Executive Summary

PepGen reported Q4 2024 net loss of $22.242M and EPS of $(0.68), with year-end cash, cash equivalents and marketable securities at $120.191M, guiding cash runway “into 2026” .
Initial DM1 Phase 1 data showed robust splicing correction after a single dose: mean 12.3% at 5 mg/kg (n=6) and 29.1% at 10 mg/kg (n=4), with a favorable emerging safety profile; 15 mg/kg results are expected in 2H 2025 .
DMD program updates: CONNECT1 10 mg/kg cohort fully enrolled with data guided for Q3 2025; CONNECT2 remains open in the UK, while the US IND is on clinical hold (December 2024), with PepGen working with FDA to resolve questions .
Key near-term catalysts are DM1 splicing data progression and regulatory clarity for CONNECT2; program timelines were refined (e.g., CONNECT1 10 mg/kg moved from “by year-end 2025” to Q3 2025), supporting clearer milestone visibility .

What Went Well and What Went Wrong

What Went Well

Robust single-dose splicing correction in DM1: “mean splicing correction of 12.3% and 29.1%” at 5 and 10 mg/kg cohorts, respectively, alongside dose-dependent drug tissue concentration increases, reinforcing EDO nuclear delivery thesis .
Management emphasized platform validation: “We believe these data contribute to the growing evidence of our novel EDO platform’s potential to deliver the drug to the nucleus” (CEO James McArthur) .
Cash runway maintained: year-end cash and securities of $120.191M anticipated to fund operations into 2026, providing financing visibility through multiple data readouts .

What Went Wrong

US FDA clinical hold on CONNECT2-EDO51 (Dec 16, 2024), delaying US enrollment; PepGen is working to address FDA questions on supportive dosing data .
Operating expenses increased year over year (Q4 R&D $18.961K vs. $16.300K; G&A $5.384K vs. $4.511K), widening quarterly net loss (Q4 net loss $22.242M vs. $19.495M) .
One treatment-related serious adverse event (abdominal pain) in the DM1 10 mg/kg cohort, potentially confounded by a prohibited off-label drug taken on dosing day, necessitating close ongoing safety monitoring .

Financial Results

Metric ($USD Thousands unless noted)	Q4 2023	Q3 2024	Q4 2024
Research and Development	$16,300	$17,722	$18,961
General and Administrative	$4,511	$5,449	$5,384
Total Operating Expenses	$20,811	$23,171	$24,345
Operating Loss	$(20,811)	$(23,171)	$(24,345)
Interest Income	$1,346	$1,826	$1,460
Other Income (Expense), net	$43	$(39)	$26
Total Other Income, net	$1,389	$1,787	$1,486
Net Loss before Income Tax	$(19,422)	$(21,384)	$(22,859)
Income Tax (Expense) Benefit	$(73)	—	$617
Net Loss	$(19,495)	$(21,384)	$(22,242)
Net Loss per Share (basic & diluted) ($)	$(0.82)	$(0.66)	$(0.68)
Weighted Avg Shares (basic & diluted)	23,816,919	32,581,542	32,602,981

Balance Sheet KPI ($USD Thousands)	Q2 2024	Q3 2024	Q4 2024
Cash, Cash Equivalents & Marketable Securities	$161,306	$138,857	$120,191

Segment breakdown: Not applicable; PepGen is a clinical-stage biotech without commercial revenue lines .
Estimates comparisons: Wall Street consensus via S&P Global was unavailable for Q4 2024 due to system limit; estimate-based beat/miss cannot be determined at this time.

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
FREEDOM-DM1 initial data (5/10 mg/kg)	Q1 2025	“Update by end of Q1 2025” (Q3)	Reported Feb 24, 2025	Achieved on time
FREEDOM-DM1 15 mg/kg single-dose cohort	2H 2025	2H 2025 (Q3)	2H 2025 (Q4)	Maintained
FREEDOM2-DM1 5 mg/kg MAD cohort	Q1 2026	Dosing initiation by year-end 2024 (Q3)	Results expected Q1 2026 (Q4)	New specificity (timeline extended to results)
CONNECT1-EDO51 10 mg/kg cohort	2025	“By year-end 2025” (Q3)	Q3 2025 (Q4)	Pulled forward (earlier in 2025)
CONNECT2-EDO51 US IND status	2024-2025	Anticipated US opening by year-end 2024 (Q3)	Clinical hold by FDA (Dec 16, 2024); working to address	Lowered (US start delayed)
Cash runway	Through 2026	“Into 2026” (Q2/Q3)	“Into 2026” (Q4)	Maintained

