Panbela Announces Sponsored Research Agreement to Evaluate Polyamine Metabolic Inhibitor Therapy in Combination with CAR-T Cell Therapy

MINNEAPOLIS, June 13, 2023 (GLOBE NEWSWIRE) — Panbela Therapeutics, Inc . (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, today announced it has entered into a sponsored research agreement with The University of Texas MD Anderson Cancer Center for the evaluation of polyamine metabolic inhibitor therapies in combination with CAR-T cell therapies in preclinical models. The initial goal of these studies will be to ascertain if eflornithine and/or ivospemin treatment will augment CAR-T mediated cytotoxicity against CD19+ large B-cell lymphoma (LBCL) cell lines.   Recently, a metabolite panel primarily consisting of polyamines was identified as predictive of poor response to anti-CD19 CAR T-cell therapy in relapsed refractory LBCL. Additionally, the polyamine (PA) uptake transport system is upregulated in LBCL and multiple myeloma (MM). Together, this suggests the potential for a polyamine targeted therapy in combination with CAR-T therapies.

“While the literature has demonstrated the relationship between polyamines and the immune system, recent research shows that an elevated polyamine metabolic profile correlated to poor response to CAR-T cell therapy. This suggests that by combining our polyamine metabolic inhibitors, such as eflornithine and ivospemin, with CAR-T cell therapy it may overcome this resistance mechanism and have the potential to improve initial response rates and durability of response,” said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. “Polyamine modulation of the immune system is an important focus for Panbela. With our first clinical proof of concept of polyamine targeted therapy in combination with a checkpoint inhibitor for patients with STK11 non-small cell lung cancer, we are excited for this research collaboration to now evaluate the potential benefit of polyamines in immune modulation for hematologic malignancies.”  

“There is a huge unmet need to improve CAR-T cell therapies for LBCL patients. Although the majority of LBCL patients can be cured with first-line therapy, the remaining ~40% will be refractory to or relapse from first-line therapy and have an average overall survival of ~6 months. Based on a recent publication by Fahrmann et al, an elevated polyamine metabolic blood signature correlated with poor response to therapy and elevated spermine synthase was prognostic for survival. Based on this data, we are excited to initiate our research collaboration to determine if modulating polyamines improves CAR-T cell activity preclinically with the hope that this may translate into a clinical benefit for LBCL patients and others with hematologic malignancies,” said Elizabeth Bruckheimer, Ph.D. Vice President & Chief Scientific Officer of Panbela.

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 (SBP-101)
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™
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
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.

About Panbela
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”.

Cautionary Statement Regarding Forward-Looking Statements
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Contact Information:

Investors:
James Carbonara
Hayden IR
(646) 755-7412
james@haydenir.com

Media:
Tammy Groene
Panbela Therapeutics, Inc.
(952) 479-1196
IR@panbela.com