cstl-20210308

Exhibit 99.1

Castle Biosciences Announces Fourth Quarter and Full-Year 2020 Results

Full-year 2020 revenues of $62.6 million, up 21% compared to 2019

Full-year 2020 dermatology test report volume up 8% compared to 2019

Full-year 2020 gross margin of 85%

Earlier today, the Company launched Integrated DecisionDx-Melanoma Test Result, Utilizing AI to Predict Individualized Risk

Conference call and webcast today at 4:30 p.m. ET

FRIENDSWOOD, Texas- March 8, 2021--Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, today announced its financial results for the fourth quarter and twelve months ended Dec. 31, 2020.

“Our execution in 2020 allowed us to successfully navigate through this unique year and further our position as the leader in genomic testing for dermatologic cancers,” said Derek Maetzold, president and chief executive officer of Castle Biosciences. “We began the year with one skin cancer test and ended the year with a suite of three tests, more than tripling our estimated in-market U.S. total addressable market (TAM) to $2 billion.

“DecisionDx®-Melanoma, DecisionDx® DiffDx™- Melanoma and DecisionDx®-SCC, our tests for cutaneous melanoma, suspicious pigmented lesions and high-risk cutaneous squamous cell carcinoma, respectively, are each designed to provide actionable information for dermatology clinicians, which helps to guide cancer management decisions and improve patient outcomes.

“We are now entering the next chapter of our growth story. Earlier today, we announced clinical availability of an artificial intelligence-based integrated DecisionDx-Melanoma test result – integrating meaningful clinical and pathologic features with tumor biology identified by our DecisionDx-Melanoma test – designed to provide a more precise prediction of risk. Further, we are developing several pipeline tests that are focused on answering clinical questions with high unmet need along the patient care continuum. We estimate these pipeline tests could add an additional $3.6 billion to our U.S. TAM, bringing our aggregate U.S. TAM to slightly more than $5.5 billion.”

Twelve Months Ended December 31, 2020, Financial Highlights

•Revenues were $62.6 million, a 21% increase compared to $51.9 million during the same period in 2019. Included in revenue for the period were positive revenue adjustments related to tests delivered in prior periods. These positive prior period revenue adjustments for the twelve months ended Dec. 31, 2020, were $0.2 million, compared to $2.5 million for the same period in 2019.

•Total gene expression profile test reports delivered in 2020 were 18,185, compared to 17,055 in 2019:

◦DecisionDx-Melanoma test reports delivered in 2020 were 16,232, compared to 15,529 in 2019. Third-party data for 2020 suggests that diagnoses of melanoma were down more than 20% over the prior year.

◦DecisionDx-SCC test reports delivered in 2020 (Aug. 31, 2020 – Dec. 31, 2020) were 485.

◦DecisionDx DiffDx-Melanoma test reports delivered in 2020 (Nov. 2, 2020 - Dec. 31, 2020) were 73.

◦DecisionDx-UM test reports delivered in 2020 were 1,395, compared to 1,526 in 2019.

◦Gross margin for the twelve months ended Dec. 31, 2020, was 85%.

•Operating cash flow was $9.9 million, compared to $7.0 million for the same period in 2019.

•Adjusted operating cash flow, excluding the effects of certain relief payments described below, was $1.5 million, compared to $7.0 million for the same period in 2019.

Cash and Cash Equivalents

As of Dec. 31, 2020, the Company’s cash and cash equivalents totaled $410 million.

Fourth Quarter Ended December 31, 2020, Financial Highlights

•Revenues were $17.3 million in the fourth quarter of 2020, compared to $17.6 million in the fourth quarter of 2019. Included in revenue for the quarters were positive revenue adjustments related to tests delivered in prior periods. These positive prior period revenue adjustments for the three months ended Dec. 31, 2020, were $3.5 million, compared to $4.3 million for the same period in 2019.

•Delivered 5,157 total gene expression profile test reports in the fourth quarter of 2020, compared to 4,914 in the same period in 2019:

◦DecisionDx-Melanoma test reports delivered in the quarter were 4,246, compared to 4,480 in the same period in 2019.

◦DecisionDx-SCC test reports delivered in the quarter were 428.

◦DecisionDx DiffDx-Melanoma test reports delivered from Nov. 2 through Dec. 31, 2020, were 73.

◦DecisionDx®-UM test reports delivered in the quarter were 410, compared to 434 in the same period in 2019.

◦Gross margin in the fourth quarter of 2020 was 85%.

•Operating cash flow was $(0.4) million in the fourth quarter of 2020, compared to $4.5 million in the fourth quarter of 2019.

•Adjusted operating cash flow, excluding the effects of certain relief payments described below, was $1.5 million in the fourth quarter of 2020, compared to $4.5 million in the fourth quarter of 2019.

Recent Clinical Evidence Highlights

•On March 8, 2021, the Company announced clinical availability of an artificial intelligence-based integrated DecisionDx-Melanoma test result. The Company validated the integration of clinicopathologic features with the tumor biology insights provided by the DecisionDx-Melanoma test. The integrated test result (ITR) is designed to provide a more precise risk prediction to further improve the clinical actionability by clinicians and their patients in helping to guide cancer management decisions. For more information, see the Company’s news release from earlier today.

•In January 2021, the Company presented data on DecisionDx-Melanoma and DecisionDx DiffDx-Melanoma at the 18th Annual Winter Clinical Dermatology Conference:

◦The virtual poster for DecisionDx-Melanoma was entitled, “Identifying predictors of sentinel lymph node metastasis in cutaneous melanoma patients using molecular and clinicopathologic high-risk features.” For 3,093 patients with T1-T4 cutaneous melanoma, authors used decision tree analysis to determine which molecular and clinicopathologic features best stratify sentinel lymph node (SLN) positivity risk and demonstrated that DecisionDx-Melanoma was the most important feature in distinguishing between high and low SLN-positivity rates (p<0.001).

◦The virtual poster for DecisionDx DiffDx-Melanoma was entitled, “Performance of a 35-gene expression profile test in suspicious pigmented lesions of the head and neck.” The study evaluated DecisionDx DiffDx-Melanoma’s accuracy in classifying pigmented lesions on the head and neck. The data demonstrated that DecisionDx DiffDx-Melanoma has the ability to be an effective tool for refining melanoma diagnoses on the head and neck and therefore improving downstream management decisions, as indicated by its high sensitivity and specificity in the study.

•Also in January 2021, the Company presented data at the Maui Derm for Dermatologists 2021 conference:

◦The virtual poster for DecisionDx-SCC was entitled, “Clinical utility of the 40-gene expression profile (40-GEP) for improved patient management decisions and disease related outcomes when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cSCC): Case Series.” Two SCC cases were presented that highlight DecisionDx-SCC’s utility in stratifying risk in SCC. The cases had very similar risk of metastasis at diagnosis as both presented with a history of immunosuppression and had identical staging (T2a per Brigham and Women’s Hospital staging; T1 per American Joint Committee on Cancer staging), but had divergent outcomes:

▪Case 1 did not recur, despite incomplete resection. This case had a low-risk (Class 1) DecisionDx-SCC result, consistent with the clinical outcome of no clinical progression.

