Executive Summary

Q4 2024 marked continued pipeline execution and balance sheet strengthening: net loss narrowed to $56.3M from $69.0M in Q3, while Spyre ended the year with $603.1M in cash and marketable securities, extending runway into 2H 2028 after a $230M equity raise in November .
Key clinical momentum: SPY001 Phase 1 interim data showed >90‑day half-life and complete α4β7 receptor occupancy out to 12 weeks at 300mg, supporting potential Q3M/Q6M subcutaneous maintenance dosing; Phase 2 UC platform trial remains on track to initiate mid‑2025 .
Broadened optionality: SPY002 advanced two anti‑TL1A antibodies into first‑in‑human trials (Dec), with interim HV data expected in Q2’25; management also added a Phase 2 RA trial for SPY002 in mid‑2025, and SPY003 remains on track for FIH start in Q1’25 .
Index inclusion and capital markets visibility: Added to Nasdaq Biotechnology Index (Dec 18) and completed a $200M offering (plus underwriter option) during Nov; company disclosed $230M in gross proceeds for the raise in Q4 materials .
Estimate comparison: Wall Street consensus (S&P Global) was unavailable for Q4 2024 at time of analysis; therefore, vs‑consensus comparisons are not included.

What Went Well and What Went Wrong

What Went Well

Strong SPY001 Phase 1 interim: human PK half‑life >90 days, complete receptor occupancy through Week 12 at 300mg, and tolerability consistent with class; supports potential Q3M/Q6M SC maintenance dosing and de‑risked transition to Phase 2 in UC mid‑2025 .
Strengthened liquidity and extended runway: year‑end cash and marketable securities of $603.1M with expected runway into 2H 2028, bolstered by $230M gross equity raise in Nov 2024 .
Portfolio breadth and combinations: SPY002 dosed in two FIH trials (Dec), SPY003 FIH remains on track for Q1’25, and preclinical combo data (TL1A + α4β7; IL‑23 + α4β7/TL1A) demonstrated enhanced efficacy and PD in models, aligning with the platform Phase 2 design .

Management quote: “We are well‑positioned and well‑capitalized to deliver a series of value‑inflecting catalysts, including three Phase 1 readouts expected in 2025 and four Phase 2 proof‑of‑concept readouts expected in 2026.” — CEO Cameron Turtle .

What Went Wrong

Continued operating losses as a clinical‑stage company: Q4 net loss of $56.3M (vs. $63.2M LY) driven by higher R&D ($50.5M) as programs move through FIH and into Phase 2 preparation .
Elevated CVR liability persists: CVR (current + non‑current) totaled ~$61.7M at year‑end, reflecting ongoing exposure to contingent outcomes, though mix shifted between current and non‑current vs. Q3 .
Estimate transparency gap: S&P Global consensus EPS/revenue for Q4 2024 was unavailable, limiting vs‑consensus framing for the quarter.

Financial Results

Quarterly progression (sequential)

Metric	Q2 2024	Q3 2024	Q4 2024
Revenue ($M)	$0.0	$0.0	$0.0
Net Loss ($M)	$(38.8)	$(69.0)	$(56.3)
Diluted EPS (Common) ($)	$(0.86)	$(1.36)	$(0.81)
R&D Expense ($M)	$32.6	$44.7	$50.5
G&A Expense ($M)	$11.5	$10.6	$10.8
Other Income/(Expense) ($M)	$5.3	$(13.6)	$5.0
Net Cash Used – Operating ($M)	$62.4	$29.4	$37.2

Year-over-year compare (Q4 2023 vs Q4 2024)

Metric	Q4 2023	Q4 2024
Revenue ($M)	$0.0	$0.0
Net Loss ($M)	$(63.2)	$(56.3)
Diluted EPS (Common) ($)	$(1.23)	$(0.81)
R&D Expense ($M)	$33.7	$50.5
G&A Expense ($M)	$14.1	$10.8
Other Income/(Expense) ($M)	$(17.3)	$5.0

Balance sheet & liquidity KPIs

KPI	Q2 2024	Q3 2024	Q4 2024
Cash & Marketable Securities ($M)	$426.3	$414.2	$603.1
Cash Runway	Well into 2027	Well into 2027	Into 2H 2028
CVR Liability – Current ($M)	$2.64	$24.74	$25.08
CVR Liability – Non‑Current ($M)	$39.56	$36.16	$36.62
Weighted Avg Shares (Qtr, Common)	45.32M	50.89M	55.26M
Non‑cash Stock Comp (Qtr) ($M)	$8.7	$13.1	$9.2

Note: No revenue segments; company is pre‑commercial .

