Cyteir Therapeutics Reports Second Quarter 2021 Financial Results and Provides Business Highlights

On August 9, 2021 Cyteir Therapeutics, Inc. ("Cyteir") (Nasdaq: CYT), a company focused on the discovery and development of next-generation synthetically lethal therapies for cancer, reported financial results for the second quarter ended June 30, 2021 and provided an update on recent business highlights (Press release, Cyteir Therapeutics, AUG 9, 2021, View Source [SID1234586131]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The successful completion of our IPO in June gives us the capital to advance our drug candidates through mid-stage clinical development and places us in a strong position to advance our lead drug CYT-0851 and develop our DNA damage response (DDR) platform. We continue to enroll patients through the dose escalation portion of the Phase 1/2 trial for CYT-0851 and we plan to begin the Phase 2 expansion trial by year-end," said Markus Renschler, MD, President and Chief Executive Officer of Cyteir. "As we continue advancing our lead program and our DDR platform, we look forward to nominating new candidates in 2022 and beyond. I’d like to thank the entire Cyteir team for their dedication and excellent execution as we develop the next generation of synthetic lethal therapies to treat cancer."

Second Quarter Business Review and Operational Updates

CYT-0851

At the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Ryan Lynch, MD of the Fred Hutchinson Cancer Center, presented an interim analysis of the Phase 1 portion of a first-in-human Phase 1/2 trial of CYT-0851. The presentation was given at an oral session at the conference.
The Phase 1 dose escalation trial portion of the Phase 1/2 trial continues to enroll patients. The 600 mg once daily cohort was recently cleared for safety and the 800 mg once daily cohort is now open for enrollment. Initiation of the Phase 2 expansion trial and Phase 1 combinations with chemotherapy are both expected by year-end.
Pipeline

Investigational New Drug (IND)-enabling studies with CYT-1853 are ongoing and an IND application is expected to be submitted in 2022. Cyteir is also advancing preclinical studies on additional targets to nominate the next target from the DDR platform.
Second Quarter Financial Results

Cash and cash equivalents: Cash and cash equivalents for the quarter ended June 30, 2021, were $198.6 million. The cash and cash equivalents total for the second quarter does not include the $15.9 million in gross proceeds raised from the exercise by the underwriters of the option to purchase additional shares of common stock.

Research and development (R&D) expenses: R&D expenses were $8.9 million for the second quarter of 2021 versus $3.6 million for the same period in 2020. The year-over-year increase in R&D spending in the comparative periods was due primarily to increased R&D and clinical activity and increased headcount.

General and administrative (G&A) expenses: G&A expenses were $2.4 million for the second quarter of 2021 compared to $0.9 million for the same period in 2020. The year-over-year increase in G&A expenses was primarily due to increased headcount.

Net loss: Net loss was $11.3 million, or $4.83 per share in the second quarter of 2021 compared to $4.5 million, or $3.18 per share in the second quarter of 2020.

Celcuity Inc. Reports Second Quarter 2021 Financial Results and Provides Corporate Update

On August 9, 2021 Celcuity Inc. (NASDAQ:CELC), a clinical-stage biotechnology company pursuing an integrated companion diagnostic and therapeutic strategy for treating patients with cancer, reported financial results for the second quarter ended June 30, 2021 and summarized recent business progress (Press release, Celcuity, AUG 9, 2021, View Source [SID1234586130]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Celcuity’s recent follow-on equity offering strengthens our balance sheet and provides additional funding to support clinical development activities for the advancement of gedatolisib, a potential first-in-class PI3K/mTOR inhibitor," said Brian Sullivan, CEO and co-founder of Celcuity. "We are also very excited about the progress we made expanding our clinical development and clinical operations teams. This positions us well to initiate, subject to feedback from the FDA, a Phase 2/3 clinical trial evaluating gedatolisib in combination with palbociclib and an endocrine therapy in patients with ER+/HER2- advanced or metastatic breast cancer in the first half of 2022."

