Stocks/SYRE

SYRE

Spyre Therapeutics, Inc.
Healthcare·Biotechnology
$73.50
$4.4B market cap
Claude Rating
4/10UNDERWEIGHT
Revenue
$90.5M
Free Cash Flow
$-185.8M
Rev Growth
+0.0%
FCF Margin
-205.3%
P/FCF
--
EV/FCF
--
Fwd EV/EBITDA
--
Fair Value
$28.00
Upside
-61.9%

Spyre Therapeutics, Inc., a preclinical stage biotechnology company, focuses on developing therapeutics for patients living with inflammatory bowel disease (IBD). It develops SPY001, a human monoclonal immunoglobulin G1 antibody designed to bind selectively to the a4ß7 integrin being developed for the treatment of IBD (ulcerative colitis and Crohn's disease). The company is also developing SPY002, a human monoclonal antibody (mAb)candidates designed to bind to tumor necrosis factor-like ligand

2-Year Price History

$74.05+111.9%
$20$30$40$50$60$70volMay 24Sep 24Jan 25May 25Sep 25Jan 26May 26

Quarterly Financials & Projections

Quarterly Waterfall ($ M)
PeriodRevEBITDAOpInNIOCFFCFCapExCashDebtSharesROICIntCovEV/EBITDA
Est2027-Q41.5-112.5---109.5---105.0-0.080.5----------
Est2027-Q31.5-105.0---102.0---97.5-0.0185.5----------
Est2027-Q21.5-97.5---94.5---90.0-0.0283.0----------
Est2027-Q11.5-90.0---87.0---82.5-0.0373.0----------
Est2026-Q42.0-85.0---83.0---78.0-0.0455.5----------
Est2026-Q32.0-80.0---78.0---74.0-0.0533.5----------
Est2026-Q25.0-75.0---72.5---70.0-0.1607.5----------
Est2026-Q12.0-70.0---68.0---64.0-0.0677.5----------
Act2026-Q10.0-75.6-75.6-69.0-57.5-57.5-0.0741.50.0346.1-36.4%----
Act2025-Q490.5-62.5-57.2-62.5-44.6-44.6-0.0756.50.0346.1-25.7%----
Act2025-Q30.0-11.2-56.9-11.2-37.1-37.1-0.0486.20.060.4-35.6%----
Act2025-Q20.0-51.9-41.9-36.7-46.6-46.6-0.0526.60.060.7-25.9%----
Act2025-Q10.0-53.6-53.6-44.8-41.0-41.0-0.0564.80.060.3-31.2%----
Act2024-Q40.0-61.3-61.3-56.3-37.2-37.2-0.0603.10.047.0-33.4%----
Act2024-Q30.0-55.4-55.4-69.0-29.4-29.4-0.0414.20.050.9-40.2%----
Act2024-Q20.0-44.2-44.2-38.8-62.3-62.3-0.0426.00.045.3-29.1%----
Act2024-Q10.0-47.8-47.8-43.9-28.5-28.5-0.0484.60.036.5-48.9%----
Act2023-Q40.0-47.8-45.9-63.2-31.0-31.0-0.0339.30.021.7-42.8%----
Act2023-Q30.0-33.2-18.3-40.1-34.6-34.6-0.0203.60.04.3------
Act2023-Q20.7-28.3-159.3-217.1-16.6-16.6-0.0235.44.33.8<-999%----
Act2023-Q10.2-17.9-18.8-18.4-17.6-17.6-0.038.54.43.8<-999%----
Act2022-Q40.2-18.3-19.2-18.8-18.1-18.1-0.055.74.62.6-640.2%----
Act2022-Q30.2-17.9-18.8-18.2-15.1-15.1-0.073.74.83.8-249.6%----
Act2022-Q20.6-21.8-22.4-22.3-20.7-20.7-0.088.64.83.3-190.8%----
Act2022-Q11.4-23.9-24.4-24.4-26.3-26.3-0.066.74.92.6-391.7%----

