Executive Summary

Q4 2024 focused on NDA-readiness for cytisinicline: Achieve reiterated filing at end of Q2 2025; ORCA-OL safety milestones achieved (300 subjects with 6-month cumulative exposure; two positive DSMC reviews; enrollment complete at 479 participants across 29 sites) .
Operating expenses rose with NDA-prep and commercialization groundwork; Q4 total OpEx $12.2M vs $12.5M in Q3 2024, net loss $12.4M; cash was $34.4M with runway into Q3 2025 .
Guidance update: vaping Phase 3 (ORCA‑V2) start moved from targeted Q3 2025 to 1H 2026 (financing dependent); planned commercial launch for smoking cessation in Q3 2026; CMC/label/3PL selection progressing .
Key stock catalysts near term: NDA submission (end Q2 2025), 120‑day safety update (≥100 subjects with 1‑year exposure during review), finalization of 3PL and payer engagement, and clarity on ORCA‑V2 financing/timing .

What Went Well and What Went Wrong

What Went Well

NDA track intact with critical ORCA‑OL safety exposure requirements met; two DSMC reviews reported no safety concerns and excellent adherence; enrollment completed rapidly (479 participants, 29 sites) .
Commercial readiness advanced: draft label finalized, packaging defined, 3PL RFP completed, payer pre‑approval information exchange planned; targeted HCP/patient segmentation refined to focus on high‑volume varenicline prescribers and highly motivated quitters .
Management additions bolster execution: Mark Oki appointed CFO; two new directors (Dr. Kristen Slaoui, Nancy Phelan) add commercialization/corporate development expertise .
Quote: “We are thrilled… to have the NDA submission on track for the end of next quarter… bringing cytisinicline to market as the first new FDA‑approved nicotine dependence treatment in nearly 20 years” – CEO Rick Stewart .

What Went Wrong

Sequential G&A remained elevated at ~$4.9M; management acknowledged it as a starting point heading into 2025, indicating continued OpEx pressure during pre‑launch build .
Vaping Phase 3 timing deferred: prior target to commence around Q3 2025 shifted to first half of 2026, contingent on financing; introduces timeline risk for label expansion .
No product revenues; pre‑commercial profile limits estimate comparability and heightens dependency on external financing and careful cash management (runway into Q3 2025) .

Financial Results

Metric	Q4 2023	Q2 2024	Q3 2024	Q4 2024
Revenue ($USD Millions)	—	—	—	—
Research & Development ($USD Millions)	$2.11	$5.11	$7.61	$7.30
General & Administrative ($USD Millions)	$2.27	$3.32	$4.86	$4.89
Total Operating Expenses ($USD Millions)	$4.39	$8.43	$12.47	$12.19
Net Loss ($USD Millions)	$(5.48)	$(8.46)	$(12.51)	$(12.36)
Basic & Diluted EPS ($USD)	$(0.26)	$(0.25)	$(0.36)	$(0.36)
Cash, Cash Equivalents & Marketable Securities ($USD Millions)	$15.5	$61.3	$42.9	$34.4
Weighted Avg Shares (basic & diluted)	21,165,760	34,318,709	34,355,050	34,510,786

Notes: Revenue/margins not applicable (pre‑commercial; no revenue line disclosed) .

KPIs (program execution)

KPI	Q2 2024	Q3 2024	Q4 2024
ORCA‑OL Enrollment (participants)	— (active enrollment across 29 sites)	479	479
Trial Sites (#)	29	29	29
DSMC Reviews Completed (#)	—	1st DSMC positive (no safety concerns)	2 DSMC positives (no safety concerns)
Subjects with ≥6‑month cumulative exposure (#)	—	—	≥300 achieved (NDA requirement met)

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cytisinicline NDA Submission (Smoking Cessation)	Q2 2025	“On track first half 2025”	“End of next quarter (end of Q2 2025)”	Maintained/timed (clarified)
Cash Runway	2025	“Runway into second half of 2025”	“Runway into Q3 2025”	Clarified (tightened window)
Vaping Phase 3 (ORCA‑V2) Start	2025–2026	“Target Q3 2025 commence”	“1H 2026; financing dependent”	Lowered/Delayed
Commercial Launch (Smoking Cessation)	2026	Not disclosed	“Planned Q3 2026”	New disclosure
120‑Day Safety Update (≥100 subjects at 1‑year exposure)	NDA review period	Not explicitly dated	“Submit during review; expect reach in Q2 2025”	Clarified milestone timing

