Tranexamic Acid

Additional results from largest body of evidence on attenuated androgen use in HAE reinforce need for access to safer and more tolerable HAE prophylaxis optionsRESEARCH TRIANGLE PARK, N.C., June 02, 2024 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced new real-world evidence showing that patients with hereditary angioedema (HAE) who have normal C1-inhibitor (HAE-nC1-INH) level and function had a reduction in monthly attack rates after starting oral, once-daily ORLADEYO® (berotralstat). The data were presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress in Valencia, Spain. “The diagnosis of HAE patients with normal C1-inhibitor is complicated and often delayed by the lack of an easily measurable biochemical marker. This multicenter case series provides clinically relevant evidence that berotralstat can also reduce the frequency and duration of episodes in the C1 normal population,” said Dr. Isabelle Boccon-Gibod, department of internal medicine and immunology, Grenoble Alps University Hospital, who presented the findings at EAACI. Six patients with HAE-nC1-INH were included in the analysis. All had received previous long-term prophylaxis (LTP), and one remained on concurrent LTP. After six months of treatment with berotralstat, five patients showed a 75 to 100 percent reduction of their HAE attack rate, and one patient, who was on a concurrent dose of tranexamic acid, showed a 29 percent reduction in their HAE attack rate. No adverse events related to berotralstat were noted in five of the six patients. One patient experienced gastrointestinal symptoms upon initiation, which became milder after the first two weeks and did not lead to treatment discontinuation. Adverse Health Outcomes and Patient and Physician Perspectives of Attenuated Androgen Use in Hereditary Angioedema Additional new results presented at EAACI demonstrate the adverse health outcomes associated with attenuated androgen use as a prophylactic treatment for HAE. The study also documents that these adverse outcomes cause increased reluctance among physicians to use attenuated androgens in clinical practice. The study highlights the importance of access to recent targeted HAE prophylactic therapies, in line with current World Allergy Organization/EAACI guidelines which recommend that targeted therapies are utilized for first-line long term prophylaxis, and the use of androgens is reserved only as second-line long-term prophylaxis. “This study presents the latest and largest body of evidence documenting that HAE prophylactic treatment with attenuated androgens is associated with short-term adverse outcomes and serious long-term risks that include increased cardiovascular events, liver damage, and cancer. The prevalent and wide-ranging adverse outcomes associated with attenuated androgen use in HAE reinforce that safer and more tolerable treatment options should be preferred and made accessible for HAE prophylaxis,” said Marcus Maurer, professor of dermatology and allergology at Charité - Universitätsmedizin Berlin and Fraunhofer Institute for Translational Medicine and Pharmacology. The study assessed 108 prospective and retrospective studies published between January 1980 and July 2023 that reported quantitative outcomes associated with attenuated androgen use in patients with HAE. These included four clinical trials, 43 observational studies, 37 case reports/series, and 24 reviews. Studies of patient and physicians’ attitudes and perception of risk regarding attenuated androgens were also included. Adverse outcomes associated with attenuated androgen use included increased body weight, menstrual irregularities, virilization, myalgia, acne and liver damage, including liver cancer. Patients and physicians cited concerns with the use of attenuated androgens related to tolerability, fear of adverse events, and long-term adherence. A three-part survey conducted in the United States noted that the unwillingness to prescribe attenuated androgens among physicians increased from 18 percent in 2010 to 60 percent in 2019, following approval of the first newer LTP treatments. About ORLADEYO® (berotralstat)ORLADEYO® (berotralstat) is the first and only oral therapy designed specifically to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years and older. One capsule of ORLADEYO per day works to prevent HAE attacks by decreasing the activity of plasma kallikrein. U.S. Indication and Important Safety Information INDICATIONORLADEYO® (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. Limitations of use The safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for the