PDE4B

– Company has received a No Objection Letter from Health Canada in response to submission of its Phase 1 Clinical Trial Application (CTA) – The study is a Phase 1 Single Ascending Dose (SAD) /Multiple Ascending Dose (MAD) and food effects (FE) and includes multiple dose treatment of UC patients; Global UC market is expected to grow to nearly $10 Billion by 2028 Oct. 10, 2024 -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade,” “Palisade Bio” or the “Company”), a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases, today announced that it has received a No Objection Letter from Health Canada for its Phase 1 human clinical study for PALI-2108 for the treatment of UC. “We are thrilled to receive a No Objection Letter from Health Canada in response to our Clinical Trial Application. This achievement marks the most important milestone to date for our PALI-2108 development program. We continue to believe in the potential of PALI-2108 to be the first approved PDE4 inhibitor for UC and more importantly, provide a much-needed effective and safe solution for UC patients still experiencing significant medical need. Our team remains focused on continuing preparations for the initiation of our Phase 1 clinical trial which is on track to commence before year end,” commented J.D. Finley, Chief Executive Officer. PALI-2108 is an orally administered PDE4 inhibitor prodrug which is locally bioactivated in the colon and is in development for patients affected by UC. The Phase 1 study will evaluate PALI-2108 in a single-center, double-blind, placebo-controlled study focused on safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers, alongside an open-label study involving a patient cohort with UC. As previously announced, the Company has established dose levels and trial design for PALI-2108 and plans to enroll approximately 90 patients across the SAD, FE, MAD and UC cohorts. “Patients are actively seeking new and more effective treatment options for their ulcerative colitis. Currently, existing therapies achieve complete remission in fewer than a quarter of patients, and many of the most effective treatments involve injections or carry black box warnings due to serious side effects. A safe and effective oral medication for UC would be highly desirable for the majority of patients,” said Florian Rieder, MD, a member of the Palisade Bio Clinical Advisory Board and Associate Staff in the Department of Gastroenterology, Hepatology, and Nutrition, as well as an Investigator in the Department of Pathobiology at the Cleveland Clinic. The primary objective of the study will be to assess the safety and tolerability of single (healthy subjects) and repeated (healthy subjects and UC patients) oral doses of PALI-2108. Secondary objectives include determining the plasma, urinary, and fecal (MAD healthy subjects and UC patients only) pharmacokinetics (PK) of PALI-2108 and its metabolites following PALI-2108 single (healthy subjects) and repeated (healthy subjects and UC patients) oral doses, as well as the effect of food on the PK of PALI-2108 and its metabolites following a single oral dose in healthy subjects. Exploratory objectives will include PDE4-related pharmacodynamic (PD) biomarkers, concentrations of the active form of PALI-2108, high sensitivity C-reactive protein (hsCRP), fecal calprotectin (CalPro), colonic tissue Absolute Lymphocyte Count (ALC), Modified Mayo score, as well as colonic histological changes in UC patients following repeated PALI-2108 oral doses. Preparations for the clinical study remain ongoing and the Company is on track commence site initiation and enrollment for the study before year end. 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. The content above comes from the network. if any infringement, please contact us to modify.