Earnings Call Themes & Trends

Topic	Previous Mentions (Q2 2024)	Previous Mentions (Q3 2024)	Current Period (Q4 2024)	Trend
NDA Readiness & ORCA‑OL	Initiated ORCA‑OL; ≥half of 650 enrolled; plan DSMC reviews; NDA 1H25 on track	Enrollment complete (479); 1st DSMC positive; 300 subjects expected late Jan/Feb; NDA process detailed	300 subjects achieved; 2 DSMC positives; 3‑month data lock/QC underway; file end Q2 2025	Accelerating; on track
Vaping Breakthrough & Label Expansion	Breakthrough therapy granted; EoP2 planned	Public/regulatory engagement; Phase 3 target Q3 2025	FDA EoP2 successful; Phase 3 in 1H 2026 (financing)	Timing deferred; scope affirmed
Commercial Readiness (Label/3PL/Payers)	Kickoff planning; focus on payer evidence and pre‑approval comms	Foundational projects; digital‑first launch model	Draft label finalized; packaging set; 3PL RFP completed; payer engagement planned; targeted HCP/patient segments	Advancing execution
Manufacturing/CMC Preparedness	Debt refinance and runway; no CMC specifics	Manufacturing timeline dependencies noted	CMC sections “almost done”; external consultants engaged; quality focus	Strengthening quality
COPD/comorbidity strategy	Vaping harms context noted	COPD burden, partnering interest flagged	COPD abstinence benefits highlighted; potential partner discussions (not near‑term)	Narrative building

Management Commentary

“All of our resources are now dedicated to a successful NDA submission, acceptance and approval… planned commercial launch in the third quarter of 2026.” – CEO Rick Stewart .
“We successfully reached… 300 subjects with cumulative six months… and expect 1‑year exposure data on ≥100 subjects in Q2 2025, submitted with the 120‑day safety update.” – CMO Cindy Jacobs .
“We developed a draft product label… finalized packaging… completed the 3PL selection RFP… will begin engaging payers via preapproval information exchange.” – CCO Jaime Xinos .
“Cash, cash equivalents and marketable securities were $34.4M… sufficient runway into Q3 2025.” – CFO Mark Oki .
“Cytisinicline has shown up to 2.5x better efficacy than the previous market‑leading prescription product with a far more benign side effect profile.” – CEO Rick Stewart (non‑head‑to‑head) .

Q&A Highlights

CMC readiness: “CMC sections are almost done… standard routine NDA… best‑of‑best consultants engaged” (Jacobs) .
Access strategy: considering “specialty‑light” pharmacy; step‑edits mitigated via medical exceptions; focus on patients resistant to varenicline (Xinos/Jacobs) .
Financing/partners: COPD/comorbidity partnerships of interest but focus remains on NDA; strategic partner could optimize U.S./global revenue, but Achieve prepared to launch solo (Stewart) .
G&A trajectory: $4.9M considered a starting point; intent to manage down (Oki) .
Vaping Phase 3 design: powered for higher placebo; ~800 subjects, 12‑week regimen; >90% power (Jacobs) .

Estimates Context

Metric	Q4 2024 Consensus	Reported Result	Surprise
Primary EPS Consensus Mean	Unavailable*	$(0.36)	N/A
Revenue Consensus Mean ($USD Millions)	Unavailable*	— (no revenue reported)	N/A

Values retrieved from S&P Global.* Consensus estimates for ACHV were not available for the relevant period, and ACHV reported no product revenues.

Implications: With no revenue and negative EPS, estimate frameworks remain limited; near‑term revisions likely focus on OpEx/cash runway assumptions and timing/risk around NDA submission and ORCA‑V2 start .

Key Takeaways for Investors

Near‑term catalyst density: NDA submission (end Q2 2025), acceptance (≈74 days post‑submission), 120‑day safety update (≥100 subjects at 1‑year) – monitor timelines and FDA interaction quality .
Execution quality signals: two positive DSMC reviews; rapid ORCA‑OL enrollment; comprehensive QA and consultant support for CMC/clinical summaries .
Commercial readiness advancing: label/packaging/3PL nearly in place; payer engagement and distribution strategy targeted to ensure script fulfillment; segmentation to high‑volume prescribers should support initial uptake .
Timeline reset on vaping Phase 3: start deferred to 1H 2026 and financing dependent; temper multi‑label trajectory expectations and model capital needs accordingly .
Cash discipline: $34.4M cash; runway into Q3 2025; watch for financing/partnering updates to bridge to launch and ORCA‑V2 initiation .
Narrative momentum: management positioning cytisinicline as first new nicotine dependence therapy in ~20 years with differentiated tolerability/efficacy; COPD/comorbidity potential could expand TAM post‑approval .
Trading lens: stock likely to react to filing/acceptance milestones, DSMC updates, CMC readiness, and any partnering/financing disclosures; delays to ORCA‑V2 or NDA could be negative; clarity on 3PL/payer access and brand identity could be positive .

Citations: Q4 2024 8‑K/press release ; Q4 2024 earnings call ; Q3 2024 8‑K/call ; Q2 2024 8‑K/call .

ACHIEVE LIFE SCIENCES, INC. (ACHV)·Q4 2024 Earnings Summary