▪Case 2 developed local recurrence and regional metastasis, and eventually died from SCC, despite clear surgical margins. This case had a highest-risk (Class 2B) DecisionDx-SCC result, consistent with clinical progression. The study authors concluded that incorporating DecisionDx-SCC as a prognostic factor with traditional clinicopathologic risk factors can improve stratification of high-risk SCC patients with at least one risk factor, thereby informing risk-appropriate management strategies.

•In February 2021, the Company presented data on DecisionDx-Melanoma at the 19th Annual South Beach Symposium:

◦The first poster was entitled, “31-Gene expression profiling improves risk stratification in patients with T1 cutaneous melanoma.” Univariate analysis of the study data showed DecisionDx-Melanoma to be a stronger predictor of recurrence-free survival (RFS) than SLN status. Additionally, multivariable analysis showed DecisionDx-Melanoma to be a strong, independent predictor of RFS. With Class 2B RFS status similar to SLN positive status, Class 2B patients warrant follow-up strategies similar to SLN positive patients.

◦The second DecisionDx-Melanoma poster was entitled, “The clinical and financial impact of the 31-gene expression profile testing on sentinel lymph node biopsy patients selection in patients with T1b cutaneous melanoma.” The authors analyzed all clinical DecisionDx-Melanoma tests that were reported from Jan. 3, 2019 through Sept. 4, 2020. The data showed that 75% of eligible patients with T1b tumors had a Class 1A result and could potentially forego sentinel lymph node biopsy (SLNB). The authors estimate that foregoing SLNB in these patients could reduce healthcare expenditures by up to $120 million in SLNB-related costs.

•For a summary of Castle’s 2020 business and clinical evidence highlights, please see the Company’s news release from Jan. 13, 2021. Find the release here: Castle Biosciences Announces Preliminary Fourth Quarter and Full Year 2020 Results.

Conference Call and Webcast Details

Castle Biosciences will hold a conference call on Monday, March 8, 2021, at 4:30 p.m. Eastern time to discuss its fourth quarter and full-year 2020 results and provide a corporate update.

A live webcast of the conference call can be accessed here: https://edge.media-server.com/mmc/p/9pwwmi9c or via the webcast link on the Investor Relations page of the Company’s website (www.castlebiosciences.com). Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until March 29, 2021.

To access the live conference call via phone, please dial 877-282-2581 from the United States and Canada, or +1 470-495-9479 internationally, at least 10 minutes prior to the start of the call, using the conference ID 3834669.

There will be a brief Question & Answer session following management commentary.

Use of Non-GAAP Financial Measures (UNAUDITED)

In this release, we use the metric of Adjusted Operating Cash Flow, which is a non-GAAP financial measure and is not calculated in accordance with generally accepted accounting principles in the United States (GAAP). This non-GAAP financial measure reflects adjustments to net cash provided by operating activities to remove the effects of two payments we received associated with government aid to healthcare providers due to COVID-19, which we believe are not indicative of our ongoing operations.

We use Adjusted Operating Cash Flow internally because we believe this metric provides useful supplemental information in assessing our cash flow performance from our core ongoing business activities by removing the effects of these items on our operating cash flows. We believe this metric is also useful to investors as a supplement to GAAP measures in analyzing the performance of our business. However, this non-GAAP financial measure may be different from non-GAAP financial measures used by other companies, even when the same or similarly titled terms are used to identify such measures, limiting their usefulness for comparative purposes. This non-GAAP financial measure is not meant to be a substitute for net cash provided by (used in)

operating activities reported in accordance with GAAP and should be considered in conjunction with our financial information presented on GAAP basis. Accordingly, investors should not place undue reliance on non-GAAP financial measures. Reconciliations of this non-GAAP financial measure to the most directly comparable GAAP financial measure are presented in the table at the end of this press release.

About Castle Biosciences

Castle Biosciences (Nasdaq: CSTL) is a commercial-stage dermatologic cancer company focused on providing physicians and their patients with personalized, clinically actionable genomic information to make more accurate treatment decisions. The Company currently offers tests for patients with cutaneous melanoma (DecisionDx®-Melanoma, DecisionDx®-CMSeq), cutaneous squamous cell carcinoma (DecisionDx®-SCC), suspicious pigmented lesions (DecisionDx® DiffDx™-Melanoma) and uveal melanoma (DecisionDx®-UM, DecisionDx®-PRAME and DecisionDx®-UMSeq). For more information about Castle’s gene expression profile tests, visit www.CastleTestInfo.com. Castle also has active research and development programs for tests in other dermatologic diseases with high clinical need. Castle Biosciences is based in Friendswood, Texas (Houston), and has laboratory operations in Phoenix, Arizona. For more information, visit www.CastleBiosciences.com.

DecisionDx-Melanoma, DecisionDx-CMSeq, DecisionDx-SCC, DecisionDx DiffDx-Melanoma, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq and are trademarks of Castle Biosciences, Inc.

Forward-Looking Statements

The information in this press release contains forward-looking statements and information within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning the effects of the COVID-19 pandemic on our business and our efforts to address its impact on our business, statements concerning the estimated size of our total addressable market or our existing and pipeline products, the impact of our tests, including DecisionDx-Melanoma, DecisionDx-SCC and DecisionDx DiffDx-Melanoma, on patient treatment plans, our prospects and plans and the objectives of management. The words “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation, the effects of the COVID-19 pandemic on our business and our efforts to address its impact on our business, the timing and amount of revenue we are able to recognize in a given fiscal period, the level and availability of reimbursement for our products, our ability to manage our anticipated growth and the risks set forth in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed with the SEC on November 9, 2020, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law.

The COVID-19 situation continues to evolve and brings along with it a high level of uncertainty surrounding potential future impacts. Therefore, trends in test report volumes, order data and new ordering clinician data is not necessarily indicative of the Company’s results of operations that can be expected for future interim periods or for the year ending December 31, 2021.

Investor and Media Contact:

Camilla Zuckero

+1 832-835-5158

[email protected]

CASTLE BIOSCIENCES, INC.

CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE (LOSS) INCOME

(in thousands, except per share data)


	Three Months Ended December 31,				Twelve Months Ended December 31,
	2020		2019		2020		2019
	(unaudited)		(unaudited)		(unaudited)
NET REVENUES	$	17,299	$	17,635	$	62,649	$	51,865
COST OF SALES	2,673		2,011		9,685		7,310
Gross margin	14,626		15,624		52,964		44,555
OPERATING EXPENSES AND OTHER OPERATING INCOME
Research and development	4,581		3,159		13,256		7,385
Selling, general and administrative	14,959		9,852		48,132		29,842
Other operating income1	(1,882)		—		(1,882)		—
Total operating expenses, net	17,658		13,011		59,506		37,227
Operating (loss) income	(3,032)		2,613		(6,542)		7,328
Interest income	19		280		373		312
Interest expense	(395)		(766)		(2,634)		(4,571)
(Loss) gain on extinguishments of debt	(1,397)		—		(1,397)		5,213
Other expense, net	—		—		—		(2,933)
(Loss) income before income taxes	(4,805)		2,127		(10,200)		5,349
Income tax expense	84		72		84		72
Net (loss) income and comprehensive (loss) income	(4,889)		2,055		(10,284)		5,277
Convertible preferred stock cumulative dividends	—		—		—		2,156
Accretion of redeemable convertible preferred stock to redemption value	—		—		—		130
Net (loss) income and comprehensive (loss) income attributable to common stockholders	$	(4,889)	$	2,055	$	(10,284)	$	2,991

(Loss) earnings per share attributable to common stockholders:
Basic	$	(0.23)	$	0.12	$	(0.54)	$	0.35
Diluted	$	(0.23)	$	0.11	$	(0.54)	$	(0.21)
Weighted-average shares outstanding:
Basic	20,833		17,295		18,929		8,584
Diluted	20,833		18,600		18,929		8,658

1For the three and twelve months ended December 31, 2020, reflects the recognition of other income associated with relief funds we originally received from the U.S. Department of Health and Human Services (HHS) in April 2020.

CASTLE BIOSCIENCES, INC.

CONDENSED BALANCE SHEETS

(in thousands)


	December 31,
	2020		2019
	(unaudited)
ASSETS
Current Assets
Cash and cash equivalents	$	409,852	$	98,845
Accounts receivable, net	12,759		14,648
Inventory	2,217		1,237
Prepaid expenses and other current assets	4,766		1,951
Total current assets	429,594		116,681
Long-term accounts receivable, net	1,096		870
Property and equipment, net	7,102		2,060

Other assets – long-term	1,536		135
Total assets	$	439,328	$	119,746

LIABILITIES AND STOCKHOLDERS’ EQUITY
Current Liabilities
Accounts payable	$	2,098	$	1,865
Accrued compensation	9,108		5,779
Medicare advance payment	6,615		—
Other accrued liabilities	3,055		1,812
Current portion of long-term debt	—		5,833
Total current liabilities	20,876		15,289
Long-term debt	—		19,289
Noncurrent portion of Medicare advance payment	1,735		—
Deferred rent and other liabilities	1,026		55
Total liabilities	23,637		34,633
Stockholders’ Equity
Common stock	25		17
Additional paid-in capital	478,162		137,308
Accumulated deficit	(62,496)		(52,212)
Total stockholders’ equity	415,691		85,113
Total liabilities and stockholders’ equity	$	439,328	$	119,746

CASTLE BIOSCIENCES, INC.

CONDENSED STATEMENTS OF CASH FLOWS

(in thousands)


	Twelve Months Ended December 31,
	2020		2019
OPERATING ACTIVITIES	(unaudited)
Net (loss) income	$	(10,284)	$	5,277
Adjustments to reconcile net (loss) income to net cash provided by operating activities:
Depreciation	472		354
Stock compensation expense	8,309		1,249

Amortization of intangibles	—		4
Amortization of debt discounts and issuance costs	839		1,925
Other non-cash interest	—		442
Loss (gain) on extinguishment of debt	1,397		(5,213)
Change in fair value of preferred stock warrant liability	—		619
Change in fair value of embedded derivative	—		237
Change in fair value of convertible promissory note accounted for under the fair value option	—		2,077
Other	(16)		—
Change in operating assets and liabilities:
Accounts receivable	1,663		(896)
Prepaid expenses and other current assets	(2,815)		(1,276)
Inventory	(980)		(355)
Other assets	(1,401)		(85)
Accounts payable	169		557
Accrued compensation	3,329		1,208
Medicare advance payment	8,350		—
Other accrued liabilities	561		879
Deferred rent and other liabilities	272		12
Net cash provided by operating activities	9,865		7,015
INVESTING ACTIVITIES
Purchases of property and equipment	(4,751)		(937)
Proceeds from sale of property and equipment	3		—
Net cash used in investing activities	(4,748)		(937)
FINANCING ACTIVITIES
Proceeds from public offerings of common stock, net of underwriting discounts, commissions and offering costs	330,041		65,931
Proceeds from exercise of preferred stock warrants	—		49
Proceeds from issuance of convertible promissory notes, net of issuance costs	—		11,695
Proceeds from issuance of convertible promissory note and common stock warrant, net of issuance costs	—		9,236
Proceeds from issuance of term debt, net of issuance costs	—		1,776

Repayments on term debt	(27,359)		—
Repayments on line of credit	—		(1,791)

Proceeds from exercise of common stock options	1,593		1,174
Proceeds from contributions to the employee stock purchase plan	1,615		218
Net cash provided by financing activities	305,890		88,288
NET CHANGE IN CASH AND CASH EQUIVALENTS	311,007		94,366
Beginning of period	98,845		4,479
End of period	$	409,852	$	98,845

CASTLE BIOSCIENCES, INC.

Reconciliation of Non-GAAP Financial Measures (UNAUDITED)

The table below presents the reconciliation of adjusted operating cash flow, which is a non-GAAP measure. See "Use of Non-GAAP Financial Measures (UNAUDITED)" above for further information regarding the Company's use of non-GAAP financial measures.


	Three Months Ended December 31,				Twelve Months Ended December 31,
	2020		2019		2020		2019
(in thousands)
Adjusted operating cash flow
Net cash (used in) provided by operating activities (GAAP)	$	(430)	$	4,493	$	9,865	$	7,015
Medicare advance payment1	—		—		(8,350)		—
HHS provider relief funds2	1,882		—		—		—
Adjusted operating cash flow (Non-GAAP)	$	1,452	$	4,493	$	1,515	$	7,015

__________________

1In April 2020, we received an advance payment of $8.3 million from the Centers for Medicare & Medicaid Service (CMS), which will be applied against future Medicare claims that we submit for reimbursement beginning in April 2021. Originally, recoupment was to begin in August 2020, but recent legislation amended the recoupment schedule such that recoupment will begin in April 2021 and continue for a period of up to 17 months. We recorded the receipt of the payment as a liability on our balance sheet and, in accordance with GAAP, it is included in net cash provided by operating activities in the period received. We have excluded receipt of the advance payment from adjusted operating cash flow, but as future claims are submitted for reimbursement and applied against this balance, we expect to include the advance payment in adjusted operating cash flow to the extent that Medicare claims submitted for reimbursement have been applied to the balance.

2Reflects cash activity in the three months ended December 31, 2020 associated with the HHS provider relief funds.

