EX-99.1 2 d183644dex991.htm EX-99.1 EX-99.1

Exhibit 99.1 Restoring Intestinal Barrier Health Corporate Presentation | October 2021 PALI (NASDAQ) | palisadebio.com


Forward Looking Statements Statements in this presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding our research and clinical development plans, strategy, regulatory matters, market size and opportunity and our ability to complete certain milestones. Words such as “believe,” “anticipate,” “could,” “estimate,” “aim,” “target,” “plan,” “expect,” “intend,” “will,” “may,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. These forward-looking statements are based on the beliefs of the Company’s management as well as assumptions that may never materialize or prove to be incorrect. Such statements reflect the current views of the Company with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company, including, without limitation, risks inherent in developing pharmaceutical products, future results from the Company’s ongoing and planned clinical trials, the Company’s ability to obtain adequate financing to fund its planned clinical trials and other expenses, trends in the industry, changes in the competitive landscape, delays or disruptions due to the COVID-19 pandemic, the legal and regulatory framework for the industry and future expenditures. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. The actual results may vary from the anticipated results and the variations may be material. Other factors that may cause the Company's actual results to differ from current expectations are discussed in the Company's filings with the Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. These forward-looking statements should not be taken as forecasts or promises, nor should they be taken as implying any indication, assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or, in the case of the assumptions, fully stated in this presentation. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this presentation is given. Except as required by law, Palisade Bio assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates. Caution should be exercised when interpreting results from separate trials involving separate product candidates. Differences exist between trial designs and subject demographics, which limit the conclusions that can be drawn from comparisons across different trials. This presentation includes statistical and other industry and market data that we obtained from industry publications, third-party research, surveys and studies. The information has been obtained from sources believed to be reliable, although there is no guarantee regarding the accuracy or completeness of such information. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. 2


Palisade Bio – Developing Targeted Inhibitors of Digestive Proteases Scientific Platform Palisade Bio develops drugs to treat diseases caused by Technology digestive-enzyme leak producing inflammation and tissue damage LB1148 is an oral liquid protease inhibitor administered at home as a bowel prep for major surgeries, and has demonstrated Phase 3-Ready Lead Drug positive clinical results in two large indications: Candidate 1) accelerating the return of postoperative bowel function, and 2) reducing post-surgical adhesions 3


Lead Drug: LB1148 4


Lead Drug Candidate LB1148 – Highlights of Potential Path to Commercialize for Surgery Patients LB1148 can be taken at home prior to hospitalization; ideal Large Commercial Opportunity reimbursement scenario for commercializing a very large surgical market (20% of the market could lead to over $1.5 billion in revenues) Oral digestive enzyme inhibitor has demonstrated clinical benefit in Clinical Safety & Efficacy multiple surgical studies Prior approvals provide precedent pathway for pivotal trial design Path to Approval and regulatory reviews; LB1148 progressing to pivotal studies 5


Unmet Need – The Time to Postoperative GI Recovery Postoperative return of bowel function is often a limiting determinant of hospital discharge Major Surgeries • Patients generally do not leave hospital until they have a bowel movement • Lack of GI recovery: Gastrointestinal – Causes pain and bloating – Major discomfort If we save one day on length of stay, we will realize $20M more in profits annually. Abdominal – Extends hospital stay – Mark A. Talamini, MD, MBA – Increases medical costs Chair of Surgery, SUNY Stony Brook Gynecological LB1148 has demonstrated a 1.1 to 1.3-day reduction in hospital length of stay. Cardiovascular Average hospital expenses per inpatient day = $2,400 6


Unmet Need – Reducing Post-surgical Adhesions Adhesion are a widespread and potentially severe problem after surgery: • Up to 93% of abdominal procedures result in post-surgical adhesions • #1 cause of secondary female infertility • #1 cause of bowel obstruction (up to 75%) Non-Adhesion Adhesion th Difference • 10 most frequent cause of emergency surgery Complications Complications Length of Stay 5.2 days 7.2 days 38% • 80% of emergency surgery deaths Rehospitalization $22,500 $29,800 $7,326/pt. Costs • 400,000 adhesiolysis surgeries in US annually • $2.3B in medical costs in US annually Sources: J Chir Viscerale. 2012;149(2):114-126. doi:10.1016/j.jviscsurg.2011.11.006 Causes of female infertility, UpToDate 2020 Etter, K., et. Al.. Impact of postcolectomy adhesion-related complications on healthcare utilization. Clin. Outcomes Res. 10, 761–771 (2018) 7