AI Analysis

LLM Evaluations

Claude4/10UNDERWEIGHTFV: $28.00

Spyre Therapeutics is a high-risk, binary-outcome biotech trading at ~$2.5B market cap with no recurring revenue and a Phase 2 readout catalyst in Q2 2026. The extended half-life antibody platform for IBD is scientifically interesting (85-90 day half-lives enabling quarterly/biannual dosing), but the stock already prices in significant clinical success. The governance structure is problematic: 6%+ annual structural dilution through evergreen provisions and related-party warrant grants, cost-plus billing to insider-controlled entities, and aggressive insider selling create a persistent per-share value destruction that erodes returns even in a clinical success scenario. With $757M cash and ~$65M/quarter burn, the runway extends to H2 2028, but additional dilutive raises are inevitable. The 19% short interest and crowded IBD competitive landscape (Takeda's Entyvio, Merck's TL1A program, J&J) suggest the market is deeply divided. At current valuation, you need to believe SYRE will generate blockbuster-level revenues AND that the dilution machine won't consume shareholder value - a tall order for a company years from commercialization.

Catalyst Phase 2 SKYLINE-UC data readout for SPY001 in Q2 2026 is the key binary catalyst. Positive efficacy and safety data could validate the platform and drive 50%+ upside; a miss could send the stock down 60%+.
Risk Phase 2 clinical failure in the Q2 2026 SKYLINE-UC readout would destroy the investment thesis, as the entire ~$2.5B market cap is predicated on clinical success in a single therapeutic area with zero commercial revenue to support the valuation.
Trend
STABLE
Mgmt
4/10
Quarter
6/10
Exp. Move
-2.0%

Valuation & Metrics

Market Stats

Price$73.50
Market Cap$4.4B
Enterprise Value$3.7B
P/S Ratio49.1x
P/FCF--
EV/FCF--
FCF Margin (TTM)-205.3%
FCF Yield-4.2%
Dividend Yield (TTM)--
Annual Dilution474.2%
CurrencyUSD

TTM Financial Snapshot

Revenue$90.5M
Net Income$-179.4M
Free Cash Flow$-185.8M

Revenue Growth (YoY)+0.0%
EBITDA Margin-222.4%
Net Margin-198.3%
FCF Margin-205.3%
CapEx % of Revenue0.0%
SBC % of Revenue31.8%
ROIC-30.9%
WC Change % Rev-2.9%
Interest Coverage--

DCF Fair Value Estimate

$-0.36
-100.5% upside
Fair Enterprise Value$-1.3B
− Net Debt$-741M
= Fair Equity$-125M
Revenue Growth-45.5% → 8.0%
FCF Margin-205.3% → 25.0%
Discount Rate18.0%
Terminal EV/FCF20.0x

Forward Outlook & Risk

Short Interest

Short % of Float23.2%
Short Shares12.2M
Days to Cover10.0
Change (vs Prior)+4.7%
Short % Float History
23.20%-0.70pp
20.0%22.0%24.0%26.0%28.0%04-3007-1509-1511-1401-1504-30

Options

Call IV (ATM)75%
Put IV (ATM)73%
ATM Spread6.5%
Call $OI (near money)$385K
Put $OI (near money)$161K
ATM ExpiryJuly 17, 2026 (56D)
ATM Strike$75.0
Major Expirations6
Near-money chain · July 17, 2026
StrikeCall Bid/AskCall OIPut Bid/AskPut OI
$55.00$18.00/$22.800--/$4.900
$60.00$14.00/$18.800--/$4.9010
$65.00$11.00/$15.401$1.55/$6.400
$70.00$8.10/$12.900$3.50/$8.300
$75.00$6.00/$10.800$6.50/$10.800
$80.00$4.00/$8.500$9.50/$14.200
$85.00$2.65/$7.500$13.00/$17.800
$90.00$1.65/$6.400$17.00/$21.300
Snapshot: 2026-05-22

