LEAP THERAPEUTICS, INC. (LPTX)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 showed disciplined cost control with lower operating expenses and a narrower net loss per share ($0.37) despite remaining a pre-revenue biotech; cash ended at $47.2M .
• Wall Street EPS was essentially in line: Actual EPS of $(0.37) vs S&P Global consensus of $(0.36); revenue was expected at $0 and remained $0 as the company is pre-revenue (S&P Global) . Values with asterisk from S&P Global: EPS estimate and revenue estimate*.
• Strategic update/catalyst: strong updated Part B DeFianCe data in MSS CRC, including statistically significant ORR and PFS benefits in DKK1-high and VEGF‑naïve subgroups, supporting a registrational Phase 3 path; management engaged a financial advisor to explore BD partnerships .
• Trend: sequential reductions in R&D and total opex from Q2→Q3→Q4, and improving quarterly net loss per share (Q2: $(0.52) → Q3: $(0.44) → Q4: $(0.37)), extending operating runway efforts, albeit with cash declining to $47.2M at year end .

What Went Well and What Went Wrong

• What Went Well

  • Clinical efficacy: Updated DeFianCe Part B data showed a 32% higher ORR (IA) and 3.5-month longer PFS for DKK1‑high (upper quartile) patients (ORR IA: 48.0% vs 15.8%, PFS 9.36 vs 5.88 months), with OS benefit (HR 0.09) versus control .
  • Broader subgroup strength: In VEGF‑naïve patients, ORR improved by 22% (IA) and PFS by 2.6 months (10.94 vs 8.34 months), with OS trending favorably; management emphasized registrational readiness and potential accelerated approval strategy .
  • Clear strategic tone: “We believe that there is a compelling opportunity to move forward with a registrational study for sirexatamab...,” CEO Douglas Onsi noted, highlighting a biomarker‑selected Phase 3 path and first‑line opportunity for VEGF‑naïve patients .

• What Went Wrong

  • Cash draw: Cash decreased from $62.8M (Q3) to $47.2M (Q4), reflecting operating cash use despite cost discipline .
  • Continued net losses: Quarterly net loss remained significant at $(15.4)M (Q4), though improved vs Q3 $(18.2)M and Q2 $(20.1)M .
  • No updated runway in Q4 release: Unlike Q3 (which indicated funding into Q2 2026), the Q4 materials did not reiterate runway guidance; the company is pursuing BD to support late‑stage development .

Financial Results

Quarterly P&L snapshot (oldest → newest)

Q4 YoY comparison

Versus Estimates (S&P Global)

Values with asterisk are retrieved from S&P Global.

KPIs

Note: LPTX reports no product revenues; segment breakdown not applicable in the period .

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• Strategic message: “We believe that there is a compelling opportunity to move forward with a registrational study for sirexatamab... and to advance FL‑501 towards clinical trials.” – Douglas E. Onsi, CEO .
• On DKK1‑high and VEGF‑naïve populations: “Updated data confirms that sirexatamab can generate significantly higher ORR and longer PFS... With more sirexatamab‑treated patients currently continuing on study drug... there is potential for the dataset to continue to strengthen.” – Cynthia Sirard, MD, CMO .
• On regulatory path: Management discussed a biomarker‑selected Phase 3 with potential accelerated approval on ORR and full approval on OS, with hierarchical testing (upper quartile → upper median) .
• On BD: “Leap has engaged a leading financial advisor to explore business development opportunities to further the development of sirexatamab.” .

Q&A Highlights

• Phase 3 design and biomarker hierarchy: Management favors focusing on DKK1‑high (upper quartile) with hierarchical testing to upper median to maximize chance of success and enable an accelerated approval on ORR with OS confirmatory endpoint .
• Inclusion criteria across subgroups: Outcomes across other subgroups (e.g., RAS status, prior EGFR) are largely explained by DKK1 level and VEGF‑naïve status; management sees DKK1 or VEGF status as primary drivers rather than excluding by other factors .
• Companion diagnostic: Current data generated on SomaScan (aptamer) and validated by ELISA; working with a partner to ready an assay for Phase 3 patient selection .
• Development prioritization (if capital unconstrained): First, a second‑line DKK1 biomarker‑selected trial (potential accelerated approval on ORR); then a first‑line VEGF‑naïve study to broaden label .

Estimates Context

• S&P Global consensus EPS for Q4 2024 was $(0.36)* versus actual $(0.37), essentially in line; revenue was estimated at $0.0* and remains $0 as the company is pre‑revenue . Values with asterisk are retrieved from S&P Global.
• Estimate revisions: With strengthened efficacy signals and a clearer Phase 3 path, Street models may adjust timelines (Phase 3 start/BD timing) rather than near‑term P&L, given pre‑revenue status .

Key Takeaways for Investors

• Clinical inflection: Statistically significant efficacy in DKK1‑high and VEGF‑naïve subgroups in DeFianCe Part B underpins a credible registrational Phase 3 and potential accelerated approval path, a key stock catalyst .
• Strategy/BD: Engaging a financial advisor signals intent to partner for Phase 3 scale and commercialization, which could de‑risk funding and execution .
• Cost discipline: Sequential decline in opex and narrowing quarterly EPS loss (Q2→Q3→Q4) reflects operating control, though cash fell to $47.2M, keeping financing/BD in focus .
• Biomarker edge: DKK1‑directed strategy with emerging CDx readiness may enable patient selection and regulatory advantage; VEGF‑naïve data also opens a first‑line path .
• Near‑term catalysts: Further data maturation (PFS/OS), Phase 3 design disclosure, BD outcomes, and AACR FL‑501 preclinical poster in April 2025 .
• Risk balance: Pre‑revenue status, clinical/regulatory execution risk, and cash trajectory remain key considerations despite strong subgroup signals .
• Trading lens: Headlines around Phase 3 initiation plans, BD partnerships, and any additional efficacy updates (especially OS) are likely to drive share volatility and re‑rating potential .