Executive Summary

Q4 2024 delivered modest revenue and a narrower EPS loss versus consensus, alongside a materially strengthened balance sheet post-IPO; revenue was $0.212M and diluted EPS was $(0.64), beating S&P Global consensus of $0.150M revenue and $(0.6867) EPS, respectively, while net loss was $(20.7)M . Revenue and EPS estimates marked with * are from S&P Global.
Cash, cash equivalents, and marketable securities rose to $420.8M at year-end 2024, extending the operating runway to early 2028 (from second half of 2027 previously), a key support for multi-program execution .
Portfolio update: SEP-786 (PTH1R agonist) was discontinued in February 2025 due to reversible Grade 3 bilirubin elevations; management is advancing next‑gen oral PTH1R agonists with plans to select a development candidate by end-2025 and expects SEP‑631 (MRGPRX2 NAM) Phase 1 initiation in 2025 .
Near-term stock catalysts include clinical initiation for SEP‑631 in 2025 and selection of a next‑gen PTH1R agonist by end‑2025; Q4 results beat consensus modestly and the runway extension supports sentiment despite SEP‑786 discontinuation .

What Went Well and What Went Wrong

What Went Well

Balance sheet strength: Year-end cash and marketable securities of $420.8M support operations into early 2028, de-risking near-term financing needs .
Estimate beats: Q4 revenue of $0.212M topped S&P Global consensus of $0.150M* and diluted EPS of $(0.64) beat $(0.6867)*, aided by $3.89M of interest and other income . Revenue and EPS estimates marked with * are from S&P Global.
Strategic pipeline continuity: Despite SEP‑786 discontinuation, management emphasized advancing next‑gen PTH1R agonists and moving SEP‑631 into clinic; “With an experienced team, powerful platform and strong balance sheet, we believe we are well positioned to execute on our mission to develop multiple impactful GPCR medicines.” — CEO Jeffrey Finer .

What Went Wrong

Program setback: Discontinuation of SEP‑786 following two unanticipated Grade 3 unconjugated bilirubin elevations in MAD portion of Phase 1; though reversible and without liver injury, this removes the lead PTH1R asset from near-term readouts .
Higher operating spend: R&D rose to $19.3M and G&A to $5.6M in Q4 2024 versus $10.3M and $3.1M in Q4 2023, reflecting scale-up post-IPO and portfolio progress .
YoY comparability headwind: Q4 2023 included a $(47.6)M gain on sale of non‑financial asset, producing positive net income of $34.9M; absence of such one‑time gains in Q4 2024 and higher OpEx yielded a $(20.7)M net loss .

Financial Results

P&L Comparison (oldest → newest)

Metric	Q4 2023	Q3 2024	Q4 2024
Revenue ($USD Millions)	$0.118	$0.176	$0.212
Research & Development ($USD Millions)	$10.326	$17.832	$19.317
General & Administrative ($USD Millions)	$3.100	$4.894	$5.613
Interest & Other Income ($USD Millions)	$1.268	$1.891	$3.890
Net (Loss) Income ($USD Millions)	$34.894	$(20.523)	$(20.668)
Diluted EPS ($USD)	$1.91	$(8.40)	$(0.64)

Actual vs S&P Global Consensus (Estimates marked with *)

Metric	Q3 2024 Actual	Q3 2024 Consensus*	Q4 2024 Actual	Q4 2024 Consensus*
Revenue ($USD Millions)	$0.176	$0.000*	$0.212	$0.150*
Diluted EPS ($USD)	$(8.40)	N/A*	$(0.64)	$(0.6867)*

Notes: Q4 revenue beat by ~$0.062M (~41%); Q4 EPS beat by ~$0.047. Values with * retrieved from S&P Global.

Balance Sheet and Liquidity KPIs (period-end)

KPI	12/31/2023	9/30/2024	12/31/2024
Cash, Cash Equivalents & Marketable Securities ($USD Millions)	$88.483	$137.512	$420.789
Working Capital ($USD Millions)	$105.764	$120.180	$343.975
Total Assets ($USD Millions)	$130.867	$174.281	$456.554
Total Liabilities ($USD Millions)	$20.026	$37.532	$36.507
Total Stockholders’ Equity/Deficit ($USD Millions)	$(38.374)	$(87.408)	$420.047

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash Runway	Corporate	Into second half of 2027	Into early 2028	Raised/Extended
SEP‑631 (MRGPRX2 NAM)	Clinical	IND‑enabling; future Phase 1 planned	Phase 1 initiation expected in 2025	Maintained/Timed
PTH1R Program	Clinical	SEP‑786 Phase 1 data mid‑2025 expected	SEP‑786 discontinued; select next‑gen oral PTH1R agonist candidate by end‑2025	Strategic pivot
Revenue, Margins, OpEx, OI&E, Tax Rate	Q4/FY	Not provided	Not provided	Maintained (no quantitative guidance)

Earnings Call Themes & Trends

Note: No Q4 2024 earnings call transcript was available in our document catalog; themes reflect press releases and 8‑K disclosures.