Forward Projections & Estimates

NTM Revenue Growth-87.8%
Forward FCF Margin-2600.0%
Forward EBITDA Margin-2818.2%
Forward P/FCF--
Forward EV/FCF--
Forward Int. Coverage--
Model Risk Score10/10
Bankruptcy Odds12%
Est. Borrow Rate15.0%
Terminal EV/FCF20.0x
LT Growth15.0%
LT FCF Margin25.0%

Employees

Headcount73
Revenue / Employee$1,239,644
Gross Profit / Employee$0
2022: 69 → 2023: 30 → 2024: 65 → 2025: 102 (14% CAGR)

Cash Runway

47.9months
WATCH

Institutional Ownership

Headline & net flow

NET BUYING

In Q1 2026 so far (quarter still filing), institutions are net buyers — bought 16.0% of float, sold 9.3%. 6 filers moved >1% of shares (4 buying, 2 selling).

Net flow · Q1 2026still filing
+6.7% of float (net)
Bought 16.0% · Sold 9.3%
116 filers reported (last quarter: 156)

Ownership composition

Active
76.3%(+57.3% YoY)
175 filers
hedge / family / endowment
Retail funds
Fidelity, Schwab, 401(k)
Passive
11.8%(+8.3% YoY)
6 filers
Vanguard, iShares, SPDR
Market makers
0.1%(+0.1% YoY)
8 filers
Citadel, Susquehanna
Insiders
1.9%
Form 4 — latest per insider
0%25%50%75%100%2023-092024-032024-092025-032025-092026-03
ActiveRetail fundsPassiveMarket makersRetail direct

Top holders

Fund$ valueCost basisΔ QoQΔ YoYα lifeFund AUM
FMR LLC$594M$28.52+$7.2M+$138M+0.3%$1.89T
BlackRock, Inc.Passive$278M$27.98−$44K+$98.3M-0.2%$5.69T
RTW INVESTMENTS, LP$210M$23.64+$0+$27.7M-2.3%$9.26B
Fairmount Funds Management LLC$203M$22.45+$0+$0+4.4%$1.38B
PERCEPTIVE ADVISORS LLC$191M$28.89+$36.0M+$74.1M-1.5%$5.04B
VR Adviser, LLC$186M$24.68+$0+$50.4M-2.6%$2.68B
DRIEHAUS CAPITAL MANAGEMENT LLC$141M$23.00−$4.6M+$3.7M+0.3%$13.60B
STATE STREET CORPPassive$131M$29.04+$17.4M+$45.9M-0.2%$2.89T
Paradigm Biocapital Advisors LP$98.7M$29.70+$24.7M−$8.6M+2.0%$4.69B
Commodore Capital LP$96.5M$23.04−$24.0M−$3.8M-0.2%$1.73B
TCG Crossover Management, LLC$95.9M$23.49+$0+$95.9M+4.5%$3.50B
TANG CAPITAL MANAGEMENT LLC$95.4M$15.72+$0−$8.0M-5.3%$1.93B
WELLINGTON MANAGEMENT GROUP LLP$92.0M$30.54+$13.9M+$11.7M+0.1%$533.98B
Capital International Investors$88.1M$21.37−$88.1M−$32.6M+0.4%$424.78B
GEODE CAPITAL MANAGEMENT, LLCPassive$86.8M$28.32+$3.1M+$33.4M+2.3%$1.61T
JANUS HENDERSON GROUP PLC$83.6M$29.49−$8.7M+$31.0M+1.5%$209.29B
RA CAPITAL MANAGEMENT, L.P.$81.8M$32.76+$0+$81.8M-4.0%$9.44B
PRICE T ROWE ASSOCIATES INC /MD/$80.6M$25.85−$159K+$68.1M-0.2%$864.93B
Remedium Capital Partners, LLC$73.5M$32.76+$0+$73.5M+44.0%$281M
Affinity Asset Advisors, LLC$64.5M$18.36−$7.7M+$40.2M+1.1%$1.60B
Cost basis is a volume-weighted estimate from accumulation periods within our 13F history; holders who built their position before our window started will show a stale basis. % above the cost basis is the unrealized gain at the current price.

