Executive Summary

Q4 2021 showed a sharp sequential reset in operating spend: license revenue was $1.04M and net loss narrowed to $(33.5)M (EPS $(0.53)) from Q3’s $(66.7)M (EPS $(1.12)), driven by materially lower R&D/manufacturing outlays following the FDA’s September EUA decline .
Full-year 2021 loss was $(236.6)M on R&D of $213.1M (including $143.9M in manufacturing costs), ending the year with $70.0M cash and just $2.25M of working capital—implying a tight liquidity position absent new financing or a revenue catalyst .
2022 catalysts: NIH ACTIV-5/BET-B topline in late Q1/early Q2; if supportive (CRP<150 mg/L), the company plans to amend its U.S. EUA filing and pursue EU/UK submissions; additional read-throughs from CAR-T (SHIELD), aGvHD (RATinG), CMML (PREACH-M) programs provide diversification beyond COVID-19 .
S&P Global consensus estimates were unavailable for HGEN (mapping missing), so vs-consensus comparisons cannot be provided; note this limits “beat/miss” framing for Q4 [Values retrieved from S&P Global unavailable due to mapping error].

What Went Well and What Went Wrong

What Went Well

Expense reset improved P&L trajectory: R&D fell to $29.36M in Q4 from $60.81M in Q3, shrinking net loss to $(33.54)M (EPS $(0.53)) vs. Q3’s $(66.74)M (EPS $(1.12)) .
External validation: LIVE-AIR Phase 3 results published in The Lancet Respiratory Medicine; commentary noted lenzilumab “can improve the likelihood of survival without the need for mechanical ventilation, with a safety profile similar to that of placebo” .
Clear 2022 regulatory plan: “We look forward to the announcement of the topline data from…ACTIV-5/BET-B…late Q1 or early Q2…[and] plan to…submit an amendment to our application for [U.S.] EUA…as well as regulatory submissions in the European Union and United Kingdom,” CEO Cameron Durrant stated .

What Went Wrong

Regulatory setback: FDA declined EUA on Sept 8, 2021; company scaled back or canceled certain manufacturing agreements and noted some CMOs failed to make spec product, adding execution and supply risk .
Cash burn and liquidity: 2021 operating cash burn was $184.0M; year-end cash was $70.0M and working capital was $2.25M, highlighting near-term financing risk without regulatory or partnership milestones .
Scale of 2021 spend: R&D jumped to $213.1M (driven by $143.9M in manufacturing), contributing to full-year net loss of $(236.6)M and underscoring sensitivity to authorization timing .

Financial Results

P&L trend (oldest → newest)

Metric	Q2 2021	Q3 2021	Q4 2021
License Revenue ($USD Millions)	$1.036	$1.036	$1.037
R&D Expense ($USD Millions)	$63.012	$60.811	$29.358
G&A Expense ($USD Millions)	$8.076	$6.204	$4.024
Net Loss ($USD Millions)	$(70.803)	$(66.739)	$(33.540)
Diluted EPS ($USD)	$(1.20)	$(1.12)	$(0.53)

Notes: Margins are not meaningful given de minimis license revenue and development-stage expense structure.

Balance sheet liquidity (oldest → newest)

Metric	Q2 2021	Q3 2021	Q4 2021
Cash & Cash Equivalents (end of period, $USD Millions)	$120.536	$76.500	$70.016
Working Capital ($USD Millions)	$71.326	$9.138	$2.246

Additional cash flow context: Net cash used in operating activities was $48.0M for Q3 2021 and $184.0M for full-year 2021 .

Guidance Changes

No numeric financial guidance was issued. Management provided qualitative 2022 objectives:

Metric/Objective	Period	Previous Guidance	Current Guidance	Change
ACTIV-5/BET-B topline timing	Late Q1/Early Q2 2022	None	“Announcing topline results from ACTIV-5/BET-B in COVID-19”	New
EUA path (U.S.)	2022	None	Prepare/submit amended EUA if ACTIV-5/BET-B supports CRP<150 mg/L subgroup	New
UK/EU regulatory	2022	None	Respond to MHRA info requests; file EU CMA under accelerated approval	New
Managed access (Europe)	2022	None	Commence shipments under LenzMAP in UK/multiple EU countries	New
Pipeline initiations	1H22	None	Initiate SHIELD (CAR-T), RATinG (aGvHD), C-SMART (COVID in cancer); continue PREACH-M (CMML)	New

Earnings Call Themes & Trends

(There was no Q4 earnings call transcript in our corpus; themes reflect company press releases and December 2 corporate update.)

