Executive Summary

Q4 2024 marked continued pipeline momentum: TNG462 secured Orphan Drug Designation in pancreatic cancer, and the FDA cleared the IND for brain-penetrant PRMT5 inhibitor TNG456 in January 2025; cash, cash equivalents and marketable securities were $257.9M, funding operations into 3Q 2026 .
Collaboration revenue was $4.1M and total revenue $4.1M (no license revenue in the quarter), while R&D of $33.9M and G&A of $11.1M drove a net loss of $37.7M ($0.35/sh), up YoY from a $30.8M ($0.32/sh) loss .
Management is prioritizing TNG462 (PRMT5, MTAP-deleted tumors) toward monotherapy registrational studies in pancreatic cancer next year and initiating multiple combination trials in 1H25; TNG456 is expected to begin Phase 1/2 enrollment in 1H25 .
Near-term catalysts: 2025 TNG462 data update (pancreatic and lung focus), start of combination trials, TNG456 trial initiation, and a 2025 clinical update for TNG260 (CoREST inhibitor) .

What Went Well and What Went Wrong

What Went Well

Regulatory and development momentum: TNG462 received FDA Orphan Drug Designation in pancreatic cancer; the FDA cleared the TNG456 IND, and TNG456 also received Fast Track Designation in February 2025 for MTAP-deleted tumors and in combination with abemaciclib in NSCLC .
Management confidence and clarity on path to registration: “We expect that the TNG462 data we plan to disclose in 2025 will provide meaningful differentiation and solidify our clinical development plan, with a goal of initiating our first TNG462 monotherapy registrational study in pancreatic cancer next year,” said CEO Barbara Weber, M.D. .
Positive program read-through from prior quarter: TNG462 showed clinical activity and durability across multiple tumor types (e.g., 43% ORR in cholangiocarcinoma, n=7) and an improving safety/tolerability profile, supporting selection as the lead PRMT5 program .

What Went Wrong

Sequential revenue step-down as collaboration revenue normalized and no license revenue in Q4: total revenue fell to $4.1M from $11.6M in Q3 (no licensing in Q4), reflecting timing of collaboration cost recognition and absence of Q2’s $12M license fee .
Operating burn widened YoY: R&D rose to $33.9M (from $31.3M) and G&A to $11.1M (from $9.1M) as programs advanced and personnel costs increased, raising the quarterly net loss to $37.7M from $30.8M YoY .
GBM path required pivot: prior update indicated TNG908 lacked adequate CNS exposure in GBM (no partial responses in 23 patients at active doses), necessitating the move to next-gen TNG456 for CNS indications .

Financial Results

P&L comparison (YoY and sequential)

Metric ($USD Millions except per-share)	Q4 2023	Q3 2024	Q4 2024
Collaboration Revenue	$5.4	$11.6	$4.1
License Revenue	$0.0	$0.0	$0.0
Total Revenue	$5.4	$11.6	$4.1
R&D Expense	$31.3	$33.3	$33.9
G&A Expense	$9.1	$11.2	$11.1
Total Operating Expenses	$40.4	$44.5	$45.0
Loss from Operations	$(35.0)	$(32.9)	$(40.9)
Other Income, net	$4.3	$3.8	$3.3
Net Loss	$(30.8)	$(29.2)	$(37.7)
Net Loss per Share (diluted)	$(0.32)	$(0.27)	$(0.35)

Notes: Q3 2024 line items are “Three months ended September 30, 2024”; Q4 2024 and Q4 2023 are from “Three months ended December 31” .

Liquidity

Metric	Q3 2024	Q4 2024
Cash, Cash Equivalents & Marketable Securities	$293.3M (as of Sep 30, 2024)	$257.9M (as of Dec 31, 2024)
Cash Runway	Into 3Q 2026	Into 3Q 2026

No segment reporting is applicable; the company reports collaboration and license revenue without operating segments .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash runway	Multi-year	Into 2027 (as of Q2 2024)	Into 3Q 2026 (as of Q3 and reiterated Q4)	Lowered in Q3; maintained in Q4
TNG462 clinical data update	Program timing	“Comprehensive PRMT5 update in 2H 2024” (delivered Nov 6, 2024)	Additional TNG462 data update in 2025	New 2025 update after delivering 2H24
TNG462 combinations (with RAS(ON), pembro, etc.)	1H 2025	Begin enrolling 1H 2025	Begin enrolling 1H 2025	Maintained
TNG462 registrational plan	2026+	Not previously specified	Targeting first monotherapy registrational study in pancreatic cancer next year (post-2025 data)	New/clarified path
TNG456 IND/Phase 1/2 start	1H 2025	Planned to enter clinic 1H 2025	IND cleared (Jan 2025); begin enrolling 1H 2025	De-risked; maintained timing
TNG260 update	2025	Data expected in 2025	Clinical update in 2025	Maintained

Earnings Call Themes & Trends

No Q4 2024 earnings call transcript was located in our document system; the company may not have held a public call or a transcript was not available. We therefore track themes using the prior two quarter press releases and the Q4 earnings press release .

