β-glucuronidase

Findings demonstrate that the microbiome and enzymes are sufficient in mouse, dog, and Normal Healthy Volunteers (NHV) and Ulcerative Colitis (UC) patients Company advancing toward commencement of Phase 1 human clinical study of PALI-2108 for the treatment of UC before year end Carlsbad, CA, July 29, 2024 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (the “Company”), a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases, today announced the successful completion of a microbiome study demonstrating that beta-glucuronidase is present at similar levels among dog, mouse, and human microbiota as well as within healthy humans and those with Crohn’s disease (CD) and ulcerative colitis (UC). “We are pleased to bolster our growing body of data for PALI-2108. The study completed by CosmosID, which uses direct identification of beta-glucuronidase by multiple databases, indicates that the presence of this enzyme is not significantly different among the species or between healthy and disease human cohorts. This allows the prodrug to break down in the areas of the GI tract where we are trying to deliver the active drug and confirms our previous findings of adequate bioactivation of PALI-2108 in NHV and UC patients’ stool,” commented Dr. Mitch Jones, CMO of Palisade Bio. Publicly available data for dog, mouse, and human whole genome metagenomic sequencing was obtained from the NCBI Sequence Read Archive (https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/sra). These samples were found by searching for metagenomic data for the specific host species and further filtered for Illumina paired-end whole genome sequencing (WGS) data. These data samples were subsampled to 6 million reads each to allow for accurate functional pathway and gene identification while keeping the maximum number of samples for comparison. After subsampling, the samples were uploaded to the CosmosID-HUB (app.cosmosid.com) for functional identification of genes, enzymes, and pathways utilizing the MetaCyc, Gene Ontology, and Enzyme Commission databases. Findings from the study demonstrated that although there are overall significant differences by species among the functional data as a whole, beta-glucuronidase-specific functions are not significant. The superpathway of beta D-glucuronoside degradation does show significant differences by species, but this pathway does not directly identify the enzyme beta-glucuronidase. Beta-D-glucuronoside is the substrate for beta-glucuronidase (MetaCyc pathway), which may imply that the enzyme is present. However, direct identification of beta-glucuronidase by both EC and GO databases indicate that the presence of this enzyme is not significantly different among the species or between healthy and disease human cohorts. Palisade continues to advance PALI-2108 for the treatment of moderate-to-severe UC toward a Phase 1 clinical study, expected to be initiated before the end of 2024. The Company’s PALI-1908 candidate is a microbiota-activated PDE4 inhibitor prodrug that leverages the advancements made with PALI-2108 and is being developed for the treatment of fibro stenotic Crohn’s Disease. About Palisade Bio Palisade Bio is a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases. The Company believes that by using a targeted approach with its novel therapeutics it will transform the treatment landscape. For more information, please go to www.palisadebio.com. Forward Looking Statements This communication contains “forward-looking” statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the Company’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the extent of our cash runway; our ability to successfully develop our licensed technologies; estimates about the size and growth potential of the markets for our product candidates, and our ability to serve those markets, including any potential revenue generated; future regulatory, judicial, and legislative changes or developments in the United States (U.S.) and foreign countries and the impact of these changes; our ability to maintain the Nasdaq listing of our securities; our ability to build a commercial infrastructure in the U.S. and other markets; our ability to compete effectively in a competitive industry; our ability to identify and qualify manufacturers to provide API and manufacture drug product; our ability to enter into commercial supply agreements; the success of competing technologies that are or may become available; our ability to attract and retain key scientific or management personnel; the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for additional financing; our ability to obtain funding for our operations; our ability to attract collaborators and strategic partnerships; and the impact of the COVID-19 pandemic or any global event on our business, and operations, and supply. Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements are based upon the Company’s current expectations. Forward-looking statements involve risks and uncertainties. The Company’s actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the Company’s ability to advance its nonclinical and clinical programs, the uncertain and time-consuming regulatory approval process; and the Company’s ability to secure additional financing to fund future operations and development of its product candidates. Additional risks and uncertainties can be found in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and Quarterly Report on Form 10-Q, filed with the Securities and Exchange Commission (“SEC”) on March 26, 2024 and May 13, 2024, respectively. These forward-looking statements speak only as of the date hereof and the Company expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the Company’s expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. Investor Relations ContactJTC Team, LLCJenene Thomas 833-475-8247PALI@jtcir.com Source: Palisade Bio