Second Quarter 2021 Business Highlights and Other Recent Developments

In early April, Celcuity entered into a worldwide licensing agreement with Pfizer for the exclusive right to develop and commercialize gedatolisib.
Celcuity closed two significant financings to support development of gedatolisib. In early April, Celcuity entered into a debt financing agreement with Innovatus Life Sciences Lending Fund I, LP to provide up to $25.0 million in term loans with the first tranche of $15.0 million funded at closing. In early July, Celcuity completed a follow-on public offering that raised gross proceeds of approximately $56.3 million.
In April, Celcuity presented results of studies evaluating gedatolisib, inavolisib (a PI3K-α inhibitor), and navitoclax (a BCL inhibitor) in breast and ovarian patient tumors in two posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The results showed that gedatolisib inhibited nine times more signaling test activity in tumors with hyperactive RAS network signaling, on average, than inavolisib, when evaluated at equal concentrations with the CELsignia test.
In June, Celcuity announced the addition of Igor Gorbatchevsky, MD, as VP of Clinical Development and Jill Krause as VP of Clinical Operations to Celcuity’s leadership team. Dr. Gorbatchevsky has over two decades of hands-on oncology drug development experience, including successful regulatory IND and NDA/BLA filings across several drug classes. Ms. Krause has deep clinical operations expertise, including over nine years of experience managing and executing trials in breast cancer. Since joining Celcuity, Dr. Gorbatchevsky and Ms. Krause have each added key members to their respective teams.
In July, results from a 17-patient Phase 1 study that evaluated the safety and preliminary activity of gedatolisib combined with carboplatin and paclitaxel were published in the journal, Clinical Cancer Research1 . The study was designed to explore the hypothesis that inhibition of the PI3K/mTOR pathway can promote sensitivity to platinum-based treatment. The objective response rate (ORR) was 65% (11/17) patients: eight partial responses (PR) and three complete responses (CR) were reported. The stable disease rate was 17% (3/17). Promising results were observed in patients with advanced clear cell ovarian carcinoma (CCOC), a tumor type with poor prognosis generally considered to be chemo resistant. The ORR in patients with CCOC was 80% (8/10), of which 3/10 (30%) reported a CR. Among nine previously platinum-treated patients, 45% (4/9) had a PR (two patients with CCOC, one low grade serous ovarian cancer and one NSCLC). The drug combination was found to be tolerable with a manageable safety profile.
Second Quarter 2021 Financial Results

Unless otherwise stated, all comparisons are for the second quarter ended June 30, 2021, compared to the second quarter ended June 30, 2020.

The following discussion should be read in conjunction with our unaudited condensed consolidated financial statements and related notes on Form 10-Q for the second quarter ended June 30, 2021.

Total operating expenses were $13.6 million for the second quarter of 2021, compared to $2.2 million for the second quarter of 2020.

Research and development (R&D) expenses were $13.1 million for the second quarter of 2021, compared to $1.8 million for the second quarter of 2020. The increase during the second quarter of 2021 compared to the prior year, primarily resulted from a $10.0 million upfront license fee related to the execution of the Pfizer license agreement, which included $5.0 million of non-cash expense for the issuance of common stock. The remaining increase in expenses related to compensation, clinical validation and laboratory studies and legal expenses.

General and administrative (G&A) expenses were $0.6 million for the second quarter of 2021, compared to $0.4 million for the second quarter of 2020. The increase in the second quarter of 2021 arose primarily from higher professional fees associated with being a public company, director and officer insurance and non-cash stock-based compensation.

