On February 28, 2023 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported financial results for the fourth quarter and year ended December 31, 2022 and provided a corporate update (Press release, Celldex Therapeutics, FEB 28, 2023, View Source [SID1234627827]).

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!

"Celldex made significant progress over the past year advancing our pipeline. We reported multiple positive data sets from our Phase 1b barzolvolimab program, including updated results from the Phase 1b multi-dose study in chronic spontaneous urticaria this past weekend at AAAAI," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "Our Phase 2 studies in both inducible and spontaneous urticaria are enrolling as planned and we expect to complete accrual of the Phase 2 CSU study by the end of the third quarter and, importantly, will be in a position to report topline data from this study either late this year or in the first quarter of 2024."

Mr. Marucci continued, "We continue to expand the barzolvolimab program into indications where we believe its unique mechanism could potentially provide new therapeutic options to patients suffering from these difficult diseases and look forward to initiating our Phase 2 study in eosinophilic esophagitis in the first half of 2023 and to presenting Phase 1 data from our prurigo nodularis program later this year. We also made considerable progress on our bispecific platform in 2022, advancing several candidates focused on important targets in inflammatory diseases and are poised to initiate a Phase 1 study of CDX-585, our ILT4 and PD-(L)1 oncology candidate, later this year. Finally, in direct support of our growth, we recently welcomed Dr. Rita Jain to the Celldex Board of Directors and we look forward to her contributions as we continue to advance our programs into later stage development."

Recent Business Highlights

On February 16, 2023, Celldex announced that Rita Jain, M.D. was appointed to the Company’s Board of Directors. Dr. Jain is a rheumatologist and most recently served as Executive Vice President, Chief Medical Officer of ChemoCentryx, Inc. She currently serves as a member of the Board of Directors for Provention Bio, Inc. and serves on the supervisory board of AM Pharma. Celldex believes her deep background in drug development strongly complements the current Board’s skills and experiences.

Recent Program Highlights

Barzolvolimab – KIT Inhibitor Program

Barzolvolimab is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells.

In June and July 2022, Celldex announced that the first patients have been dosed in the Phase 2 clinical studies of barzolvolimab for the treatment of Chronic Spontaneous Urticaria (CSU) and the two most common forms of chronic inducible urticaria (CIndU) – cold urticaria (ColdU) and symptomatic dermographism (SD). These randomized, double-blind, placebo-controlled, parallel group Phase 2 studies are evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategies. Based on current enrollment projections, Celldex anticipates that enrollment to the CSU study will be completed by the end of Q3 2023 and plans to report topline data either late this year or in the first quarter of 2024.

Data from the Phase 1b multiple dose study in patients with antihistamine refractory CSU were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting on Sunday, February 26, 2023 by Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin and a lead investigator on the study.

AAAAI 2023 Data Summary:

As of the data cut-off date on November 29, 2022, enrollment was complete with 45 patients with moderate to severe CSU refractory to antihistamines enrolled and treated [35 barzolvolimab (n=9 in 0.5 mg/kg; n=8 in 1.5 mg/kg; n=9 in 3.0 mg/kg; n=9 in 4.5 mg/kg) and 10 placebo]. The 0.5 mg/kg, 1.5 mg/kg and 3.0 mg/kg cohorts had completed study participation through 24 weeks; 6 of 9 patients in the 4.5 mg/kg cohort had completed through the week 20 visit. Complete data were included for all patients in dose levels through 3.0 mg/kg through 24 weeks. All available data for the 4.5 mg/kg and placebo dose levels were presented for adverse events. Activity data for the 4.5 mg/kg dose level were reported through week 20. Activity data for the 0.5 mg/kg and placebo group were only included through week 12 because, as expected, most patients from these groups had significant symptoms ahead of week 24 and discontinued follow up. Two patients did not receive all doses of study treatment [4.5 mg/kg (1), placebo (1)].

— Barzolvolimab resulted in rapid, marked and durable responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment. The 1.5 mg/kg, 3.0 mg/kg and 4.5 mg/kg dose groups showed similar markedly improved urticaria symptoms and disease control with sustained durability up to 24 weeks.

— Mean reduction from baseline in urticaria activity (UAS7) at week 12 of 67% in the 1.5 mg/kg dose group (n=8), 67% in the 3.0 mg/kg dose group (n=9) and 82% in the 4.5 mg/kg dose group (n=9). Complete response (UAS7=0) at week 12 of 57% in the 1.5 mg/kg dose group, 44% in the 3.0 mg/kg dose group and 67% in the 4.5 mg/kg dose group.