Only Single Competitor for Each Indication, Yet Competitors Demonstrate Precedent Pathway for FDA Approval Return of Bowel Function Post-surgical Adhesions • Limitations: • Limitations: – In-patient hospital administration only – Only product approved for abdominal surgery – Short-term use only – Only approved for laparotomy – Restrictive REMS program • Can not be used for laparoscopic surgeries which comprise a growing percentage of the market Black-box warning: – Only reduces adhesions between the abdominal wall and the underlying viscera • Increased incidence of myocardial infarction – Disrupts surgical process and extends duration of • Available only through restricted program - REMS anesthetics 8


Postoperative Complications are Driven by Proteolytic Activity Cascade of disease mechanisms Injury Protease leak (surgery or ↑ Proteolytic activity and translocation hypoperfusion) ↑ Tissue damage/permeability ↑ Autodigestion ↑ Microbiome imbalance/pathology ↑ Pathologic cell signaling activity ↑ Inflammatory cell activation/infiltration ↑ Receptor degradation Healthy intestine Compromised mucosal barrier Proteolytic intestinal Postoperative permeation complications • Delayed recovery • Ileus • Adhesions • Intestinal injury (from surgery or hypoperfusion during surgery) triggers a • Inflammation cascade of disease mechanisms and leads to postoperative complications • Destructive feedback loop where protease leakage leads to additional intestinal damage 9


LB1148 Prevents Intestinal Damage: Rapidly Reseals the Barrier Hypoperfusion Injury Hypoperfusion Injury 100 75 50 Control – TXA LB1148 25 • Continuous epithelial • Permeable epithelial 0 barrier barrier Control Sham LB1148 • Intact villi structure • Loss of villi tissue Oral TXA • Robust basal membrane • Basal membrane structure compromised • No tissue damage • Lymph vessel damage Source: Delano 2013. Rat Shock Model of Hypoperfusion Source: Study#LBS-NC-SMAO-002 Rat SMAO model of intestinal hypoperfusion (DOF) 10 % Intact Villi


LB1148 Overview: Pipeline in a Product – Multiple Indications Drug/Class Indication Research Pre-clinical Phase 1 Phase 2 Phase 3 GI Surgery Postoperative return of bowel LB1148* Neonatal cardiac function Oral broad-spectrum surgery protease inhibitor* Prevention of post-surgical abdominal adhesions *Commercial rights to LB1148 in Greater China (excluding Taiwan) have been out-licensed to Newsoara 11


Restoring Bowel Function 12


GI Surgery Phase 2: Significantly Accelerated Return of GI Function th Median 75 Percentile • P=0.0008 • Hazard ratio=1.8 1.5 day improvement 1.1 day improvement 13 LBS-POI-201 CSR


LB1148 Accelerates Return of GI Function – Phase 3 Ready • Consistent statistically significant clinical efficacy in 3 completed clinical studies – 28% improvement in time to return of bowel function after GI surgery in phase 2 (p<0.001) – 48% improvement in time to return of bowel function after GI surgery in phase 1 (vs. placebo in Entereg study 314*) • 1.3-day reduction in hospital LOS vs. expected LOS at time of admission (p<0.03) nd • Zero post-surgical abdominal adhesions documented in 2 look surgeries – 30% improvement in time to return of bowel function after cardiovascular (CV) surgery (p<0.001) • 1.0-day reduction in ICU length of stay (LOS) (ns) • 1.1-day reduction in hospital LOS (ns) • Fast Track designation granted for pediatric cardiac surgery program • Strong IP portfolio, including issued patents on LB1148 drug product • 6.9 million addressable patients in the US 14 Source: Entereg Prescribing Information


Preventing Post-surgical Adhesions 15


GI Surgery Study Results: Zero Adhesions in Three Surgery Patients nd • 3 of 11 patients required a 2 surgery unrelated to adhesions – Opportunity to visualize and measure adhesions nd • For the three patients with a 2 surgery: • extent – No adhesions • severity – No evidence of inflammation Principal investigator’s report: As a surgeon who has performed thousands of abdominal surgeries, the absence of adhesions in three follow-up surgery patients is entirely unexpected 16


LB1148 Commercial Opportunity 17


Illustrative Patient Journey: GI Surgery with LB1148 Administration Drug is taken at home: • Reimbursed by patient’s q Bowel prep pharmacy benefit (no q Anti-nausea q Antibiotics cost to hospital) Pharmacy q LB1148 Physician’s Office • Doesn’t disrupt the Prescription filled 2 Pre-op physical in clinic; 1 at pharmacy Physician writes prescription surgeon’s practice Likely covered by pharmacy benefit In-patient surgery 4 3 Preoperative medications taken at home 5 Recovery at home 18 LB1148 LB1148


