NFKB1

Researchers who identified the first patient mutations on the NFkB1-gene, cooperated with international clinicians to identify and characterize a plethora of unreported NFKB1 variants on patients with immune system related illnesses. Researchers from the Institute of Biotechnology, University of Helsinki, pioneers in identifying the first patient mutations on the NFkB1-gene, cooperated with international clinicians to identify and characterise a plethora of unreported NFKB1 variants on patients with immune system related illnesses. In many cases, the identification of a genetic defect in a patient is of great importance for the treatment and prognosis of patients with rare diseases. NFKB1, a transcription factor, causes changes in gene expression and is activated by stress and immune related signaling pathways. Mutations in the NFkB1 have previously been linked to common variable immune deficiency (CVID). Two new studies may bring further relief for patients with hereditary gene defect in immune system "These studies have significantly expanded the associations of NFKB1 variants to immune system dysfunction -- the connections which we first reportedin 2017, " says research director Markku Varjosalo from the Institute of Biotechnology, University of Helsinki Researchers identified two new NFKB1 variants in two families suffering from common variable immune deficiency. Both identified NFKB1 variants caused reduced expression of the NFKB1 protein and lead to an altered gene expression and increased inflammation response in patient cells. Interaction analysis again showed loss of interactions for one of the variants but not the other. Another group of researchers studied a cohort of 47 NFKB1 mutations previously reported in patients, out of which 25 did not appear to behave differently from wild type NFKB1. The other 22 mutations were found to have adverse effects on NFKB1 which ranged from increased NFKB1 protein degradation, reduced DNA binding of NFKB1 to overall reduced NFKB1 function through altered protein structure: This may hint towards their likely pathogenicity. Analysis of NFKB1 variant protein interactions showed varied effects from loss of interaction with NFKB family proteins to some variants interactions appearing similar to wild type NFKB1. "These projects are excellent examples of fruitful international multidisciplinary research collaborations between the University of Helsinki and the leading clinical research hospitals and centers in Europe. Our findings significantly deepen the understanding of the molecular mechanisms underlying NFKB1, and other autoinflammatory and autoimmune diseases associated with altered NFkB1 expression or function," says Varjosalo. "Also, our results yet again suggest that targeted inhibition of certain key NFkB signaling pathway components is an attractive therapeutic approach for treating these diseases which could be collectively paraphrased as diseases of NF-kB signaling."

Study results appeared in "Biomaterials Advances", a highly respected peer-reviewed journal, showcasing growing medical recognition of Company's patented RNA delivery platform for extrahepatic targets. Company's RNA delivery platform demonstrated effectiveness in mitigating abdominal aortic aneurysm progression and rupture in murine model. HAMILTON, BERMUDA / ACCESSWIRE / July 12, 2022 / Altamira Therapeutics ("Altamira" or the "Company") (NASDAQ:CYTO), a company dedicated to developing therapeutics that address important unmet medical needs, today announced the publication of a peer-reviewed article in the scientific journal Biomaterials Advances titled, "Peptide-siRNA nanoparticles targeting NF-κB p50 mitigate experimental abdominal aortic aneurysm (AAA) progression and rupture" that covers a study conducted by a research group at Washington University, St. Louis, MO. The article, which was co-authored by Altamira's Chief Scientific Officer, Samuel Wickline, MD, reported the study's key findings that the Company's peptide-based OligoPhore™ delivery platform using siRNA is effective in mitigating abdominal aortic aneurysm (AAA) progression and rupture in a preclinical murine model study. The study was designed, conducted, and analyzed independently of Altamira, and sponsored in part by research grants from the National Institutes of Health and the Veterans Administration. The peptide-based RNA delivery platform was invented at Washington University and licensed to Altamira, which is now under development as OligoPhore for delivery of siRNA and as SemaPhore™ for mRNA. Abdominal Aortic Aneurysm is a Severe Condition Lacking Non-Surgical Treatment Options AAA is a progressive vascular condition that accounts for approximately 15,000 deaths per year in the United States due to rupture. AAA