Eflornithine Hydrochloride

MINNEAPOLIS, Sept. 24, 2024 (GLOBE NEWSWIRE) -- Panbela Therapeutics, Inc. (OTCQB: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, today announced the first patient enrolled in a Phase I dose escalation study to evaluate CPP-1X-S (eflornithine sachets) in STK11 mutant non-small cell lung cancer (NSCLC). The initial goal of the Phase I trial will be to determine the maximum tolerated dose of eflornithine in combination with the immune checkpoint inhibitor Keytruda, while evaluating efficacy and then moving into a Phase II efficacy trial. Data from the Phase I trial is expected by mid-2025, with a look to start the Phase II trial in 2024. The trial entitled “Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway- Deficient NSCLC” is a Phase I/II trial where Phase I is a dose escalation study establishing the safety, toxicity and recommended Phase II dose of CPP-1X-S in combination with Keytruda in patients with STK11 mutant NSCLC at approximately one academic medical center in the United States. Detailed information on the trial can be located at https://clinicaltrials.gov/study/NCT06219174?term=DFMO&rank=4. “Options for combining new agents with standard of care immunotherapy is critical to overcoming the reduced levels of anti-tumor T cells and immune evasion that is observed in STK11 mutant tumors,” said Jhanelle Gray, M.D., Principal Investigator of the clinical trial, Chair of Moffitt’s Department of Thoracic Oncology and Co-Leader of Moffitt’s Molecular Medicine Program. “By working with Panbela, we are using CPP-1X-S to modulate polyamine levels and potentially restimulate the immune system, which may be a valuable therapeutic strategy to target these hard-to-treat tumors.” “With the recent approval of CPP-1X (DFMO) for neuroblastoma, the first oncology approval for a polyamine targeted therapy, we’re really excited to have the first patient enrolled in the Phase I trial for CPP-1X-S led by Moffitt Cancer Center,” said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. “Preclinical studies have shown that polyamine modulation has the potential to restimulate the immune system. This trial allows us to explore the potential of CPP-1X-S clinically in the STK11 mutant NSCLC population which historically have a poor response to checkpoint inhibitor therapy. Once the safety of CPP-1X-S in combination with Keytruda is established in this Phase I trial, the planned Phase II trial will determine the potential efficacy of combining polyamine targeted therapies with checkpoint inhibitors hopefully demonstrating the first clinical proof of concept of this unique approach. In addition to the possibility of providing a better treatment option for this patient population, we are excited to evaluate the role of eflornithine and ivospemin as modulators of the immune system in combination with other immunotherapies such as CAR-T therapy for tumors where response rates have been low with immunotherapy.” About Panbela’s 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 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-1XCPP-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 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 eligible for quotation on the OTCQB 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,” “believe,” “can,” “design,” “expect,” “focus,” “intend,” “looking forward,” “may,” “plan,” “positioned,” “potential,” and “will.” 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 capital, on acceptable terms or at all, required to implement our business plan; (ii) our lack of diversification and the corresponding risk of an investment in our Company and the corresponding risk of potential deterioration of our financial condition and results due to failure to diversify; (iii) our ability to obtain and maintain our listing on a national securities exchange; (iv) results, progress and success of our randomized Phase Ia/Ib and Phase II/III clinical trials; (v) our ability to demonstrate the safety and effectiveness of our product candidates: ivospemin ( SBP-101 ), Flynpovi, and eflornithine (CPP-1X); (vi) potential delays or risks to the success of our randomized Phase II/III clinical trial resulting from a termination in our relationship with our CRO; (vii) 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; (viii) the market acceptance and level of future sales of our product candidates, SBP-101, Flynpovi and CPP-1X ; (ix) 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 ; (x) the rate of progress in establishing reimbursement arrangements with third-party payors; (xi) the effect of competing technological and market developments; (xii) the costs involved in filing and prosecuting patent applications and enforcing or defending patent claims; and (xiii) 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