– Completion of nonclinical safety and toxicity studies, Phase 1 clinical trial design and established Maximum Recommended Starting Dose – Completion of pre- Clinical Trial Application (CTA) meeting with Health Canada – Submission of the CTA for the Phase 1 clinical study of Normal Healthy Volunteers and ulcerative colitis patients – On track towards clinical site initiation and dosing of first patient in Phase 1 human clinical study before year end Carlsbad, CA, Sept. 25, 2024 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade,” “Palisade Bio” or the “Company”), a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases, today provided an update on its progress toward the launch of its Phase 1 human clinical study for PALI-2108 for the treatment of ulcerative colitis (UC). The Company’s lead program, PALI-2108, is a locally activated PDE4 inhibitor prodrug in development for treating patients with moderate to severely active UC. Leveraging advanced machine learning, the Company’s research has identified a measurable threshold of elevated PDE4B expression across more than 1,600 patients and 10 studies, identifying over-expressing patients in over 70% of cases. This finding supports the potential for an FDA-approved test that uses PDE4B expression as a reliable marker for patient enrichment. The Company believes this will lead to better UC patient selection, thereby increasing the efficacy of Palisade’s PDE4-inhibiting prodrug therapeutic. Additionally, the Company is advancing a second approach featuring six PDE4-related biomarkers, which has demonstrated superior performance compared to benchmark tests and is specifically tailored for PDE4 inhibition, providing a targeted solution to improve therapeutic outcomes. The integration of PCR-based assays aimed at potential FDA approval will ensure precision in patient targeting. These developments underscore the Company’s commitment to leading the field of precision medicine for UC, advancing personalized treatment strategies that promise to transform patient care. “We are excited to announce significant progress in our development of precision medicine tests designed to optimize treatment for moderate to severely active UC patients. We are also pleased with the continued progress of our PALI-2108 program. UC represents a significant challenge for patients who need therapies that provide effective remission rates, are non-immunosuppressive, and have improved safety profiles. Our team continues to execute on the clinical and regulatory steps necessary for the launch of our Phase 1 study and remains confident in our timeline to initiate before year-end,” commented Dr. Mitch Jones, CMO of Palisade Bio. The Company has submitted a CTA for its Phase 1 study of PALI-2108, which will be a single-center, double-blind, placebo-controlled study focused on safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers, alongside an open-label study involving a patient cohort with UC. As previously announced, the Company has established dose levels and trial design for PALI-2108 and plans to enroll approximately 90 patients across the SAD, FE, MAD and UC cohorts. The primary objective of the study is to assess the safety and tolerability of single (healthy subjects) and repeated (healthy subjects and UC patients) oral doses of PALI-2108. Secondary objectives include determining the plasma, urinary, and fecal (MAD healthy subjects and UC patients only) pharmacokinetics (PK) of PALI 2108 and its metabolites (PALI-0008 and PALI-0708) following PALI-2108 single (healthy subjects) and repeated (healthy subjects and UC patients) oral doses, as well as the effect of food on the PK of PALI-2108 and its metabolites (PALI-0008 and PALI-0708; if applicable) following a single oral dose in healthy subjects. Additionally, the Company recently held a pre-CTA consultation meeting with Health Canada with the objective of presenting its SAD-MAD-FE Phase 1 program in normal healthy volunteers for PALI-2108. Palisade believes it achieved its objective of understanding Health Canada’s expectations and regulations governing clinical study design, which assisted in the submission of the CTA to commence the Company’s Phase 1 study. 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; the timing and outcome of our current and anticipated applications and studies related to our product candidates; 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 most recent Quarterly Report on Form 10-Q for the period ended June 30, 2024, filed with the Securities and Exchange Commission on March 26, 2024 and August 12, 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 908-824-0775PALI@jtcir.com