M a r c h 8 , 2 0 2 1 Tra n s fo r m i n g t h e m a n a ge me nt o f d e r mato l o g i c c a n c e rs

D I S C L A I M E RS F O R W A R D - L O O K I N G S T A T E M E N T S The information in this presentation contains forward-looking statements and information within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning the effects of the COVID-19 pandemic on our business and our efforts to address its impact on our business, our anticipated milestones, including expected commercial availability of our pipeline products and revenue generation therefrom, estimated total addressable market attributable to our existing and pipeline products, the impact of our tests, including DecisionDx-Melanoma, DecisionDx-SCC and DecisionDx DiffDxMelanoma, including the effectiveness of integrating the i31-GEP algorithm into our DecisionDx- Melanoma test, our plans for commercial expansion, including anticipated growth of our sales team, our prospects and plans and the objectives of management. The words “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward- looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward- looking statements, including, without limitation, the effects of the COVID-19 pandemic on our business and our efforts to address its impact on our business, the timing and amount of revenue we are able to recognize in a given fiscal period, unexpected delays in planned launch of our pipeline products, the level and availability of reimbursement for our products, our ability to manage our anticipated growth and the risks set forth in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed with the SEC on November 9, 2020, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law. DecisionDx, DecisionDx-UM, DecisionDx-Melanoma, and the Castle Biosciences logo are the registered trademarks of Castle Biosciences, Inc. This presentation may also contain trademarks and trade names that are the property of their respective owners. 2

TRANSFORMING THE MANAGEMENT OF SKIN CANCER EXPANSIVE BODY OF EVIDENCE SUITE OF SKIN CANCER PROGNOSTIC AND DIAGNOSTIC TESTS STRONG FINANCIAL POSITION ROBUST PIPELINE L E A D I N G D E R M ATO LO G I C D I A G N O S T I C S C O M PA N Y 3 CULTURE OF INNOVATION

F I N A N C I A L S U M M A RY 4 Q A N D Y E A R - E N D 2 0 2 0 4Q20 4Q19 Twelve months ended 12/31/20 Twelve months ended 12/31/19 Revenue $17.3M $17.6M $62.6M $51.9M Total GEP test reports 1 5,157 4,914 18,185 17,055 Total Derm test reports 1 4,747 4,480 16,790 15,529 Operating Cash Flow $(0.4)M $4.5M $9.9M $7.0M Adj. Operating Cash Flow 2 $1.5M $4.5M $1.5M $7.0M Gross Margin 85% 89% 85% 86% Cash & Cash Equivalents $410M (as of 12/31/20) $99M (as of 12/31/19) 1 Castle had two commercially available GEP tests in 2019. 2See Non-GAAP reconciliations at the end of this presentation. 4

Indication/ Test outcome Trade Name Reimbursement Status Peer-Reviewed Publications Primary Customers Initial Launch Targets Initial addressable market, patients2 Estimated U.S. TAM Cutaneous melanoma/ Risk of metastasis MCR, MCRA Commercial – in process 28 Derms (including Mohs), Surgeons __ ~130k patients classified as Stage I, II or III ~$540M Cutaneous squamous cell carcinoma/ Risk of metastasis Expected draft LCD in 2021 4 Derms (including Mohs) ~4,300 current customers3 ~200k w/ high-risk features ~$820M Suspicious pigmented lesions/ Melanoma status Expected draft LCD in 2021 2 Dermpaths, Derms ~1,850 current dermpath customers4 ~300k patients w/indeterminant biopsy ~$600M Pipeline Tests Target launches anticipated by the end of 2025 N/A N/A Expected to utilize existing dermatologic sales channels To be announced To be announced ~$3.6B E S T I M AT E D ~ $ 5 . 5 B U. S . TOTA L A D D R E S S A B L E M A R K E T 1 I n m a r ke t a n d p i p e l i n e t e s t s , l e v e r a g i n g e s t a b l i s h e d d e r m a t o l o g i c s a l e s c h a n n e l s 1U.S. TAM = Total addressable market based on estimated patient population assuming average reimbursement rate among all payors. 2 Annual U.S. incidence for Stage I, II o r III melanoma estimated at 130,000; Annual U.S. incidence for squamous cell carcinoma estimated at 1,000,000 with addressable market limited to carcinomas with one or more high risk features; Annual U.S. incidence for suspicious pigmented lesion biopsies estimated at 2,000,000 with addressable market limited to the 15% with an indeterminant biopsy. 3Clinicians who ordered DecisionDx-Melanoma in LTM (as of 12/31/2020) 4Pathologists who provided clinical specimens for DecisionDx-Melanoma in LTM (as of 12/31/2020) -MCR = Medicare. MCRA = Medicare Advantage; current customer estimates based on LTM. 5

Pipeline Expansion 2022 C A S T L E ’ S L O N G - T E R M R E V E N U E G R O W T H P OT E N T I A L 6 CUTANEOUS MELANOMA 2021 SQUAMOUS CELL CARCINOMA CUTANEOUS MELANOMA ADDITIONAL TESTS FOR DERMATOLOGIC DISEASES 2025 (Expanded LCD effective Dec 2020) (Potential LCDs effective in 2022) (Expected launches ~2025)

T H E C A S T L E A P P R O A C H CAP-accredited, CLIA- certified commercial labs Identify dermatologic diseases with high unmet medical need, where genomic information has the potential to improve management decisions Suite of skin cancer tests designed to provide clinicians with precise, personalized information, enabling more accurate treatment plan decisions Leveraging artificial intelligence, tests are designed to provide actionable information based on tumor gene expression patterns Test results inform management decisions within nationally accepted treatment guidelines 7

Informing clinical decision making for patients with invasive melanoma

If melanoma, clinician orders to answer SLNB and/or management questions: • Is the risk of SLN-positivity high enough to warrant referral for the SLNB surgery? • What is the individual risk of recurrence? D E C I S I O N D X - M E L A N O M A : A F T E R D I A G N O S I S O F C A N C E R 9 Patient presents with mole to PCP or dermatologist Physician may order biopsy Biopsy results received: • Positive for melanoma • Negative • Uncertain malignant potential Physician may order SLNB, if warranted per clinicopathological features and Management plan determined, based on personalized risk

Gerami et al. Clin Cancer Res 2015; Gerami et al. JAAD 2015; Zager et al. BMC Cancer 2018; Gastman et al. JAAD 2019 D E C I S I O N D X - M E L A N O M A : A F T E R D I A G N O S I S F O R M O R E A C C U R AT E R I S K A S S E S S M E N T S qPCR: open array card, 31-gene expression profile CM tumor tissue RNA isolation RT-PCR: cDNA generation and amplification, RT-PCR GEP analysis with a proprietary algorithm to predict class Stage I – III melanoma diagnosis Class 1A Lowest risk of recurrence and/or metastasis within 5 years Class 2B Highest risk of recurrence and/or metastasis within 5 years 10 Class 1B/2A Increased risk of recurrence and/or metastasis within 5 years

