Panbela Therapeutics, Inc. · OTC:PBLA
Panbela Therapeutics — Investor Presentation (March 2023)
39 slides from Panbela Therapeutics's investor presentation, Mar 9, 2023
Slide 1: Investor Presentation March 2023
Investor Presentation March 2023 Last modified March 9, 2023
Slide 2: Disclaimers
Disclaimers Certain statements in this presentation are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and are provided under the protection of the safe harbor for forward-looking statements provided by that Act. Forward-looking statements are b
Slide 3: Combined Company Presents A Unique Opportunity
Combined Company Presents A Unique Opportunity: Multi-Targeted Approach to Reset Dysregulated Biology Scientific focus on polyamines, key regulators of normal biology altered in many disease states 1 Multiple near term inflection points PP acquisition completed in 2022 to create complementary, multi
Slide 4: Highly Experienced Management Team with Proven Track Record
Highly Experienced Management Team with Proven Track Record Proven orphan and oncology drug discovery, development and commercialization expertise Dr. Jennifer Simpson Chief Executive Officer 15+ Years Sue Horvath Chief Financial Officer 15+ Years Rachel Bragg VP, Clinical Development 14+ Years Dr.
Slide 5: Dysregulation of the Polyamine Pathway Leads to Disease
Dysregulation of the Polyamine Pathway Leads to Disease Initial focus on oncology and autoimmune disease -enhancing anti-tumor activity, preventing tumor growth, and modulating the immune system Cancer Pancreatic Familial Adenomatous Polyposis (FAP) Colorectal Ovarian STK11 Mutant NSCLC Neuroblastom
Slide 6: Pipeline and Milestones
Preclinical IND Ready Phase I Phase II Phase III Milestones PDA (First Line Metastatic) PDA Neoadjuvant Ovarian Familial Adenomatous Polyposis (FAP) (Partnered6i.n6US; CPP Pursuing EU/Asia Approval) Colon Cancer Risk Reduction (NCI Fund via Partnership with SWOG) Phase III Ongoing; Interim Analysis
Slide 7: Potential Market Opportunity for Lead Programs
Potential Market Opportunity for Lead Programs Pancreatic Cancer FAP Colorectal Cancer Ovarian Cancer Incidence of 1L Metastatic Pancreatic Cancer 57K in US ~190K in EU ~247K Incidence of FAP ~30K in US ~50K in EU ~80K Incidence of Colorectal Cancer ~150K in US ~340K in EU ~490K Incidence of Ovarian
Slide 8: Complementary Pharmacotherapies Targeting Dysregulation
Complementary Pharmacotherapies Targeting Dysregulation Pipeline Objective The objective of Panbela’s pipeline is the utilization of pharmacotherapies to reduce/normalize increased disease- associated polyamines using complementary pharmacotherapies Combined pipeline pharmacotherapies hit different
Slide 9: SBP-101
SBP-101 Panbela Therapeutics,
Slide 10: Preliminary Efficacy of SBP-101 + Gemcitabine/Nab-paclitaxel in First-Line Metastatic PDAC
Preliminary Efficacy of SBP-101 + Gemcitabine/Nab-paclitaxel in First-Line Metastatic Pancreatic Ductal Adenocarcinoma BEST OVERALL RESPONSE Overall Response Disease Control CR PR SD PD SBP-101 (0.40 mg/kg) + G/A* (Ph Ia COHORT 2) n=7 0 5 (71%) 2 (29%) 0 5/7 (71%) 5/7 (71%) SBP-101 (0.40 mg/kg) + G/
Slide 11: Efficacy Comparison
Efficacy ComparisonTreatment OS PFS ORR DCR PDCL-SBP-101-031 14.6 months 6.5 months 48.3% 82.8% 4.8%FOLFIRINOX2 11.1 months 6.4 months 31.6% 70.2% 15.2%Modified FOLFIRINOX3 10.2 months 6.1 months 35.1% 86.5% 13.5%Gemcitabine + Abraxane – Phase 1/24 12.2 months 7.9 months 48% 68% 16%Gemcitabine + Abr
Slide 12: SBP-101 + Gemcitabine/Nab-paclitaxel Overall Survival
SBP-101 + Gemcitabine/Nab-paclitaxel Overall Survival* Cohort 2 N=7: 2 patients with long term survival. • One still alive at 33.1 months • One deceased at 30.3 months Cohort 4+1b = 6 patients still alive • One complete response (Recist) • One clinical complete response (no detectable tumor) * Data
Slide 13: SBP-101 Demonstrated a Similar Safety Profile to Gemcitabine/Nab-paclitaxel
SBP-101 + Gemcitabine/Nab-paclitaxel Demonstrated a Similar Safety Profile to Gemcitabine/Nab-paclitaxel in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Safety Results Grade ≥3 AEs of Special Interest N SBP- 101% G+A %** Hematologic Events Neutropenia 20 40% 38% Leukopenia 0 - 31% Anemia 9