iStock/ Mihaela Rosu Clinical trial results shared by Boehringer Ingelheim and Insilico Medicine showed improvement in idiopathic pulmonary fibrosis, an intractable lung disease for which current treatment options fail to stop progression, but the data were limited, leaving experts wanting. Patients with idiopathic pulmonary fibrosis got a double helping of good news in the clinical trials arena last week as Boehringer Ingelheim and Insilico Medicine each reported positive data from their respective trials. The results indicate that both companies’ idiopathic pulmonary fibrosis (IPF) drug candidates might be able to stop or reverse decline in lung function—something no current treatments can offer. But experts cautioned that the data drops were light on the details and that more information is needed before either asset can be accurately evaluated. A progressive interstitial lung disease disproportionately affecting older adults, IPF is characterized by lung scarring, inflammation, fatigue and shortness of breath. It ultimately leads to respiratory failure and death within 3–5 years of diagnosis. As its name suggests, the origin of IPF is unknown. “IPF is a very complex, multifactorial and very idiopathic process,” Insilico co-CEO Alex Zhavoronkov told BioSpace . There is no cure for IPF and current treatment is designed to minimize symptoms, maintain quality-of-life and slow progression, Allison Reiss, an associate professor at NYU Grossman Long Island School of Medicine, told BioSpace in an email. She added that “mainstay treatment” consists of Boehringer’s Ofev (nintedanib) and Roche’s Esbriet (pirfenidone), both antifibrotic drugs, along with pulmonary rehabilitation. However, Zhavoronkov said, “neither of these drugs are extremely well tolerated,” and they only slow down decline in forced vital capacity (FVC), a key measure of lung function in IPF. “Usually, you see the decline on the standard of care.” Insilico, Boehringer See Improvements in Key IPF Indicator On Sept. 16, Boehringer reported that its IPF drug candidate nerandomilast elicited a significant improvement in FVC at 52 weeks versus placebo in the Phase III FIBRONEER-IPF trial of 1,177 patients. FIBRONEER-IPF “is the first IPF Phase III trial in a decade to meet its primary endpoint,” Ioannis Sapountzis, Boehringer’s head of global therapeutic areas, said in a statement. Reiss said she would like further specifics in regard to that endpoint. “[Boehringer Ingelheim] said [the study] met the endpoint, which means that those on the drug performed better on the forced vital capacity test, but on both doses or one of the doses? And how much better?” Trial participants were given either 9 mg or 18 mg of nerandomilast twice a day or a placebo for at least 52 weeks. Additionally, Reiss is seeking more information on the secondary endpoints: time to an IPF exacerbation, first hospitalization for respiratory cause, or death. She noted, however, that nerandomilast’s mechanism of action is promising. By preferentially blocking the phosphodiesterase 4B enzyme, she explained, “PDE4B inhibitors interfere with the function of a very specific form of the phosphodiesterase enzyme so that this class of drugs may be able to reduce inflammation and fibrosis in IPF with less side effects than a drug that would inhibit multiple forms of the enzyme.” In an emailed statement, a Boehringer spokesperson told BioSpace the company has a strong focus on IPF, given the high unmet need. The company plans to present full data and analyses from FIBRONEER-IPF in the first half of 2025. Insilico, meanwhile, reported similarly positive results on its much smaller Phase IIa trial of 60 patients with IPF. Specifically, the company released results the day after Boehringer showing that its ISM001-055 met the primary endpoint of safety and secondary efficacy endpoints, demonstrating a dose-dependent improvement in FVC over 12 weeks. Zhavoronkov acknowledged that the study is “not powered enough for me to go out and make super big claims . . . but when you see the chart, it’s very clear that you see that the drug is working.” Insilico is currently awaiting the results of a second, parallel Phase IIa trial. Next, Zhavoronkov said the company expects to run a Phase IIb study but added that the team wants to meet with regulators to understand the regulatory pathway. He suggested there could be potential for the candidate to be fast-tracked. “If you see the improvements in forced vital capacity, and it’s strong enough evidence to convince the regulators, maybe patients should be on the drug right now,” he told BioSpace . ISM001-055—which was wholly designed using Insilico’s generative AI engine referencing millions of data including patents, research publications, grants and clinical trial databases—targets Traf2- and NCK- interacting kinase (TNIK). Zhavoronkov explained that, due to the prevalence of IPF in people 65 years and older, Insilico was looking for targets that were also “very strongly implicated” in aging, Zhavoronkov said. “We were looking for a dual-purpose target.” TNIK scored high in six hallmarks of aging, and there was significant overlap in hallmarks of IPF, he said. However, Reiss said she is “pretty skeptical” about the approach. She noted that while TNIK is present in the lungs and “does regulate transforming growth factor-β signaling, which is important in IPF,” it is mostly found in the gastrointestinal system. Reiss added that the duration of the study was too short and the number of subjects was too small to draw any conclusions about ISM001-055’s efficacy. “[We’ll] have to wait and see,” she said.