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Summit Therapeutics Inc. (SMMT)·Q3 2025 Earnings Summary

Executive Summary

  • Summit announced intent to submit a BLA in Q4 2025 for ivonescimab plus chemotherapy based on global Phase III HARMONi results; FDA previously indicated a statistically significant OS would be expected, but Summit is proceeding given totality of efficacy/safety and unmet need .
  • HARMONi-6 (Akeso-sponsored, China) showed clinically meaningful superiority of ivonescimab + chemo vs tislelizumab + chemo in 1L squamous NSCLC: mPFS 11.14 vs 6.90 months; HR=0.60; ORR 75.9% vs 66.5%; manageable safety; Lancet publication concurrent with ESMO 2025 .
  • GAAP Q3 2025 net loss was $(231.8)mm (EPS $(0.31)); non-GAAP net loss $(101.0)mm (EPS $(0.13)); GAAP OpEx rose on stock-based compensation modifications earlier in the year; cash and equivalents $238.6mm .
  • Consensus EPS tracking shows a significant miss in Q3 (actual $(0.311) vs est. $(0.059))*; operational catalysts include protocol amendment splitting HARMONi-3 analyses by histology to accelerate squamous readout and a $500mm private placement at $18.74/share (post-quarter) to bolster funding .

What Went Well and What Went Wrong

What Went Well

  • Ivonescimab demonstrated a statistically significant and clinically meaningful PFS improvement vs PD‑1 + chemo in 1L squamous NSCLC (HARMONi‑6): HR=0.60; mPFS 11.14 vs 6.90 months; benefits across PD‑L1 subgroups (TPS<1% HR 0.55; TPS≥1% HR 0.66) .
  • Management highlighted validation of a tolerable safety profile even in high-risk squamous populations (central tumors, vessel encasement, hemoptysis), differentiating ivonescimab from prior PD‑1+VEGF combinations administered separately: “This clearly differentiates ivonescimab…” .
  • Expansion beyond lung: initiation of HARMONi‑GI3 (global Phase III) in 1L unresectable metastatic MSS CRC using FOLFOX backbone, supported by Phase II ORR 81.8% and DCR 100% in FOLFOXIRI cohort (Akeso) .

What Went Wrong

  • EPS missed consensus materially in Q3, reflecting elevated GAAP OpEx from stock-based comp earlier in the year and ongoing Phase III expansions (GAAP OpEx $234.2mm; non-GAAP OpEx $103.4mm) .
  • FDA previously indicated significant OS is expected for marketing authorization in HARMONi; Summit will file BLA despite OS not reaching statistical significance at primary analysis (HR 0.79; p=0.057), increasing regulatory uncertainty .
  • VEGF‑related Grade ≥3 AEs were higher vs tislelizumab (7.5% vs 2.3%), with more Grade ≥3 hemorrhage events (5 vs 2), though overall discontinuations/deaths were comparable; will require continued clinician education on safety profile .

Financial Results

EPS vs Estimates

MetricQ1 2025Q2 2025Q3 2025
GAAP Diluted EPS ($)$(0.09) $(0.76) $(0.31)
Non-GAAP Diluted EPS ($)$(0.07) $(0.12) $(0.13)
EPS Consensus Mean ($)$(0.088)*$(0.095)*$(0.059)*

Values with asterisks retrieved from S&P Global.

Operating Expenses and Cash

Metric ($USD Millions)Q1 2025Q2 2025Q3 2025
GAAP Operating Expenses$66.8 $568.4 $234.2
Non-GAAP Operating Expenses$55.7 $89.6 $103.4
GAAP R&D Expense$51.2 $208.0 $131.1
Non-GAAP R&D Expense$47.1 $79.4 $90.5
GAAP G&A Expense$15.6 $360.4 $103.1
Non-GAAP G&A Expense$8.6 $10.2 $12.9
Cash & Equivalents + ST Investments$361.3 $297.9 $238.6

Revenue vs Estimates

MetricQ1 2025Q2 2025Q3 2025
Revenue Consensus Mean ($)$0.0*$0.0*$77.198mm*
Reported Revenue ($)Not presented in release (pre-commercial) Not presented in release (pre-commercial) Not presented in release (pre-commercial)

Values with asterisks retrieved from S&P Global.

Note: Summit’s condensed operating statements focus on OpEx and net loss without a revenue line, consistent with pre-commercial stage reporting .

Segment Breakdown

No reportable segments disclosed (biopharma development-stage reporting) .