is an inflammatory process with excessive local production of extracellular matrix degrading enzymes, leading to dilatation and rupture of the abdominal aorta. AAA is a complex disease associated with male gender, advanced age, hypertension, hypercholesterolemia, coronary artery disease, atherosclerosis, and cigarette smoking. Presently, open surgical repair of large AAA is an effective option in preventing death from rupture. Although effective, open surgical repair is recommended only for large aneurysms and can be associated with high post-operative mortality. Given the high mortality rate associated with surgical treatment, and the advanced age of patients with AAA, which may preclude them from undergoing major surgery, medical treatment represents an attractive alternative approach. However, at present there is no medical therapy specific to the fundamental disease process and standard of care is primarily supportive with cholesterol lowering agents and beta blockers. Study Highlights The study identified the NF-κB p50 and p65 subunits as key modulators of the inflammatory process contributing to the development of AAA. The knockdown of NF-κB subunits using siRNA delivered by Altamira's peptide-based nanoparticles was shown to mitigate aneurysm progression and rupture in two different experimental models. Since the p50 knockdown was more effective at preventing rupture, the article discussed that p50 represents a preferable target for rational drug design in AAA treatment since it lacks a transactivating domain and its knockdown may carry less risk of adverse effects. "This study's results reinforce our hypotheses that the NF-κB pathway, with both p50 and p65 subunits contributing, is a primary driver of potentially lethal or severe inflammatory conditions and, accordingly, present high-value targets for our patented peptide-based delivery platform," said Dr. Wickline. "We are strongly encouraged by the findings of this study and see this as an important milestone as we advance our RNA delivery platform technology to suppress the critical molecular drivers of inflammatory vascular diseases. "Our patented OligoPhore platform for extrahepatic delivery of nucleotide therapeutics offers significant potential for the treatment of AAA and other inflammatory indications that currently lack safe or low-risk efficacious therapeutics," Dr. Wickline added. About Biomaterial Advances Biomaterials Advances sits within Elsevier's biomaterials science portfolio alongside Biomaterials, Materials Today Bio and Biomaterials and Biosystems. As part of the broader Materials Today family, Biomaterials Advances offers authors rigorous peer review, rapid decisions, and high visibility. The journal publishes on topics at the interface of the biomedical sciences and materials engineering. For more information, visit: About OligoPhore OligoPhore is a versatile platform for safe and effective delivery of oligonucleotides such as siRNA (small interfering ribonucleic acid) into target cells. It is based on a proprietary 21 amino acid peptide that can engage any type of RNA in rapid self-assembly into a polyplex. The polyplex has a size, charge, and other physical features that allow it to escape hepatic clearance and thus to reach other target tissues than the liver. OligoPhore protects the RNA payload from degradation in the circulation and allows for rapid cellular uptake, while enabling pH-dependent nucleotide endosomal escape and cytoplasmic delivery. Effective delivery and positive treatment outcomes have been demonstrated in more than 10 murine models of disease for targets in the NF-κB family, various members of the ETS transcription factor family, and targets in the JNK and TAM pathways. About Altamira Therapeutics Altamira Therapeutics (NASDAQ:CYTO) is dedicated to developing therapeutics that address important unmet medical needs. The Company is currently active in three areas: the development of RNA therapeutics for extrahepatic therapeutic targets (OligoPhore™ / SemaPhore™ platforms; preclinical), nasal sprays for protection against airborne viruses and allergens (Bentrio™; commercial) or for the treatment of vertigo (AM-125; Phase 2), and the development of therapeutics for intratympanic treatment of tinnitus or hearing loss (Keyzilen® and Sonsuvi®; Phase 3). Founded in 2003, it is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: Forward-Looking Statements This press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or Altamira Therapeutics' strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may", "might", "will", "should", "expects", "plans", "anticipates", "believes", "estimates", "predicts", "projects", "potential", "outlook" or "continue", or the negative of these terms or other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. 