MINNEAPOLIS, Aug. 13, 2024 (GLOBE NEWSWIRE) -- Panbela Therapeutics, Inc. (OTCQB: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, today provides a business update and reports financial results for the quarter ended June 30, 2024. As previously announced, management is hosting an earnings call today at 4:30 p.m. ET. Q2 2024 and Recent Highlights: Clinical Phase 3 ASPIRE clinical trial received favorable third independent safety review: DSMB recommended continuation without modification.Completed Oral Presentation at Digestive Disease Week (DDW): Evaluation of the Safety and Efficacy of Eflornithine (Difluoromethylornithine, DFMO) in Patients with Gastric Premalignant Conditions in the High Incidence Areas of Latin American.Provided revised timing for the interim data analysis for its ongoing ASPIRE trial, evaluating ivospemin (SBP-101) in combination with standard-of-care for metastatic pancreatic ductal adenocarcinoma (mPDAC). The analysis is now expected in Q1 2025 due to a lower-than-anticipated event rate, which suggests the potential for improved survival outcomes for patients in the trial. Financial / Business Gained eligibility for quotation of common stock on the OTCQB.Issuance of a New Patent in the US and Canada for Claims of a Fixed Dose Combination of Eflornithine and Sulindac. Jennifer K. Simpson, PhD, MSN, CRNP, President & CEO of Panbela, commented: "In the second quarter, we continued to make significant progress in our clinical programs and corporate initiatives. Our Phase III ASPIRE clinical trial received a favorable third independent safety review, with the Data and Safety Monitoring Board (DSMB) recommending continuation without modification. We were also honored to have an oral presentation at Digestive Disease Week (DDW), where we evaluated the safety and efficacy of eflornithine (difluoromethylornithine, DFMO) in patients with gastric premalignant conditions in high incidence areas of Latin America. Furthermore, we recently announced revised timing for the interim data analysis of our ongoing ASPIRE trial, evaluating ivospemin (SBP-101) in combination with standard-of-care for metastatic pancreatic ductal adenocarcinoma (mPDAC). Due to a lower-than-anticipated event rate, which suggests the potential for improved survival outcomes for patients in the trial, the analysis is now expected in Q1 2025. This is a testament to the potential of our lead candidate, ivospemin, and its ability to make a meaningful difference in the lives of patients with mPDAC. As we move forward, Panbela remains committed to advancing our clinical programs, exploring new indications, and creating value for our stockholders. With several key milestones on the horizon, including the highly anticipated overall survival interim analysis in our Phase III ASPIRE Trial, we are excited about the future and the potential impact our therapies can have on patients in need." Second Quarter ended June 30, 2024 Financial Results General and administrative expenses were approximately $1.1 million in the quarter, compared to $1.6 million in the same period last year. The decrease is due primarily to reduced legal and compensation expense. Research and development expenses were approximately $7.0 million, compared to $4.2 million in the same period last year. This increase is primarily due to significant growth in the number of active sites and enrollment in project ASPIRE. Net loss in the quarter was approximately $7.1 million, or $1.47 per diluted share, compared to a net loss of $5.8 million, or $159.15 per diluted share, in the same period last year. This increased loss is due to the incremental research and development expenses. Total cash was $59,000 as of June 30, 2024. Total current assets were $0.8 million and current liabilities were $16.8 million as of the same date. In April, Panbela’s partner in Pediatric Neuroblastoma, US WorldMeds®, provided a nondilutive payment of approximately $0.8 million in exchange for a reduction in the potential future milestone payments. In July, Panbela secured a loan from this same partner for $1.5 million. Notes payable, plus accrued interest, on the balance sheet, the result of the acquisition of Cancer Prevention Pharmaceuticals, Inc., totaled approximately $4.3 million. The current portion of the notes payable plus accrued interest totaled approximately $1.1 million. Conference Call Information Toll Free: 888-506-0062International: 973-528-0011Participant Access Code: 405072Webcast Link: https://www.webcaster4.com/Webcast/Page/2556/50956 Conference Call Replay Information Toll Free: 877-481-4010International: 919-882-2331Replay Passcode: 50956Webcast Replay: https://www.webcaster4.com/Webcast/Page/2556/50956 The replay will be available within approximately two hours after the completion of the call for approximately one year. 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/study/NCT03412799. 