LB1148 Has Large Global Market Opportunity US Market Partnered 1.1 million open heart surgeries China: w/ Newsoara 5.7 million abdominal surgeries EU and ROW Opportunities 20-40% market penetration could translate to Potential to partner with US rights or >$2B revenue independently M&A – Shows Value of Adhesion Market USA Strategy Commercialize by marketing to 5,000 Baxter acquired the medical device hospitals Seprafilm from Sanofi for $350M in 2020 • 3.5X sales 19


5800 Armada Dr, Suite 210 Carlsbad, CA 92008 858-704-4900 IR@palisadebio.com PALI (Nasdaq) www.palisadebio.com 20


Appendix Slides 21


LB1148 - Expeditious Regulatory Pathway; Limited Competition • Novel oral formulation comprised of FDA-approved components – Broad-spectrum serine protease inhibitor (tranexamic acid) – Known safety profile – Plan to utilize 505(b)(2) pathway for approval • Fast-track designation for – Reducing surgical adhesions – Reducing postoperative GI dysfunction for pediatric patients undergoing open heart surgery • Issued patents on drug product • No new approved drug for postoperative ileus since 2008 – Entereg has austere black box warning, onerous REMS protocols, and limited utilization 22


Entereg: Only Drug Approved for Accelerating Return of GI Function • Provides a precedent pathway to FDA approval • Developed by GSK/Adolor/Cubist and now owned by Merck • Indicated to improve post-op recovery of bowel function – Phase 3 demonstrated*: • 17-hour improvement in return of bowel function • 7-hour improvement in hospital length of stay Black-box warning: • Entereg MOA carries safety risks – LB1148 has completely different MOA • Increased incidence of myocardial infarction • Limitations include*: • Available only through restricted program - REMS – In-patient hospital administration only – Short-term use only Entereg’s FDA approval provides regulatory – Restrictive REMS program – Black Box warning for severe side effects roadmap LB1148 clinical trial design • Utilized in few hospitals 23 * Entereg Prescribing Information


LB1148 Program Overview Pipeline in a Product – Multiple Indications Accelerate Return of Reduce Post-surgical Postoperative GI Function Adhesions Abdominal Surgery Cardiovascular Gastrointestinal Surgery Surgery 24


Cardiovascular Surgery (Hypoperfusion Injury) 25


CV Surgery Completed Phase 2: Study Design Screening Period CV Surgery Postoperative / Discharge Follow-up Day -42 to -1 Day 0* Day 1-14 Day 30 LB1148 Placebo Cardiovascular Surgery Scope & Timelines Study Design Primary Endpoint: Secondary Endpoints: • 120 patients undergoing • Open-heart CV surgery • Time to return of bowel function • ICU length of stay elective cardiac surgery requiring cardio-pulmonary (defined by first bowel • Hospital length of stay bypass movement) • Single center • Organ function • Randomized, double-blind, • CRO: IQVIA • Inflammatory response placebo-controlled, in subjects • Data announced in 2020 • Glucose control undergoing CABG and/or heart valve replacement surgery • Randomized 1:1 • 7.5 grams QD on Days 0, 1, and 2 26 * Study Day 0 is the day of surgery.


CV Surgery Phase 2: Significant Improvement in Bowel Function Top-line data highlights • 30% improvement in return of bowel function – Highly statistically significant; p<0.001 – Median time to bowel recovery: 31.7 hours on LB1148 vs. 45.0 hours on placebo – Same endpoint will be used for Phase 3 • 1.0-day reduction in ICU LOS (ns) • 1.1-day reduction in hospital LOS (ns) • No LB1148-related adverse events LB1148 Placebo n=58 n=52 27


GI Surgery: Return of Bowel Function (Physical Injury) 28


Completed GI Surgery Study: 1 Study, 2 Indications, 2 Data Readouts: Return of Bowel Function and Adhesion Prevention Screening Period GI Surgery Postoperative / Discharge Follow-up Adhesion Assessment Day -42 to -1 Day 0 Day 1-14 Day 30 Second Surgery LB1148 Study drug given as a split dose GI Surgery 2-6 hours prior to surgery 6-12 hours prior to surgery Scope & Timelines Study Design Functional Indications Adhesion Indications nd • 11 subjects • Open label, investigator- • Return of bowel function At time of 2 surgery: sponsored, single-arm study of • Single site in Los Angeles, CA • Hospital length of stay • Adhesions extent LB1148 in subjects undergoing • Bowel obstruction • Adhesions severity elective GI surgery • Hospital re-admittance • Patients take 700 mL of LB1148 as a split dose prior to surgery 29