treatment of acute HAE attacks. Additional doses or dosages of ORLADEYO higher than 150 mg once daily are not recommended due to the potential for QT prolongation. IMPORTANT SAFETY INFORMATION An increase in QT prolongation was observed at dosages higher than the recommended 150 mg once-daily dosage and was concentration dependent. The most common adverse reactions (≥10% and higher than placebo) in patients receiving ORLADEYO were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease. A reduced dosage of 110 mg taken orally once daily with food is recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C). Berotralstat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein. P-gp inducers (eg, rifampin, St. John’s wort) may decrease berotralstat plasma concentration, leading to reduced efficacy of ORLADEYO. The use of P-gp inducers is not recommended with ORLADEYO. ORLADEYO at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. For concomitant medications with a narrow therapeutic index that are predominantly metabolized by CYP2D6 or CYP3A4, appropriate monitoring and dose titration is recommended. ORLADEYO at a dose of 300 mg is a P-gp inhibitor. Appropriate monitoring and dose titration is recommended for P-gp substrates (eg, digoxin) when coadministering with ORLADEYO. The safety and effectiveness of ORLADEYO in pediatric patients <12 years of age have not been established. There are insufficient data available to inform drug-related risks with ORLADEYO use in pregnancy. There are no data on the presence of berotralstat in human milk, its effects on the breastfed infant, or its effects on milk production. To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see full Prescribing Information. About BioCryst Pharmaceuticals BioCryst Pharmaceuticals is a global biotechnology company with a deep commitment to improving the lives of people living with complement-mediated and other rare diseases. BioCryst leverages its expertise in structure-guided drug design to develop first-in-class or best-in-class oral small-molecule and protein therapeutics to target difficult-to-treat diseases. BioCryst has commercialized ORLADEYO® (berotralstat), the first oral, once-daily plasma kallikrein inhibitor, and is advancing a pipeline of small-molecule and protein therapies. For more information, please visit www.biocryst.com or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: BioCryst’s ability to successfully implement its commercialization plans for ORLADEYO, which could take longer or be more expensive than planned; the commercial viability of ORLADEYO, including its ability to achieve market acceptance; the FDA or other applicable regulatory agency may require additional studies beyond the studies planned for products and product candidates, may not provide regulatory clearances which may result in delay of planned clinical trials, may impose certain restrictions, warnings, or other requirements on products and product candidates, may impose a clinical hold with respect to product candidates, or may withhold, delay, or withdraw market approval for products and product candidates; BioCryst’s ability to successfully manage its growth and compete effectively; risks related to the international expansion of BioCryst’s business; and actual financial results may not be consistent with expectations, including that revenue, operating expenses and cash usage may not be within management’s expected ranges. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, which identify important factors that could cause the actual results to differ materially from those contained in BioCryst’s forward-looking statements. BCRXW Contacts:John Bluth+1 919 859 7910jbluth@biocryst.com Niamh Lyons+353 87 639 7083nlyons@biocryst.com

– Rapid advancement of PALI-2108 towards Phase 1 clinical study for the treatment of moderate-to-severe ulcerative colitis; On track to commence Phase 1 before year end – Formation of Clinical Advisory Board – Sufficient cash on hand to execute on business plan and achieve significant clinical milestones into 2025 Carlsbad, CA, March 27, 2024 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade”, “Palisade Bio” or the “Company”), a pre-clinical biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases, today reported its financial results for the full year 2023 and provided a corporate update. Recent Highlights The Company formed its Clinical Advisory Board and appointed preeminent Key Opinion Leaders, Bruce Sands, MD, MS and Florian Rieder, MD;The exercise in February 2024, of 3,422,286 previously issued warrants to purchase common stock resulting in gross