Gastrointestinal polyps

Rare disease charity PTEN Research Foundation welcomes two new senior leaders from the pharmaceutical industry, Professor Sir Mene Pangalos and Dr Donald Ogilvie to the Foundation’s Scientific Advisory Board (SAB). By strengthening its scientific oversight, the Foundation hopes to further progress and accelerate its mission to fund and facilitate research that will lead to better treatments and improved outcomes for people with PTEN Hamartoma Tumour Syndrome (PHTS). CHELTENHAM, England--(BUSINESS WIRE)-- PTEN Research Foundation, a charity which funds and facilitates research with the aim of developing new and better treatments for the rare disease PTEN Hamartoma Tumour Syndrome (PHTS), today announced that it has further strengthened its scientific oversight of activities with two new senior leaders, Dr Donald Ogilvie and Prof Sir Mene Pangalos, joining the Foundation’s Scientific Advisory Board (SAB). This press release features multimedia. View the full release here: Prof Sir Menelas (Mene) Pangalos DSc PhD FRSB FMedSci HonFBPhS FRS (Photo: Business Wire) “We are honoured that two such senior leaders with a wealth of drug development experience have agreed to join the Foundation’s Scientific Advisory Board,” said Thomas Pepper, Chief Executive of PTEN Research Foundation. “The SAB has a critical role in steering the Foundation’s scientific strategy and we continue to be privileged that senior leaders from pharma and biotech, as well as academic physicians and scientists with a deep knowledge of PHTS, have been willing to join the Board and guide the Foundation’s mission.” PHTS is a condition caused by an alteration in the PTEN gene. Such an alteration, which may be inherited from the mother or father, or occur spontaneously during embryonic development, can affect multiple organs and result in a variety of symptoms. These include macrocephaly (enlarged head circumference), learning difficulties, autism spectrum disorder, vascular anomalies (abnormal growth of the blood vessels), gastrointestinal polyps (growths in the gut), and hamartomas (benign lesions of the skin and other tissues). In addition, people with PHTS have a significantly increased risk of developing cancer of the breast, thyroid and endometrium (lining of the womb). Notes for Editors About Dr Donald Ogilvie MA DPhil Donald is an independent scientific consultant providing expert advice on cancer drug discovery to academic, industrial, and venture capital organisations. Donald obtained an MA in Biochemistry at the University of Oxford, UK, in 1980, before working at the John Radcliffe Hospital, Oxford, for eight years on the role of proteases in cancer, then on inherited connective tissue disorders. The latter was the basis of his DPhil degree. In 1988, Donald joined ICI which subsequently became Zeneca then AstraZeneca. For most of his twenty-year career in the pharmaceutical industry, he worked on cancer drug discovery and early clinical development projects. He was directly responsible for the delivery of ten novel cancer development compounds, several of which have progressed to phase II & III clinical trials and two, so far, to regulatory approval. Between 2009 and 2017, Donald set up and led the academic Drug Discovery Unit at the Cancer Research UK Manchester Institute (University of Manchester, UK). Under his leadership, the team built a drug discovery infrastructure and a leading cancer project portfolio. During this period, three projects, including one with a development compound, were successfully licensed to downstream partners. Donald is a co-author on more than ninety peer-reviewed academic publications. About Prof Sir Menelas (Mene) Pangalos DSc PhD FRSB FMedSci HonFBPhS FRS Until Spring 2024 Mene held the role of Executive Vice President, Research and Development at AstraZeneca being responsible for R&D from discovery through to late-stage development covering Cardiovascular, Renal, Metabolism, Respiratory, Immunology, Microbial Science and Neuroscience areas. Prior to this, he served as Executive Vice-President of AstraZeneca’s Innovative Medicines & Early Development Biotech Unit and Global Business Development. During his time with AstraZeneca, Mene led the transformation