GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - LISATA THERAPEUTICS INC

Financial Performance:

• Secured $225 million via a private placement financing to fund operations and clinical development.
• Capital runway extends through the middle of 2028, supporting two phase 3 programs.
• Company is currently a pre-revenue clinical-stage biopharmaceutical entity following a reverse merger.
• No specific debt, profit margin, or cash flow metrics were disclosed as the focus is on R&D execution.

Guidance and Future Outlook:

• 2027 identified as a pivotal year with multiple clinical catalysts for both lead programs.
• Key milestone: Selection of dose for a half-life extended version of MARS001 and completion of Phase 2b data for Severe Hypertriglyceridemia (SHGT) by end of next year.
• Targeting Phase 3 initiation for both SHGT and Acromegaly within the current funding window.
• Acromegaly Phase 2 interim data expected by year-end, with full proof-of-concept data also anticipated by year-end.
• Long-term goal includes expanding the NGPTL4 program into broader cardiovascular indications (remnant cholesterol, ASCVD) via future partnership opportunities.

Business Segments and Product Lines:

• Lead Asset (MARS001): First-in-class antibody targeting ANGPTL4 for Severe Hypertriglyceridemia (SHGT).
  • Clinical data (TIMI 78) presented at AHA showed efficacy scaling with baseline triglycerides: ~40% reduction in patients <300 mg/dL, rising to 70-72% in patients >500 mg/dL.
  • Differentiates from APOC3 class by avoiding dysglycemia, worsening diabetes, and hepatic fat accumulation.
  • Mechanism directs triglycerides to adipose tissue rather than the liver.
• Second Asset: First-in-class antibody targeting the Growth Hormone Receptor for Acromegaly.
  • Targets the ~2/3 of patients who fail to achieve IGF-1 control on current Somatostatin Receptor Ligands (SRLs).
  • Demonstrated IGF-1 suppression in healthy volunteers exceeding the benchmark of Pfizer's Pegvisomant (49% suppression).
  • Clinical trial design includes monotherapy (naive patients) and combination therapy with background SRLs.
  • Goal is biweekly subcutaneous dosing via auto-injector, contrasting with daily dosing of current alternatives.
• Pipeline: Development of next-generation siRNA adipose-directed programs to follow the lead monoclonal antibody.

Market and Competitive Landscape:

• SHGT Market: Projected >$10 billion in the U.S. over time, currently being built by Ionis (Leqvio) and Arrowhead; Mireya aims to capture market share via a differentiated metabolic safety profile.
• Acromegaly Market: Addressable U.S. market estimated at $1 billion based on current SRL projections; Mireya aims to address double the patient volume by targeting non-responders to SRLs (approx. 30,000 total U.S. patients, 50% uncontrolled).
• Competition: Differentiates from APOC3 inhibitors by lacking glucose-elevating effects; differentiates from Pegvisomant by offering better durability and dosing convenience.

Risks and Challenges:

• Statistical Power: The high efficacy (70-72%) in the >500 mg/dL cohort is based on a small sample size (~12 patients); larger Phase 2b studies are required to confirm this trend.
• Clinical Validation: Reliance on healthy volunteer data to predict Phase 2/3 outcomes in Acromegaly carries inherent biological risk.
• Market Adoption: Success depends on physicians choosing this new entrant over established APOC3 therapies in the face of a potentially slower commercial rollout.
• Dosing Logistics: Achieving biweekly dosing and auto-injector compatibility in Phase 3 is a critical execution hurdle.

Management Commentary and Tone:

• Tone is highly confident and optimistic, emphasizing "first-in-class" validation and strong human genetics.
• Management expresses strong belief in the ANGPTL4 mechanism's ability to outperform the APOC3 class regarding safety (specifically diabetes management).
• CEO and CFO emphasized the company is "well-financed" and "laser-focused" on SHGT while acknowledging the larger potential for cardiovascular expansion.
• Management highlighted the strategic advantage of entering a market where competitors (Ionis, Arrowhead) are already building commercial infrastructure.

Analyst Questions and Answers:

• Efficacy Scaling: Explained that ANGPTL4 is PPAR-gamma regulated, inducing gene expression 10-20 fold in high triglyceride states, leading to superior efficacy in severe cases compared to constitutively expressed targets like APOC3.
• Safety Profile: Confirmed no increase in glucose in diabetic patients and no hepatic fat signal, contrasting with the class effects of APOC3 inhibitors.
• Market Dynamics: Discussed that market acceptance will likely follow a "Leqvio-like" trajectory over time, with the primary opportunity being new starts in diabetic patients who currently avoid APOC3 drugs.
• Acromegaly Data: Confirmed that healthy volunteer data suggests the new drug can match Pegvisomant's efficacy but with superior dosing (biweekly vs. daily) and tolerability.

Other Key Points:

• The reverse merger is still in process, with Lissata serving as the active ticker at the time of the call.
• Data presented at the American Heart Association (AHA) and published in the New England Journal of Medicine were cited as key validation points.
• The company aims to address the specific unmet need of patients who cannot tolerate or respond to existing lipid-lowering or acromegaly therapies due to metabolic side effects or dosing burdens.