Trading behavior

Smart-money alpha (lifetime, %/qtr)NEUTRAL
Holders
+1.26%
avg per quarter
Holders (ex-self)
+1.08%
excl. this stock
Buyers (this Q)
+0.73%
111 buyers · $0.84B in
Sellers (this Q)
+0.47%
54 sellers · $-0.26B out
alpha coverage: 100% of $ has a lifetime-alpha record
Holder behavior on this stocksource: stock
On big dips (−10%+)
+0.4%
how holders react when this stock falls
On quiet Qs
-33.8%
−10% to +10% baseline
On rallies (+10%+)
+3.2%
how they react when this stock rises
Holders' portfolio flow this Q
+75.0%
inflows — adds are organic
Sellers' portfolio flow this Q
+581.9%
Sellers grew AUM elsewhere — opinionated cut of this stock.
▸ Compare to holder-profile behavior (across all their stocks)
Holder dip (any stock)
-4.8%
Holder mid (any stock)
-2.8%
Holder rally (any stock)
-1.0%

Top Holders Over Time

5-year share-count history (top 10 holders by peak, incl. exited) + price

09.7M19.4M29.0M38.7M$12$22$31$41$502023-092024-032024-092025-032025-092026-03
hover the chart for per-quarter detailprice (right axis)
FMR LLC11.8MRTW INVESTMENTS, LP4.2MFairmount Funds Management LLC4.0MPERCEPTIVE ADVISORS LLC3.8MVR Adviser, LLC3.7MDRIEHAUS CAPITAL MANAGEMENT LLC2.8MCapital International Investors1.7MParadigm Biocapital Advisors LP2.0MCommodore Capital LP1.9MTCG Crossover Management, LLC1.9M

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Analyst Coverage

Analyst Coverage
Price Targets
Last Quarter (11 analysts)$88.642060.0%
Last Year (13 analysts)$82.381210.0%
Current Price$73.50

Corporate

Executive Compensation (2023-2025)

Direct Pay$16.7M
Incentive & Other$128.6M
Total Compensation$145.2M
% of Revenue159.3%

Insider Trading (last 12mo)

Open-market only (Form 4 P-Purchase + S-Sale). Excludes grants, option exercises, tax withholding, gifts.
Officers & directors
Buys ($, 12mo)
$0
0 txns · 0 insiders · 0 sh
Sells ($, 12mo)
$18.49M
14 txns · 4 insiders · 342,219 sh
Recent transactions
DateSideInsiderTitleSharesPriceDollarsOwned $
2026-05-08SELLHENDERSON MICHAEL THOMASdirector80,000$74.40$5.95M$6.59M
2026-05-01SELLBurrows Scott Lofficer: Chief Financial Officer12,500$71.37$892K$6.99M
2026-05-01SELLSloan Sheldonofficer: Chief Medical Officer78,333$71.50$5.60M$0
2026-05-01SELLTurtle Camerondirector, officer: Chief Executive Officer15,000$71.37$1.07M$43.72M
2026-04-01SELLBurrows Scott Lofficer: Chief Financial Officer7,500$49.34$370K$4.84M
2026-04-01SELLSloan Sheldonofficer: Chief Medical Officer7,958$50.00$398K$0
2026-04-01SELLTurtle Camerondirector, officer: Chief Executive Officer15,000$49.33$740K$30.95M
2026-03-03SELLBurrows Scott Lofficer: Chief Financial Officer2,500$40.65$102K$3.98M
2026-03-02SELLTurtle Camerondirector, officer: Chief Executive Officer15,000$42.19$633K$27.11M
2026-02-02SELLTurtle Camerondirector, officer: Chief Executive Officer15,000$32.80$492K$21.57M
2026-01-02SELLTurtle Camerondirector, officer: Chief Executive Officer15,000$30.68$460K$20.61M
2025-12-01SELLTurtle Camerondirector, officer: Chief Executive Officer15,000$29.02$435K$19.94M
2025-11-03SELLTurtle Camerondirector, officer: Chief Executive Officer45,000$23.33$1.05M$16.37M
2025-09-02SELLBurrows Scott Lofficer: Chief Financial Officer18,428$16.26$300K$1.59M

