Executive Summary

Q4 2024 was a cash-preserving, pre‑revenue quarter with materially lower operating expenses and a narrower net loss, while management advanced a clear near‑term catalyst: Phase 3 topline for epetraborole in TR‑MAC targeted for 2Q25. Cash, cash equivalents and investments were $88.6M at 12/31/24, with runway “through 2027” under the current strategic plan .
EPS modestly beat Wall Street consensus: Q4 2024 EPS was -$0.25 vs consensus -$0.26, a ~$0.003 beat; revenue consensus was $0.00 given pre‑revenue status (Values retrieved from S&P Global).
The statistical analysis plan was amended to select QOL‑B respiratory domain as the primary endpoint for Phase 3, aligning with FDA guidance for PRO‑based endpoints in NTM‑MAC and following the Arikayce precedent—management will unblind Phase 3 data in 2Q25, subject to FDA timing .
Upcoming catalysts: epetraborole Phase 3 topline (2Q25), Phase 1 start for AN2‑502998 (Chagas) mid‑2025, melioidosis Phase 2 initiation 2H25, and first oncology development candidate(s) advancing in 2H25—key drivers of narrative and stock reaction potential .

What Went Well and What Went Wrong

What Went Well

Alignment of Phase 3 primary endpoint with FDA guidance (QOL‑B PRO), increasing clarity on registrational path; CEO: “we updated our statistical analysis plan to select QOL-B as the primary efficacy endpoint…plan to unblind and announce topline results in the second quarter” .
Operating discipline: Q4 OpEx fell to $8.60M from $14.01M in Q3 and $15.88M in Q2; net loss improved to $7.52M in Q4 from $12.75M in Q3 and $14.44M in Q2 .
Pipeline momentum and financing runway: cash resources of $88.6M at year‑end; runway to 2027 supports multiple inflection points (Chagas, melioidosis, oncology) .

What Went Wrong

The EBO‑301 Phase 2/3 program was terminated in August 2024 after Phase 2 showed no sputum culture conversion advantage at Month 6 (key secondary endpoint), creating clinical and regulatory uncertainty despite PRO signals .
Pre‑revenue status persisted; the company remains dependent on trial outcomes and external validation, and reported ongoing net losses (Q4 net loss: $7.52M) .
Restructuring underscores operational reset and program refocus; Q3 incurred $2.24M restructuring charges, though Q4 showed a small reversal (‑$0.01M) .

Financial Results

Quarterly Progression (oldest → newest)

Metric ($USD Millions unless noted)	Q2 2024	Q3 2024	Q4 2024
Research & Development	$12.15	$8.29	$5.40
General & Administrative	$3.73	$3.48	$3.21
Restructuring Charges	$0.00	$2.24	-$0.01
Total Operating Expenses	$15.88	$14.01	$8.60
Other/Interest Income	$1.45	$1.27	$1.08
Net Loss	-$14.44	-$12.75	-$7.52
EPS (basic & diluted)	-$0.48	-$0.43	-$0.25

Q4 Year-over-Year

Metric ($USD Millions unless noted)	Q4 2023	Q4 2024
Research & Development	$14.92	$5.40
General & Administrative	$3.90	$3.21
Restructuring Charges	$0.00	-$0.01
Total Operating Expenses	$18.82	$8.60
Interest Income	$1.92	$1.08
Net Loss	-$16.90	-$7.52
EPS (basic & diluted)	-$0.57	-$0.25

Cash Position

Metric	Q2 2024 (6/30/24)	Q3 2024 (9/30/24)	Q4 2024 (12/31/24)
Cash, Cash Equivalents & Investments	$104.5M	$93.4M	$88.6M

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Epetraborole Phase 3 topline timing	2Q25	“mid‑2025” topline from 97 Phase 3 completers, subject to FDA discussions	“plan to unblind and announce topline results in the second quarter of 2025,” subject to FDA timing	Clarified/pulled forward to 2Q25
Phase 3 primary endpoint	Current Phase 3 dataset	Planning to seek FDA alignment on SAP for Phase 3 completers	QOL‑B respiratory domain PRO selected as primary endpoint; SAP amended and submitted to FDA	Defined/Aligned with guidance
Cash runway	2025–2027	“Through 2027” under current operating plan	“Through 2027” under current strategic plan	Maintained
AN2‑502998 (Chagas)	Mid‑2025	Phase 1 initiation mid‑2025	Phase 1 initiation mid‑2025 (unchanged)	Maintained
Melioidosis (epetraborole)	2H25	Phase 2 PoC to begin 2H25	Phase 2 PoC planned 2H25 (unchanged)	Maintained
Oncology program	2H25	Up to three development compounds in 2025	First oncology candidate(s) advancing into development in 2H25	Clarified scope/timing

Earnings Call Themes & Trends

Note: No Q4 2024 earnings call transcript was available in our document catalog; Q&A not assessed (we searched but found none).

