017 with the mission to improve patients’ lives by challenging prevalent conventions about the causes and treatment approaches of neurodegenerative diseases, and to bring to market innovative therapeutics for important conditions caused by innate immune system activation in persistent post-surgical pain, dementias, and opioid use disorder. Based on the first generation non-oral peptide, with demonstrated safety and effectiveness in multiple controlled trials for improving cognitive endpoints in more severely impaired individuals (1, 2, 3), the company’s new oral lead compound RAP-103 is near Phase 1 ready and is shown to be well tolerated in preclinical toxicity studies with rapid brain entry and stability. Forward looking statement: Creative Bio-Peptides is currently completing IND-enabling studies and is currently raising funding to begin clinical trials in mid-2023.