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Prelude Therapeutics Inc (PRLD)·Q4 2024 Earnings Summary

Executive Summary

  • Prelude Therapeutics reported FY 2024 results alongside Q4 2024 program updates; cash, cash equivalents and marketable securities were $133.6M at Dec 31, 2024 with runway into Q2 2026 .
  • Clinical proof-of-concept for PRT3789 (IV SMARCA2 degrader) was reinforced, with confirmed partial responses in SMARCA4‑deficient NSCLC, gastric and esophageal cancers; Phase 2 pembrolizumab combination trial has been initiated .
  • PRT7732 (oral SMARCA2 degrader) entered Phase 1; interim data expected in 2H 2025, adding optionality to the SMARCA strategy .
  • Strategic focus tightened: company plans to seek a partner for continued advancement of CDK9 program PRT2527 beyond Phase 1, while advancing SMARCA platforms and Precision ADCs .

What Went Well and What Went Wrong

What Went Well

  • First-in-class SMARCA2 degrader program progressed with confirmed clinical activity: “we were the first to establish that selectively targeting SMARCA2…could represent an important new class of therapy” (CEO) .
  • Combination strategy advancing: Phase 2 PRT3789 + pembrolizumab initiated; docetaxel combination shows acceptable safety profile to date .
  • Platform breadth increased: oral SMARCA2 degrader PRT7732 in Phase 1 with 2H 2025 interim data planned; Precision ADCs presented preclinical proof‑of‑concept with superior efficacy vs traditional cytotoxic ADC payloads .

What Went Wrong

  • Elevated cash burn with FY 2024 net loss of $127.2M and total operating expenses of $146.7M; cash and marketable securities declined from $179.8M (Q2) to $153.6M (Q3) to $133.6M (Q4) .
  • Limited quarterly granularity in the Q4 release (company furnished FY statements but did not disclose standalone Q4 revenue/EPS), constraining direct “vs prior quarter” comparisons .
  • CDK9 strategy de‑prioritized: while Phase 1 data showed activity, management plans to seek a partner for future development, reflecting resource allocation pressures in the current capital environment .

Financial Results

FY Performance

MetricFY 2023FY 2024
Revenue from license agreement ($USD Thousands)$0 $7,000
Research and Development ($USD Thousands)$103,393 $117,995
General and Administrative ($USD Thousands)$28,884 $28,719
Total Operating Expenses ($USD Thousands)$132,277 $146,714
Net Loss ($USD Thousands)$(121,832) $(127,173)
Net Loss per Share ($USD)$(2.02) $(1.68)

Quarterly Trend (cash and selected P&L items)

MetricQ2 2024Q3 2024Q4 2024
Cash + Marketable Securities ($USD Millions)$179.8 $153.6 $133.6
Revenue from license agreement ($USD Thousands)$0 $3,000 — (not disclosed)
Net Loss ($USD Thousands)$(34,740) $(32,271) — (not disclosed)
Net Loss per Share ($USD)$(0.46) $(0.43) — (not disclosed)

Notes: The company furnished FY statements in its Q4 2024 8-K/press release; standalone Q4 revenue/EPS were not disclosed .

Clinical KPIs (efficacy and dosing evolution)

KPIEarlier Cut (Oct 24, 2024)Updated Cut (Nov 30, 2024)Trend
Monotherapy Class 1 patients with confirmed PRs4/26 (2 NSCLC, 2 esophageal) 5/32 (2 NSCLC, 2 esophageal, 1 gastric) Improving with higher doses
ORR at doses ≥283 mg (Class 1 NSCLC/Upper GI)n/a23.1% (3/13) Higher dose cohorts showing more responses
Monotherapy dose escalation statusUp to 665 mg weekly Ongoing at 665 mg weekly Advanced without MTD identified
Docetaxel combination safetyAcceptable profile, no DLTs reported Acceptable profile; early cohorts through 500 mg + docetaxel Maintained combinability

Guidance Changes

MetricPeriodPrevious GuidanceCurrent GuidanceChange
Cash runwayCorporate“into 2026” (Q2/Q3) “into second quarter of 2026” Maintained; clarified timing
PRT3789 monotherapy dose escalationProgramConclude by year-end 2024 Nearing conclusion; at 665 mg weekly Maintained trajectory
PRT3789 + pembrolizumabProgramPhase 2 trial anticipated to initiate in Q4 2024 Phase 2 trial initiated Raised to “initiated”
PRT7732 (oral SMARCA2 degrader)ProgramIND authorized; enter Phase 1 in 2H 2024 Phase 1 underway; interim data in 2H 2025 Timelines extended with clinical start confirmed
PRT2527 (CDK9 inhibitor)ProgramInterim Phase 1 data in Q4 2024 Seek partner beyond completion of current Phase 1 Strategy shifted (partner-led beyond Ph1)