of R&D productivity through the development and implementation of the “5R” framework resulting in a greater than four-fold increase in success rates compared to industry averages. In parallel, he has championed an open approach to working with academic and other external partners, changing the nature of academic-industry collaboration. In addition, Mene led and oversaw AstraZeneca’s R&D response to COVID-19; maintaining existing clinical trials and delivery of medicines to patients, responding to the UK government’s call for supporting its national testing effort, and discovering and developing new preventative and treatment approaches to the disease. This work involved partnering with Oxford University in the global development of a vaccine and ensuring broad and equitable access at no profit during the pandemic, the discovery and development of a long-acting antibody combination for those who could not be vaccinated, as well as exploring AstraZeneca’s existing portfolio as potential treatment options against the disease. The team were awarded the Copley Medal by the Royal Society in 2023. Mene previously held senior R&D roles at Wyeth and GSK. Mene holds Honorary Doctorates from Glasgow University and Imperial College, London, is a Fellow of the Academy of Medical Sciences, the Royal Society of Biology and Clare Hall, University of Cambridge and is a Visiting Professor at The Wolfson Centre at King’s College. He co-chairs the UK Life Sciences Council Expert Group on Innovation, Clinical Research and Data and is a member of the Life Sciences Industrial Strategy Implementation Board. He is also on the Boards of The Francis Crick Institute and The Judge Business School, Cambridge University, and is a member of the Life Sciences Vision Advisory Group. Mene was awarded the 2019 Prix Galien Medal, Greece for his scientific research and named Executive of the Year at the 2019 Scrip Awards. In 2019, Mene was awarded the honour of a Knighthood by Queen Elizabeth II for his services to UK science. In 2021 Mene was awarded an Honorary Fellowship of the British Pharmacological Society. In 2022 Mene was elected as a Fellow of The Royal Society and an honorary professor of Cambridge University Medical School. About PHTS PHTS is a rare genetic disorder caused by alteration in the PTEN (phosphatase and tensin homolog) gene that results in a variety of symptoms in multiple organs. These alterations, which may be inherited from the mother or father or occur spontaneously during embryonic development, can result in a variety of symptoms. These include macrocephaly (enlarged head circumference), learning difficulties, autism spectrum disorder, vascular anomalies (abnormal growth of the blood vessels), gastrointestinal polyps (growths in the gut), and hamartomas (benign lesions of the skin and other tissues). In addition, people with PHTS have an increased lifetime risk of developing cancer, particularly breast, thyroid, and endometrial (lining of the womb) cancer. Estimating the prevalence of PHTS is complex due to the varied presentations and diagnoses patients can have and because some features (e.g. benign breast lesions) also commonly occur in the general population. The prevalence of PHTS is estimated to be about 1 in 200,000, although this is likely to be an underestimate. There are currently no health authority-approved treatments specific to PHTS, and clinical management consists mainly of cancer surveillance and supportive care. The need for cancer surveillance and lifelong supportive care places a high burden on affected individuals, their families and on healthcare systems. About PTEN Research Foundation PTEN Research Foundation was established as a charity under English law in 2017 (charity number 1173589). The Foundation’s mission is to fund and facilitate research that will lead to new and better treatments for individuals with PHTS. PTEN Research Foundation aims to have transformative therapies available as treatment options for people with PHTS within 10 years. The Foundation’s strategy is centred on the generation of preclinical and clinical evidence that will enable the Foundation, and others (both academic collaborators and industry), to develop treatment options for people with PHTS.