Topic	Previous Mentions (Q-2: Q2 2024)	Previous Mentions (Q-1: Q3 2024)	Current Period (Q4 2024)	Trend
PTH1R Program	Not found	SEP‑786 Phase 1 ongoing; data mid‑2025 expected	SEP‑786 discontinued; advancing next‑gen oral PTH1R agonists; candidate selection by end‑2025	Changed/Pivot
SEP‑631 (MRGPRX2 NAM)	Not found	IND‑enabling; planning Phase 1	Phase 1 initiation expected in 2025	Progressing
TSHR NAM (Graves/TED)	Not found	Advancing toward candidate selection with supportive preclinical data	Continuing progression toward development candidate	Steady
Incretin Receptor Program	Not found	Advancing oral single/multi‑acting GLP‑1/GIP/GCGR agonists; favorable PK, weight loss in models	Ongoing lead progression toward candidate(s)	Steady
Capital & Runway	Not found	Cash $137.5M; runway into H2 2027	Cash $420.8M; runway into early 2028	Strengthened
Leadership	Not found	CMO appointment (Sep 2024)	CFO appointment (Jan 2025)	Strengthened team
Safety/Regulatory	Not found	Not highlighted	Reversible Grade 3 bilirubin elevations in SEP‑786 MAD prompted discontinuation; mechanism under investigation	New Risk Noted

Management Commentary

“Our Native Complex Platform continues to produce a deep pipeline of oral small molecule programs… With an experienced team, powerful platform and strong balance sheet, we believe we are well positioned to execute on our mission to develop multiple impactful GPCR medicines.” — Jeffrey Finer, M.D., Ph.D., CEO .
On SEP‑786: Two reversible Grade 3 unconjugated bilirubin elevations (no ALT/AST/GGT elevations, no liver injury/cholestasis/hemolysis); non‑clinical studies underway to investigate mechanism; early on‑target pharmacology signals (serum calcium increase, endogenous PTH decrease) observed before discontinuation .
Corporate: Appointment of CFO Gil Labrucherie in Jan 2025, bringing >25 years of biopharma finance/legal leadership .

Q&A Highlights

No Q4 2024 earnings call transcript was available in our document catalog; no Q&A themes to report this quarter.

Estimates Context

Q4 2024: Revenue $0.212M vs $0.150M consensus* (beat ~41%); diluted EPS $(0.64) vs $(0.6867)* (beat by ~$0.047). Interest and other income of $3.89M supported the EPS beat despite higher OpEx .
Q3 2024: Revenue $0.176M vs $0.000M consensus* (immaterial beat given sparse coverage); EPS consensus not available*, actual diluted EPS was $(8.40) .
Coverage: Q4 had 3 estimates for both revenue and EPS; Q3 had 1 revenue estimate and no EPS consensus*. Values with * retrieved from S&P Global.

Key Takeaways for Investors

Balance sheet resilience: ~$420.8M cash/marketable securities and runway into early 2028 underpin multi‑asset development and reduce financing overhang .
Pipeline execution: Near‑term catalyst is SEP‑631 Phase 1 initiation in 2025; mid‑term is selection of a next‑gen oral PTH1R agonist by end‑2025, sustaining the endocrinology thesis despite the SEP‑786 setback .
Estimate recalibration: Post‑discontinuation, models should shift value from SEP‑786 to next‑gen PTH1R and SEP‑631; Q4 beats were modest and driven partly by interest income rather than operating leverage .
Operating scale-up: Sustained R&D and G&A increases reflect clinical transition; monitor OpEx trajectory versus pipeline milestones to gauge capital efficiency .
Risk management: Safety signal in SEP‑786 elevates modality risk for PTH1R agonists; watch for non‑clinical mechanism clarity and how next‑gen candidates mitigate bilirubin elevation risk .
Strategic talent: CFO and earlier CMO appointments enhance execution capacity; supports clinical and corporate development pace .
Trading implications: Near-term sentiment hinges on clinical initiation timelines and clarity on next‑gen PTH1R candidate; absent numeric guidance, catalyst timing and any additional disclosures will likely drive the stock.

Values marked with * retrieved from S&P Global.

Septerna, Inc. (SEPN)·Q4 2024 Earnings Summary