Slide 14: Phase III Pancreatic Cancer Trial in Previously Untreated Metastatic PDAC
Phase III Pancreatic Cancer Trial in Subjects Previously Untreated for Metastatic Pancreatic Ductal Adenocarcinoma A Randomized, Double-Blind, Placebo Controlled Study of Nab-Paclitaxel and Gemcitabine with or Without SBP-101 OS-Overall Survival PFS-Progression Free Survival ORR – Overall Response R
Slide 15: FLYNPOVI: A combination of CPP-1X and Sulindac
FLYNPOVI: A combination of CPP-1X and Sulindac
Slide 16: Lead Product Opportunity – CPP-1X and Sulindac (Flynpovi)
Lead Product Opportunity – CPP-1X and Sulindac (Flynpovi) Familial Adenomatous Polyposis (FAP) A genetic disease caused by APC mutations where colon polyps develop early in life Nearly 100% of patients will develop colon cancer if the polyps are left untreated Prevalence 1-in-10,000 ~30K in US ~50K
Slide 17: FAP-310 Trial: Time to Delay FAP-related Event Endpoint
FAP-310 Trial: “Time to Delay FAP-related Event” Endpoint CPP FAP 310 global study Time to delay FAP-related events Composite Endpoint including surgeries, polyp removal, and upper GI scoring system (“Spigelman”)*; based on FDA/EMA recommendation-first ever “event” trial inFAP Surgical endpoints mos
Slide 18: No Lower GI Surgeries for Flynpovi Combination
No Lower GI Surgeries for Flynpovi Combination Event Rate Distribution of FAP-Related Surgery Events in Lower GI Surgery Events Eflornithine Sulindac Overall (N=57) (N=58) (N=171)Need colectomy 3 4 7 Need proctectomy 1 1 2 Need pouch resection 4 1 5 Total Surgical Events 8 6 14 Event Rate 8/57 (14%)
Slide 19: Delay in Lower GI Surgery Events
Delay in Lower GI Surgery Events 100 (Vertical hashmarks “|” denote when patient comes off study) 90 80 Treatment Groups 70 ES Sulindac 60 Eflornithine 50 0 6 12 18 24 30 36 42 48 Time from Randomization Date to FAP-related Event (Months) ES 54 46 39 33 27 22 15 8 1 Sulindac 53 44 35 28 23 15 11 6 1
Slide 20: Rationale for Efficacy of Flynpovi in the Lower Gastrointestinal Tract
Rationale for Efficacy of Flynpovi in the Lower Gastrointestinal Tract of FAP Patients Microbiome Diet APC MYC MAD1 K-RAS ODC Put Polyamines Growth/Tissue Repair/Neoplasia • Polyamines drive uncontrolled growth, polyposis, and cancer. • Polyamines can by synthesized but also derived from the diet an
Slide 21: High Concentrations of the Microbiota Contribute to the Impact of Polyamines in The LGI
High Concentrations of the Microbiota Contribute to the Impact of Polyamines in The LGI The microbiota increases steadily along the gastrointestinal tract. ◦ Small numbers in the stomach but very high concentrations in the colon. ◦ Areas of the LGI contain up to nine orders of magnitude (109) more b
Slide 22: Adverse Events of Special Interest
Adverse Events of Special Interest Adverse Events of Special Interest Flynpovi (Eflornithine + Sulindac Combination) N=56 Subjects (%) Sulindac Eflornithine N=57 N=56 Subjects (%) Subjects (%) Anemia 1 (1.8) 5 (8.8) 2 (3.6) Myelosuppression 0 1 (1.8) 0 Thrombocytopenia 0 3 (5.3) 1 (1.8) Cardiovascul
Slide 23: Basis for FDA Complete Response Letter
Basis for FDA Complete Response Letter Clinical Single pivotal study efficacy was based on exploratory post-hoc analysis using a modified primary endpoint in a subgroup of the intent-to treat population o Asked to perform a new study focused on FAP patients with an intact lower- GI tract which showe
Slide 24: Moving Ahead: New Phase III Trial
Moving Ahead: New Phase III Trial North America Licensee funding next trial FDA and EMA focus on new Phase III trial: Lower GI focus (LGI), informed by positive data from FAP-310 and regulatory feedback Reaffirm current clarity & acceptable aspects of CMC, clin pharm, and non- clinical package Ini
Slide 25: Summary of Approach to Approval
Summary of Approach to Approval Strong Results in the Lower GI Focus on Lower GI: statistically significant p-values and hazard ratios for clinically meaningful surgical endpoints—emphasized by regulators—in Phase III pivotal trial Expected safety profile over 2-4 years of daily dosing in Phase III