Topic	Previous Mentions (Q2 2024 and Q3 2024)	Current Period (Q4 2024)	Trend
PRMT5 program differentiation (TNG462)	Q2: Comprehensive PRMT5 data promised for 2H24 . Q3: Positive activity, durability; moving into full development; 43% ORR in cholangiocarcinoma (n=7) .	ODD granted for pancreatic cancer; 2025 data update planned focusing on pancreatic and lung cancers .	Strengthening validation and path to registrational plan
Combination strategy	Q3: Planned combos with RAS(ON) (RMC-6236/9805), osimertinib, pembrolizumab (start 1H25) .	TNG462 combos reiterated; begin enrolling 1H25 .	On track
CNS/GBM strategy	Q3: TNG908 active ex-CNS but inadequate CNS exposure in GBM; pivot to TNG456 .	TNG456 IND cleared; received Fast Track; plan to enroll 1H25 (mono and combo with abemaciclib) .	De-risked; execution next
Regulatory milestones	Limited prior explicit designations; focus on program updates .	Orphan Drug (TNG462, pancreatic) and Fast Track (TNG456) designations achieved .	Positive
Cash/runway	Q2: Runway into 2027 . Q3: Runway into 3Q26 .	Runway into 3Q26 reiterated .	Stable after Q3 reset

Management Commentary

“We are starting 2025 with momentum in TNG462… We expect that the TNG462 data we plan to disclose in 2025 will provide meaningful differentiation… with a goal of initiating our first TNG462 monotherapy registrational study in pancreatic cancer next year.” — Barbara Weber, M.D., CEO .
“Based on these promising early clinical data, the Company plans to initiate multiple targeted and standard of care combination studies with TNG462… These trials are expected to begin enrolling in the first half of 2025.” .
Prior quarter color: “Clinical data from the phase 1/2 trial demonstrate that TNG462 has potentially best-in-class characteristics… we are moving rapidly into the next phase of development… in preparation for registrational trials in NSCLC and pancreatic cancer.” — Barbara Weber, M.D. .
“Early data from the TNG462 phase 1/2 clinical trial demonstrate activity, durability and tolerability… we are introducing TNG456… anticipated to enter the clinic in the first half of next year.” — Adam Crystal, M.D., Ph.D., President, R&D .

Q&A Highlights

No Q4 2024 earnings call transcript found in our document set; no Q&A to summarize. We will update if a transcript becomes available [Search attempts returned none].

Estimates Context

S&P Global consensus estimates for Q4 2024 EPS and revenue were not retrievable at this time due to a data access limit; therefore, we cannot provide a results-vs-consensus comparison for this quarter. Values would have been retrieved from S&P Global if available.

Key Takeaways for Investors

Tangible regulatory momentum increases credibility of the PRMT5 franchise: ODD for TNG462 (pancreatic) and IND clearance plus Fast Track for TNG456 de-risk timelines and potential addressable populations .
2025 is a catalyst-rich year: TNG462 data update (pancreatic/lung focus), multiple combination trials starting (RAS(ON) tri-complex inhibitors, pembrolizumab), and TNG456 first-in-human study initiation .
Path to registration is now articulated for TNG462 monotherapy in pancreatic cancer, with plans to initiate the first registrational study next year pending 2025 data—an important shift from exploration to potential pivotal development .
Cash of $257.9M funds operations into 3Q26, supporting the heightened clinical activity; investors should monitor burn as multiple combination trials ramp .
GBM strategy has pivoted to TNG456 given TNG908’s insufficient CNS exposure; early execution on TNG456 (enrollment start, combination with abemaciclib) is a key proof point for CNS efficacy .
Revenue remains driven by collaboration recognition and episodic licensing; R&D intensity is expected to persist as clinical programs expand, maintaining net losses in the near term .
Upcoming data and study starts are likely to be the primary stock catalysts; absence of consensus estimate comparisons this quarter limits near-term “beat/miss” framing, placing more weight on pipeline readouts and regulatory progress (S&P Global estimates unavailable this period).

Appendix: Additional Relevant Press Releases (Q4 2024 context)

Positive TNG462 clinical data and PRMT5 program update (Nov 6, 2024): activity and durability across multiple tumor types, 43% ORR in cholangiocarcinoma (n=7), selection of TNG462 for full development, introduction of TNG456 for CNS tumors, and planned combinations with RAS(ON) agents and pembrolizumab .
Q3 2024 financials (Nov 6, 2024) for sequential context: cash $293.3M and runway into 3Q26; net loss $(29.2)M, EPS $(0.27) .

Tango Therapeutics, Inc. (TNGX)·Q4 2024 Earnings Summary