Executive Summary

Q4 2021 was dominated by a transformational pipeline shift and the accounting impact of the sapanisertib/mivavotinib acquisition; the quarter recognized $50.9M of R&D expense related to the asset purchase, driving a net loss of $69.2M and diluted EPS of $(0.92) .
Revenue was $0.0 in Q4 (full-year 2021 revenue $9.8M from Incyte/Antengene collaborations), down versus Q3’s $6.8M milestone-driven revenue and Q2’s $3.0M licensing revenue .
Cash, cash equivalents and investments ended at $59.5M; management expects, with a $10.0M offering priced on March 29, 2022, runway through Q2 2023, a change from prior “into 2023” guidance .
Catalysts: initiation of two Phase 2 trials in H1 2022 and first data by Q1 2023 for mivavotinib (ABC DLBCL, MyD88/CD79 subsets) and sapanisertib (NRF2-mutated sqNSCLC) .

What Went Well and What Went Wrong

What Went Well

Precision-oncology pipeline strengthened with acquisition of two mid-stage assets, each with demonstrated single-agent activity; trials are designed around biomarker-defined populations for potentially efficient paths to registrational studies .
Clear operational readiness: program transfers and regulatory reviews completed; site activation proceeding in parallel, supporting guidance for initial Phase 2 data by Q1 2023 .
Preclinical innovation continues: first data from internally discovered synthetic-lethality target VPS4A to be presented at AACR, with lead optimization underway; management flagged broad opportunity across solid tumors with VPS4B deletions .

Key quote: “2021 was a transformational year… our acquisition of two promising clinical-stage investigational therapies… significantly contributed to our pipeline… 2022 will be an exciting year as we initiate two phase 2 clinical trials… We plan to share data… by the first quarter 2023.”

What Went Wrong

KEAPSAKE (telaglenastat) discontinued in November 2021 after interim analysis demonstrated lack of clinical benefit in NSCLC, removing a prior development pillar and contributing to portfolio transition .
Q4 2021 P&L sharply impacted by $50.9M R&D related to asset acquisition (cash $10.0M plus $40.9M value of preferred stock), leading to a larger net loss and EPS miss versus prior quarters’ trend .
Timing slippage: Phase 2 initiation guidance moved from “Q1 2022” (Q3 communication) to “first half of 2022,” modestly delaying program starts .

Financial Results

Quarterly P&L (oldest → newest)

Metric	Q2 2021	Q3 2021	Q4 2021
Revenue ($USD Millions)	$3.0	$6.8	$0.0
Research & Development ($USD Millions)	$12.8	$11.6	$13.7
R&D – Asset Acquisition ($USD Millions)	—	—	$50.9
General & Administrative ($USD Millions)	$4.5	$6.3	$4.6
Total Operating Expenses ($USD Millions)	$17.3	$17.9	$69.2
Net Loss ($USD Millions)	$(14.3)	$(11.2)	$(69.2)
Net Loss per Share (Basic & Diluted, $)	$(0.19)	$(0.15)	$(0.92)
Weighted Avg Shares (Millions)	74.1	74.1	75.0

Year-over-Year Q4 Comparison

Metric	Q4 2020	Q4 2021
Revenue ($USD Millions)	$0.0	$0.0
Research & Development ($USD Millions)	$17.1	$13.7
General & Administrative ($USD Millions)	$5.6	$4.6
R&D – Asset Acquisition ($USD Millions)	—	$50.9
Total Operating Expenses ($USD Millions)	$22.7	$69.2
Net Loss per Share (Basic & Diluted, $)	$(0.32)	$(0.92)

Notes:

Full-year 2021 revenue totaled $9.8M, driven by collaboration payments (Incyte milestone in Q3; Antengene licensing in Q2); no revenue recognized in Q4 .

KPIs and Balance Sheet (end of period; oldest → newest)

KPI	Q2 2021	Q3 2021	Q4 2021
Cash, Cash Equivalents & Investments ($USD Millions)	$92.2	$84.5	$59.5
Working Capital ($USD Millions)	$81.5	$72.8	$47.4
Total Assets ($USD Millions)	$97.9	$90.0	$64.8
Total Stockholders’ Equity ($USD Millions)	$83.0	$74.4	$8.4

Segment breakdown: Not applicable (no commercial segments reported) .

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Cash Runway	Company Runway	“Into 2023” (as of Q3)	“Through Q2 2023” (with $10M offering)	Clarified/end-date specified
Phase 2 Initiations (mivavotinib, sapanisertib)	Start Timing	“Q1 2022”	“H1 2022”	Delayed (broadened window)
Initial Phase 2 Data Readouts	Data Timing	“12–18 months” (implied from start)	“By Q1 2023”	Firmed timeline
Financing	Transaction	N/A	Priced $10.0M equity+warrants; close expected Apr 1, 2022	New capital source