Slide 26: Polyamines & Immune Dysregulation
Polyamines & Immune Dysregulation
Slide 27: Role of Polyamines in Immune Dysregulation
Role of Polyamines in Immune Dysregulation Immune systems require multiple soluble and cellular components, including polyamines, for a normal immune function High levels of polyamines are present in tumor cells and in autoreactive B- and T-cells in autoimmune diseases Dysregulation of polyamines ca
Slide 28: Role of Polyamines in Diffuse Large B Cell Lymphoma (DLBCL)
Role of Polyamines in Diffuse Large B Cell Lymphoma (DLBCL) MYC overexpression in relapsed/refractory DLBCL prior to CAR-T cell therapy negatively associated with durable response to CAR-T cell therapy. Polyamine metabolism upregulation through oncogenic MYC is a common metabolic irregularity in agg
Slide 29: Rationale for Eflornithine/anti-PD-1 Combination
Rationale for Eflornithine/anti-PD-1 Combination Targeting Ornithine decarboxylase (ODC) using eflornithine unmasks antitumor T cell immune response by weakening of tumor-induced immune suppression that is mediated by Myeloid- Derived Tumor Suppressor Cells (MDSCs). The addition of anti-PD-1 prevent
Slide 30: CPP-1X-S
CPP-1X-S Panbela Therapeutics | 39
Slide 31: Rationale for CPP-1X-S in STK11 Mutant NSCLC
Rationale for CPP-1X-S (Eflornithine Sachets) in STK11 Mutant NSCLC In preclinical tumor models, eflornithine treatment improves anti-PD-1 efficacy by: Increasing tumor-specific cytotoxic T-cell populations Increasing expression of PD-1 on tumor-associated CD8+ T cells ~10% of NSCLC cancers have STK
Slide 32: STK11 Mutant NSCLC Investigator-Initiated Trial
STK11 Mutant NSCLC Investigator-Initiated Trial Collaborating with investigators at Moffitt Cancer Center on Phase I/II trial: “Targeting Ornithine Decarboxylase as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient Non-Small Cell Lung Cancer” Patient Population Stage IV NSCLC Immune Chec
Slide 33: Business Overview
Business Overview
Slide 34: Barriers to Entry – Flynpovi/CPP-1X
Barriers to Entry – Flynpovi/CPP-1X Orphan status (7 years exclusivity US; 10 years exclusivity EU) for CPP-1X ◦ Granted in US and EU for FAP ◦ Granted in US and EU for Neuroblastoma ◦ Granted in US for Gastric cancer and Pancreatic cancer Pharmaceutical Composition Patent ◦ Fixed dose combination e
Slide 35: Barriers to Entry – SBP-101
Barriers to Entry – SBP-101 Orphan status (7 for years exclusivity US; 10 years exclusivity EU) for SPB-101 ◦ Granted in US and EU for pancreatic cancer METHODS FOR PRODUCING (6S,15S)-3,8,13,18-TETRAAZAICOSANE-6,15-DIOL ◦ PCT application filed January 29, 2019 ◦ Granted in United States, India ◦ Pen
Slide 36: Summary of Milestones
Summary of Milestones 1H 2023 Open Phase I Ovarian Cancer Trial Open- Phase I NSCLC Trial Open- Neoadjuvant Pancreatic Cancer Trial Open – Phase II Type I onset Diabetes Trial Futility Analysis Phase III Colon Cancer Risk Reduction Trial (PACES) Publication of Phase I Type I early onset Diabetes Dat
Slide 37: Financial Position - Cash and Debt
Financial Position - Cash and Debt (unaudited) Cash and Debt Cash at 9/30/22 941,000 Estimated net proceeds from public sale of equity on 10/3/22 5,200,000 Estimated net proceeds sale of equity via Company ATM through 1/20/23 1,639,000 Estimated net proceeds public sale of equity on 1/30/23 13,700,0
Slide 38: Capital Stock
Capital Stock (unaudited) Panbela (1) Common Stock at 9/30/22 519,596 Shares issued on 10/3/22 and Prefunded warrants exercised prior to 12/31/22 502,500 Shares sold via Company ATM through 1/20/23 469,168 Shares issued on 1/30/23 and Prefunded warrants exercised prior to 2/1/23 6,674,929 Fractional
Slide 39: Summary
Summary: Unique Scientific Approach: Resetting dysregulation via polyamine pathway Broad, late-stage de-risked pipeline opportunities Multiple partnerships supporting development programs Significant market potential Multiple data readouts expected Experienced management team
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