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These risks and uncertainties also include, but are not limited to, those described under the caption "Risk Factors" in Altamira Therapeutics' Annual Report on Form 20-F for the year ended December 31, 2021, and in Altamira Therapeutics' other filings with the SEC, which are available free of charge on the Securities Exchange Commission's website at: . Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those indicated. All forward-looking statements and all subsequent written and oral forward-looking statements attributable to Altamira Therapeutics or to persons acting on behalf of Altamira Therapeutics are expressly qualified in their entirety by reference to these risks and uncertainties. You should not place undue reliance on forward-looking statements. 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Curis scientists discover novel IRAK4 nuclear localization and describe potential use as a biomarker IRAK4 along with NF-kB p50/p65 localization to the nucleus is associated with improved response to emavusertib Promising clinical and preclinical analysis showcases the potential of emavusertib in treating pCNSL LEXINGTON, Mass., June 10, 2022 /PRNewswire/ -- Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, today announced the presentation of novel findings on biomarker development for IRAK4 inhibitor emavusertib, collaborative work from the University of Florida in primary CNS lymphoma (pCNSL), and clinical data from the TakeAim Leukemia and TakeAim Lymphoma studies at the 2022 European Hematology Association (EHA) Hybrid Congress currently taking place in Vienna, Austria and online until June 12, 2022. "We are delighted to share with our colleagues in Europe our findings regarding IRAK4's previously undescribed localization in the nucleus of cancer cells. It appears that when IRAK4 is found in the nucleus with active NF-kB proteins p50 and p65, using a technique which we refer to as 'triple staining,' this triple nuclear presence is associated with better responses to emavusertib," said James Dentzer, President and Chief Executive Officer of Curis. "Also at EHA this year, collaborative work by Dr. Duane Mitchell's team at the University of Florida is being presented on the potential role of emavusertib in treating pCNSL, including data on one patient who achieved a complete response following previous treatment with ibrutinib," Mr. Dentzer continued. "And finally, in addition to this foundational work on IRAK4 biology, we are presenting data from our TakeAim Lymphoma and TakeAim Leukemia studies as we continue to spread the word on IRAK4 and the utility of inhibiting this important target to our European colleagues." Curis scientists have discovered previously unknown nuclear accumulation of IRAK4 selectively in acute myeloid leukemia (AML) cells whereas nuclear IRAK4 was not detectable in mature myeloid cells (#2609). IRAK4 nuclear accumulation is significantly correlated with NF-kB activation in bone marrow samples from de novo AML patients and in AML cell lines. The detection of IRAK4 and NF-kB (phospho-p50 and phospho-p65) using nuclear staining of blasts in AML bone marrow samples was defined as 'triple-positive,' and patients whose cells did not stain for the nuclear presence of any of the three markers were termed 'triple-negative.' Treatment with emavusertib led to a significant decrease in bone marrow blast count in AML patients whose bone marrow sample was triple-positive, whereas no significant decrease in bone marrow blast count was detected in triple-negative cases. The goal of the Company's biomarker work is to develop a companion diagnostic for emavusertib that is broadly applicable and is intended to identify the patients most likely to benefit from emavusertib treatment. Research from Curis collaborators at the University of Florida in pCNSL (#2715) show that, in a patient treated on the TakeAim Lymphoma study in the combination arm following a previous ibrutinib containing regimen, the combination of emavusertib and ibrutinib resulted in a complete response. The team also observed that IRAK-4 and NF-kB proteins have elevated expression levels in human pCNSL. Further, in preclinical work, the team showed that emavusertib achieves therapeutically relevant concentrations in brain parenchyma and shows single-agent activity in an aggressive model of pCNSL. Also presented at the EHA meeting were previously presented data from the TakeAim Leukemia (#3975) and TakeAim Lymphoma (#3875) studies. TakeAim Leukemia is being orally presented, and TakeAim Lymphoma is the subject of a poster at the meeting. The data from these studies were also presented at the American Society of Clinical Oncology meeting last week