Executive Summary

Q2 2025 was an execution quarter: GPCR expanded its aleniglipron (oral GLP‑1) clinical program (ACCESS/ACCESS II extensions plus three new Phase 2 studies) while reiterating year‑end 2025 topline timing and maintaining a cash runway “through at least 2027.” R&D ramped as planned, driving a larger net loss, but liquidity remains strong at $786.5M as of June 30, 2025 .
EPS was essentially in line: Q2 2025 EPS of -$0.36 versus the -$0.36 consensus; no revenue was expected or reported (pre‑commercial). Trend is disciplined spending supporting data generation into year‑end catalysts.*
Strategy tilted more overtly toward combination therapies: management emphasized the shift to “combinability” and long‑term weight‑loss maintenance, positioning aleniglipron as a backbone oral agent and advancing an oral amylin (ACCG‑2671) toward Phase 1 by year‑end 2025 .
Near‑term stock drivers: (1) ACCESS/ACCESS II 36‑week topline by year‑end 2025; (2) initiation of three incremental aleniglipron studies (maintenance switch, body composition, T2DM); (3) ACCG‑2671 Phase 1 start by year‑end 2025 .

What Went Well and What Went Wrong

What Went Well
- ACCESS/ACCESS II fully on track for year‑end topline; program broadened with longer‑duration and higher‑dose data and additional supportive studies to optimize Phase 3 positioning .
- Clear strategic narrative around combinability and scalability of oral small molecules; CEO: “we are excited to lead the way with a highly scalable pipeline of oral small molecule medicines designed to address the substantial unmet needs in obesity” .
- Strong liquidity ($786.5M) and reiterated runway through at least 2027, funding the expanded study set (excluding registrational Phase 3) .
What Went Wrong
- Operating expenses stepped up meaningfully as programs scale: R&D $54.7M vs $22.1M YoY; G&A $15.7M vs $11.3M, widening net loss to $61.7M vs $26.0M YoY .
- No revenue and limited P&L leverage near term; interest income sequentially declined ($8.9M vs $9.6M in Q1), offering less offset to higher OpEx .
- No Q2 earnings call transcript available in the document set, limiting color on trial operations and Phase 3 planning details this quarter (we searched but found none).

Financial Results

Income statement highlights (GAAP; $USD Millions, oldest → newest)

Metric	Q4 2024	Q1 2025	Q2 2025
R&D Expense ($M)	$33.5	$42.9	$54.7
G&A Expense ($M)	$13.6	$13.4	$15.7
Total Operating Expenses ($M)	$47.1	$56.3	$70.5
Interest & Other Income, net ($M)	$10.7	$9.6	$8.9
Net Loss ($M)	$(36.5)	$(46.8)	$(61.7)

Liquidity

Metric	Q4 2024 (Dec 31)	Q1 2025 (Mar 31)	Q2 2025 (Jun 30)
Cash, Cash Equivalents & Short‑Term Investments ($M)	$883.5	$836.9	$786.5

EPS vs. Consensus (S&P Global; oldest → newest)

Metric	Q1 2025	Q2 2025
EPS Actual ($)	-0.27*	-0.36*
EPS Consensus Mean ($)	-0.2309*	-0.3633*
Surprise ($)	-0.0391*	+0.0033*
EPS – # of Estimates	9*	9*
Revenue Consensus Mean ($)	0.00*	0.00*

Notes: GPCR is pre‑revenue; no revenue was reported in the Q2 press release and statement of operations begins with operating expenses .
*Values retrieved from S&P Global.

Year‑over‑year (Q2 2025 vs Q2 2024)

Metric	Q2 2024	Q2 2025
R&D Expense ($M)	$22.1	$54.7
G&A Expense ($M)	$11.3	$15.7
Net Loss ($M)	$(26.0)	$(61.7)

KPI – Program scale and design

KPI	Q4 2024	Q1 2025	Q2 2025
ACCESS enrollment	~220 pts (max 120 mg; 4‑week titration)	~220 pts (on track)	OLE added; longer‑term data collection
ACCESS II enrollment	~80 pts (180/240 mg; 4‑week titration)	~80 pts (on track)	Extended to 44 weeks for added safety/efficacy at higher doses
Topline timing	YE25 for both	YE25 for both	YE25 for both (maintained)
New supportive studies	—	—	Maintenance switch (Q3 start), body composition (Q3 start), T2DM (Q4 start)
Cash runway	≥2027	≥2027	≥2027 (maintained)

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
ACCESS topline	36‑week; YE25	YE25 (Q4’24, Q1’25)	YE25	Maintained
ACCESS II topline	36‑week; YE25	YE25 (Q4’24, Q1’25)	YE25	Maintained
ACCESS II duration	36 weeks	36 weeks	Double‑blind extension to 44 weeks	Expanded (New)
Aleniglipron maintenance switch study	12‑week study	Not previously guided	Enrollment start Q3 2025	New
Aleniglipron body composition study	40‑week study	Not previously guided	Enrollment start Q3 2025	New
Aleniglipron T2DM study	38‑week study	Not previously guided	Start Q4 2025	New
ACCG‑2671 (oral amylin)	Phase 1 start	By YE25 (Q4’24, Q1’25)	By YE25	Maintained
Cash runway	Liquidity	Through ≥2027 (Q4’24, Q1’25)	Through ≥2027	Maintained

Earnings Call Themes & Trends

Note: We did not find a Q2 2025 earnings call transcript in the document set after targeted searches; themes below reflect press releases and program updates for Q4 2024, Q1 2025, and Q2 2025.

