Executive Summary

Q3 2025 results were broadly in line with expectations: diluted EPS was −$0.32 versus Wall Street consensus of −$0.32*, and net loss widened to $12.75M from $3.90M in Q3 2024 as R&D spending ramped for nimacimab clinical development . Cash, cash equivalents and short-term investments totaled $35.3M, with runway into 2027 per management .
Clinically, the CBeyond Phase 2a dataset continued to strengthen the combination thesis: nimacimab + semaglutide achieved −13.2% weight loss at 26 weeks vs −10.25% for semaglutide alone (~30% relative improvement), with no added GI burden or neuropsychiatric signals; weight regain was markedly blunted post-treatment (18.1% vs 49.8%) .
Management is pivoting to a combination-focused development path while continuing dose-ranging to unlock monotherapy efficacy; the 26-week extension study is fully enrolled (43 patients) with data expected in Q1 2026 .
Near-term catalysts include finalized Phase 2 design, PK/PD model readout and manufacturing/formulation progress aimed at high-concentration dosing and cost-of-goods reduction .
Stock narrative catalysts: durable post-incretin maintenance potential and synergy in combo could expand addressable market and support estimate revisions once extension data are disclosed .

What Went Well and What Went Wrong

What Went Well

Combination efficacy/safety: nimacimab + semaglutide delivered −13.2% weight loss at 26 weeks vs −10.25% for semaglutide alone (p=0.0372) with no observed plateau, and no additive GI burden or neuropsychiatric events .
Durability and body composition: rebound weight gain post-treatment was blunted (18.1% vs 49.8%) and waist circumference fell an additional 3.17 cm; lean-to-fat ratio improved to 0.26 vs 0.13 for semaglutide alone (p=0.0126) .
Management execution and conviction: “a holistic review provides us with additional confidence that nimacimab’s biology is active…we are shifting our focus to a combination development pathway” — Punit Dhillon, CEO .

What Went Wrong

Monotherapy efficacy miss: the 200 mg monotherapy arm did not meet the primary endpoint at 26 weeks; preliminary PK suggests suboptimal exposure and need for higher dosing .
Operating losses widened: quarterly net loss increased to $12.75M as R&D spend rose to $9.36M vs $4.88M last year, reflecting manufacturing and clinical costs .
Scale/statistical power concerns: only 43 patients enrolled in the 26-week extension; analysts questioned whether that is sufficient for statistically significant insights (management emphasized expected separation in combo arms) .

Financial Results

Note: Skye reports no product revenue; financials are driven by operating expenses and net loss.

Metric ($USD Millions unless noted)	Q3 2024	Q2 2025	Q3 2025	Q3 2025 Consensus
R&D Expense	$4.88	$14.34	$9.36	—
G&A Expense	$4.64	$3.91	$3.91	—
Operating Loss	$4.97	$18.24	$13.26	—
Net Loss	$3.90	$17.62	$12.75	—
Basic/Diluted EPS ($)	−$0.10	−$0.44	−$0.32	−$0.32*
Cash & Short-term Investments (period-end)	—	$48.60	$35.31 (cash $18.44; ST investments $16.87)	—

EPS comparison: Actual −$0.32 vs consensus −$0.32 (inline)*.
Revenue consensus was $0.0 across the last three quarters (biotech development stage)*.

Values marked with * are from S&P Global consensus (Primary EPS Consensus Mean; Revenue Consensus Mean). Values retrieved from S&P Global.

Guidance Changes

Metric	Period	Previous Guidance (Q2 2025)	Current Guidance (Q3 2025)	Change
Cash runway	Through at least Q1 2027	Fund projected operations and clinical milestones through at least Q1 2027	Fund projected operations and key clinical milestones into 2027	Maintained
CBeyond 26-week extension data	Q1 2026	Extension enrolling; data expected in 2026	Extension fully enrolled; 26-week extension readout expected Q1 2026	Clarified timing/fully enrolled
Development focus	Next study planning	Prepare Phase 2b dose-ranging protocol after topline; combination optionality discussed	Shifted focus to combination pathway; finalize next Phase 2 design; continue monotherapy dose-ranging	Strategically raised emphasis on combo

Earnings Call Themes & Trends

Topic	Previous Mentions (Q1 & Q2)	Current Period (Q3 2025)	Trend
Combination strategy (nimacimab + GLP-1)	Preclinical data showed additive effects with tirzepatide; planning dose-ranging path	26-week clinical data confirmed ~30% relative improvement vs semaglutide; no added GI burden; pursuing combo-focused Phase 2	Strengthening (from preclinical thesis to clinical validation)
Monotherapy dose optimization	Acknowledged need for higher exposures; Phase 2b envisioned as monotherapy dose-ranging	200/300 mg appeared suboptimal; PK/PD supports higher dosing; plan to go higher	Raising doses (data-driven)
Durability/maintenance indication	Preclinical rebound mitigation; positioning for maintenance opportunity	12-week post-treatment showed 18% regain vs 50% for semaglutide; physicians/KOLs positive on “dosing holidays” concept	Increasing strategic focus
CMC/formulation & cost of goods	Collaboration for higher-concentration formulation; supply readiness	Advancing high-concentration formulation; device options; cost-of-goods optimization to align with Medicare pricing dynamics	Advancing; commercial readiness lens
Regulatory path	Protocol amendments; planning regulatory engagement post-readout	Maintenance may require monotherapy approval; plan ongoing agency discussions for mono and combo paths	Clarified dependencies
Safety profile	No neuropsychiatric signals in DMC reviews; peripheral restriction emphasized	No neuropsychiatric or additive GI burden in Phase 2a; room to increase dose remains	De-risking; supports dose escalation