Earnings Call Themes & Trends

Topic	Previous Mentions (Q-2 and Q-1)	Current Period (Q4)	Trend
DM1 clinical efficacy and EDO delivery	Planned FREEDOM Phase 1 update; EDO nuclear delivery thesis articulated	Robust single-dose splicing correction (12.3%/29.1%); dose-dependent tissue levels; favorable safety	Positive data momentum; platform validation reinforced
DMD CONNECT1 clinical execution	5 mg/kg cohort data (exon skipping, dystrophin increases); protocol optimization; expand 10 mg/kg cohort	10 mg/kg fully enrolled; data guided for Q3 2025; safety monitoring updates (hypomagnesemia, eGFR pause and recovery)	Execution continuing; safety under review; timeline clarified
Regulatory interactions	Anticipated US opening for CONNECT2 by year-end 2024	FDA clinical hold for CONNECT2 US; ongoing engagement to address dosing support	Negative US regulatory development; remediation in progress
Cash runway and financing visibility	Into 2026 (Q2/Q3)	Into 2026 reiterated	Stable runway guidance
Safety profile across programs	EDO51 well tolerated at 5 mg/kg (CONNECT1)	DM1: favorable emerging safety; one treatment-related SAE potentially confounded; no renal/electrolyte AEs	Generally favorable; isolated events monitored

Management Commentary

“We reported initial results from FREEDOM-DM1, which showed robust splicing correction… [data] contribute to the growing evidence of our novel EDO platform’s potential to deliver the drug to the nucleus” — James McArthur, PhD, President & CEO .
“These results far exceeded our expectations for splicing correction… [10 mg/kg] surpasses those reported to date in multi-dose clinical trials… strong indicator of our EDO technology’s potential” — James McArthur, PhD .
“As of January 23, 2025, all treatment related adverse events in CONNECT1 have been mild… decreased eGFR… has improved… we will continue to closely monitor safety” — Paul Streck, MD, Head of R&D .

Q&A Highlights

Company hosted a webcast at 8:00 a.m. ET to review FREEDOM-DM1 data and provided call-in details; exhibits included a clinical data update slide deck .
Clarifications in press materials addressed assay exclusions (splicing index outside range; biopsy not collected due to procedure-related pseudoaneurysm), ensuring transparency on evaluable participants .
Safety clarifications included no adverse events related to electrolytes or renal biomarkers in DM1 cohorts, with most TEAEs mild/moderate; one treatment-related SAE potentially confounded by off-label medication .

Estimates Context

S&P Global consensus EPS and revenue estimates for Q4 2024 were unavailable at the time of this analysis due to a data access limit; as a result, beat/miss versus Wall Street cannot be determined at this time. When available, comparisons will be anchored to S&P Global consensus.

Key Program KPIs

KPI	Q2 2024	Q3 2024	Q4 2024
DM1 FREEDOM mean splicing correction at 5 mg/kg (%)	—	—	12.3% (n=6)
DM1 FREEDOM mean splicing correction at 10 mg/kg (%)	—	—	29.1% (n=4)
DM1 dose-dependent muscle tissue concentration (Day 28)	—	—	Increase at 5 mg/kg (n=6) and 10 mg/kg (n=5)
DMD CONNECT1 mean exon 51 skipping (%) at 5 mg/kg	2.15% (biceps, wk13)	—	—
DMD CONNECT1 mean muscle-adjusted dystrophin increase (% from baseline)	+0.70% (wk13)	—	—
DMD CONNECT1 mean absolute dystrophin increase (% of normal, from baseline)	+0.26% (wk13)	—	—

Implications and Why

DM1 efficacy signal and dose-dependent pharmacology underpin the EDO nuclear delivery thesis, supporting potential for functional benefits with repeat dosing in FREEDOM2 (MAD), a meaningful de-risking step for platform and asset .
US clinical hold in CONNECT2 introduces timeline risk in DMD; however, continued dosing in Canada and UK operations mitigate overall program momentum while regulatory engagement continues .
Cash runway into 2026 provides a buffer to deliver multiple readouts (FREEDOM 15 mg/kg 2H 2025; CONNECT1 10 mg/kg Q3 2025; FREEDOM2 5 mg/kg Q1 2026) without immediate financing pressure, stabilizing execution capacity .

Estimates Context and Potential Revisions

Consensus estimates (EPS, revenue) could not be retrieved; in future, positive DM1 data and clarified DMD timelines may drive revised R&D spend phasing and cash runway assumptions, while lack of commercial revenues keeps EPS sensitivity primarily tied to opex and interest income .

Key Takeaways for Investors

Robust single-dose DM1 splicing correction (12.3%/29.1%) and favorable emerging safety increase confidence ahead of multi-dose FREEDOM2 readouts; watch for 15 mg/kg data in 2H 2025 .
DMD program execution continues (CONNECT1 10 mg/kg fully enrolled), with data guided to Q3 2025; monitor Canadian safety updates (hypomagnesemia/eGFR) and Health Canada information requests .
US CONNECT2 clinical hold is the principal regulatory overhang; outcome and timing of FDA dialogue are key stock drivers for DMD exposure .
Cash runway into 2026 reduces near-term financing risk, aligning capital with sequential data catalysts across DM1 and DMD .
Near-term trading focus: incremental DM1 biomarker/functional signals and any material regulatory updates; medium-term thesis hinges on converting splicing correction into functional benefit in MAD settings .

Notes: No 8-K-furnished earnings call transcript was available in the reviewed filings; analysis is based on 8-K exhibits and press releases. All financial and program facts are cited from the company’s 8-K and press releases as referenced above.

PepGen Inc. (PEPG)·Q4 2024 Earnings Summary