Order Flow (FINRA, ~3w lag)

18.1%retail+6.7pp
37.2%dark-1.3pp
week of 2026-04-13
10%20%30%40%24-1125-0225-0525-0825-1126-0226-04retail (non-ATS)dark (ATS)
Off-exchange volume from FINRA. Retail = non-ATS (wholesaler PFOF + broker internalization). Dark = ATS (dark-pool crossing networks, institutional). Lit-exchange = remainder.

Filing Risk Analysis

Filing Risk Scores

Spyre Therapeutics: A Related-Party ATM Machine with Volatile Contingent Liabilities

Overall Risk
6/10
Fraud
3/10
Dilution
9/10
Insolvency
2/10
Earnings Overstated
4/10
Hidden Liabilities
7/10
Legal
3/10
Audit Warnings
2/10
Hidden Upside
8/10
Contextually Acceptable
6/10

Counter-Thesis

Counter-Thesis & Recent News

📰 Recent News

Spyre recently reported a strong finish to 2025, ending the year with $756.5 million in cash and marketable securities, extending its runway into H2 2028. A key positive catalyst was the early completion of enrollment for SPY001 in the Phase 2 SKYLINE-UC trial, with initial readouts now expected in Q2 2026. Additionally, positive Phase 1 PK data for SPY001 and SPY003 showed half-lives exceeding 85–90 days, supporting potentially best-in-class quarterly or biannual maintenance dosing (Sources: GlobeNewswire, Feb 2026; BioSpace, Jan 2025).

🐻 Bear Case

The bear thesis focuses on the company's high valuation (~$3.4B market cap) relative to its early clinical stage and the fact that it is currently pre-revenue with a high burn rate ($62.5M net loss in Q4 2025). Skeptics point to historical immunogenicity risks with next-gen antibodies and the challenge of competing in a crowded IBD market dominated by giants like Merck and Takeda (Sources: Public.com; StockTitan, Feb 2026).

🚩 Red Flags

Notable red flags include consistent insider selling, with the CEO and CFO selling shares under 10b5-1 plans in early 2026. The stock also trades at a high price-to-book ratio (5.8x) compared to the biotech sector average (2.6x), making it vulnerable to any clinical data setbacks in the upcoming 2026 readouts (Sources: Perplexity/Insider Tracking, March 2026; InvestingPro).

⚔️ Competitive Threats

SYRE faces intense competition in the IBD and rheumatic disease markets from established players like Takeda (Entyvio), Merck (following its Prometheus acquisition for TL1A), and J&J. The primary threat is whether competitors can achieve similar dosing convenience or if SYRE's 'rational combination' therapy fails to show superior efficacy over existing monotherapies (Sources: Seeking Alpha, Sept 2025; PR Newswire, June 2025).

💬 Customer Sentiment

Investor and analyst sentiment remains overwhelmingly bullish, potentially squeezing shorts. There is a unanimous 'Buy' or 'Strong Buy' consensus among 16 major analysts, with price targets ranging from $58 to $73. Institutional ownership is high at approximately 80.4%, signaling strong conviction from 'smart money' that the company's extended half-life antibodies will redefine the standard of care (Sources: MarketBeat, Feb 2026; Directorstalk, Feb 2026).