KPIs (Clinical Efficacy – HARMONi-6, ITT)

KPIValue
Median PFS (ivonescimab + chemo)11.14 months (95% CI: 9.86, NE)
Median PFS (tislelizumab + chemo)6.90 months (95% CI: 5.82, 8.57)
Stratified HR for PFS0.60 (95% CI: 0.46, 0.78; p<0.0001)
ORR (ivonescimab vs tislelizumab)75.9% vs 66.5%
DoR (ivonescimab vs tislelizumab)11.20 vs 8.38 months

Guidance Changes

MetricPeriodPrevious GuidanceCurrent GuidanceChange
BLA submission (ivonescimab + chemo; HARMONi)Q4 2025Not previously setSubmit in Q4 2025New
HARMONi‑3 squamous enrollment completionH1 2026Combined ITT (single analysis)Separate histology analyses; squamous complete H1 2026Refined (protocol amended)
HARMONi‑3 squamous PFS analysisH2 2026Combined ITT (single analysis)Separate analysis; squamous PFS H2 2026Refined
HARMONi‑3 non‑squamous enrollment completionH2 2026Combined ITT (single analysis)Separate analysis; non‑squamous complete H2 2026Refined
HARMONi‑3 non‑squamous PFS analysisH1 2027Combined ITT (single analysis)Separate analysis; non‑squamous PFS H1 2027Refined
HARMONi‑GI3 (CRC) site activations (US)Q4 2025Not applicableBegin clinical site activations by year‑endNew

Earnings Call Themes & Trends

TopicQ1 2025 (prior)Q2 2025 (prior)Q3 2025 (current)Trend
Regulatory strategy (BLA)Topline HARMONi expected mid‑2025; FDA fast track noted Positive PFS; FDA expects OS; timing of filing under consideration File BLA in Q4 2025 despite OS non‑sig at primary; rationale based on totality Increasing conviction to file
Trial design evolution (HARMONi‑3)Global 1L NSCLC all‑comers Enrollment continued Protocol amended to independent ITT by histology; larger N (600/1,000) De-risking, acceleration
Safety narrative (VEGF-related events)N/AChina approvals; interim OS trend; tolerability acceptable Manageable safety in squamous; counsel education on bleeding risk Education emphasis
Pipeline expansionISTs and MD Anderson collaboration; Pfizer ADC plans Revolution Medicines RAS(ON) combo collaboration Launch of HARMONi‑GI3 in CRC; continued ADC/RAS combos planned Broadening
Funding runwayCash $361.3mm Cash $297.9mm; ATM expanded to $360mm Cash $238.6mm; post‑quarter $500mm private placement closed Strengthened post‑quarter

Management Commentary

  • “Based on the results of the HARMONi clinical trial, we plan to submit a Biologics License Application… in the fourth quarter of 2025.”
  • “Protocol amendment: PFS and OS statistical analyses for both dual primary endpoints will be conducted separately by histology… expected enrollment: 600 squamous, 1,000 non‑squamous.”
  • “Ivonescimab provided a significant and clinically meaningful PFS benefit… across negative, low, and high PD‑L1 expression.”
  • “We sought to expand the ivonescimab clinical development program beyond NSCLC… HARMONi‑GI3… first global study beyond NSCLC.”
  • “We have an ATM out there… I invested a few weeks ago… inbound interest in additional capital.”

Q&A Highlights

  • OS timing and powering: Management deferred detailed OS timing to Akeso but suggested a review “next year,” noting events‑driven analyses and that HARMONi‑6 PFS HR beat powered assumptions .
  • BLA rationale without sig OS: Team cited totality of data and precedents (e.g., approvals without sig OS in similar settings) while acknowledging FDA’s prior expectation for OS; they will proceed and engage the FDA .
  • HARMONi‑3 protocol amendment impact: Split analyses designed to de‑risk regulatory path, power each histology, and accelerate squamous readout; non‑squamous enrollment also proceeding quickly .
  • CRC Phase III details: Stratification factors exist; site activations planned for US by year‑end; Phase II data across multiple chemo backbones informed FOLFOX selection .
  • Funding: Post‑quarter private placement of ~$500mm at market price; management emphasized continued interest and strategic control over development .