Topic	Previous Mentions (Q2 2024)	Previous Mentions (Q3 2024)	Current Period (Q4 2024)	Trend
Epetraborole in TR‑MAC	Phase 2 met PRO validation objective; no sputum culture conversion advantage; program terminated; analysis ongoing	Nominally significant PRO signals (QOL‑B, MACrO2); plan to re‑engage FDA; potential Phase 3 reinitiation; ~97 Phase 3 completers	SAP amended; QOL‑B set as Phase 3 primary endpoint; topline planned 2Q25, subject to FDA timing	Greater regulatory clarity; near‑term data catalyst
FDA alignment on endpoints	Post‑hoc/PRO exploration	Alignment sought; Arikayce precedent cited	Explicit selection of QOL‑B per FDA guidance	Progressing toward registrational pathway
Chagas (AN2‑502998)	Phase 1 expected mid‑2025	Phase 1 expected mid‑2025	Phase 1 expected mid‑2025	Steady execution
Melioidosis	Phase 2 planned 2H25; observational trial completing	200‑pt observational trial completed (Oct‑24); Phase 2 planned 2H25	Topline observational data expected 2Q25; Phase 2 planned 2H25	Building evidence base; timeline firming
Oncology expansion	Platform exploration	Up to three development compounds in 2025	First oncology candidate(s) to advance in 2H25	Increasing commitment
Cash runway/OpEx	Runway through 2027	50% expenditure reduction; runway through 2027	Runway through 2027	Maintained discipline

Management Commentary

CEO framing of Phase 3 endpoint and near‑term topline: “we updated our statistical analysis plan to select QOL-B as the primary efficacy endpoint…plan to unblind and announce topline results in the second quarter…engage with the FDA to explore potential registrational pathways” — Eric Easom, Co‑Founder, Chairman, President & CEO .
On clinical unmet need and PRO signals (Q3): “epetraborole may provide clinical improvement…as measured by two patient‑reported outcome instruments…including the same instrument recently selected for the primary endpoint in the Arikayce TN‑MAC pivotal trial” — Eric Easom .
External clinical context (Q3): “Treatment options for patients with refractory MAC lung disease are extremely limited…epetraborole represents a potentially significant advancement” — Stephen J. Ruoss, M.D., Stanford .

Q&A Highlights

No Q4 2024 earnings call transcript located; therefore, no Q&A themes or clarifications to report (we searched for an earnings call transcript and found none).

Estimates Context

Q4 2024 EPS came in at -$0.25 vs consensus -$0.26; surprise +$0.003 (beat). Revenue consensus was $0.00, consistent with pre‑revenue status (Values retrieved from S&P Global).
With operating expense reductions and interest income partially offsetting losses, estimates may drift toward slightly narrower EPS losses if OpEx discipline continues while awaiting Phase 3 outcomes.

Q4 2024 vs Consensus

Metric	Consensus	Actual	Surprise
EPS ($)	-$0.255*	-$0.252	+$0.003*
Revenue ($USD Millions)	$0.00*	n/a	n/a

*Values retrieved from S&P Global.

Key Takeaways for Investors

Phase 3 topline for epetraborole in TR‑MAC (2Q25) is the dominant near‑term catalyst; endpoint selection (QOL‑B) aligns with FDA guidance, improving odds of a clear regulatory dialogue .
Operating discipline is evident: Q4 OpEx fell 39% vs Q3 and 46% vs Q2; EPS loss narrowed QoQ and YoY, providing incremental de‑risking of cash runway .
The company remains pre‑revenue and dependent on clinical outcomes; stock likely trades on clinical/regulatory headlines rather than fundamentals until Phase 3 clarity arrives .
Pipeline breadth offers secondary catalysts: Chagas Phase 1 (mid‑2025), melioidosis Phase 2 (2H25), oncology candidate(s) (2H25), each adding optionality to the story .
Watch for FDA feedback on the amended SAP before topline unblinding; timing and language could materially impact sentiment and perceived registrational path .
Cash runway through 2027 mitigates financing risk across multiple data events; monitor further OpEx trajectory and potential business development to extend runway .
Trading implication: pre‑data drift likely muted; the stock’s risk/reward skews to binary outcomes around Phase 3 PRO efficacy and FDA reception—position sizing should reflect clinical trial headline risk.

References: Q4 2024 8‑K 2.02 press release and financials ; Q3 2024 press release and 8‑K ; Q2 2024 8‑K .

AN2 Therapeutics, Inc. (ANTX)·Q4 2024 Earnings Summary