— Well-controlled disease (UCT≥ 12) at week 12 of 75% in the 1.5 mg/kg dose group, 63% in the 3.0 mg/kg dose group and 89% in the 4.5 mg/kg dose group.

— Patients with prior omalizumab therapy had similar symptom improvement as all patients.

— Barzolvolimab was well tolerated with a favorable safety profile; effects of multiple dose administration were consistent with observations in single dose studies. Most AEs were mild or moderate in severity and resolved while on study.
On December 6, 2022, Celldex announced data from the Company’s open label Phase 1b clinical trial of barzolvolimab in patients with antihistamine refractory chronic inducible urticarias, including new data from the Phase 1b 1.5 mg/kg cohort conducted in cold urticaria and long term follow data from the Phase 1b 3.0 mg/kg cohorts conducted in cold urticaria and symptomatic dermographism. The data were presented at the GA²LEN Global Urticaria Forum (GUF) held in Berlin, Germany.

GUF 2022 Data Summary:

Cold Urticaria 1.5 mg/kg intravenous cohort oral presentation: "Cold urticaria patients achieve complete response with 1.5 mg/kg barzolvolimab"

10 patients received a single intravenous infusion of barzolvolimab at 1.5 mg/kg. Patients had high disease activity as assessed by provocation threshold testing. All patients had disease refractory to antihistamines and five patients had disease refractory to omalizumab. Safety results were reported for all 10 patients; activity results were reported for the 9 patients who received a full dose of barzolvolimab, including four patients with omalizumab refractory disease.

— All 9 of 9 (100%) patients evaluable for activity treated at 1.5 mg/kg experienced a complete response as assessed by provocation threshold testing, including 4 patients with disease refractory to omalizumab. Rapid onset of responses after dosing were observed with 6 of 9 patients experiencing complete response within a week of dosing. Responses were durable with a median duration of response of 51+ days (7+ weeks).

— Improvements in disease activity as reported by Urticaria Control Test (UCT) were consistent with the completed responses as measured by provocation testing. All patients entered the cohort with poorly controlled disease. Following barzolvolimab administration, all patients achieved well controlled disease with 7 of 9 achieving complete control.

— A single 1.5 mg/kg dose of barzolvolimab resulted in rapid, marked and durable suppression of serum tryptase. The kinetics of tryptase depletion mirrored changes in provocation threshold and UCT.

— Barzolvolimab was generally well tolerated and the safety profile at 1.5mg/kg was similar to the profile observed with 3.0 mg/kg. No new treatment emergent AEs of concern were noted.

Long-term follow up 3.0 mg/kg intravenous cold urticaria and symptomatic dermographism poster presentation: "Barzolvolimab-induced response and mast cell suppression are durable and linked"

21 patients received a single infusion of barzolvolimab at 3.0 mg/kg, including 11 (10 evaluable for activity) patients with cold urticaria and 10 with symptomatic dermographism. Patients had high disease activity as assessed by provocation threshold testing at baseline and poorly controlled disease by UCT. All patients had disease refractory to antihistamines and three patients had disease refractory to omalizumab. As previously reported, a single 3.0 mg/kg IV dose was generally well tolerated and demonstrated a 95% complete response (negative provocation testing) and 100% well controlled urticaria by Urticaria Control Test (UCT), including in all patients with disease refractory to omalizumab. Profound reduction in serum tryptase and skin mast cells during the 12 week follow up period were observed.

14 patients consented to the optional long term follow up evaluation (6 cold, 8 symptomatic dermographism); 10 of the 14 still had complete control of their disease as assessed by provocation testing at week 12. Data were collected at one or more timepoints beyond week 12 through week 36.

— Most patients had return of symptoms and/or loss of urticaria control between 12 and 36 weeks. Remarkably, two patients remained provocation negative at 36 weeks, and four had well controlled disease (UCT ≥12) 36 weeks post dosing.

— Serum tryptase exhibited a similar rate of recovery as clinical symptoms, while skin mast cells return at a slower rate.