Patent includes Composition of Matter claims for both PALI-2108 and PALI-1908 programs Patent includes broad claims for “Gut Microbiota Bioactivated PDE4 Inhibitor Precursors” with similar structure to PALI-2108 and PALI-1908 This patent family provides Composition of Matter coverage beyond 2042 PALI-2108 is in development to treat patients with active moderate-to-severely active Ulcerative Colitis (UC) PALI-1908 is in development to treat patients with active fibro stenotic Crohn’s Disease (CD) Carlsbad, CA, July 19, 2024 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (the “Company”), a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases, today announced that European Patent Office (EPO) has issued a decision to grant notice for patent number 4,157,853 titled, “Gut Microbiota Bioactivated PDE4 Inhibitor Precursors.” Based on the intention to grant notice, the Company expects the EPO to issue a patent July 31, 2024. In addition to this European patent and recently allowed Canadian patent, the Company continues to strengthen its global intellectual property portfolio surrounding PALI-2108 with submitted and planned submissions of additional patent applications. J.D. Finley, Chief Executive Officer of Palisade commented, “We are pleased to further expand our global patent estate for our PALI-2108 and PALI-1908 programs with this European patent. PALI-2108 continues to demonstrate encouraging data and bolster our confidence in its potential as a next-generation therapeutic option for patients with inflammatory bowel disease. As we continue to execute on the development pathway forward for PALI-2108 and PALI-1908, we remain committed to strengthening our global intellectual property portfolio.” The patent claims include coverage for the proprietary composition of PALI-2108, the Company’s orally administered, locally acting colon-specific Phosphodiesterase-4 (PDE4) inhibitor prodrug in development for patients affected by Ulcerative Colitis (UC). PALI-2108’s unique design, incorporating a galactose-derived sugar moiety, potentially allows for minimal absorption until cleaved by the colonic bacterium enzyme β-glucuronidase. This feature is intended to ensure localized bioactivation, leading to colon-specific distribution with limited systemic exposure, as shown by a tissue distribution study. Palisade continues to advance PALI-2108 for the treatment of moderate-to-severe UC toward a Phase 1 clinical study, expected to be initiated before the end of 2024. The Company’s PALI-1908 candidate is a microbiota-activated PDE4 inhibitor prodrug that leverages the advancements made with PALI-2108 and is being developed for the treatment of fibro stenotic Crohn’s Disease. Palisade Bio is a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases. The Company believes that by using a targeted approach with its novel therapeutics it will transform the treatment landscape. For more information, please go to www.palisadebio.com. Forward Looking Statements This communication contains “forward-looking” statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the Company’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the extent of our cash runway; our ability to successfully develop our licensed technologies; estimates about the size and growth potential of the markets for our product candidates, and our ability to serve those markets, including any potential revenue generated; future regulatory, judicial, and legislative changes or developments in the United States (U.S.) and foreign countries and the impact of these changes; our ability to maintain the Nasdaq listing of our securities; our ability to build a commercial infrastructure in the U.S. and other markets; our ability to compete effectively in a competitive industry; our ability to identify and qualify manufacturers to provide API and manufacture drug product; our ability to enter into commercial supply agreements; the success of competing technologies that are or may become available; our ability to attract and retain key scientific or management personnel; the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for additional financing; our ability to obtain funding for our operations; our ability to attract collaborators and strategic partnerships; and the impact of the COVID-19 pandemic or any global event on our business, and operations, and supply. Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements are based upon the Company’s current expectations. Forward-looking statements involve risks and uncertainties. The Company’s actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the Company’s ability to advance its nonclinical and clinical programs, the uncertain and time-consuming regulatory approval process; and the Company’s ability to secure additional financing to fund future operations and development of its product candidates. Additional risks and uncertainties can be found in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and Quarterly Report on Form 10-Q, filed with the Securities and Exchange Commission (“SEC”) on March 26, 2024 and May 13, 2024, respectively. These forward-looking statements speak only as of the date hereof and the Company expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the Company’s expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. Investor Relations ContactJTC Team, LLCJenene Thomas 833-475-8247PALI@jtcir.com Source: Palisade Bio

On April 1, 2024, Sutro Biopharma, a NASDAQ-listed American company, and the renowned French pharmaceutical company Ipsen, entered into a global exclusive licensing agreement. The agreement covers Sutro's investigational ADC (Antibody-Drug Conjugate) candidate, STRO-003. Under the terms of the deal, Ipsen will make an upfront payment of $90 million to Sutro and potentially pay up to $900 million in milestone payments. This is Ipsen's first major investment in the ADC field. STRO-003 is a next-generation ADC targeting ROR1 (Receptor Tyrosine Kinase-Like Orphan Receptor 1). This ADC uses exatecan (iexabepilone) as the payload, delivered through a β-glucuronidase-cleavable linker. In addition to STRO-003, Sutro has other ADC candidates in clinical development, including FRa ADC and CD74 ADC, as well as TF ADC in preclinical stages. The company is also collaborating with Astellas on immunostimulatory ADCs (iADCs) in preclinical research. In the ROR1 ADC space, other notable candidates include CS5001 from LegoChem/Cornerstone, Zilovertamab Vedotin (MK-2140) from Merck/VelosBio, a bispecific antibody-drug conjugate from Bolt Biotherapeutics, and NBE-002 from BI/NBE Therapeutics. According to recent clinical data from Cornerstone, CS5001 has demonstrated promising anti-tumor activity and a favorable safety profile across various solid tumors and hematological malignancies. This transaction not only highlights the immense potential of ADC technology in targeted cancer therapy, but also reflects the intense competition among domestic and international pharmaceutical companies in this field. A thorough analysis of the current clinical and market landscape of ROR1 ADCs will help us better understand the future development trends of innovative medicines.