I N T E G R AT E D T E S T R E S U LT i 3 1 - G E P u t i l i z e s a r t i f i c i a l i n t e l l i g e n c e d e s i g n e d t o p r o v i d e a m o r e p r e c i s e p r e d i c t i o n o f S L N p o s i t i v i t y r i s k 11 The new Integrated Test Result incorporates traditional clinicopathologic factors with the DecisionDx-Melanoma continuous score designed to provide a precise, personalized likelihood of sentinel lymph node positivity

Cutaneous melanoma diagnosis A F T E R D I A G N O S I S , T W O C L I N I C A L Q U E S T I O N S H E L P G U I D E M E L A N O M A M A N A G E M E N T C H O O S I N G R I S K - A P P R O P R I AT E L E V E L O F M A N A G E M E N T I S K E Y SLN = sentinel lymph node; SLNB = sentinel lymph node biopsy. Source: NCCN Guidelines for Cutaneous Melanoma v3.2020 What is the individual risk of recurrence? Higher RiskLower Risk 12 Tumor thickness, ulceration, SLN status and DecisionDx-Melanoma Tumor thickness, age and DecisionDx-Melanoma Is the risk of SLN-positivity high enough to warrant referral for the SLNB surgery? Potential Sentinel lymph node biopsy surgical procedure

D E C I S I O N D X - M E L A N O M A I N F O R M S B OT H R I S K A S S E S S M E N T S , N O W W I T H i 3 1 - G E P TO P R E D I C T S L N P O S I T I V I T Y R I S K Vetto et al. Future Oncol 2019; Marks et al SKIN J Cutaneous Med 2019 NEW i31-GEP algorithm Risk of existing metastasis to SLN For SLNB eligible patients with: DecisionDx-Melanoma informs management (clinical follow- up, referrals, imaging, adjuvant therapy) Risk of recurrence • T ≥0.3 mm • T1a with adverse features • T1b-T4 DecisionDx-Melanoma informs use of SLNB 13 For patients with: 31-GEP continuous score + Breslow Thickness Ulceration Mitotic rate Age i31-GEP algorithm integrates test score with clinicopathologic factors for precise and personalized risk Class 1A: lowest risk Class 1B/2A: increased risk Class 2B: highest risk

D E C I S I O N D X - M E L A N O M A S T R AT I F I ES R I S K O F P O S I T I V E S L N TO I N F O R M D I S C U S S I O N S Objective: right treatment, right patient, right time Text sources: 1Systematic review of 21 articles representing 9,047 patients (Moody Eur J Sur Onc 2016); 2Morton NEJM 2014; 3False negative rate definition limited to metastasis to the regional lymphatics, not to distant metastasis or death. Median false negative rate = 17.6%; 3Sondak & Zager Ann Surg Oncol 2010 Graph sources: • SLN = sentinel lymph node; SLNB = sentinel lymph node biopsy. MCR=Medicare Cost Report. • Source: AJCC v7 J Clin Oncol 2009; SEER data release 2017; Morton et al. N Engl J Med 2014; Whiteman et al. J Invest Dermatol 2015; Shaikh et al. J Natl Cancer Inst 2016; Poklepovic and Carvajal. Oncology 2018; Sondak and Zager. Ann Surg Oncol 2010. Moody et al. Euro Jrnl Surg Onc 2017. LIMITATIONS OF CURRENT STAGING TO INFORM SLNB SURGERY 12% 11% 18% $20-24k SLNB Positivity Average Complication Rate Median Regional False Negative Rate Average Reimbursed Cost SLNB: risky, poor prognostic tool • 88% SLNB recipients negative • Anesthesia risks, surgical complications: 11% 1 • False negative: 5% - 21%3 • No survival benefit, low sensitivity: • 2/3 of melanoma deaths were SLN-negative 2 14

S O LU T I O N 1 : D E C I S I O N D X - M E L A N O M A I N F O R M S S L N B S U R G E RY D I S C U S S I O N S I N T 1 a – T 4 M E L A N O M A S I31-GEP is designed to take patients from population-based risk to more precise, personalized risk to guide SLNB discussions DecisionDx-Melanoma could result in 74% fewer SLNB surgeries, potentially saving U.S. healthcare system $250M1,3 1Vetto et al. Future Oncol 2019. 2Hsueh et al. Poster discussion abstract, ASCO 2019. 3Clearview health economic model, data on file. T1-T2 tumors are ≤2.0mm thick (“Breslow’s” thickness or depth). MSS = melanoma specific survival. OS = overall survival. DMFS = distant metastasis free survival. RFS = recurrence free survival. n/r = not reported. Outcomes confirmed in prospective, multi-center study2 15

Text sources:1Poklepovic and Carvajal. ONCOLOGY 2018; 2Ribas et al. JAMA 2016; 3Schadendorf et al. Eur J Can 2017; 4Robert et al. J Clin Oncol 2017; 5Joseph et al. Clin Cancer Res 2018; 6SEER data release 2017; 7Whiteman et al. J Invest Dermatol 2015; 8Shaikh et al. J Natl Cancer Inst 2016 Graph sources: AJCC v7 J Clin Oncol 2009; SEER data release 2017; Morton et al. N Engl J Med 2014; Whiteman et al. J Invest Dermatol 2015; Shaikh et al. J Natl Cancer Inst 2016; Poklepovic and Carvajal. Oncology 2018; Sondak and Zager. Ann Surg Oncol 2010. Moody et al. Euro Jrnl Surg Onc 2017. P R O B L E M 2 : U N D E R - M A N A G E M E N T E V I D E N T I N M E L A N O M A C U R R E N T R I S K A S S E S S M E N T S M I S S PAT I E N T S W I T H A G G R E S S I V E T U M O R B I O L O G Y 34% 66% “High-risk” patients “Low-risk” patients DEATHS FROM MELANOMAEarly detection, lower tumor burden associated with better therapy responses, survival outcomes1-5 Appropriate surveillance, including imaging of high-risk patients, is critical1-5 AJCC clinicopathologic factors are helpful clinically, but majority of deaths occur in patients diagnosed with early-stage disease6-8 Prognostic accuracy must improve to determine the most appropriate melanoma management strategy for each patient 16

