New Risk • May 04
New major risk - Share price stability The company's share price has been highly volatile over the past 3 months. It is more volatile than 90% of American stocks, typically moving 16% a week. This is considered a major risk. Share price volatility increases the risk of potential losses in the short-term as the stock tends to have larger drops in price more frequently than other stocks. It may also indicate the stock is highly sensitive to market conditions or economic conditions rather than being sensitive to its own business performance, which may also be inconsistent. Currently, the following risks have been identified for the company: Major Risks Less than 1 year of cash runway based on free cash flow trend (-US$13m free cash flow). Share price has been highly volatile over the past 3 months (16% average weekly change). Earnings are forecast to decline by an average of 24% per year for the foreseeable future. Shareholders have been substantially diluted in the past year (59% increase in shares outstanding). Revenue is less than US$1m. Minor Risks Currently unprofitable and not forecast to become profitable over next 3 years (US$27m net loss in 3 years). Market cap is less than US$100m (US$19.5m market cap). Announcement • May 03
Cadrenal Therapeutics Announces End-Of-Phase 2 Meeting with the Fda and Pivotal Phase 3 Registration Path for Cad-1005 in Heparin-Induced Thrombocytopenia Cadrenal Therapeutics, Inc. had a major regulatory milestone after successfully completing its End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) and receiving guidance on key elements of the Phase 3 pivotal trial for CAD-1005, the Company’s investigational first-in-class 12-lipoxygenase (12-LOX) inhibitor for heparin-induced thrombocytopenia (HIT). The meeting with the FDA provided critical guidance on protocol design, study population, dosing, background therapy, exposure, the safety database, and the primary endpoint of new or worsening thrombotic events. After considering FDA feedback on a pivotal registration study, Cadrenal plans to advance directly to a randomized, blinded, placebo-controlled Phase 3 study evaluating CAD-1005 added to the current standard of care for patients with HIT. Phase 2 data showed a greater than 25% absolute reduction in thrombotic events when CAD-1005 was added to standard anticoagulant therapy. Cadrenal’s planned pivotal Phase 3 study - the first randomized, blinded, placebo-controlled registration trial in HIT – will evaluate CAD-1005 in approximately 120 patients across up to 50 clinical centers worldwide and is intended to support a projected NDA submission in 2029. Patients with suspected HIT will be randomized to CAD-1005 or placebo while receiving standard-of-care anticoagulant therapy and treated for up to 14 days during hospitalization. The primary endpoint – centrally adjudicated - is the incidence of new or worsening thrombotic events in patients with Serotonin Release Assay (SRA)-confirmed HIT, with at least one planned interim analysis. CAD-1005 is being investigated for the treatment of immune-mediated thrombocytopenia by targeting the underlying pathophysiologic mechanisms that current therapies do not. Heparin is the most widely used in-hospital anticoagulant, with more than 12 million patients receiving it in the United States each year. Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening immune-mediated complication of heparin administration that occurs when antibodies to heparin activate platelets, leading to clots throughout the circulatory system, markedly lowering platelet counts, and increasing the risk of bleeding. Complications of HIT include deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, amputation, and death, with mortality rates for HIT exceeding 20% in some studies. CAD-1005 is the only treatment in clinical development that targets the underlying immune drivers of HIT. CAD-1005 is an investigational therapy under evaluation for the treatment of suspected HIT. CAD-1005 is designed to selectively inhibit 12-LOX, a pathway integral to the primary immune mechanisms that drive HIT. Unlike existing therapies for HIT, which are directed only at preventing thrombotic complications, this approach targets the primary underlying cause of HIT. CAD-1005 has received Orphan Drug Designation (ODD) and Fast Track designation from the U.S. Food and Drug Administration, as well as orphan drug status from the European Medicines Agency. New Risk • Apr 26
New major risk - Shareholder dilution The company's shareholders have been substantially diluted in the past year. Increase in shares outstanding: 59% This is considered a major risk. Shareholder dilution occurs when there is an increase in the number of shares on issue that is not proportionally distributed between all shareholders. Often due to the company raising equity capital or some options being converted into stock. All else being equal, if there are more shares outstanding then each existing share will be entitled to a lower proportion of the company's total earnings, thus reducing earnings per share (EPS). While dilution might not always result in lower EPS (like if the company is using the capital to fund an EPS accretive acquisition) in a lot cases it does, along with lower dividends per share and less voting power at shareholder meetings. Currently, the following risks have been identified for the company: Major Risks Less than 1 year of cash runway based on free cash flow trend (-US$13m free cash flow). Earnings are forecast to decline by an average of 24% per year for the foreseeable future. Shareholders have been substantially diluted in the past year (59% increase in shares outstanding). Revenue is less than US$1m. Minor Risks Currently unprofitable and not forecast to become profitable over next 3 years (US$27m net loss in 3 years). Share price has been volatile over the past 3 months (15% average weekly change). Market cap is less than US$100m (US$16.9m market cap). 