Net loss for the second quarter of 2021 was $14.0 million, or $1.11 loss per share, compared to a net loss of $2.2 million, or $0.21 loss per share, for the second quarter of 2020. Non-GAAP adjusted net loss for the second quarter of 2021 was $8.3 million, or $0.66 loss per share, compared to non-GAAP adjusted net loss of $1.8 million, or $0.17 loss per share, for the second quarter of 2020. Non-GAAP adjusted net loss excludes stock-based compensation expense, issuance of common stock and non-cash interest. Because these items have no impact on Celcuity’s cash position, management believes non-GAAP adjusted net loss better enables Celcuity to focus on cash used in operations. For a reconciliation of financial measures calculated in accordance with generally accepted accounting principles in the United States (GAAP) to non-GAAP financial measures, please see the financial tables at the end of this press release.

Net cash used in operating activities for the second quarter of 2021 was $7.6 million, compared to $1.6 million for the second quarter of 2020.

At June 30, 2021, Celcuity had cash and cash equivalents of $41.6 million, compared to cash and cash equivalents of $11.6 million at December 31, 2020. On April 8, 2021, Celcuity paid an upfront license fee of $5.0 million in conjunction with the Pfizer gedatolisib license agreement and received $14.4 million of net proceeds from a debt financing agreement. On July 1, 2021, Celcuity completed a follow-on equity offering of common stock that resulted in gross proceeds of approximately $56.3 million. After the follow-on offering, Celcuity had approximately $94.4 million of cash on hand.

Anticipated Milestones

Celcuity expects to achieve the following potential milestones over the next twelve months:

Announce an additional clinical trial collaboration utilizing the CELsignia platform in the second half of 2021.
Initiate a Phase 2/3 clinical trial for gedatolisib in patients with ER+/HER2- metastatic breast cancer in the first half of 2022, subject to feedback from the FDA.
Provide an update on the lifecycle development plan for gedatolisib in the first half of 2022.
Provide interim results from the FACT-1 and FACT-2 trials in late 2021 or early 2022.
Webcast and Conference Call Information

The Celcuity management team will host a webcast/conference call at 4:30 p.m. ET today to discuss the second quarter financial results and provide a corporate update. To participate in the teleconference, domestic callers should dial 1-844-369-8770 and international callers should dial 862-298-0840. A live webcast presentation can also be accessed using this weblink: View Source . A replay of the webcast will be available on the Celcuity website following the live event.

Pliant Therapeutics Provides Corporate Update and Reports Second Quarter 2021 Financial Results

On August 9, 2021 Pliant Therapeutics, Inc. (Nasdaq: PLRX) ("the Company"), a clinical stage biotechnology company focused on discovering and developing novel therapeutics for the treatment of fibrosis, reported second quarter 2021 financial results
(Press release, Pliant Therapeutics, AUG 9, 2021, View Source [SID1234586129]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Driven by our progress throughout the second quarter, enrollment continues to be on track for our Phase 2a trials of PLN-74809 in IPF and PSC with strong advancement in our development stage oncology and DMD programs," said Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant Therapeutics. "PLN-74809 continues to demonstrate a favorable safety profile as additional dose cohorts from the single and multiple ascending dose Phase 1a trial show PLN-74809 to be generally well tolerated at all dose levels tested, with a predictable pharmacokinetic profile similar to previous dose cohorts."

Second Quarter and Recent Highlights

Single ascending dose (SAD) cohorts up to 640 mg and multiple ascending dose (MAD) cohorts up to 320 mg completed in extended Phase 1a dose escalation trial of PLN-74809 in healthy volunteers. PLN-74809 has completed dosing of additional SAD cohorts of up to 640 mg and MAD cohorts of up to 320 mg once daily dose in an extended dose escalation trial. The pharmacokinetic profile remains generally dose proportional with PLN-74809 continuing to be generally well tolerated, with no severe adverse events or serious adverse events reported.

Enrollment on track for PLN-74809 Phase 2a trial in idiopathic pulmonary fibrosis (IPF). INTEGRIS-IPF is a 12-week randomized, dose-ranging, double-blind, placebo-controlled trial evaluating the safety, tolerability, and pharmacokinetics of PLN-74809 in IPF patients. This trial is evaluating exploratory endpoints including quantitative lung fibrosis score, or QLF, imaging as well as pulmonary function tests. Enrollment is currently on track to be completed by the end of 2021.

