Panbela Therapeutics, Inc. (PBLA) is a clinical-stage biopharmaceutical company dedicated to developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs. The company's lead assets, ivospemin (SBP-101), Flynpovi™ (eflornithine (CPP-1X) and sulindac), and eflornithine (CPP-1X), provide a multi-targeted approach to reset dysregulated biology present in many types of diseases such as cancer and autoimmunity.

Panbela's primary objective is to utilize pharmacotherapies that can reduce or normalize increased disease-associated polyamines, which are essential for the growth and survival of many tumors. The company's lead candidates have the potential to suppress and prevent tumor growth, enhance anti-tumor activity of other anti-cancer agents, and modulate the immune system.

Business Overview

Ivospemin (SBP-101)

Panbela has exclusively licensed the worldwide rights to ivospemin from the University of Florida Research Foundation, Inc. The company has completed an initial clinical trial of ivospemin in patients with previously treated locally advanced or metastatic pancreatic cancer. This was a Phase I, first-in-human, dose-escalation, safety study, which enrolled 29 patients across six cohorts. No drug-related bone marrow toxicity or peripheral neuropathy was observed at any dose level.

In 2018, Panbela began enrolling patients in a Phase Ia/Ib study of the safety, efficacy and pharmacokinetics of ivospemin administered in combination with two standard-of-care chemotherapy agents, gemcitabine and nab-paclitaxel. A total of 50 subjects were enrolled, and interim results presented in January 2022 showed a median overall survival of 12.0 months in cohort 4 and the Phase Ib expansion.

In January 2022, Panbela announced the initiation of a new global, randomized, double-blind, placebo-controlled Phase II/III clinical trial, referred to as ASPIRE. The trial is evaluating ivospemin in combination with gemcitabine and nab-paclitaxel, a standard pancreatic cancer treatment regimen, in patients previously untreated for metastatic pancreatic cancer. The trial is being conducted at approximately 94 sites across the United States, Europe, and Asia-Pacific. As of March 31, 2024, there were 88 sites open in 10 countries, and the trial had exceeded 50% enrollment. Panbela projects that full enrollment of approximately 600 patients will be completed by the first quarter of 2025.

The independent Data Safety Monitoring Board (DSMB) has met twice for a prespecified safety analysis, most recently in November 2023, and recommended the trial continue without modification. The interim data analysis based on overall survival, originally projected to be available by the middle of 2024, is now expected in the first quarter of 2025, as the patients are living longer than expected, which may suggest a survival benefit.

Flynpovi (eflornithine (CPP-1X) and sulindac)

Panbela has an exclusive worldwide license to commercialize Flynpovi from the Arizona Board of Regents of the University of Arizona. In a Phase III study, the efficacy and safety of the combination of eflornithine and sulindac, known as Flynpovi, was compared with either drug alone in adults with familial adenomatous polyposis (FAP). While the study failed to meet the primary endpoint, a post-hoc analysis showed that none of the patients in the Flynpovi arm progressed to a need for lower gastrointestinal (LGI) surgery for up to 48 months, compared with 7 (13.2%) and 8 (15.7%) patients in the sulindac and eflornithine (CPP-1X) arms, respectively.

In April 2023, Panbela regained the North American rights to develop and commercialize Flynpovi in patients with FAP, as a result of the termination of the licensing agreement between CPP and One-Two Therapeutics Assets Limited. The company plans to seek FDA and EMA guidance on a registration path with a focus on the LGI patient population.

Panbela also has an ongoing double-blind, placebo-controlled Phase III trial of Flynpovi, called the PACES trial, to prevent recurrence of high-risk adenomas and second primary colorectal cancers in patients with stage 0-III colon or rectal cancer. The PACES trial is funded by the National Cancer Institute (NCI) in collaboration with the Southwest Oncology Group (SWOG) and successfully passed a pre-planned futility analysis in June 2023.

Eflornithine (CPP-1X)/eflornithine sachets (CPP-1X-S)

Panbela has IND applications for eflornithine from 2009 and 2018. There is a trial evaluating eflornithine sachets in STK11 mutation patients with non-small cell lung cancer that is open and recruiting patients. For eflornithine tablets, a Phase II trial in early onset Type I diabetes was opened on January 11, 2023 in collaboration with Indiana University and the Juvenile Diabetes Research Foundation (JDRF).

Additionally, eflornithine is being evaluated with high dose testosterone and enzalutamide in metastatic castration-resistant prostate cancer in a Phase II trial. On July 17, 2023, Panbela divested certain rights, titles, and interests in its eflornithine pediatric neuroblastoma program to US WorldMeds®, receiving an initial payment of $400,000 and an additional $775,000 in April 2024.

Financials

Panbela has incurred losses of $132.6 million since 2011, including a net loss of $7.1 million for the three months ended March 31, 2024. The company also incurred negative cash flows from operating activities of approximately $9.4 million for the same period. As of March 31, 2024, Panbela had cash of approximately $260,000, working capital deficit of $8.7 million, and stockholders' deficit of $3.2 million.

In January 2024, the company completed a registered public offering of common stock, pre-funded warrants, and warrants, resulting in net proceeds of approximately $8.1 million. However, Panbela needs to raise additional capital to continue its operations and execute its business plan, including completing required future trials and pursuing regulatory approvals.

The company's common stock was suspended from trading on Nasdaq in March 2024 and is now eligible for quotation on the OTCQB under the symbol "PBLA". Panbela is pursuing a new listing of its common stock on a national securities exchange.

Outlook

Panbela's projected first-half 2024 milestones include enrolling the first patient in the non-small cell lung cancer Phase I trial, announcing gastric cancer prevention Phase II results, and obtaining FDA and EMA feedback for a global registration trial in FAP.

In the second half of 2024, the company anticipates opening the neoadjuvant pancreatic cancer trial, opening the Phase II ovarian trial, publishing the final Phase I/Ib metastatic pancreatic trial data, and obtaining FDA and EMA feedback for a global registration trial in FAP.

In 2025, Panbela expects the overall survival interim analysis for the Phase III ASPIRE trial in the first quarter and the opening of the non-small cell lung cancer Phase II trial in the first half of the year.

Risks and Challenges

Panbela faces several risks and challenges, including its ability to obtain additional financing, the success of its development efforts, its ability to obtain marketing approval for its product candidates in the United States, Australia, the European Union, or other markets, and ultimately its ability to market and sell its product candidates. The company's reliance on third-party contract research organizations (CROs) to conduct its clinical trials also poses a risk, as the CRO for the ASPIRE trial has notified Panbela of its intent to terminate the relationship if the company is unable to pay the balance due within a satisfactory timeframe.

Conclusion

Panbela Therapeutics is a clinical-stage biopharmaceutical company with a diverse pipeline of innovative therapeutic candidates targeting various diseases, including cancer and autoimmunity. The company's lead assets, ivospemin, Flynpovi, and eflornithine, have the potential to significantly improve outcomes for patients with urgent unmet medical needs. Despite the challenges of advancing its programs and securing additional financing, Panbela remains committed to developing disruptive therapeutics and creating value for its shareholders. The company's upcoming milestones, including the interim analysis for the pivotal ASPIRE trial, will be crucial in determining the future direction of Panbela Therapeutics.