MINNEAPOLIS, June 26, 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 announces a poster presentation highlighting the results for CPP-1X (also known as α-Difluoromethylornithine (DFMO) or Eflornithine) in recent onset type 1 diabetes at the Endocrine Society meeting, which was held June 15-18, 2023. The work reflects the Company’s ongoing collaboration with Indiana University (IU) School of Medicine.
The research is part of a multi-site clinical trial led by Indiana University School of Medicine, supported by funding from JDRF, the leading global type 1 diabetes (T1D) research and advocacy organization. The preclinical data were generated by Raghavendra Mirmira's laboratory at the University of Chicago. Panbela Therapeutics is providing the drug at no cost to researchers and was not involved in the design and analysis of these studies.
“These preclinical studies examined the role of ornithine decarboxylase (ODC) on β cell stress that occurs in T1D. Results showed that stressed human islet cells treated with CPP-1X had alterations in several pathways such as antigen presentation, and reactive oxygen species.” said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. “Together with data from recent onset T1D patients treated with CPP-1X in the multi-site randomized, placebo-controlled Phase I trial, these results suggest that inhibition of ODC by CPP-1X may preserve β cell function in response to stress.”
"These results expand on the previously presented work identifying potential mechanisms for CPP-1X and its potential role in the clinical management of recent onset type 1 diabetes.” said Dr. Simpson “We are excited to support the recently initiated IU and JDRF-funded Phase II trial in recent onset T1D and the goal of developing effective novel therapies for patients with unmet medical needs.”
The poster investigates the mechanism of polyamines and polyamine inhibition by CPP-1X on β cell stress that plays a role in the onset of type 1 diabetes in in vitro and ex vivo models. Human islet cells were either treated with vehicle or CPP-1X and RNA sequencing and proteomics were performed. Results showed that CPP-1X treatment of stressed human islets cells resulted in altered pathways related to endoplasmic reticulum-related protein processing, antigen presentation, and reactive oxygen species. In vivo studies in mice with β cell-specific deletion of ODC showed improved glucose tolerance, increased β cell mass, and reduced incidence of diabetes following streptozotocin treatment.
In the Phase 1 dose range finding study of in patients with recent onset T1D, CPP-1X was well tolerated and a dose dependent inhibition of ODC was observed. An exploratory secondary analysis showed that at the two highest dose levels, treatment with CPP-1X stabilized C-peptide areas under the curve compared to placebo. When assessing immune cell populations, there were no differences between the placebo and CPP-1X patients.
Results from these studies suggest that CPP-1X is a safe, oral treatment option that may improve β cell function and/or survival in recent onset T1D.
Details of the presentation are as follows:
Title: Deletion or inhibition of Ornithine Decarboxylase Protects Islet β-Cell Health and is Associated with Preserved Residual C-peptide in Persons with Recent Onset Type 1 Diabetes
Abstract Control Number: 7860
Poster Board Number: THU-277
Session Number: P14
Session Type: Poster Abstract
Session Title: Diabetes & Vascular Disease: Clinical Diabetes
Additional meeting information can be found on the Endocrine Society website: https://www.endocrine.org/meetings-and-events/endo2023/program
The poster will also be available on the Company's website at https://panbela.com/events-presentations/
About Panbela’s Pipeline
The 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 and ovarian cancer. The combined development programs have a steady cadence of anticipated catalysts with programs ranging from pre-clinical to registration studies.
Ivospemin 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.
Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increasing polyamine export and catabolism. In a Phase III 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 III 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), 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 (eflornithine) is being developed as a single agent tablet or high dose powder sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase I or Phase II investigator-initiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity.
Panbela 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”.
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Panbela Therapeutics, Inc.