Topic	Previous Mentions (Q4 2024 and Q1 2025)	Current Period (Q2 2025)	Trend
Oral GLP‑1 progress (aleniglipron)	Enrollment complete; YE25 topline expected ; fully enrolled and “on track” for YE25	Topline by YE25 reiterated; ACCESS OLE and ACCESS II 44‑week extension implemented	Execution steady; dataset expanded
Combination strategy	Positioning oral GLP‑1 as backbone; robust oral combo pipeline	“Field shifts towards combinability… excited to lead” with scalable oral pipeline	Increasing emphasis on combo paradigm
Oral amylin (ACCG‑2671)	Candidate selected; Phase 1 by YE25	IND‑enabling ongoing; Phase 1 by YE25; new preclinical data shown at ADA	On plan; external validation datapoints
New supportive studies	—	Maintenance switch (Q3), body composition (Q3), T2DM (Q4)	Broader Phase 3‑enabling dataset
Cash runway	≥2027 reiterated	≥2027 reiterated	Stable
Non‑GLP‑1 pipeline	APJR: Phase 1 done; long‑term tox ongoing	LPA1R (IPF): Phase 1 SAD/MAD complete with clean safety signals	Pipeline breadth inching forward

Management Commentary

“The ACCESS and ACCESS II studies for aleniglipron… remain on track for topline data readouts by the end of the year… we have initiated additional supplementary studies to ensure we are well positioned for Phase 3 and to maximize the therapeutic and competitive potential of this program.” – Raymond Stevens, Ph.D., CEO .
“As the obesity field shifts towards combinability of multiple targets and long‑term weight loss maintenance, we are excited to lead the way with a highly scalable pipeline of oral small molecule medicines…” – Raymond Stevens, Ph.D., CEO .
Q1 context: “We continue to make strong progress with the Phase 2b ACCESS and ACCESS II studies… on track for data readout by the end of the year.” – Raymond Stevens, Ph.D., CEO .

Q&A Highlights

No Q2 2025 earnings call transcript was available in the document set after targeted searches of earnings‑call‑transcript and other‑transcript categories; therefore, there is no Q&A to summarize for this period.

Estimates Context

EPS: Q2 2025 EPS of -$0.36 was essentially in line with the -$0.363 consensus (9 estimates). Q1 2025 EPS of -$0.27 compared to -$0.231 consensus (9 estimates). Revenue consensus was $0 for both periods, consistent with pre‑commercial status.*
Implications: With expenses rising to support expanded studies, consensus is likely to track OpEx cadence rather than revenue/GM dynamics; estimate changes should key off trial timelines and any incremental CMC/Phase 3 enabling costs.
*Values retrieved from S&P Global.

Key Takeaways for Investors

Execution into year‑end catalysts: YE25 topline readouts for ACCESS/ACCESS II remain the central driver; dataset expanded with OLE, 44‑week double‑blind extension at higher doses, and three supportive studies .
Strategic position for combinations: Management is explicitly orienting toward combinability (oral GLP‑1 backbone plus amylin and other targets), an area of increasing competitive focus .
Balance sheet durability: $786.5M in cash and investments as of 6/30 supports operations and planned clinical milestones through ≥2027 (excluding registrational Phase 3), reducing near‑term financing risk .
P&L trajectory: Operating expenses are scaling with clinical activity; YoY net loss widened as expected (R&D +$32.6M YoY). Monitor quarterly cadence as new studies start in 2H25 .
Upcoming milestones: Initiate maintenance switch and body composition studies in Q3 2025; T2DM study in Q4 2025; ACCG‑2671 Phase 1 by YE25 .
Trading lens: Near‑term moves are likely to center on oral GLP‑1 and oral amylin read‑across and any competitive dataflow; primary binary is YE25 ACCESS/ACCESS II outcomes, with supportive readouts and trial initiations shaping sentiment into those events .
Diligence focus areas: Tolerability at higher doses (180/240 mg), durability/maintenance in OLE and switch study, body composition effects, and T2DM efficacy/safety profile that could de‑risk broader Phase 3 design .

Citations

Q2 2025 8‑K and Exhibit 99.1 press release (financials, program updates, quotes):
Q1 2025 8‑K and Exhibit 99.1 press release (financials, program updates, quotes):
Q4 2024 8‑K and Exhibit 99.1 press release (financials, program updates):

Structure Therapeutics Inc. (GPCR)·Q2 2025 Earnings Summary