Management Commentary

“With the positive combination data, we are shifting our focus to a combination development pathway while simultaneously planning to further understand nimacimab’s potential benefit in a monotherapy setting.” — Punit Dhillon, CEO .
“We ended Q3 with cash and cash equivalents and short-term investments totaling $35.3 million. We expect our current working capital to fund operations and key clinical milestones into 2027.” — Kaitlyn Arsenault, CFO .
“We showed synergistic efficacy with nimacimab plus semaglutide… nearly a 30% improvement with this combination, with no observed plateau at 26 weeks.” — Punit Dhillon .
“We feel very confident… there is a dose response. As we get to better exposures, we will see better weight loss as both monotherapy and in combination.” — Chris Twitty, CSO .
“If we were to do maintenance therapy with nimacimab as a monotherapy, that would require monotherapy approval.” — Puneet Arora, CMO .

Q&A Highlights

PK/PD and dose-response: Management sees credible exposure-response slopes; higher dosing expected to improve monotherapy efficacy; Phase 2b will pursue dose-ranging .
Extension sample size/statistics: With 43 patients, management expects clear separation in combo arms; monotherapy insights will mainly refine PK/PD and dosing strategy .
Maintenance market opportunity: KOLs/physicians responded positively to blunted rebound data; potential for dosing holidays without losing weight-loss gains .
Safety at higher doses: No neuropsychiatric signals and limited GI concerns to date; mechanism suggests muted GI effects vs GLP-1s; safety will be monitored as doses increase .
Study design and timelines: Management intends 26-52 week dosing windows in Phase 2; the extension will inform durability and dose selection; regulatory interactions will shape mono/combo pathways .

Financial Results Detail and KPIs

KPI	Value	Context
Cash + ST investments	$35.31M (cash $18.44M; ST investments $16.87M)	Runway into 2027
R&D spend (Q3 2025)	$9.36M	Up vs $4.88M in Q3 2024
G&A spend (Q3 2025)	$3.91M	Down vs $4.64M in Q3 2024
Net loss (Q3 2025)	$12.75M; EPS −$0.32	Versus Q2 2025 net loss $17.62M; EPS −$0.44

CBeyond Phase 2a Clinical KPIs

Metric	Placebo	Semaglutide Alone	Nimacimab 200 mg	Nimacimab 200 mg + Semaglutide
% weight change (mITT, 26w)	−0.26% (SE 0.88)	−10.25% (SE 1.09)	−1.52% (SE 0.89)	−13.2% (SE 1.02)
Semaglutide-subtracted (26w)	—	—	—	−2.95% (p=0.0372)
Lean-to-fat ratio change	0.02 vs placebo	0.13	—	0.26 (p=0.0126 vs sema)
Waist circumference change	—	−8.09 cm (SE 1.20)	—	−11.26 cm (SE 1.16); Δ −3.17 cm (p=0.0492)
Post-treatment 12-week weight regain	—	49.8%	—	18.1% (p=0.006 vs placebo group at 12 weeks)
Neuropsychiatric AEs	—	—	None increase vs placebo	None increase vs sema
GI AEs (combo arms)	—	Nausea 29.2%, constipation 25.0%	—	Nausea 32.1%, constipation 7.1%; overall GI burden not increased vs sema

Estimates Context

EPS comparison by quarter (consensus vs actual):
- Q1 2025: −$0.29* vs actual −$0.28
- Q2 2025: −$0.30* vs actual −$0.44
- Q3 2025: −$0.32* vs actual −$0.3239 (≈−$0.32)
Revenue consensus was $0.0* across Q1–Q3 2025, consistent with development-stage status.

Values marked with * are from S&P Global consensus (Primary EPS Consensus Mean; Revenue Consensus Mean; Primary EPS – # of Estimates; Revenue – # of Estimates). Values retrieved from S&P Global.

Key Takeaways for Investors

Combination path is the core near-term value driver; Phase 2 design will emphasize nimacimab + GLP-1 with dose optimization supported by PK/PD modeling .
Maintenance/“dosing holiday” profile is a differentiated angle: blunted rebound could enable more durable real-world outcomes and broaden payer/physician appeal .
Safety de-risking continues: no neuropsychiatric signals and no additive GI burden at 200 mg combination; supports latitude to escalate dosing in monotherapy and combo .
Cash runway into 2027 reduces near-term financing risk; watch for manufacturing/formulation progress to improve cost of goods and support competitive pricing .
Expect estimate revisions around Q1 2026 as 52-week extension data read out; positive durability and dose-response confirmation would be meaningful catalysts .
Near-term trading implications: inline EPS and strengthened clinical narrative may support sentiment; upside skew tied to Phase 2 design clarity and any interim PK/PD disclosures .
Medium-term thesis: a peripherally restricted CB1 antibody with combo synergy and maintenance durability has potential to complement the incretin backbone, expanding TAM while addressing tolerability and persistence gaps .

Skye Bioscience, Inc. (SKYE)·Q3 2025 Earnings Summary