Earnings Call Themes & Trends

Topic	Q2 2021 (8/5)	Q3 2021 (11/9–11/10)	Q4 2021 (3/31–4/1)	Trend
Biomarker-Driven Strategy	Emphasis on KEAP1/NRF2 (telaglenastat) and CF (CB-280); DepMap collaboration	Pivot to mivavotinib/sapanisertib acquisitions; biomarker focus reiterated	Execution plan for biomarker-enriched Phase 2 designs; liquid NGS enrichment	Strategy sharpened; programs operationalized
Program Discontinuations	None	Telaglenastat KEAPSAKE discontinued (lack of benefit)	Strategy reallocates resources to new assets	Wind-down completed; resources redirected
Clinical Execution Readiness	KEAPSAKE enrollment; CB-280 dose escalation	New CMO; site selection for new trials	Transfers/regulatory reviews complete; site activation underway	Increasing confidence and clarity
Dosing Strategy Optimization	Not discussed	Plans for refinement; single-agent activity noted in prior studies	Induction dosing for mivavotinib; BID vs QD exploration for sapanisertib	Fine-tuning dosing to balance efficacy/tolerability
Preclinical/VPS4A	Not discussed	Synthetic lethality platform introduced	VPS4A inhibitors advancing; AACR poster; prevalence context	Platform progressing to lead optimization
Financing/Macro	Strong cash position $92.2M	$84.5M cash; savings from KEAPSAKE stop	$59.5M cash; $10M offering; runway thru Q2 2023	Runway maintained via financing; lower cash post-acquisition

Management Commentary

CEO strategic message: “We… established our focus on biomarker-driven approaches… our acquisition of two promising clinical-stage investigational therapies… complemented our in-house programs… 2022 will be an exciting year as we initiate two phase 2 clinical trials… We plan to share data… by the first quarter 2023.”
CMO on trial design: “We plan to initiate a Phase 2 trial in relapsed/refractory non-GCB (ABC) DLBCL… enrich MyD88 and CD79b mutated tumors using liquid NGS… efficacy data… could position the company to initiate a registrational study… targeting an accelerated approval pathway.”
CFO on runway: “Cash and cash equivalents totaled $59.5 million… together with proceeds from our recently priced $10 million public offering will be sufficient to meet our operating plan through the second quarter of 2023.”

Q&A Highlights

Trial start/operational status: Transfers from Takeda and regulatory reviews completed; site activation and enrollment underway, supporting Q1 2023 data timing .
Execution confidence: Biomarker-driven populations and curated NGS databases at selected sites enable rapid identification/enrollment; leveraging KEAPSAKE infrastructure .
Readout scope: Open-label studies with ORR endpoints and rapid time-to-response (1–2 cycles) in both programs could yield meaningful datasets by Q1 2023 .
Dosing strategies: Mivavotinib induction dosing to achieve rapid disease control then maintenance; sapanisertib exploring lower BID dosing to improve exposure/tolerability over 3 mg QD .
VPS4 program: Homozygous VPS4B deletion 1–3% across solid tumors; heterozygous much more prevalent (e.g., ~two-thirds colorectal/pancreatic), supporting large opportunity; program in lead optimization .

Estimates Context

Wall Street consensus (S&P Global) for Q2–Q4 2021 EPS and revenue was unavailable due to missing CIQ mapping for CALA; we attempted retrieval but could not access estimates. Comparisons to consensus cannot be made at this time (Values would be retrieved from S&P Global if available).
Given Q4’s one-time R&D asset acquisition expense and no revenue recognition, we would expect models to adjust near-term operating expense and cash runway assumptions; management clarified runway through Q2 2023 and slightly broadened trial start timing .

Key Takeaways for Investors

The story is now a biomarker-driven oncology pivot with two mid-stage assets; near-term catalysts are H1 2022 trial starts and initial data by Q1 2023 that could inform registrational paths in defined subpopulations (ABC DLBCL; NRF2-mutated sqNSCLC) .
Q4’s P&L is not indicative of ongoing burn due to the $50.9M asset acquisition accounting; underlying R&D and G&A trends declined y/y, reflecting telaglenastat wind-down .
Financing extends runway to Q2 2023, sufficient to reach both programs’ Phase 2 data; equity+warrants structure implies potential dilution but de-risks operational execution .
Clinical execution confidence is supported by biomarker prevalence and site-level NGS infrastructure; induction dosing and BID strategies aim to optimize efficacy/tolerability early .
VPS4A synthetic lethality program offers optionality beyond oncology clinical assets, with AACR data and a broad prevalence backdrop (homozygous: 1–3%; heterozygous high in CRC/PDAC) .
Watch for any further timing updates (initiation windows, first data) and additional capital needs if timelines extend; the clarified runway and trial design detail reduce execution risk signals .

Appendix: Additional Data (Full Year Highlights)

Full-year 2021 revenue: $9.8M vs none in 2020 (collaboration payments from Incyte and Antengene) .
Full-year R&D: $53.4M vs $71.0M in 2020; Full-year G&A: $20.9M vs $20.4M; Full-year net loss: $115.1M .
Balance sheet (12/31/21): cash $59.5M; total assets $64.8M; stockholders’ equity $8.4M; convertible preferred stock $40.7M (from acquisition accounting) .

Calithera Biosciences, Inc. (CALA)·Q4 2021 Earnings Summary