Executive Summary

Intellia reported Q4 2024 collaboration revenue of $12.9M, R&D of $116.9M, G&A of $32.4M, and net loss of $128.9M; cash and marketable securities ended at $861.7M, with runway into 1H 2027 .
Management emphasized accelerated late-stage execution: first patient dosed in Phase 3 HAELO (NTLA-2002), Phase 3 MAGNITUDE enrollment tracking ahead with >550 total patients expected by year-end, and MAGNITUDE-2 (PN) first patient targeted for 1Q25 .
Corporate restructuring aims to cut GAAP OpEx by ~5–10% y/y in 2025; ~$8M severance expected in Q1 2025; commercial build-out for a 2027 U.S. launch of NTLA-2002 is underway .
Catalysts: longer-term HAE Phase 1/2 data in 2025, Phase 1 ATTR updates in 2025, continued rapid Phase 3 enrollment, and U.S. RMAT designation for nex-z in ATTRv-PN supporting potential accelerated pathways .

What Went Well and What Went Wrong

What Went Well

“We are off to an excellent start in 2025 with renewed focus and strong operational execution across our three, pivotal Phase 3 studies” — CEO John Leonard; HAELO first patient dosed, MAGNITUDE enrollment ahead, MAGNITUDE-2 screening active .
Strong clinical signals: HAE Phase 2 showed many patients achieving “functional cure” (attack-free and off chronic therapy); ATTR Phase 1 showed deep, rapid, durable TTR reduction with associated stabilization/improvement in cardiac/neuropathy markers .
Cash runway extended: $861.7M cash/securities at year-end 2024; funding into 1H 2027; restructuring to lower GAAP OpEx 5–10% in 2025 to support commercial investments .

What Went Wrong

Operating expenses rose y/y: Q4 R&D increased to $116.9M (from $109.0M), G&A to $32.4M (from $29.0M), contributing to continued net losses; stock-based comp remains material (R&D $24.4M; G&A $15.2M in Q4) .
Collaboration revenue remains modest and variable (Q4: $12.9M vs Q3: $9.1M vs Q2: $7.0M), highlighting reliance on external milestones and partner reimbursements .
Program discontinuations and workforce reduction (~27%) reflect pipeline prioritization pressures; ~$8M severance in Q1 2025 introduces near-term cost noise .

Financial Results

Metric ($USD Millions unless noted)	Q2 2024	Q3 2024	Q4 2024
Collaboration Revenue	$6.96	$9.11	$12.87
R&D Expense	$114.21	$123.38	$116.88
G&A Expense	$31.79	$30.50	$32.44
Net Loss	$(146.98)	$(135.71)	$(128.90)
Net Loss per Share ($)	$(1.52)	$(1.34)	$(1.27)
Cash & Marketable Securities (period-end)	$939.87	$944.68	$861.73

YoY (Q4 2024 vs Q4 2023)

Metric	Q4 2023	Q4 2024
Collaboration Revenue ($mm)	$(1.92)	$12.87
R&D Expense ($mm)	$108.98	$116.88
G&A Expense ($mm)	$28.99	$32.44
Net Loss ($mm)	$(132.16)	$(128.90)
Net Loss per Share ($)	$(1.46)	$(1.27)
Cash & Marketable Securities ($mm)	$1,012.09	$861.73

Segment breakdown: Not applicable; revenue consists primarily of collaboration revenue .

Selected KPIs

KPI	Q2 2024	Q3 2024	Q4 2024
Weighted Avg Shares (mm)	96.98	101.00	101.86
Interest Income ($mm)	$12.42	$12.12	$10.63
Other Income (Expense), net ($mm)	$(7.93)	$9.06	$7.55

Estimates comparison: S&P Global consensus was unavailable at time of execution; comparison to estimates is not included.

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
HAELO (NTLA-2002) enrollment completion	2H 2025	Phase 3 initiated in Oct 2024; active screening (Q3)	First patient dosed Jan; complete enrollment 2H 2025	Clarified schedule; progress reaffirmed
NTLA-2002 BLA filing	2H 2026	Submit BLA in 2026 (stated earlier)	Submit BLA 2H 2026; plan for 2027 U.S. launch	Timing specified; launch plan added
MAGNITUDE (ATTR-CM) enrollment	2025	Tracking ahead of projections; >35 sites (Q3)	Enrollment ahead; >550 total pts expected by year-end	Raised enrollment visibility
MAGNITUDE-2 (ATTRv-PN) first dose	1Q 2025	“On track to initiate by year-end” (Q3); FDA IND cleared	Actively screening; on track to dose first patient 1Q25	Slightly shifted start to early 2025
Cash runway	Through	Late 2026 (Q3)	Into 1H 2027 (Q4)	Extended runway
GAAP OpEx	CY 2025	Not quantified	Down ~5–10% y/y; ~$8M severance in Q1 2025	New cost guidance