Guidance Changes

Metric/Item	Period	Previous Guidance	Current Guidance	Change
Cash Runway	Multi‑year	“Well into 2027” (Q3’24)	“Into 2H 2028” (Q4’24)	Raised runway
SPY001 – UC Phase 2 Start	Mid‑2025	Platform trial planned 2025	On track mid‑2025 start	Timing specified
SPY001 – Dosing Profile	Maintenance	Target Q8‑12W (preclinical/expectations)	Human PK supports Q3M/Q6M SC	Improved optionality
SPY002 – FIH Status	2H 2024/1H 2025	FIH in Q4’24; HV interim 1H’25	FIH initiated Dec 2; HV interim Q2’25	Achieved; timing affirmed
SPY002 – RA Expansion	2025–2026	Not disclosed	Phase 2 RA start mid‑2025; topline 2026	New indication
SPY003 – FIH Start	Q1 2025	Accelerated to Q1’25	Remains on track Q1’25	Maintained
UC Platform Trial Scope	2025	Monotherapies + combos	Monotherapies + combinations; 500 pts design noted	Maintained/expanded details
Capital Markets	Nov 2024	N/A	$200M offering priced; $230M gross proceeds disclosed	New financing

Earnings Call Themes & Trends

Note: No Q4’24 earnings call transcript was available in the document set; themes reflect Q2–Q4 disclosures and Q4 press commentary.

Topic	Previous Mentions (Q2, Q3)	Current Period (Q4)	Trend
Pipeline execution (SPY001)	FIH dosing started; interim data YE’24 expected	Interim: >90‑day half‑life, full receptor occupancy, tolerability; Phase 2 UC mid‑2025	Positive de‑risking
TL1A (SPY002)	Two candidates chosen; FIH planned Q4’24; strong preclinical half‑life	FIH initiated; HV interim data Q2’25; RA Phase 2 mid‑2025	Execution + label expansion
IL‑23 (SPY003)	Candidate nominated; FIH 1H’25; acceleration to Q1’25 announced	Remains on track for Q1’25 FIH start	On‑track
Combinations	Preclinical combo efficacy/PD at UEGW	New ECCO preclinical data (TL1A+α4β7 superiority in colitis models)	Building momentum
Liquidity/runway	$426M (Q2), runway into 2027	$603M at YE; runway into 2H 2028	Strengthened
Capital markets/index	—	$200M offering; added to Nasdaq Biotech Index	Enhanced visibility

Management Commentary

“In 2024, we initiated first‑in‑human studies for three of our next‑generation antibodies and delivered outstanding interim Phase 1 results for SPY001... We are well‑positioned and well‑capitalized to deliver a series of value‑inflecting catalysts” — Cameron Turtle, CEO .
“New preclinical data for SPY120 [TL1A+α4β7] demonstrated superiority to either monotherapy in mouse models of colitis and no PK interaction in NHPs when coadministered” .
“SPY003 remains on track to initiate a FIH trial in the first quarter of 2025” .

Q&A Highlights

No Q4 2024 earnings call transcript found in the document set; no Q&A to report. If a live call occurred, a transcript was not available in the filings/press materials reviewed.

Estimates Context

S&P Global consensus EPS and revenue estimates for Q4 2024 were unavailable due to access limitations at the time of analysis; therefore, vs‑consensus comparisons are not included. Results are presented vs prior quarter and prior year from company filings.

Key Takeaways for Investors

Clinical de‑risking for SPY001 increases confidence heading into the mid‑2025 UC Phase 2 start; quarterly/twice‑yearly maintenance dosing could be a differentiation lever if efficacy translates in patients .
Multiple 2025 catalysts (SPY002 HV interim, SPY003 HV interim 2H’25, SPY001 longer‑term Phase 1 data) and 2026 POC readouts create a steady cadence for news flow and potential stock inflection points per management’s timeline .
Expanded TAM through RA adds a second large indication for SPY002, diversifying outcomes while leveraging the same anti‑TL1A mechanism .
Balance sheet removes near‑term financing overhang; runway into 2H 2028 supports completion of multiple Phase 2 studies under a master protocol design .
Watch CVR liability and related‑party expense dynamics; while non‑cash factors improved “Other income/(expense)” in Q4, the CVR exposure remains material on the balance sheet .
With no commercial revenue, valuation remains driven by clinical data quality, speed of execution, and competitive positioning in α4β7, TL1A, and IL‑23 classes; combo data and dosing convenience are emerging differentiators .
Absence of published consensus limited beat/miss framing this quarter; future comps should normalize once estimate availability resumes.

References:

Q4 2024 8‑K and Exhibit 99.1 press release: financials, runway, and program updates .
Q4 2024 press release duplicate (PR Newswire) with identical financials and quotes .
SPY001 interim (Nov 12, 2024): half‑life >90 days, receptor occupancy, and Phase 2 design .
SPY002 FIH initiation (Dec 2, 2024): two trials, HV interim in Q2’25 .
SPY003 acceleration (Oct 14, 2024): FIH Q1’25 track .
Capital markets: $200M offering (Nov 18–19) ; added to Nasdaq Biotechnology Index (Dec 18) .
Q3 2024 8‑K/press release: sequential financials and prior guidance .
Q2 2024 press release: earlier liquidity and guidance baselines .

Spyre Therapeutics, Inc. (SYRE)·Q4 2024 Earnings Summary