— Drug related adverse events noted during the study all resolved.
Celldex has completed enrollment in the barzolvolimab Phase 1b open label study in chronic inducible urticaria. Patient follow up continues in the cholinergic cohort and is planned for presentation in mid-2023.
Celldex has closed enrollment at 24 patients in the barzolvolimab Phase 1b multi-center, randomized, double-blind, placebo-controlled study in patients with prurigo nodularis (PN), a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. Data from this study is planned for presentation in the second half of 2023.
Celldex plans to initiate a Phase 2 international trial of barzolvolimab in eosinophilic esophagitis (EoE), the most common type of eosinophilic gastrointestinal disease, in the first half of 2023.
Bispecific Antibody Platform

CDX-585 – Bispecific ILT4 & PD-(L)1

CDX-585 combines highly active PD-1 blockade with anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells. ILT4 is emerging as an important immune checkpoint on myeloid cells.

CDX-585 has successfully completed GMP manufacturing and IND-enabling studies to support clinical development. CDX-585 will initially be developed for the treatment of solid tumors either as monotherapy or in combination with other oncologic treatments and is expected to enter the clinic in 2023 in patients with advanced malignancies.
Fourth Quarter and Twelve Months 2022 Financial Highlights and 2023 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2022 were $305.0 million compared to $323.5 million as of September 30, 2022. The decrease was primarily driven by cash used in operating activities of $21.8 million, partially offset by proceeds from option exercises and unrealized gains due to higher interest rates. At December 31, 2022, Celldex had 47.2 million shares outstanding.

Revenues: Total revenue was $1.6 million in the fourth quarter of 2022 and $2.4 million for the year ended December 31, 2022, compared to $0.3 million and $4.7 million for the comparable periods in 2021. The decrease in revenue for the twelve months ended December 31, 2022 compared to the twelve months ended December 31, 2021 was primarily due to a decrease in services performed under our manufacturing and research and development agreements with Rockefeller University and Gilead Sciences.

R&D Expenses: Research and development (R&D) expenses were $22.9 million in the fourth quarter of 2022 and $82.3 million for the year ended December 31, 2022, compared to $14.7 million and $53.3 million for the comparable periods in 2021. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial, barzolvolimab contract manufacturing, and personnel expenses.

G&A Expenses: General and administrative (G&A) expenses were $6.6 million in the fourth quarter of 2022 and $27.2 million for the year ended December 31, 2022, compared to $6.2 million and $20.5 million for the comparable periods in 2021. The increase in G&A expenses was primarily due to our settlement agreement with SRS, barzolvolimab commercial planning and stock-based compensation expenses.

Changes in Fair Value Remeasurement of Contingent Consideration: The Company recorded a $6.9 million gain on fair value remeasurement of contingent consideration for the twelve months ended December 31, 2022, primarily due to the Company’s decision to deprioritize the CDX-1140 program in the second quarter of 2022.

Litigation Settlement Related Loss: The Company recorded a one-time loss of $15.0 million in the second quarter of 2022 related to the $15.0 million paid to SRS pursuant to our settlement agreement.

Net Loss: Net loss was $26.5 million, or ($0.56) per share, for the fourth quarter of 2022, and $112.3 million, or ($2.40) per share, for the year ended December 31, 2022, compared to a net loss of $20.1 million, or ($0.43) per share, for the fourth quarter of 2021 and $70.5 million, or ($1.64) per share, for the year ended December 31, 2021. The litigation settlement related loss had a ($0.32) impact on net loss per share for the twelve months ended December 31, 2022. The gain on fair value remeasurement of contingent consideration had a $0.15 impact on net loss per share for the twelve months ended December 31, 2022.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at December 31, 2022 are sufficient to meet estimated working capital requirements and fund planned operations through 2025, which include our ongoing Phase 1b studies in urticaria and prurigo nodularis and our ongoing and planned Phase 2 studies in CSU, CIndU and EoE.

On February 28, 2023 Catalent, Inc. (NYSE: CTLT), the leader in enabling the development and supply of better treatments for patients worldwide, reported its fourth Corporate Responsibility Report (Press release, Catalent, FEB 28, 2023, https://www.catalent.com/catalent-news/catalent-publishes-fourth-annual-corporate-responsibility-report/ [SID1234627821]). for its fiscal year 2022, which ended June 30, 2022. The report highlights Catalent’s progress against its previously published targets and commitments in the areas of environmental, social, and governance (ESG). It also includes disclosures meeting the standards set by the Sustainability Accounting Standards Board (SASB) and the Task Force on Climate-Related Financial Disclosures (TCFD).

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!

Catalent’s fiscal 2022 saw the company help millions of people lead healthier lives through its development and supply of medicines and consumer health products, manufacturing 80 billion doses across approximately 8,000 different products, its highest ever patient-reach. Additionally, over the 12-month period Catalent enabled its customers to launch 150 new medicines and health products.