Earnings Call Themes & Trends

Topic	Previous Mentions (Q2 2024)	Previous Mentions (Q3 2024)	Current Period (Q4 2024)	Trend
HAE “functional cure” profile	Goal is single-dose, attack-free, off chronic therapy; Phase 2 met endpoints; 50mg selected	8/11 attack-free in 50mg cohort; strong enthusiasm for Phase 3 HAELO	First patient dosed in HAELO; extended follow-up expected to reinforce functional cure profile	Strengthening evidence; advancing to registrational
ATTR-CM deep/rapid TTR reduction	Plan for Phase 1 update incl. NT-proBNP, 6MWT; MAGNITUDE enrollment ahead	NEJM/AHA Phase 1: 90% mean reduction at 12m; low event rates; Class III inclusion	Reiterated sustained deep TTR reduction and potential stabilization/improvement; >550 pts in 2025	Positive momentum; potential interim advantages
ATTRv-PN RMAT/design	PN Phase 3 ex-U.S., ~50 pts; blind landmark at 18m	FDA cleared IND; placebo-controlled; mNIS+7 and day-29 TTR endpoints	RMAT granted; active screening; dose first patient 1Q25	Regulatory support; expedited path
Commercial build & reimbursement	Early commercial planning; leadership hires	Enrollment enthusiasm; broad ex-U.S. strategy considered	HAE reimbursement addressed; outpatient infusion; 2027 launch footprint “tiny and neat”	Building infrastructure; payer engagement underway
Platform expansion (gene insertion)	NTLA-3001 design; nonhuman primates normal AAT; redosing proof-of-concept	On track to dose first patient by year-end; multi-tissue expansion	3001 program continuation; future gene writing adjuncts	Broadening tools; clinical validation next
Cost discipline & runway	Cash ~$940M; runway late 2026	Cash ~$945M; runway late 2026	Cash $861.7M; runway 1H 2027; OpEx down 5–10% y/y in 2025	Improved runway; restructuring benefits

Management Commentary

“We are off to a strong start in 2025… we’re making remarkable headway with enrollment across our late-stage studies” — CEO John Leonard .
“With HAELO well underway, we believe 2002 is well positioned to be the first ever onetime treatment for people living with HAE… first approved using in vivo CRISPR gene editing” — CMO David Lebwohl .
“Across all 36 [ATTR-CM] patients, a single dose of nex-z led to rapid, deep and sustained serum TTR reduction… mean 12-month reduction 90%, residual TTR 17 µg/mL” — Company summary (Q4 PR) and reiterated on call .
“We expect to complete enrollment of the HAELO study in the second half of 2025 and submit a Biologics License Application in the second half of 2026 to support plans for U.S. launch in 2027” — Q4 PR .
“We expect year-over-year declines in GAAP operating expenses of approximately 5% to 10%… and ~$8 million in severance and other employee termination-related costs [Q1 2025]” — CFO Ed Dulac .

Q&A Highlights

OpEx trajectory: Peak OpEx is behind; restructuring benefits accrue through 2025; steady-state in 2026; costs begin to sunset in 2027 as Phase 3 enrollments complete .
MAGNITUDE events/interim: Event rates expected similar to recent trials; favorable Phase 1 event rates suggest potential for earlier favorable interim outcomes; design unchanged for now .
Competitive landscape (Alnylam): Deeper, faster TTR reduction is viewed as critical; one-and-done profile and lower absolute TTR vs silencers (e.g., AMVUTTRA) highlighted .
HAE commercialization/reimbursement: Outpatient, simple regimen; functional cure profile as core value; active payer discussions underway .
PN study design: Placebo-controlled ex-U.S. with mNIS+7 at 18 months; FDA agreed design via IND; RMAT enables closer FDA interactions .

Estimates Context

S&P Global consensus estimates for Q4 2024 EPS and revenue were unavailable at the time of execution due to data access limits; therefore, results vs estimates cannot be presented here.

Key Takeaways for Investors

NTLA’s clinical execution de-risks the path to multiple BLAs: HAE (BLA 2H 2026), ATTR-CM (robust Phase 3 enrollment), and ATTRv-PN (RMAT, efficient 50-patient design) .
The HAE “functional cure” narrative is a key stock catalyst; extended follow-up in 2025 could reinforce the one-and-done value proposition for NTLA-2002 .
ATTR profile shows deep, rapid, durable TTR knockdown with associated clinical stabilization/improvement; competitive positioning vs silencers appears favorable on absolute TTR reduction and convenience .
Cash runway extended into 1H 2027 with OpEx discipline; near-term severance charges are one-time; commercial investments ramp thoughtfully toward 2027 .
Watch for 2025 data readouts (HAE Phase 1/2 longer-term, ATTR Phase 1 updates), MAGNITUDE enrollment milestones and any interim analysis disclosures; potential for accelerated PN pathways via RMAT .
Partner dynamics (Regeneron co-promote option for nex-z) and payer engagement will shape commercial strategy; U.S. launch footprint described as lean .
Risk factors: clinical event accrual timing, regulatory feedback, competition from stabilizers/silencers, and execution of restructuring/commercial build .

Additional Q4 2024 Press Releases (Context)

HAELO Phase 3 initiated (Oct 7, 2024): global randomized 2:1 design; crossover at week 28; primary endpoint attacks from week 5–28 .
RMAT designation for nex-z in ATTRv-PN (Nov 25, 2024): supports potential accelerated approval discussions and priority review .

Prior Quarter References (Trend Analysis)

Q3 2024: Cash $944.7M; revenue $9.1M; R&D $123.4M; net loss $135.7M; FDA cleared MAGNITUDE-2 IND; HAELO initiation; ATTR Phase 1 AHA/NEJM data preview .
Q2 2024: Cash $939.9M; revenue $7.0M; R&D $114.2M; net loss $147.0M; HAE Phase 2 met primary and secondary endpoints; selected 50mg dose for Phase 3; MAGNITUDE enrollment ahead; redosing proof-of-concept .

Intellia Therapeutics, Inc. (NTLA)·Q4 2024 Earnings Summary