GI Surgery Study Results: 48% Faster than Historical Control GI Surgery 2.3-days earlier first bowel movement 48% better than historical control Data highlights: • 48% improvement in return of bowel function – Approvable endpoint • No LB1148-related AEs Placebo (Entereg Study 314) Source: Ludwig K, et. al.. Arch Surg. 2008 Nov;143(11):1098-105. doi: 10.1001/archsurg.143.11.1098. PMID: 19015469. 30


GI Surgery Study Results: Significant Improvement in Hospital Length of Stay Versus Expected LOS GI Surgery 1.3-day improvement in LOS 20% reduction p = 0.03 Patient’s actual length of stay (LOS) was compared to expected LOS as determined from their billing code at time of admission (GMLOS) 31 Time from Surgery to Discharge (Days)


GI Surgery (PROFILE) Phase 2 – Partnered Study Screening Period GI Surgery Postoperative / Discharge Follow-up Adhesion Assessment Day -42 to -1 Day 0 Day 1-14 Day 30 Up to 7 months after initial surgery LB1148 Placebo Study drug given as a split dose GI Surgery 2-6 hours prior to surgery 6-10 hours prior to surgery Scope Study Design Functional Indications Adhesion Indications nd • 120 patients • Randomized, double-blind, Primary Endpoint: At time of 2 surgery: placebo-controlled, multi-site • 6 sites in China • Time to return of GI function • Presence of adhesions Phase 2 trial st GI2: (1 bowel movement) • Impact of adhesions on bowel • Evaluate LB1148 for return of Secondary Endpoints: function and pain GI function and adhesions in • Hospital LOS subjects undergoing elective • Hours to resolution of POI bowel resection with a laparotomy or minimally invasive approach with planned stoma take-down 32


GI Surgery Phase 2: Significantly Accelerated Return of GI Function th Median 75 Percentile • P=0.0008 • Hazard ratio=1.8 1.5 day improvement 1.1 day improvement Data Repeated from Body of Presentation 33 LBS-POI-201 CSR


GI Surgery Phase 2: Safe and Well Tolerated • LB1148 was well tolerated • Drug-related adverse events – LB1148 = 10.9% – Placebo = 4.8% • The most common drug-related AEs were GI disorders – LB1148 4.7% – Placebo 3.2% • No drug-related serious adverse events occurred in the trial 34


GI Surgery: Reduction of Adhesions (Physical Injury) 35


Unmet Need - Post-surgical Adhesions Develop in up to 93% of Abdominal Procedures* • Adhesions are scar tissue that forms during the healing process that bind tissues/organs that are not normally connected – HYPOTHESIS: Proteases, released as a result of bowel manipulation during surgeries, lead to adhesion formation • Bands of adhesions can constrict organs and tissues, causing organ strangulation and pain • Surgical re-intervention required after 6-10% of GI/GYN procedures to Image used with permission from Clear Passage Physical Therapy, http://www.clearpassage.com/adhesions- and-scar-tissue/abdominal-and-pelvic-adhesions-post-surgical-adhesions/ remove adhesions** * J Chir Viscerale. 2012;149(2):114-126. doi:10.1016/j.jviscsurg.2011.11.006 36 ** Ward, B. C. & Panitch, A. Abdominal adhesions: Current and novel therapies. J. Surg. Res. 165, 91–111 (2011).


LB1148 Reduces Adhesions by 63% in Animal Studies Animals receiving LB1148 before LB1148 dramatically reduces the surgery had 63% fewer adhesions number of post-surgical adhesions Reduced all types of adhesions: bowel to bowel, bowel to abdominal wall, bowel to viscera, etc. 37 Source: LBS-NC-IL-ADH-0003 DOF


FDA Approved ADEPT for Pelvic Surgery with Only a 10% Reduction in Adhesions FDA approved ADEPT based on only 10% of patients achieving “success” (defined as a decrease ≥ 3 sites with adhesions) 38 Source: Adept (4% icodextrin) Package Insert; March 2006 www.accessdata.fda.gov/cdrh_docs/pdf5/P050011B.pdf


5800 Armada Dr, Suite 210 Carlsbad, CA 92008 858-704-4900 IR@palisadebio.com PALI (Nasdaq) www.palisadebio.com 39