cash proceeds to the Company of $2.5 million;Presentation of positive preclinical data of its lead asset, PALI-2108 at the 2024 Crohn’s & Colitis Congress; andGiiant Pharma, Inc., the Company’s joint development partner, received the second milestone payment to assist in funding PALI-2108 from the US Crohn’s and Colitis Foundation, through its IBD Ventures program. “2023 was a transformative year for Palisade Bio as we strategically shifted into the autoimmune, inflammatory, and fibrotic disease space, with the focus on our precision medicine approach in inflammatory bowel disease,” commented J.D. Finley, Chief Executive Officer. “As a result of the progress made by our development team, we are on track to launch the Phase 1 study of PALI-2108 by the end of 2024. We are looking forward to the advancement of our lead program to bring our product candidates into clinical trials and to increase our value for all stakeholders.” PALI-2108 Development Program The Company continues to advance its lead program, PALI-2108, for the treatment of moderate-to-severe ulcerative colitis (UC) toward a Phase 1 clinical study. PALI-2108 is an orally administered, locally acting colon-specific phosphodiesterase-4 (PDE4) inhibitor prodrug in development for patients affected by UC. Upcoming Target Milestones Complete ongoing IND/CTA-enabling tox studies by the end of the second quarter of 2024;Complete nonclinical IND/CTA-enabling activities by the end of the third quarter of 2024;Submit initial IND/CTA prior to the end of 2024; andInitiate Phase 1a/b prior to the end of 2024. Precision Medicine Approach Additionally, the Company is in the process of developing a genetic- or biomarker-based precision medicine approach that, if developed, will aid patients and physicians in selecting patients most likely to respond to PDE4 inhibitor therapy with PALI-2108. The Company is working with a strategic collaborator on development and has completed curation of a pipeline including over 1600 UC patients clinical and biomarker data and is in ongoing discussions with potential partners with access to additional patient data to support development of an FDA-approved test. The Company plans to leverage this expertise and infrastructure to fuel a growing pipeline of validated and high-priority autoimmune, inflammatory, and fibrotic disease product candidates. Summary of Financial Results for the Year Ended December 31, 2023 As of December 31, 2023, the Company had cash, cash equivalents and restricted cash of $12.5 million. The Company believes it has sufficient cash to fund its currently planned operations into the first quarter of 2025. Net operating loss was $13.1 million for the year ended December 31, 2023 compared to $15.7 million for the year ended December 31, 2022. Included in the net operating loss for the year ended December 31, 2023 was license revenue of $0.3 million, of which there was none in 2022, and restructuring costs of $0.2 million in 2023, compared to restructuring costs of $0.4 million in 2022. Research and development expenses were $6.9 million for the year ended December 31, 2023, an increase of $0.3 million, or approximately 5% compared to the year ended December 31, 2022. The year-over-year increase is attributable to increased costs associated with the Giiant License Agreement, which we entered into on September 1, 2023, as well an increase in employee-related costs and employee recruiting costs, which were partially offset by a decrease in costs directly related to our development of LB1148, which we ceased in August of 2023. General and administrative expenses decreased from $8.8 million for the year ended December 31, 2022 to $6.2 million for the year ended December 31, 2023. The decrease of $2.6 million, or 26%, was primarily as a result of cost-saving opportunities implemented by us in the third and fourth quarters of 2022, including those associated with the 2022 Cost-Reduction Plan. General and administrative employee compensation costs for the year ended December 31, 2023 decreased by approximately $1.4 million compared to the year ended December 31, 2022, primarily due to an approximately $0.9 million decrease in salaries and benefits and an approximately $0.5 million decrease in stock-based compensation expense. Other decreases in general and administrative expenses for the year ended December 31, 2023 compared to the year ended December 31, 2022 include: (i) an approximately $0.3 million decrease in professional fees, including accounting and legal fees and financial printing costs, (ii) an approximately $0.3 million decrease in investor and public relations costs and shareholder services costs, (iii) an approximately $0.2 million decrease in consultants and contract labor costs, (iv) an approximately $0.2 million decrease in general and administrative employee recruiting costs, and (v) an approximately $0.2 million decrease in insurance costs. About Palisade Bio Palisade Bio is a pre-clinical 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 StatementsThis 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, filed with the Securities and Exchange Commission (“SEC”) on March 26, 2024. 