Earnings Call Themes & Trends

TopicPrevious Mentions (Q2/Q3)Current Period (Q4/FY)Trend
SMARCA2 degrader clinical efficacyESMO oral selection; early PRs; monotherapy escalation ongoing Confirmed PRs across NSCLC/upper GI; higher-dose ORR 23.1%; escalation at 665 mg Strengthening efficacy signal at higher doses
Combinations strategyPlanning docetaxel; pembrolizumab combo planned Docetaxel cohorts ongoing; Phase 2 pembrolizumab initiated Execution moving from planning to active
Supply chain/tariffs/macroNot highlightedMinimal short-term impact expected; proactive manufacturing/API planning Watching policy; mitigations in place
Regulatory interactions (Project Optimus)Not highlightedAnticipated dose optimization considerations pre‑registration Planning for dose optimization
Oral vs IV strategyOral entering clinic Oral underway; daily dosing may deepen target engagement; IV retained for certain indications Complementary modalities
Precision ADC platformPreclinical PoC presented Continued progress; partner AbCellera; candidate nomination targeted in 2025 Advancing toward development candidate

Management Commentary

  • CEO: “we were the first to establish that selectively targeting SMARCA2 in patients with SMARCA4‑deficient cancers could represent an important new class of therapy” .
  • CMO: “we are encouraged by the promising activity shown to date by PRT3789…for patients who have limited treatment options” .
  • CMO (on dose response/durability): “we are seeing…more responders at the higher doses…gastric patient…deepened their response…at the 500‑milligram dose” .
  • CEO (on ADCs): collaboration with AbCellera aims to “circumvent payload‑related resistance…toxicities” and create a leadership position in Precision ADCs .

Q&A Highlights

  • Macro/supply chain: Tariffs seen as minimal near-term risk; company has pre‑planned manufacturing/API to mitigate disruptions .
  • NIH cuts: potential long-term ecosystem impact; near-term clinical site operations/trial enrollment tracking to plan .
  • PRT3789 efficacy dynamics: faster responses in esophageal; deepening and durable responses in lung (PR sustained >8 months) .
  • Dose selection/Project Optimus: no DLTs to date; dose triangulation likely; potential additional patients pre‑registration per regulatory expectations .
  • Oral vs IV: oral CRBN-based daily dosing may deepen target engagement; IV VHL-based remains important for indications like esophageal .
  • Combination strategy: preclinical synergy with docetaxel supports aggressive advancement; clinical combinability profile clean so far .

Estimates Context

  • Attempts to fetch S&P Global consensus EPS and revenue for Q4 2024 and prior quarters failed due to daily request limit; consensus comparisons are unavailable at this time [GetEstimates error].
  • As a result, no beat/miss assessment versus Wall Street consensus can be made. If needed, we can re‑query S&P Global estimates once access is restored.

Key Takeaways for Investors

  • SMARCA2 program de‑risking continues: confirmed PRs and dose‑response at higher levels, with Phase 2 pembrolizumab combo initiated; the narrative has shifted from feasibility to execution at scale .
  • Cash runway into Q2 2026 provides a multi‑data‑read window (docetaxel combo and monotherapy backfill in 2H 2025; oral PRT7732 interim in 2H 2025) to drive value inflections .
  • Oral degrader broadens TAM and development options; IV retained for select indications—portfolio approach increases probability of success across SMARCA4‑mutated cancers .
  • Precision ADCs (SMARCA2/4 degrader payloads) could open mutation‑agnostic pathways with potentially better efficacy/tolerability than traditional cytotoxic ADCs; watch for 2025 development candidate nomination .
  • CDK9 program remains a source of optionality via partnering; interim activity observed, but capital allocation favors SMARCA platforms .
  • Near-term catalysts: additional PRT3789 updates (backfill cohorts at higher doses) and first PRT7732 clinical data in 2H 2025; clarity on dose selection and combination efficacy will likely drive estimate revisions and the stock narrative .

References:

  • FY/Q4 press release and 8‑K:
  • Q3 2024 press release:
  • Q2 2024 press release:
  • Other relevant releases (Q4): EORTC‑NCI‑AACR and ASH updates:
  • Barclays fireside chat transcript (Q&A):