0 1 2 3 4 5 6 7 8 9 10 Archival, Multi-center1 Disease-Free Survival Stage I-II AJCC high risk DecisionDx-Melanoma Class 2 0 5 10 15 20 25 30 Prospective, Multi-center4 Recurrence-Free Survival Stage I-II 0 1 2 3 4 5 6 7 8 9 10 Archival, Multi-center2 Melanoma Specific Survival Stage I-III 0 1 2 3 4 5 6 7 8 9 10 Prospective, Multi-center3 Recurrence-Free Survival Stage I-III H a za rd R a ti o ( m u lt iv a ri a te )* H a za rd R a ti o ( m u lt iv a ri a te )* ** ** ** ** ** ** ** ** ** ** S O LU T I O N 2 : D E C I S I O N D X - M E L A N O M A I S A S I G N I F I C A N T, I N D E P E N D E N T P R E D I C TO R O F O U TC O M E S *Hazard ratio is continuous for thickness, categorical for other endpoints; **Statistically significant Data shown are from the first and most recent publications for archival and prospective studies 1Gerami et al. Clin Cancer Res 2015. 2Gastman et al. Jrnl Amer Acad Dermatol 2019. 3Hsueh et al. Jrnl Hematol Oncol 2017. 4Podlipnik et al. Jrnl Eur Asso Veneral and Derm 2019. AJCC high risk Age DecisionDx-Melanoma Class 2 Thickness Mitotic rate Ulceration SLN+ DecisionDx-Melanoma Class 2 Thickness Mitotic rate Ulceration SLN+ DecisionDx-Melanoma Class 2 17

Low Risk Stage I-IIA High Risk Stage IIB-III NCCN Risk Category Prado et al. SKIN J Cutan Med 2018:suppl 2. n=690 D E C I S I O N D X - M E L A N O M A F U R T H E R S T R AT I F I ES R I S K O F R E C U R R E N C E B E YO N D A J C C ( 8 T H E d . ) S TA G I N G 18 STAGE M e la n o m a -S p e ci fi c S u rv iv a l (M S S ) (% ) 100% 90% 80% 70% 60% I 99.6% ≈AJCC IA 89.5% ≈AJCC IIIA 98% II >99% ≈AJCC IA 84.7% ≈AJCC IIIB 90% III 94.8% ≈AJCC IIA 61.2% ≈AJCC IIIC+ 77% Castle Class 1A MSS Castle Class 2B MSS AJCC MSS

S O LU T I O N 2 : D E C I S I O N D X - M E L A N O M A C H A N G E D M A N A G E M E N T F O R 5 0 % O F PAT I E N T S 1Berger, et al. 2016 Curr Med Res Opin; 2Dillon et al. 2018 Skin; 3Farberg et al. 2017 Jrnl Drugs Derm; 4Schuitevoerder, et al. 2018 Jrnl Drugs Derm. Changes in patient management include: Imaging and labs Sentinel lymph node biopsy guidance Clinical visit frequency Referrals Study Design # of Patients % Change in Management Berger1 Prospectively tested cohort, multi-center. Retrospective pre-test / post-test management. 156 53% Dillon2 Prospective, multi-center: pre-test / post-test management 247 49% Farberg3 169 physician impact study: patient vignettes with pre-test / post-test management n/a 47-50% Schuitevoerder4 Prospectively tested cohort, single center. Retrospective pre-test / post-test management; modeling of prospective cohort 91 52% 4 consecutive clinical impact studies: 47-53% change in risk-of-recurrence-based management 19

D E C I S I O N D X - M E L A N O M A : W E L L - S T U D I E D, I N F O R M S C A N C E R M A N A G E M E N T D E C I S I O N S * A C C O R D I N G T O S O R T S Y S T E M , U S E D B Y A A D Patients included in studies including independent validation >7,700 Peer-reviewed, published studies including 2 meta-analyses 28 Demonstrated change in management for 1 of 2 patients tested 50% Level 1A evidence* 1A Patients with a DecisionDx-Melanoma order from over 6,800 clinicians 68,000+ Covered by Medicare and multiple private insurers with an industry- leading patient assistance program Medicare+ 20

Identifying the risk of metastasis in patients with cutaneous squamous cell carcinoma with one or more risk factors

PAT I E N T J O U R N E Y: W H E R E D E C I S I O N DX - S C C F I T S 22 Patient referred to a dermatologist who performs a skin exam History and physical • Complete skin exam • Regional lymph node exam Skin biopsy Lesion suspicious for skin cancer discovered by patient or PCP Diagnosis of SCC with≥1 risk factor Order placed for Test results received for Treatment plan defined • Curettage and electrodesiccation • Standard excision • Excision with wide margins • Mohs

P R O B L E M : T H E U N M E T N E E D I N H I G H - R I S K S C C PAT I E N T S : W H O I S R E A L LY AT L O W R I S K O R H I G H R I S K F O R M E TA S TA S I S ? NCCN=National Comprehensive Cancer Network; BWH = Brigham and Women’s Hospital; AJCC = American Joint Committee on Cancer ~20% of SCC patients (200,000 annually) have one or more clinical or pathological risk factors, and a subset will develop metastasis. They suffer the majority of SCC mortality. These factors alone are often not specific enough to determine risk-appropriate treatment and further management. SCC treatment plans are guided by risk of metastasis. Risk-appropriate SCC management is currently limited by classification systems (NCCN, BWH, AJCC) with low positive predictive value (PPV). Deaths from SCC are now estimated to exceed those from melanoma. 23

200,000 high-risk patients annually; $820M U.S TAM1 Validated in 420- patient cohort of high- risk SCC from 33 U.S. centers 4 peer-reviewed publications to date; Over 1,400 patients enrolled in studies to date from 92 centers D E S I G N E D TO P R E D I C T I N D I V I D UA L M E TA S TAT I C R I S K TO I N F O R M R I S K - A P P R O P R I AT E M A N A G E M E N T 1 based on Castle estimates Incorporation of DecisionDx-SCC with traditional risk factors can improve patient classification compared to traditional risk factors alone For high-risk SCC patients with one or more risk factors Utilizing existing sales channels: dermatologists (including Mohs surgeons) 24

W O R K F LOW F O R D E C I S I O N D X - S C C : P R O C E S S I D E N T I C A L TO D E C I S I O N D X - M E L A N O M A qPCR: open array card 34 discriminant gene targets and 6 control genes Class 1 low metastatic risk (~50% of results)a Class 2A moderate metastatic risk (~40% of results) Class 2B high metastatic risk (<10% of results) SCC tumor tissue RNA isolation RT-PCR: cDNA generation and amplification Analysis of GEP with a proprietary algorithm to determine Class and metastatic risk Wysong et al. JAAD 2020; Data on file, Castle Biosciences NCCN Guidelines for Squamous Cell Skin Cancer v1.2020, Likhacheva et al. Pract Radiat Oncol 2020, Farberg et al. CMRO 2020, Litchman et al. CMRO 2020, Teplitz et al. JDD 2019, Alam et al. JAAD 2018 . DecisionDx-SCC results can inform management decisions within established guidelines • Surgery, if feasible • Consider nodal imaging / staging • Consider oncology referral • Surgery, if feasible • Nodal imaging / staging • Consultation: radiation oncology • Consultation: medical oncology Treatment plans may include • Surgery, if feasible • Clinical nodal exam Follow-up plans may include • Clinical follow-up: 1-2x per year • Clinical nodal exam • Clinical follow-up: 2-4x per year for 3 years • Baseline and annual nodal US/CT for 2 years • Clinical follow-up: 4-12x per year for 3 years • Baseline and 4x per year nodal US/CT for 2 years Patient diagnosed with SCC and one or more risk factors 25