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 Contact JTC Team, LLCJenene Thomas 833-475-8247PALI@jtcir.com Palisade Bio, Inc.Consolidated Balance Sheets (Unaudited)(in thousands, except share and per share amounts) December 31, 2023 2022 ASSETS Current assets: Cash and cash equivalents $12,432 $12,383 Prepaid expenses and other current assets 896 2,350 Total current assets 13,328 14,733 Restricted cash 26 26 Property and equipment, net 10 10 Operating lease right-of-use asset 198 300 Other noncurrent assets 490 694 Total assets $14,052 $15,763 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $698 $1,759 Accrued liabilities 831 574 Accrued compensation and benefits 778 486 Current portion of operating lease liability 121 105 Insurance financing debt 158 88 Total current liabilities 2,586 3,012 Warrant liability 2 61 Contingent consideration obligation 61 — Operating lease liability, net of current portion 90 211 Total liabilities 2,739 3,284 Commitments and contingencies Stockholders' equity: Series A Convertible Preferred Stock, $0.01 par value, 7,000,000 shares authorized; 200,000 issued and outstanding at December 31, 2023 and December 31, 2022 2 2 Common stock, $0.01 par value; 280,000,000 shares authorized;9,270,894 and 2,944,306 shares issued and outstanding at December 31, 2023 and December 31, 2022, respectively 93 30 Additional paid-in capital 132,724 121,637 Accumulated deficit (121,506) (109,190)Total stockholders' equity 11,313 12,479 Total liabilities and stockholders' equity $14,052 $15,763 Palisade Bio, Inc.Consolidated Statements of Operations (Unaudited)(in thousands, except share and per share amounts) Year Ended December 31, 2023 2022 License revenue $250 $— Operating expenses: Research and development 6,893 6,547 General and administrative 6,202 8,764 Restructuring costs 225 410 Total operating expenses 13,320 15,721 Loss from operations (13,070) (15,721)Other income (expense): Interest expense (15) (13)Other income 785 2,584 Loss on issuance of warrants — (1,110)Total other income, net 770 1,461 Net loss $(12,300) $(14,260) Net loss available to common stockholders $(12,316) $(14,548)Basic and diluted weighted average shares used in computing basic and diluted net loss per common share 6,840,213 880,311 Basic and diluted net loss per common share $(1.80) $(16.53) Palisade Bio, Inc.Consolidated Statements of Cash Flows (Unaudited)(in thousands, except share and per share amounts) Year Ended December 31, 2023 2022 Net loss $(12,300) $(14,260)Adjustments to reconcile net loss to net cash used in operating activities: Depreciation 4 3 Noncash operating lease expense 102 164 Loss on issuance of warrants — 1,110 Fair value of contingent consideration obligation 204 — Change in fair value of warrant liabilities (59) (2,426)Stock-based compensation and related charges 624 1,032 Other (108) (233)Changes in operating assets and liabilities: Prepaid and other current assets and other noncurrent assets 705 1,027 Accounts payable and accrued liabilities (492) 399 Accrued compensation 292 (25)Operating lease liabilities (105) (151)Net cash used in operating activities (11,133) (13,360)Cash flows from investing activities: Purchases of property and equipment (4) (10)Net cash used in investing activities (4) (10)Cash flows from financing activities: Payments on insurance financing debt (391) (790)Proceeds from issuance of common stock and warrants 9,419 14,401 Proceeds from the exercise of warrants 2,758 2,274 Payment of equity issuance costs (617) (627)Proceeds from issuance of common stock under Employee Stock Purchase Plan 17 — Net cash provided by financing activities 11,186 15,258 Net increase in cash, cash equivalents and restricted cash 49 1,888 Cash, cash equivalents and restricted cash, beginning of year 12,409 10,521 Cash, cash equivalents and restricted cash, end of year $12,458 $12,409 Reconciliation of cash, cash equivalents and restricted cash to the balance sheets: Cash and cash equivalents $12,432 $12,383 Restricted cash 26 26 Total cash, cash equivalents and restricted cash $12,458 $12,409