Enrollment on track for PLN-74809 Phase 2a trial in primary sclerosing cholangitis (PSC). INTEGRIS-PSC is a 12-week randomized, dose-ranging, double-blind, placebo-controlled trial evaluating the safety, tolerability, and pharmacokinetics of PLN-74809 in PSC patients. The trial is evaluating exploratory endpoints including fibrosis biomarkers such as Pro-C3 and ELF, changes in ALP, and liver imaging. Enrollment is currently on track to be completed in the first half of 2022.

Image analysis from PLN-74809 Phase 2a positron emission tomography (PET) trial underway, including addition of a 320 mg cohort, with preliminary data anticipated upon completion of the analysis. This open-label, dose ranging trial is evaluating target receptor occupancy levels of PLN-74809 in the lungs of IPF patients across ascending single-dose cohorts, utilizing a PET tracer of the integrin αvβ6. The Company recently amended the protocol to increase the maximum dose to 320 mg. In the second quarter, the first patients were dosed in this cohort.

Preclinical stage integrin-based programs continue to progress. The Company’s early-stage programs targeting oncology and muscular dystrophies continue to advance toward the clinic. The oncology program is focused on increasing tumor checkpoint sensitivity through small molecule inhibition of αvβ8. The muscular dystrophy program is focused on improving muscle function through activation of an integrin compensatory mechanism with a monoclonal antibody.

Resources redeployed in support of ongoing PLN-74809 Phase 2a trials in IPF and PSC. Despite the rise of recently identified COVID-19 variants, the broad availability of vaccines, as well as the increased and successful measures taken over the past nine months to contain the virus have resulted in a dramatic decrease in the number of severe and critical COVID-19 patients with acute respiratory distress syndrome (ARDS). Given the declining number of addressable patients, the Company has discontinued enrollment in the PLN-74809 Phase 2a COVID-19-related ARDS trial allowing for resources to be directed toward our lead indications.
COVID-19 Preparedness
The Company continues to develop and maintain policies and procedures to enable us to operate safely and productively during the COVID-19 pandemic. The Company has experienced delays in clinical trial operations which have impacted and may further impact the expected timing of data readouts. The Company continues to work closely with clinical sites to continue site initiation and operation activities in compliance with study protocols while observing government and institutional guidelines.

Second Quarter 2021 Financial Results

Research and development expenses were $19.2 million, as compared to $17.5 million for the prior-year quarter. The increase was due primarily to employee related expenses and higher costs related to the advancement of several programs and ongoing Phase 1/2 clinical trials.
General and administrative expenses were $5.5 million, as compared to $3.0 million for the prior-year quarter. The increase was due to higher personnel-related and professional services expenses.
Net loss of $22.8 million as compared to $17.0 million for the prior-year quarter due an overall increase in expense associated with our research and development programs as well as personnel-related costs.
As of June 30, 2021, the Company had cash, cash equivalents and short-term investments of $244.0 million. The Company believes it has sufficient funds to meet its operating and capital requirements into 2023.

Idera Pharmaceuticals Reports Second Quarter 2021 Financial Results and Provides Corporate Update

On August 9, 2021 Idera Pharmaceuticals, Inc. ("Idera" or the "Company") (Nasdaq: IDRA) reported its financial and operational results for the second quarter ended June 30, 2021 (Press release, Idera Pharmaceuticals, AUG 9, 2021, View Source [SID1234586128]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our goal is to add new development or commercial-stage assets to Idera’s portfolio, and our team is very encouraged by the high quality and quantity of opportunities we have been presented with," stated Vincent Milano, Idera’s Chief Executive Officer. "Several of these prospects continue to advance, and we remain optimistic in Idera’s future potential."