Hard-to-detect colorectal pre-cancerous lesions known as serrated polyps, and the aggressive tumors that develop from them, depend heavily on the ramped-up production of cholesterol, according to a preclinical study. The finding points to the possibility of using cholesterol-lowering drugs to prevent or treat such tumors. Hard-to-detect colorectal pre-cancerous lesions known as serrated polyps, and the aggressive tumors that develop from them, depend heavily on the ramped-up production of cholesterol, according to a preclinical study from researchers at Weill Cornell Medicine. The finding points to the possibility of using cholesterol-lowering drugs to prevent or treat such tumors. In the study, published Oct. 13 in Nature Communications, the researchers analyzed mice that develop serrated polyps and tumors, detailing the chain of molecular events in these tissues that leads to increased cholesterol production. They confirmed their findings in analyses of human serrated polyps and tumors, and showed in mouse models that replicate the human cancer that blocking cholesterol production prevented the progression of these types of intestinal tumors. "Serrated-type polyps and tumors currently are not treated differently from other colorectal neoplasias, but as our work shows, they have this specific metabolic vulnerability that can be targeted," said study co-senior author Dr. Jorge Moscat, a Homer T. Hirst III Professor of Oncology in Pathology, Vice-Chair for Cell and Cancer Pathobiology in the Department of Pathology and Laboratory Medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. The other co-senior author is Dr. Maria Diaz-Meco, also a Homer T. Hirst III Professor of Oncology in Pathology and a member of the Meyer Cancer Center at Weill Cornell Medicine. The study's first author is Dr. Yu Muta, a postdoctoral associate in the Moscat/Diaz-Meco laboratories. Cholesterol is generally considered a pro-growth molecule, being a building block for cell membranes and having other growth-supporting functions. Prior studies have linked high blood cholesterol levels to various cancers, including colorectal cancers. However, it hasn't been clear that lowering cholesterol, for example with common statin drugs, can prevent colorectal cancers. "Trials of statins to prevent colorectal cancer have had conflicting results," Dr. Diaz-Meco said. "Our findings suggest that this is because targeting cholesterol has a preventive but selective effect only against polyps and tumors of this serrated type." Serrated polyps are so-called because of their sawtooth appearance under a microscope. They are flatter than ordinary colorectal polyps and can often be missed during colonoscopies. Yet the tumors into which they develop, which account for roughly 15 to 30 percent of colorectal cancers, contain many "metaplastic" cells that are particularly invasive and resistant to treatments. Several years ago, the Moscat/Diaz-Meco team linked serrated polyps and tumors to low levels of two enzymes known as aPKCs. They showed that mice engineered to lack these aPKC enzymes in their gut linings reliably form serrated polyps and then aggressive tumors. In the new study, the scientists found that in serrated-type tumors in these mice, and even in intestinal tissue poised to develop these types of cancerous lesions, cholesterol synthesis was strikingly upregulated, suggesting that cholesterol may be an early driver of tumor development. The researchers revealed how the absence of aPKC enzymes, especially in metaplastic tumor cells, unleashes the activation of a transcription factor called SREBP2, which switches on cholesterol production. Tests on colorectal polyp and tumor samples from human patients dovetailed with the mouse findings. They found, for example, that only serrated-type tumors had low aPKC levels concomitant with the accumulation of SREBP2, a driver and a marker of upregulated cholesterol biosynthesis in the serrated cancer cells. Lastly, the researchers tested a combination of two cholesterol synthesis-blocking drugs, including the widely used atorvastatin. The treatment, delivered when the low-aPKC mice were still quite young, significantly lowered the rate at which both serrated polyps and tumors later formed -- and the serrated-type tumors that did form were less aggressive than those normally arising in the untreated mice. The results indicate that targeting cholesterol could be a viable strategy for treating and preventing serrated-type colorectal tumors. The Moscat and Diaz-Meco labs are now hoping to set up an initial clinical trial of a cholesterol-lowering intervention in patients from whom serrated colorectal polyps have been removed. "Currently when these polyps are detected early with colonoscopy, they are removed and patients have to hope that they don't come back," Dr. Moscat said. "In the future, we hope to have a more active method to prevent this very aggressive form of cancer before it is fully developed and more difficult to treat."