Topic	Previous Mentions (Q2 & Q3)	Current Period (Q4)	Trend
FDA EUA status	Q2: EUA submitted; no timing from FDA . Q3: FDA declined EUA Sept 8; Type B meeting planned .	Plan to amend EUA post-ACTIV-5 if supportive (CRP<150 mg/L) .	Mixed (regulatory path defined but outcome uncertain)
UK/EU pathways	Q2: MHRA rolling review accepted; EU process started . Q3: All MHRA modules submitted; EMA rapporteurs appointed .	Responding to MHRA; plan EU CMA filing; LenzMAP access program .	Progressing
Clinical evidence	Q2: LIVE-AIR Phase 3 basis for filings . Q3: EC named lenzilumab among 10 most promising COVID therapeutics .	LIVE-AIR published in The Lancet; supportive commentary .	Strengthening validation
Manufacturing/supply	Q2: Ramp for potential launch; high manufacturing spend . Q3: Agreements amended/canceled; some CMO batches out of spec .	2021 R&D dominated by $143.9M manufacturing costs .	Spend de-risked; supply capacity contingent on approvals
Liquidity/runway	Q2 cash $120.5M . Q3 $76.5M; WC $9.1M .	Q4 cash $70.0M; WC $2.25M; 2021 op cash burn $184.0M .	Deteriorating liquidity
Non-COVID pipeline	Planning CAR-T safety (SHIELD), aGvHD (RATinG), CMML (PREACH-M) .	Initiations planned 1H22; first CMML patient dosed Oct 2021 .	Advancing

Management Commentary

“We believe that COVID-19 will become a serious endemic disease…if authorized or approved by regulatory agencies, LENZ…could address a significant unmet need in COVID-19 for the foreseeable future.” – Cameron Durrant, CEO .
“We look forward to the announcement of the topline data from…ACTIV-5/BET-B…late Q1 or early Q2…we plan to prepare and submit an amendment to our [U.S.] EUA…as well as regulatory submissions in the European Union and United Kingdom.” – Cameron Durrant .
Corporate stance on treatment access: the company urged regulators to authorize variant-agnostic inpatient treatments to address ongoing hospitalizations and mortality (excerpted from Dec 2 corporate update) .

Q&A Highlights

No Q4 2021 earnings call transcript was available in our document corpus; therefore, Q&A highlights and any guidance clarifications from a call could not be reviewed [ListDocuments: none found for HGEN earnings-call-transcript 2021-12 to 2022-03].

Estimates Context

We attempted to retrieve S&P Global (Capital IQ) consensus for Q2–Q4 2021 EPS and revenue, but the company mapping was unavailable in the SPGI dataset; as a result, Wall Street consensus and vs-consensus comparisons cannot be provided for this quarter (tool error indicated missing CIQ mapping for HGEN). Values retrieved from S&P Global were unavailable due to mapping error.

Key Takeaways for Investors

Expense reset improved sequential loss profile (EPS $(0.53) vs $(1.12) in Q3) as manufacturing spend was curtailed post-EUA decline; however, the model remains highly sensitive to regulatory outcomes given minimal revenue .
Liquidity is tight (cash $70.0M; working capital $2.25M; 2021 op cash burn $184.0M), implying a high likelihood of additional capital needs absent near-term approvals/access revenue .
Binary near-term catalyst: ACTIV-5/BET-B topline (late Q1/early Q2) focused on CRP<150 mg/L could enable an amended U.S. EUA; a positive readout would be a major stock driver; a negative readout would likely necessitate deeper cost actions and/or financing .
EU/UK paths offer alternative/regional catalysts (MHRA rolling review; EU CMA plan; LenzMAP access) that could provide initial commercial footholds and data generation, but timelines and reimbursement remain uncertain .
Manufacturing network remains a watch item—prior CMO setbacks and scaled-back commitments reduce burn but also constrain near-term supply if authorization arrives; management anticipates demand could exceed planned 2022 supply if approvals are granted .
Diversification beyond COVID-19 (CAR-T toxicity mitigation, aGvHD, CMML) provides medium-term optionality; early execution (trial initiations, early data) may help sentiment if COVID-19 timelines slip .

Appendix: Source Documents

Q4 2021 8-K with year-end press release and financials .
Q3 2021 8-K press release and financials .
Q2 2021 8-K press release and financials .
Dec 2, 2021 corporate update (Lancet publication, regulatory trajectory, pipeline) .

HUMANIGEN, INC (HGEN)·Q4 2021 Earnings Summary