Added Mr. Milano, "We also maintain our interest in the potential of tilsotolimod. Enrollment is complete and we continue to treat patients in the second stage of ILLUMINATE-206, our Phase 2 study in combination with BMS’s nivolumab and ipilimumab for patients with microsatellite-stable colorectal cancer. We also continue to support AbbVie in the form of study drug in their trial for patients with head and neck squamous cell carcinoma."

Second Quarter Financial Results
Research and development expenses for the three months ended June 30, 2021 totaled $3.9 million, compared to $5.4 million for the same period in 2020. General and administrative expense for the three months ended June 30, 2021 totaled $2.5 million compared to $2.6 million for the same period in 2020. Restructuring costs for the three months ended June 30, 2021 totaled approximately $1.2 million and relate to a reduction in force initiated in April 2021 to better align our workforce to our ongoing operational and business development activities. No such costs were incurred during the three months ended June 30, 2020. Additionally, during the three months ended June 30, 2020, we recorded $0.9 million and $15.3 million non-cash warrant revaluation loss and non-cash future tranche right revaluation loss, respectively, related to securities issued in connection with our December 2019 private placement transaction. No such non-cash losses were recognized in the three months ended June 30, 2021.

As a result of the factors above, net loss applicable to common stockholders for the three months ended June 30, 2021 was $7.6 million or $0.15 per basic and diluted share compared to a net loss applicable to common stockholders of $24.2 million or $0.72 per basic and diluted share for the same period in 2020.
Excluding the non-cash loss of approximately $16.3 million for the three months ended June 30, 2020 related to the securities issued in connection with the December 2019 private placement transaction, net loss applicable to common stockholders was $8.0 million.

Castle Biosciences Announces Second Quarter 2021 Results

On August 9, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a dermatologic diagnostics company providing personalized genomic information to improve treatment decisions, reported its financial results for the second quarter and six months ended June 30, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The Castle team delivered an exceptional quarter, which included record test report volume across each of our gene expression profile tests for a single quarter," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "We saw continued recovery trends throughout the second quarter, despite cutaneous melanoma diagnoses remaining below historical 2019 levels by approximately 12%. Our year-over-year growth in DecisionDx-Melanoma test reports of 70% reflects both gains in diagnoses compared to 2020, as well as significant gains in market penetration. Due to our strong performance and expected continued momentum, we are raising our 2021 revenue guidance for the full year to $89-93 million.

"We continue to aggressively invest in our growth initiatives, including the expansion of our commercial team and accelerated R&D investments for our marketed and pipeline tests. Beginning on July 1, 2021, our dermatology-facing commercial team approximately doubled in size to the mid-60s, and each of our sales representatives will support all four of our skin cancer genomic tests. We believe our investments will continue to support our long-term value creation plans and the improvement of patient care.

"Finally, the acquisition of the myPath Melanoma laboratory, and the resulting addition of the myPath Melanoma test to our skin cancer test services, was finalized in late May of 2021. We believe this acquisition furthers our position as the leader in dermatologic diagnostics and enables us to provide the most comprehensive offering for patients with skin cancer and difficult-to-diagnose melanocytic lesions."