Patent developed in collaboration with SanofiMINNEAPOLIS, Sept. 05, 2023 (GLOBE NEWSWIRE) -- Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical-stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, today announced an Issue Notification for the Chilean patent 1157-2018 titled “Eflornithine and Sulindac, Fixed Dose Combination Formulation”. This product, developed in collaboration with Sanofi, claims a novel composition of a fixed dose formulation of eflornithine and sulindac, which is called Flynpovi. This is Panbela’s lead investigational product for the treatment of patients with Familial Adenomatous Polyposis (FAP). The patent is valid until 2036, has issued in the US, Australia, Mexico, and Taiwan. The application is under review in additional countries. Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela Therapeutics, commented, “We’re excited to have this patent issued in Chile as this further expands our patent portfolio and supports our global clinical programs. First issued in the United States in 2021 and now in several other territories, this patent covers the novel co-formulation of Flynpovi, our lead FAP product in development." Dr. Simpson added, “We are pleased with the continued growth of our patent portfolio with this latest patent issuance. The co-formulated product described in this patent has the potential to be the first pharmacotherapy approved for patients with FAP. By co-formulating eflornithine and sulindac in the same tablet, it provided FAP patients with an easier option for administration and compliance.” About our PipelineThe pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention, ovarian cancer and diabetes. The combined development programs have a steady cadence of catalysts with programs ranging from pre-clinical to registration studies. SBP-101 IvospeminIvospemin is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. It has shown signals of tumor growth inhibition in clinical studies of metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, both exceeding what is typical for the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, ivospemin has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the previous Panbela-sponsored clinical trials provide support for continued evaluation of ivospemin in the ASPIRE trial. For more information, please visit https://clinicaltrials.gov/ct2/show/NCT03412799 . Flynpovi ™Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increase polyamine export and catabolism. In a Phase 3 clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase 3 trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP. CPP-1X EflornithineCPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer and recent onset Type 1 diabetes. Preclinical studies as well as Phase 1 or Phase 2 investigator-initiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity. About PanbelaPanbela Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing disruptive therapeutics for patients with urgent unmet medical needs. Panbela’s lead assets are Ivospemin (SBP-101) and Flynpovi. Further information can be found at www.panbela.com . Panbela’s common stock is listed on The Nasdaq Stock Market LLC under the symbol “PBLA”. Cautionary Statement Regarding Forward-Looking StatementsThis press release contains “forward-looking statements,” including within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: “anticipate,” “design,” “may,” “plan,” and “will.” Examples of forward-looking statements include statements we make regarding timing of trials and results of collaborations with third parties and future studies. All statements other than statements of historical fact are statements that should be deemed forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations, and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially and adversely from the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: (i) our ability to obtain additional funding to execute our business and clinical development plans; (ii) our lack of diversification the corresponding risk of an investment in our Company; (iii) our ability to maintain our listing on a national securities exchange; iv) progress and success of our clinical development program; (v) our ability to demonstrate the safety and effectiveness of our product candidates: ivospemin ( SBP-101 ), Flynpovi, and eflornithine (CPP-1X) (v) our ability to obtain regulatory approvals for our product candidates, SBP-101, Flynpovi and CPP-1X in the United States, the European Union or other international markets; (vii) the market acceptance and level of future sales of our product candidates, SBP-101, Flynpovi and CPP-1X ; (viii) the cost and delays in product development that may result from changes in regulatory oversight applicable to our product candidates, SBP-101, Flynpovi and CPP-1X ; (ix) the rate of progress in establishing reimbursement arrangements with third-party payors; (x) the effect of competing technological and market developments; (xi) the costs involved in filing and prosecuting patent applications and enforcing or defending patent claims; ; and (xi) such other factors as discussed in Part I, Item 1A under the caption “Risk Factors” in our most recent Annual Report on Form 10-K, any additional risks presented in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Any forward-looking statement made by us in this press release is based on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement or reasons why actual results would differ from those anticipated in any such forward-looking statement, whether written or oral, whether as a result of new information, future developments or otherwise. Contact Information: Investors:James CarbonaraHayden IR(646) 755-7412james@haydenir.com Media:Tammy GroenePanbela Therapeutics, Inc.(952) 479-1196IR@panbela.com