in Chicago. About Emavusertib (CA-4948) Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-κB protein complex. Additionally, third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutation such as SF3B1 and U2AF1. In addition to inhibiting IRAK4, emavusertib was also designed to inhibit FLT3, a known oncologic driver, which may provide additional benefit in patients with AML and MDS. About TakeAim Lymphoma The TakeAim Lymphoma study (NCT03328078) is a Phase 1/2 open-label, dose escalation, dose expansion clinical trial investigating emavusertib as monotherapy and in combination with ibrutinib in patients with R/R hematologic malignancies, such as non-Hodgkins's lymphoma and other B cell malignancies. After dose escalation in both monotherapy and combination therapy to determine the recommended Phase 2 dose (RP2D), we plan to expand four cohorts for combination treatment: marginal zone lymphoma, activated b-cell diffuse large b-cell lymphoma, primary CNS lymphoma, and patients developing adaptive resistance to ibrutinib monotherapy. The goals of the study are to determine several parameters including safety, maximum tolerated dose (MTD), RP2D and signals of activity. About TakeAim Leukemia The TakeAim Leukemia study (NCT04278768) is a Phase 1/2 dose escalation and dose expansion study examining emavusertib use as both monotherapy and in combination with azacitidine or venetoclax in patients with R/R AML or high risk MDS. After dose escalation in both monotherapy and combination therapy to determine the recommended Phase 2 dose, we plan to expand five cohorts: monotherapy in AML patients with spliceosome and FLT3 mutations, monotherapy in patients with MDS and spliceosome mutations and combination therapy with azacitidine or venetoclax in patients without spliceosome or FLT3 mutations. The goals of the study are to determine several parameters including safety, maximum tolerated dose (MTD), RP2D and signals of activity. About Curis, Inc. Curis is a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer. In 2015, Curis entered into a collaboration with Aurigene in the areas of immuno-oncology and precision oncology. As part of this collaboration, Curis has exclusive licenses to oral small molecule antagonists of immune checkpoints including the VISTA/PDL1 antagonist CA-170, and the TIM3/PDL1 antagonist CA-327, as well as the IRAK4 kinase inhibitor, emavusertib (CA-4948). Emavusertib is currently undergoing testing in the Phase 1/2 TakeAim Lymphoma trial, in patients with hematologic malignancies, such as non-Hodgkins lymphoma and other B cell malignancies, both as a monotherapy and in combination with BTK inhibitor ibrutinib, and the Phase 1/2 TakeAim Leukemia trial in patients with acute myeloid leukemia and myelodysplastic syndrome, for which it has received Orphan Drug Designation from the U.S. Food and Drug Administration. The FDA has placed a partial clinical hold on the TakeAim Leukemia and TakeAim Lymphoma trials during which no new patients will be enrolled, and current study participants benefiting from treatment may continue to be treated with emavusertib at doses of 300mg BID or lower. In addition, Curis is engaged in a collaboration with ImmuNext for development of CI-8993, a monoclonal anti-VISTA antibody, which is currently undergoing testing in a Phase 1 trial in patients with solid tumors. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge® for the treatment of advanced basal cell carcinoma. For more information, visit Curis's website at . Cautionary Note Regarding Forward-Looking Statements: This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, including, without limitation, any statements with respect to Curis's plans, strategies, objectives or financial results; statements concerning product research, development, clinical trials and studies and commercialization plans, timelines, anticipated results or the therapeutic potential of drug candidates including any statements regarding the initiation, progression, expansion, use, efficacy, dosage and potential benefits of CA-4948 in clinical trials as a monotherapy and/or as a combination therapy, the progression, use and potential benefits of CI-8993, Curis's plans and timelines to provide preliminary, interim and/or additional data from its ongoing or planned clinical trials, any statements concerning Curis's expectations regarding its interactions with the FDA or its ability to resolve the partial clinical hold of the TakeAim Leukemia study or the partial clinical hold of the TakeAim Lymphoma study, and statements with respect to mutations or potential biomarkers; and statements of assumptions underlying any of the foregoing. Forward-looking statements may contain the words "believes," "expects," "anticipates," "plans," "intends," "seeks," "estimates," "assumes," "predicts," "projects," "targets," "will," "may," "would," "could," "should," "continue," "potential," "focus," "strategy," "mission," or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements. For example, the FDA may not remove the partial clinical hold on the Phase 1/2 TakeAim Leukemia trial or the partial clinical hold on the Phase 1/2 TakeAim Lymphoma trial, or may take further regulatory action with regard to such trials; Curis may experience adverse results, delays and/or failures in its drug development programs and may not be able to successfully advance the development of its drug candidates in the time frames it projects, if at all. Curis's drug candidates may cause unexpected toxicities, fail to demonstrate sufficient safety and efficacy in clinical studies and/or may never achieve the requisite regulatory approvals needed for commercialization. Favorable results seen in preclinical studies and early clinical trials of Curis's drug candidates may not be replicated in later trials. There can be no guarantee that the collaboration agreements with Aurigene and ImmuNext will continue for their full terms, or the CRADA with NCI, that Curis or its collaborators will each maintain the financial and other resources necessary to continue financing its portion of the research, development and commercialization costs, or that the parties will successfully discover, develop or commercialize drug candidates under the collaboration. Regulatory authorities may determine to delay or restrict Genentech's and/or Roche's ability to continue to develop or commercialize Erivedge in BCC. Erivedge may not demonstrate sufficient or any activity to merit its further development in disease indications other than BCC. Competing drugs may be developed that are superior to Erivedge. In connection with its agreement with Oberland Capital, Curis faces risks relating to the transfer and encumbrance of certain royalty and royalty-related payments on commercial sales of Erivedge, including the risk that, in the event of a default by Curis or its wholly-owned subsidiary, Curis could lose all retained rights to future royalty and royalty-related payments, Curis could be required to repurchase such future royalty and royalty-related payments at a price that is a multiple of the payments it has received, and its ability to enter into future arrangements may be inhibited, all of which could have a material adverse effect on its business, financial condition and stock price. Curis will require substantial additional capital to fund its business. If it is not able to obtain sufficient funding, it will be forced to delay, reduce in scope or eliminate some of its research and development programs, including related clinical trials and operating expenses, potentially delaying the time to market for, or preventing the marketing of, any of its product candidates, which could adversely affect its business prospects and its ability to continue operations, and would have a negative impact on its financial condition and its ability to pursue its business strategies. Curis faces substantial competition. Curis and its collaborators face the risk of potential adverse decisions made by the FDA and other regulatory authorities, investigational review boards, and publication review bodies. Curis may not obtain or maintain necessary patent protection and could become involved in expensive and time-consuming patent litigation and interference proceedings. Unstable market and economic conditions, natural disasters, public health crises, political crises and other events outside of Curis's control could significantly disrupt its operations or the operations of third parties on which Curis depends and could adversely impact Curis's operating results and its ability to raise capital. For example, the COVID-19 pandemic may result in closures of third-party facilities, impact enrollment in clinical trials or impact sales of Erivedge by Genentech and/or Roche. The extent to which the COVID-19 pandemic may impact Curis's business or operating results is uncertain. Other important factors that may cause or contribute to actual results being materially different from those indicated by forward-looking statements include the factors set forth under the captions "Risk Factor Summary" and "Risk Factors" in our most recent Form 10-K and Form 10-Q, and the factors that are discussed in other filings that we periodically make with the Securities and Exchange Commission ("SEC"). In addition, any forward-looking statements represent the views of Curis only as of today and should not be relied upon as representing Curis's views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise, except as may be required by law. SOURCE Curis, Inc.