Estimates Context

  • EPS vs consensus: Q3 2025 actual GAAP EPS $(0.311) vs consensus $(0.059)* — significant miss, primarily driven by elevated OpEx and stock‐based compensation modifications earlier in 2025 leading to higher GAAP expenses; non‑GAAP EPS $(0.13) provides a clearer view of operating spending .
  • Q2 2025 actual $(0.777) vs consensus $(0.095)* — miss attributable to $466.6mm non‑cash stock option modification expense recognized in Q2 .
  • Q1 2025 actual $(0.088) vs consensus $(0.088)* — roughly in line/ slight beat .
  • Revenue estimates appear non‑indicative for a pre‑commercial stage; company’s condensed statements did not present revenue lines in Q1, Q2, or Q3 press materials .

Values with asterisks retrieved from S&P Global.

Key Takeaways for Investors

  • Regulatory inflection: BLA filing in Q4 2025 is a near‑term catalyst; ODAC risk exists given FDA’s prior emphasis on OS, but HARMONi PFS magnitude and totality could support dialogue .
  • Squamous NSCLC acceleration: HARMONi‑3 protocol amendment may enable earlier squamous PFS readout (H2 2026) with cleaner histology‑specific statistics, de‑risking approval sequencing .
  • Safety education: While overall tolerability is manageable, VEGF‑related Grade ≥3 events (hypertension, proteinuria, hemorrhage) were higher; proactive physician education should mitigate adoption concerns .
  • Balance sheet strengthened: Post‑quarter $500mm private placement provides resources for multi‑indication Phase III programs and commercial readiness planning .
  • CRC optionality: HARMONi‑GI3 opens a large MSS CRC market where PD‑1 monotherapy underperforms; FOLFOX backbone aligns with Western practice; site activations in US by year‑end .
  • Earnings optics: Expect non‑GAAP to be more indicative of operating spend trajectory amid non‑cash comp impacts; watch OpEx cadence as HARMONi‑3/‑7 and HARMONi‑GI3 scale .
  • Stock narrative drivers: Near‑term are BLA submission and FDA engagement; medium‑term are HARMONi‑3 squamous PFS, non‑squamous timeline, and progress in CRC/combination strategies .
All non-estimate metrics and statements are sourced from company filings and earnings materials:
- Q3 2025 8-K press release and exhibits **[1599298_0001599298-25-000156_a2025_prx1020xq32025earn.htm:0]** **[1599298_0001599298-25-000156_a2025_prx1020xq32025earn.htm:5]** **[1599298_0001599298-25-000156_a2025_prx1020xq32025earn.htm:10]** **[1599298_0001599298-25-000156_a20251020esmoupdateq3202.htm:7]** **[1599298_0001599298-25-000156_a2025_prx1019xesmoharmon.htm:1]** **[1599298_0001599298-25-000156_a20251020esmoupdateq3202.htm:6]** **[1599298_0001599298-25-000156_a2025_prx1017xannounceme.htm:0]** **[1599298_0001599298-25-000156_a2025_prx1017xannounceme.htm:1]** **[1599298_0001599298-25-000156_a2025_prx1019xesmoharmon.htm:2]**
- Q3 2025 earnings call transcript **[0001599298_2191435_3]** **[0001599298_2191435_5]** **[0001599298_2191435_6]** **[0001599298_2191435_8]** **[0001599298_2191435_9]** **[0001599298_2191435_10]** **[0001599298_2191435_11]** **[0001599298_2191435_13]** **[0001599298_2191435_17]**
- Q2 2025 8-K press release **[1599298_0001599298-25-000128_a2025_prx0811xq22025earn.htm:1]** **[1599298_0001599298-25-000128_a2025_prx0811xq22025earn.htm:2]** **[1599298_0001599298-25-000128_a2025_prx0811xq22025earn.htm:3]** **[1599298_0001599298-25-000128_a2025_prx0811xq22025earn.htm:4]** **[1599298_0001599298-25-000128_a2025_prx0811xq22025earn.htm:8]**
- Q1 2025 8-K press release **[1599298_0001599298-25-000088_a2025_prx0501xq12025earn.htm:1]** **[1599298_0001599298-25-000088_a2025_prx0501xq12025earn.htm:2]** **[1599298_0001599298-25-000088_a2025_prx0501xq12025earn.htm:6]** **[1599298_0001599298-25-000088_q12025earningsdeck_final.htm:2]** **[1599298_0001599298-25-000088_q12025earningsdeck_final.htm:3]**
- Oct 22, 2025 $500mm private placement 8-K **[1599298_0001193125-25-245790_d274712d8k.htm:1]**
Values with asterisks retrieved from S&P Global.