Second Quarter Ended June 30, 2021, Selected Results

Revenues were $22.8 million, an 79% increase compared to $12.7 million during the same period in 2020. Included in revenue for the period were revenue adjustments related to tests delivered in prior periods. These (negative) positive prior period revenue adjustments for the quarter ended June 30, 2021, were $(0.2) million, compared to $2.3 million for the same period in 2020.
Adjusted revenues were $22.9 million, a 120% increase, excluding the effects of revenue adjustments related to tests delivered in prior periods, compared to $10.4 million for the same period in 2020.
Total gene expression profile test reports delivered in the second quarter of 2021 were 7,007, compared to 3,314 in the same period of 2020:
DecisionDx-Melanoma test reports delivered in the second quarter of 2021 were 5,128, compared to 3,008, in the second quarter of 2020, an increase of 70%.
DecisionDx-SCC test reports delivered in the second quarter of 2021 were 784.
MyPath Melanoma and DecisionDxDiffDx-Melanoma (Castle’s comprehensive diagnostic offering) aggregate test reports delivered in the second quarter of 2021 were 627.
DecisionDx-UM test reports delivered in the second quarter of 2021 were 468, compared to 306 in the second quarter of 2020, an increase of 53%.
Gross margin for the quarter ended June 30, 2021, was 82.6%.
Adjusted gross margin for the quarter ended June 30, 2021, was 83.9%.
Operating cash flow was $(6.4) million, compared to $13.5 million for the same period in 2020.
Adjusted operating cash flow was $(4.3) million, excluding the effects of certain COVID-19-related government payments, compared to $3.3 million for the same period in 2020.
Six Months Ended June 30, 2021, Selected Results

Revenues were $45.6 million, a 51% increase compared to $30.1 million during the same period in 2020. 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 six months ended June 30, 2021, were $5.1 million, compared to $1.0 million for the same period in 2020.
Adjusted revenues were $40.5 million, a 39% increase, excluding the effects of revenue adjustments related to tests delivered in prior periods, compared to $29.1 million for the same period in 2020.
Total gene expression profile test reports delivered in the six months ended June 30, 2021, were 12,149, compared to 8,249 in the same period of 2020:
DecisionDx-Melanoma test reports delivered in the six months ended June 30, 2021, were 9,188, compared to 7,582, during the same period in 2020, an increase of 21%.
DecisionDx-SCC test reports delivered in the six months ended June 30, 2021, were 1,311.
MyPath Melanoma and DecisionDx DiffDx-Melanoma (Castle’s comprehensive diagnostic offering) aggregate test reports delivered in the six months ended June 30, 2021, were 845.
DecisionDx-UM test reports delivered in the six months ended June 30, 2021, were 805, compared to 667, during the same period in 2020, an increase of 21%.
Gross margin for the six months ended June 30, 2021, was 84.7%.
Adjusted gross margin for the six months ended June 30, 2021, was 83.4%.
Operating cash flow was $(10.1) million, compared to $13.3 million for the same period in 2020.
Adjusted operating cash flow was $(9.8) million, compared to $3.0 million for the same period in 2020.
Cash and Cash Equivalents

As of June 30, 2021, the Company’s cash and cash equivalents totaled $368 million, compared to $410 million at December 31, 2020. The decrease is primarily attributable to the acquisition of the Myriad myPath Laboratory for $33 million and cash used in operations of $10 million, including the effect of $2 million in recoupment of the Medicare advance payment the Company received last year.

2021 Revenue Guidance

Castle Biosciences is increasing its previously issued guidance for anticipated total revenue in 2021. The Company now anticipates generating $89-93 million in total revenue in 2021, compared to the previously provided guidance of $80-83 million.

Second Quarter and Recent Business and Clinical Evidence Highlights

In April, the Company announced it signed a definitive agreement to acquire the equity of Myriad myPath, LLC (Myriad myPath Laboratory), from Myriad Genetics. myPath Melanoma is a clinically validated gene expression profile (GEP) test designed to be used as an adjunct to histopathology when the distinction between a benign nevus and a malignant melanoma cannot be made confidently by histopathology alone (difficult-to-diagnose melanocytic lesions). With the acquisition, which closed in late May 2021, Castle provides the most comprehensive diagnostic offering for difficult-to-diagnose melanocytic lesions. See the Company’s news release from April 27, 2021, for more information.
In April, at the 10th World Congress of Melanoma, the Company presented data on three of its skin cancer tests, including from an independent validation study which demonstrated the i31-GEP artificial intelligence algorithm improved precision of sentinel lymph node positivity prediction in cutaneous melanoma. The poster, titled "Integration of the 31-gene expression profile test with clinicopathologic features (i31-GEP) to assess sentinel lymph node positivity risk in patients with cutaneous melanoma," highlighted the i31-GEP validation study data and demonstrated that the algorithm provided a more precise, personalized likelihood of sentinel lymph node positivity. The poster can be accessed here.