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 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 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), 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 eligible for quotation on the OTCQB under the symbol “PBLA”. Cautionary Statement Regarding Forward-Looking StatementsThis press release contains “forward-looking statements, “which can be identified by words such as: “anticipate,” “design,” “hope,” “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 capital, on acceptable terms or at all, required to implement our business plan; (ii) our lack of diversification and the corresponding risk of an investment in our Company and the corresponding risk of potential deterioration of our financial condition and results due to failure to diversify; (iii) our ability to obtain and maintain our listing on a national securities exchange; (iv) results, progress and success of our randomized Phase Ia/Ib and Phase II/III clinical trials; (v) our ability to demonstrate the safety and effectiveness of our product candidates: ivospemin ( SBP-101 ), Flynpovi, and eflornithine (CPP-1X); (vi) potential delays or risks to the success of our randomized Phase II/III clinical trial resulting from a termination in our relationship with our CRO; (vii) 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; (viii) the market acceptance and level of future sales of our product candidates, SBP-101, Flynpovi and CPP-1X ; (ix) 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 ; (x) the rate of progress in establishing reimbursement arrangements with third-party payors; (xi) the effect of competing technological and market developments; (xii) the costs involved in filing and prosecuting patent applications and enforcing or defending patent claims; and (xiii) 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 Panbela Therapeutics, Inc.Consolidated Statements of Operations and Comprehensive Loss (unaudited)(In thousands, except share and per share amounts) Three months ended June 30, Six months ended June 30, 2024 2023 Percent Change 2024 2023 Percent ChangeOperating expenses: General and administrative $1,106 $1,643 -32.7% $2,310 $2,995 -22.9%Research and development 6,997 4,234 65.3% 12,519 7,750 61.5%Operating loss (8,103) (5,877) 37.9% (14,829) (10,745) 38.0% Other income (expense): Interest income - 49 -100.0% - 65 -100.0%Gain on sale of intellectual property 775 - - 775 - - Interest expense (59) (70) -15.7% (121) (173) -30.1%Other income (expense) 248 (82) -402.4% (223) (247) -9.7%Total other income (expense) 964 (103) -1035.9% 431 (355) -221.4% Loss before income tax benefit (7,139) (5,980) 19.4% (14,398) (11,100) 29.7% Income tax benefit - 147 -100.0% 138 149 -7.4% Net loss (7,139) (5,833) 22.4% (14,260) (10,951) 30.2%Foreign currency translation adjustment (242) 68 -455.9% 217 231 -6.1%Comprehensive Loss $(7,381) $(5,765) 28.0% $(14,043) $(10,720) 31.0% Basic and diluted net loss per share$(1.47) $(159.15) -99.1% $(3.58) $(441.77) -99.2%Weighted average shares outstanding - basic and diluted 4,854,861 36,650 13146.6% 3,984,355 24,790 15972.4% Panbela Therapeutics, Inc.Consolidated Balance Sheets (unaudited)(In thousands, except share amounts) June 30, 2024 December 31, 2023ASSETS (Unaudited) Current assets: Cash and cash equivalents $59 $2,578 Prepaid expenses and other current assets 393 299 Income tax receivable 320 183 Total current assets 772 3,060 Other non-current assets 8,642 8,742 Total assets $9,414 $11,802 LIABILITIES AND STOCKHOLDERS' DEFICIT Current liabilities: Accounts payable $14,293 $9,939 Accrued expenses 1,408 1,141 Accrued interest payable 87 238 Debt, current portion 1,000 1,000 Total current liabilities 16,788 12,318 Debt, net of current portion 3,194 4,194 Total non-current liabilities 3,194 4,194 Total liabilities 19,982 16,512 Stockholders' deficit: Preferred stock, $0.001 par value; 10,000,000 authorized; no shares issued or outstanding as of June 30, 2024 and December 31, 2023 - - Common stock, $0.001 par value; 100,000,000 authorized; 4,854,931 and 480,095 issued as of June 30, 2024 and December 31, 2023 respectively; 4,854,861 and 480,025 shares outstanding as of June 30, 2024 and December 31, 2023, respectively 5 - Treasury Stock at cost; 70 shares at both of June 30, 2024 and December 31, 2023 (1) (1)Additional paid-in capital 128,223 120,043 Accumulated deficit (139,757) (125,497)Accumulated comprehensive income 962 745 Total stockholders' deficit (10,568) (4,710)Total liabilities and stockholders' deficit $9,414 $11,802 Panbela Therapeutics, Inc.Consolidated Statements of Cash Flows (unaudited)(In thousands) Six Months Ended June 30, 2024 2023 Cash flows from operating activities: Net loss$(14,260) $(10,951)Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 103 509 Non-cash interest expense 87 107 Gain on sale of intellectual property (775) - Changes in operating assets and liabilities: Income tax receivable (140) (149)Prepaid expenses and other current assets (96) (2,967)Other non-current assets 100 (5,541)Accounts payable 4,578 5,811 Accrued liabilities 30 (2,311)Net cash used in operating activities (10,373) (15,492) Cash flows from investing activities: Proceeds from sale of intellectual property 775 - Net cash provided by investing activities 775 - Cash flows from financing activities: Proceeds from public offering of common stock and warrants, net of fees and offering costs of $0.9 million and $2.1 million respectively 8,082 23,071 Cash paid for fractional shares - (9)Principal payments on notes (1,000) (1,650)Net cash provided by financing activities 7,082 21,412 Effect of exchange rate changes on cash (3) - Net change in cash (2,519) 5,920 Cash and cash equivalents at beginning of period 2,578 1,285 Cash and cash equivalents at end of period$59 $7,205 Supplemental disclosure of cash flow information: Cash paid during period for interest$272 $386 Supplemental disclosure of non-cash transactions: Cashless exercise of warrants$- $(8)