M e ta st a si s- fr e e s u rv iv a l (M FS ) Years Kaplan-Meier Estimated MFS n = 420 p < 0.0001 D E C I S I O N D X - S C C I S VA L I D AT E D TO P R E D I C T M E TA S TAT I C R I S K F O R I N D I V I D UA L S C C PAT I E N T S W I T H O N E O R M O R E R I S K FA C TO R S Wysong et al. JAAD 2020; Ibrahim et al. submitted; Data on file, Castle Biosciences. Class 1 – Low Biological Risk Less than half the general study population risk Class 2A – Moderate Biological Risk Similar to the strongest traditional factors Class 2B – High Biological Risk ≥50% risk of metastasis 26

C L A S S 2 A A N D C L A S S 2 B A R E I N D E P E N D E N T P R E D I C TO RS O F M E TA S TA S I S Deep invasion: beyond subcutaneous fat, depth >6mm, or Clark level V. Wysong et al. JAAD 2020; Ibrahim et al. submitted; Data on file, Castle Biosciences. W h a t i s t h e i m p a c t o f D e c i s i o n D x - S C C ? Immunosuppression Tumor diameter (per cm) Perineural invasion Deep invasion Poor differentiation Class 2A Class 2B Univariate Analysis Multivariate Analysis NA 1.1 (ns) 1.2 (ns) 2.1 (p<0.001) 2.3 (p<0.001) 2.3 (p<0.001) 6.9 (p<0.001) 1.5 (ns) 1.2 (p<0.001) 3.3 (p<0.001) 3.1 (p<0.001) 3.9 (p<0.001) 3.2 (p<0.001) 11.6 (p<0.001) Hazard Ratio (HR) Hazard Ratio (HR) 0 5 10 Hazard Ratio 0 5 10 azard Ratio An SCC with deep invasion is 2.1x more likely to metastasize than without. Adding a Class 2A results shifts that to 4.8x more likely to metastasize. Adding a Class 2B result shifts that to 14.5x more likely to metastasize. 27

A highly accurate and objective test for melanocytic lesions of unknown malignant potential

D E R M ATO PAT H O LO G I S T S A N D D E R M ATO LO G I S T S W O R K TO G E T H E R TO D I A G N O S E M E L A N O M A 29 Patient presents with mole to PCP or dermatologist Biopsy results received: • Positive for melanoma • Negative • Indeterminate If biopsy results show uncertain malignant potential physician orders Melanoma Diagnosis confirmed; physician can initiate management plan with Physician may order biopsy

T H E C L I N I C A L I S S U E : U N C E R TA I N T Y C R E AT E S A N O V E R - O R U N D E R - T R E AT M E N T D I L E M M A Definitive melanoma diagnoses (invasive or in situ) Definitive benign diagnoses SLNB Imaging Increased Follow-up No additional treatment Routine follow-up Clinically evaluated suspicious pigmented lesions Wide Local Excision ~2 million melanocytic skin biopsies Uncertain malignant potential Primary treatment Staging, surveillance, and follow-up options Histopathologic evaluation 30

D E C I S I O N D X D I F F DX - M E L A N O M A I S D E S I G N E D F O R U S E F O L LO W I N G I M M U N O H I S TO C H E M I S T R Y ( I H C ) A N D / O R LO C A L C O N S E N S U S Uncertain malignant potential IHC stains/recuts or local consensus conference/colleagues Uncertain malignant potential Benign Malignant Additional ancillary testing 31

RNA isolation cDNA generation and amplification • Open array card 32 discriminant gene targets and 3 control genes Analysis of GEP with a proprietary AI algorithm to determine risk Benign Suggestive of benign neoplasm Intermediate-Risk Cannot exclude malignancy Malignant Suggestive of melanoma FFPE tissue RT qPCR Dermatopathologist OR Dermatology clinician orders W O R K F LOW F O R D E C I S I O N D X D I F F DX - M E L A N O M A : P R O C E S S I D E N T I C A L T O D E C I S I O N D X - M E L A N O M A Diagnostically challenging pigmented (melanocytic) lesion 32

D E C I S I O N D X D I F F DX - M E L A N O M A : D E S I G N E D A N D VA L I DAT E D TO I M P R O V E D I A G N O S T I C R E S O LU T I O N F O R T H E B E N E F I T O F PAT I E N T C A R E All ages N=503 Age > 65 years N=178 DecisionDx DiffDx-Melanoma 95% CI DecisionDx DiffDx-Melanoma 95% CI Sensitivity 99.1% 97.9-100 99.2% 97.6-100 Specificity 94.3% 91.5-97.1 100% 100-100 PPV 93.6% 90.5-96.7 100% 100-100 NPV 99.2% 98.1-100 98.1% 94.3-100 Intermediate-risk result 3.6% 3.4% Technical success rate 96% Samples that fall in intermediate-risk zone were excluded from the calculation. PPV – positive predictive value; NPV – negative predictive value; CI – confidence interval. Estrada et al. (2020) SKIN J Cutan Med 33

I M P R O V I N G D I A G N O S T I C R E S O LU T I O N F O R T H E B E N E F I T O F PAT I E N T C A R E Interpreted in the context of other clinical, laboratory and histopathologic information, DecisionDx DiffDx-Melanoma is designed to add diagnostic clarity and confidence for dermatopathologists, while helping dermatologists better understand the clinical implications for more informed patient care Estrada et al. (2020) J Cut Med SKIN A definitive result from DecisionDx- DiffDx-Melanoma in ≥96% of lesions submitted for testing Includes multiple subtypes of lesions with uncertain malignant potential Technical success rate of 96% 5-7 day turn around time/ similar to other ancillary tests After melanoma diagnosis, clinicians can order DecisionDx- Melanoma; uses same tissue block 34

The Standard of Care for Evaluating Metastatic Risk in Uveal Melanoma

z : S TA N D A R D O F C A R E ~1,600 patients diagnosed in the U.S. annually ~97% of patients – no evidence of metastatic disease at the time of diagnosis ~30% will develop metastases within 3 years Low-risk: ~67% Low Intensity Management High-risk: ~33% High Intensity Management (Uveal Melanoma) Strong Evidence Base • 17 peer-reviewed publications, 2,000+ patients Widespread adoption • 90%+ of U.S. ocular oncology institutions order • 1,395 reports issued in 2020 Broad Coverage • 156+ million total lives covered • Medicare LCD covers patients with a confirmed diagnosis and no evidence of metastatic disease • “Existing ADLT” status effective May 2019 • 2021 Medicare rate of ~$7700 AJCC and NCCN Guideline Inclusion Uveal Melanoma – A Rare Eye Cancer 15-Gene Expression Profile (GEP) Test 36