Study methods and findings:

The study reviewed the development and validation of the i31-GEP, which deploys an artificial intelligence neural network algorithm to integrate the continuous DecisionDx-Melanoma score with histologic and clinical features on a development cohort of 1,398 patients. The i31-GEP algorithm was locked using these 1,398 patients and was then independently validated on an independent, U.S. based cohort of 1,674 patients.
The development phase identified that the DecisionDx-Melanoma score was the most important variable in predicting SLN positivity under both the variable importance assessment function (DecisionDx-Melanoma score = 100, Breslow thickness = 56, Mitotic rate = 25, ulceration = 83 and Age = 0; with 100 being the highest possible value) and log-likelihood value (DecisionDx-Melanoma score = 91.3, Breslow thickness = 53.5, Mitotic rate = 20.7, ulceration = 19.1 and Age = 10.5; with 100 being the highest possible value).
The independent validation phase showed that the i31-GEP provides a highly concordant prediction of SLN positivity rate compared to observed rates (linear regression slope of 0.999, with 1.0 representing complete concordance).
Of patients originally classified with 5-10% SLN positivity risk, i31-GEP reclassified 63% of those patients, whose actual risk of SLN positivity was outside that range in either direction (less than 5% or greater than 10%).
i31-GEP had a high negative predictive value of 98% in patients with T1-T4 tumors.
Information about the additional data presentations can be found here on the Company’s news release from April 16, 2021.

Data from an independent, prospective study was published in the American Journal of Surgery, which demonstrated DecisionDx-Melanoma’s utility for prediction of outcomes in patients with cutaneous melanoma. The publication, titled "Utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy," describes a study comparing tumor features, sentinel node biopsy (SLNB) results, and patient outcomes from a prospective database of 383 patients with cutaneous melanoma who both underwent SLNB and had their primary tumor assayed with DecisionDx-Melanoma. The study’s results demonstrated that a Class 2 (high-risk) DecisionDx-Melanoma result was significantly associated with higher rates of SLNB positivity compared to Class 1 (low risk). With respect to risk prognoses, patients who received a Class 2B DecisionDx-Melanoma result and were SLNB-positive experienced the highest recurrence rates (38%), compared to only a 2% recurrence rate for patients who were Class 1A and SLNB-negative. DecisionDx-Melanoma Class 2 results were significantly associated with poorer RFS and DMFS rates compared to Class 1 results, both in the entire cohort of 383 cases and in patients staged as "low risk" (IA-IIA) according to American Joint Committee on Cancer (AJCC) staging criteria. See the Company’s news release from April 14, 2021, for more information.
Publication of prospective, multi-center long-term outcomes data in cutaneous melanoma appeared in the peer-reviewed journal, JCO Precision Oncology, and was titled "Long-term outcomes in a multicenter, prospective cohort evaluating the prognostic 31-gene expression profile for cutaneous melanoma." The study’s key objective was to demonstrate the prognostic value of DecisionDx-Melanoma with long-term follow-up that extends the assessment time period for a previously studied cohort. The study achieved its key objective and expanded upon prior results to show the ability of the test to accurately identifying recurrence risk of patients with American Joint Committee on Cancer (AJCC) 8th Edition staging system early stage I-IIA disease. See the Company’s news release from April 13, 2021, for more information.
In May, the Company announced the launch of its innovative pipeline initiative to develop a genomic test aimed at predicting systemic therapy response in patients with moderate to severe psoriasis, atopic dermatitis and related conditions. See the Company’s news release from May 10, 2021, for more information.
In May, the Company announced a publication describing the findings of a squamous cell carcinoma (SCC) GEP expert panel in the Journal of Drugs in Dermatology. The publication provides a framework for integrating DecisionDx-SCC into clinical practice. The article, titled "Clinical Considerations for Integrating Gene Expression Profiling into Cutaneous Squamous Cell Carcinoma Management," describes the findings of a multidisciplinary expert panel, representing backgrounds from academic medical centers and community practices. The panel also included specialties clinicians, such as Mohs surgeons, surgical oncologists and a radiation oncologist. The panel reviewed traditional risk assessment practices, guidelines and expert recommendations on DecisionDx-SCC. The panel also focused on decision-making points, where information from DecisionDx-SCC might inform the clinical management of patients with SCC and one or more risk factors. See the Company’s news release from May 20, 2021, for more information.
In June, the Company announced that it received approval from the New York State Department of Health (NYSDOH) for its DecisionDx-SCC test. Castle’s laboratory in Phoenix is a NYSDOH permitted laboratory. This designation allows patients in New York to access the Company’s molecular diagnostic tests, designed to provide actionable molecular information to inform patient care decisions. The Company has previously received approvals in the state of New York for its other genomic tests, DecisionDx-Melanoma, DecisionDx-UM and DecisionDx-PRAME, as well as its next generation sequencing panels, DecisionDx-CMSeq and DecisionDx-UMSeq. See the Company’s news release from June 9, 2021, for more information.
In July and August, the Company presented evidence on its family of skin cancer tests at numerous in-person, hybrid and virtual medical conferences, including American Head & Neck Society (AHNS) 2021 International Conference, Society of Dermatology Physician Assistants (SDPA) Annual Summer Dermatology Conference, DERM 2021 and 2021 American Academy of Dermatology Association (AAD) Summer Meeting.
Conference Call and Webcast Details

Castle Biosciences will hold a conference call on Monday, Aug. 9, 2021, at 4:30 p.m. Eastern time to discuss its second quarter 2021 results and provide a corporate update.

A live webcast of the conference call can be accessed here: View Source 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 Aug. 31, 2021.

To access the live conference call via phone, please dial 844 200 6205 from the United States and Canada, or +1 646 904 5544 internationally, at least 10 minutes prior to the start of the call, using the conference ID 538115.

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

Use of Non-GAAP Financial Measures (UNAUDITED)

In this release, we use the metrics of Adjusted Revenue, Adjusted Gross Margin and Adjusted Operating Cash Flow, which are non-GAAP financial measures and are not calculated in accordance with generally accepted accounting principles in the United States (GAAP). Adjusted Revenue and Adjusted Gross Margin reflect adjustments to net revenues to exclude changes in variable consideration related to test reports delivered in previous periods. Adjusted Gross Margin also excludes acquisition-related intangible asset amortization. Adjusted Operating Cash Flow excludes the effects of cash activity associated with COVID-19 government relief payments to healthcare providers.

We use Adjusted Revenue, Adjusted Gross Margin and Adjusted Operating Cash Flow internally because we believe these metrics provide useful supplemental information in assessing our revenue and cash flow performance, respectively. We believe Adjusted Revenue and Adjusted Gross Margin are also useful to investors because they provide additional information on current-period performance by removing the effects of revenue adjustments related to tests delivered in previous periods and acquisition-related intangible asset amortization, which we believe may facilitate revenue and gross margin comparisons to historical periods. We believe Adjusted Operating Cash Flow is also useful to investors as a supplement to GAAP measures in the assessment of our cash flow performance by removing the effects of COVID-19 government relief payments, which we believe are not indicative of our ongoing operations. However, these non-GAAP financial measures 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. These non-GAAP financial measures are not meant to be substitutes for net revenues or net cash (used in) 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 these non-GAAP financial measures to the most directly comparable GAAP financial measures are presented in the tables at the end of this release.