MARKET AND FINANCIAL OVERVIEW

R E C E N T A C H I E V E M E N T S A N D E X P E C T E D F U T U R E M I L E S TO N ES 2 0 2 1 M I L E S T O N E S O N T R A C K Oct 2020: LCD expansion finalized for DecisionDx-Melanoma, effective date 12/6/20 2021: Potential draft LCD for DecisionDx-SCC and DecisionDx DiffDx-Melanoma 2020 2021 2019 2022 2H2020: Initiation of work on additional dermatology pipeline products 4Q2020: Launch of DecisionDx DiffDx-Melanoma 2022: Potential effective LCD for DecisionDx-SCC and DecisionDx DiffDx- Melanoma 3Q2020: Commercial team expansion Sept 2020: Launch of DecisionDx-SCC July 2019: IPO Dec 2019: Expanded outside sales territories to 32 = Achieved Feb 2019: Expanded outside sales territories to 23 Aug 2019: Expanded draft LCD for DecisionDx- Melanoma posted 39 1H2021: Planned commercial team expansion to ~60 2018 Dec 2018: Initial LCD effective for DecisionDx-Melanoma 2021: Planned announcement of pipeline indications 2021+: Continued evidence development for all commercialized products 2021+: Continued development of dermatologic pipeline products; potential launches in 2025

FA C TO RS D R I V I N G N E A R - A N D LO N G - T E R M G R O W T H REVENUE PROFITABILITY PIPELINE Gross Margins • 85% in 2020 • Continued margin expansion of existing products (increasing ASPs and efficiencies of scale) could be slightly offset by uptake of pipeline products ahead of reimbursement New Product Development • Launched two skin cancer tests in 2020 with estimated $1.4B+ U.S. TAM • Leverage of our existing skin cancer sales channels to support new products • Initiated new pipeline products in dermatologic diseases with high unmet need; potential to launch 3-5 new tests by the end of 2025 Test Report Volume • Commercial sales team expansion in 1H21 to ~60 Reimbursement • Strong ASP growth • DecisionDx-Melanoma $7,193 PAMA rate through 2021 • DecisionDx-UM $7,776 PAMA rate through 2021 40

C O N T I N U E D R E V E N U E G R O W T H , D R I V E N BY T E S T R E P O R T A N D A S P G R O W T H * 2018 2019 2020 Revenue *2020 ASP growth over 2019 and 2018 $62.6m $51.9m $22.8m 41

Asian Black or African American Hispanic or Latino Two or more races (not Hispanic or Latino) White Othe (n t Hispanic r Latino) Female Male Female Male C O M M I T M E N T TO D I V E RS I T Y 42 37.3% 62.7% 68.2% 31.8% 79.1% 5% 9.5 4.9% 1.5% A ll E m p lo y e e s E xe cu ti v e s E T H N I C I T Y/ R A C E G E N D E R Data as of 12/31/20, Executive= Executive Director or Regional Business Director level and above American Indian or Alaska Native Two or more races (not Hispanic or Latino) White Hispanic or Latino 86.36% 4.55% 4.55% 4.55%

THANK YOU

U S E O F N O N - G A A P F I N A N C I A L M E A S U R ES ( U N AU D I T E D ) 45 • In this presentation, we use the metric of Adjusted Operating Cash Flow, which is a non-GAAP financial measure and is not calculated in accordance with generally accepted accounting principles in the United States (GAAP). This non-GAAP financial measure reflects adjustments to net cash provided by operating activities to remove the effects of two payments we received associated with government aid to healthcare providers due to COVID-19, which we believe are not indicative of our ongoing operations. • We use Adjusted Operating Cash Flow internally because we believe this metric provides useful supplemental information in assessing our cash flow performance from our core ongoing business activities by removing the effects of these items on our operating cash flows. We believe this metric is also useful to investors as a supplement to GAAP measures in analyzing the performance of our business. However, this non-GAAP financial measure may be different from non-GAAP financial measures used by other companies, even when the same or similarly titled terms are used to identify such measures, limiting their usefulness for comparative purposes. This non-GAAP financial measure is not meant to be a substitute for net cash provided by operating activities reported in accordance with GAAP and should be considered in conjunction with our financial information presented on GAAP basis. Accordingly, investors should not place undue reliance on non-GAAP financial measures. Reconciliations of this non-GAAP financial measure to the most directly comparable GAAP financial measure are presented on the next slide.

R E C O N C I L I AT I O N O F N O N - G A A P F I N A N C I A L M E A S U R ES ( U N A U D I T E D ) The table below presents the reconciliation of adjusted operating cash flow, which is a non-GAAP measure. See “Use of Non-GAAP Financial Measures (UNAUDITED)” above for further information regarding the Company’s use of non-GAAP financial measures. 46 1. In April 2020, we received an advance payment of $8.3 million from the Centers for Medicare & Medicaid Service (CMS), which will be applied against future Medicare claims that we submit for reimbursement beginning in April 2021. Originally, recoupment was to begin in August 2020, but recent legislation amended the recoupment schedule such that recoupment will begin in April 2021 and continue for a period of up to 17 months. We recorded the receipt of the payment as a liability on our balance sheet and, in accordance with GAAP, it is included in net cash provided by operating activities in the period received. We have excluded receipt of the advance payment from adjusted operating cash flow, but as future claims are submitted for reimbursement and applied against this balance, we expect to include the advance payment in adjusted operating cash flow to the extent that Medicare claims submitted for reimbursement have been applied to the balance. 2. Reflects cash activity in the three months ended December 31, 2020 associated with the HHS provider relief funds.

APPENDIX

Stuart Pharmaceuticals Robert Cook, PhD Senior Vice President, Research & Development L E A D E RS H I P T E A M O V E RV I E W B O A R D O F D I R E C T O R SM A N A G E M E N T T E A M Derek Maetzold Founder, Director, President and CEO Frank Stokes Chief Financial Officer Bernhard Spiess Chief Business Officer Toby Juvenal Chief Commercial Officer Kristen Oelschlager, RN, CHC Chief Operations Officer Dan Bradbury Derek Maetzold Mara Aspinall Brad Cole Joe Cook, III Miles D. Harrison David Kabakoff 48


Exhibit
Number						Description
99.1						Press release issued March 8, 2021 .
99.2						Slide presentation.
104						Inline XBRL for the cover page of this Current Report on Form 8-K.


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has caused this report to be signed on its behalf by the undersigned hereunto duly authorized.


	CASTLE BIOSCIENCES, INC.


	By:	/s/ Frank Stokes
		Frank Stokes
		Chief Financial Officer
Date: March 8, 2021