"We are proud of the significant progress made in strengthening our corporate responsibility program," commented Alessandro Maselli, who became President and Chief Executive Officer of Catalent at the beginning of fiscal 2023. "I am committed to continuing to build on our achievements and deliver ambitious ESG goals, which include science-based carbon reduction targets, zero waste to landfill, greater diversity and inclusion across our talent base, and increasing support for the communities we touch. Most importantly, I am eager to drive sustainable breakthroughs in healthcare that improve the lives of patients around the world, and immensely proud of our team’s commitment to work together for maximum impact and success."

The report highlights the progress that Catalent has made in reducing its environmental impact. In the past two years, the company has cut its scope 1 and 2 greenhouse gas (GHG) emissions by 38% from its fiscal 2020 baseline and is on target to meet its goal of a 42% reduction by 2030. Additionally, Catalent is committed to reducing waste, with a goal of zero waste to landfill by 2024, and as of July 2022, 60% of the company’s sites have achieved this milestone.

Building on Catalent’s focus to create positive social impact, the report also shows that the company has continued to increase the diversity of its staff across all levels in the business. From fiscal 2021 to fiscal 2022, the company also added 38 new Employee Resource Group chapters, bringing the total to 105, which, among other things, promote inclusivity in the workforce.

Forging links in its surrounding communities, the report shows Catalent made its biggest ever philanthropic contribution, donating more than $1.3 million to nonprofit organizations around the world through grants and matches of employee gifts. The main focus of this support was in science, technology, engineering, and math (STEM) education, as well as serving patient communities and in disaster response, particularly for Ukrainian refugees, and other emergency relief.

The fiscal 2022 Catalent Corporate Responsibility Report is available at catalent.com/about us/corporate-responsibility.

Further information can be requested by contacting [email protected].

On February 28, 2023 Aravive, Inc. (Nasdaq: ARAV, "the Company"), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to batiraxcept for the treatment of pancreatic ductal adenocarcinoma cancer (PDAC) (Press release, Aravive, FEB 28, 2023, View Source [SID1234627819]).

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 FDA’s Office of Orphan Products Development grants ODD status to a drug or biological product to prevent, diagnose or treat a rare disease or condition affecting fewer than 200,000 people in the USA. Companies that are granted ODD are eligible for incentives, including tax credits for qualified clinical trials, exemption from user fees and up to seven years of market exclusivity after approval.

"Receiving Orphan Drug Designation is another important milestone for batiraxcept, and it underscores the significant unmet medical need in patients with pancreatic cancer, typically diagnosed at an incurable advanced stage with a 5-year survival rate of 11%1" said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. "Three patients from our P1b trial are still responding to treatment with 15mg/kg batiraxcept, gemcitabine and nab-paclitaxel after 1 year and one patient has a confirmed complete response. Consistent with our other clinical trials, we noted a relationship between clinical activity and batiraxcept drug levels, however highly fibrotic tumors like PDAC may require more batiraxcept than platinum-resistant ovarian cancer and clear cell renal cell cancer patients to reach the appropriate batiraxcept drug levels. Due to this characteristic of pancreatic cancer, we are testing higher doses of batiraxcept to see if we can increase the proportion of patients who benefit from the triplet regimen."

Batiraxcept (15mg/kg on Days 1 & 15) is currently being evaluated in a Phase 1b/2 trial (NCT04983407) as first-line treatment in combination with gemcitabine (1000 mg/m2 on Days 1, 8, & 15) and nab-paclitaxel (125 mg/m2 on Days 1, 8, & 15) in patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) pancreatic adenocarcinoma. The Phase 1b portion of the trial is ongoing and the dose escalation phase was initiated this month. Preliminary results from the 20mg/kg batiraxcept plus gemcitabine and nab-paclitaxel cohort are anticipated in the second half of 2023. In addition to ODD granted by the FDA in pancreatic cancer, batiraxcept was previously granted ODD by the European Commission in platinum resistant recurrent ovarian cancer (PROC) and was granted Fast Track Designation by the FDA in PROC and clear cell renal cell carcinoma (ccRCC).

On February 28, 2023 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported its financial results for the fourth quarter and twelve months ended Dec. 31, 2022 (Press release, Castle Biosciences, FEB 28, 2023, View Source [SID1234627818]).

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!

"In 2022, we delivered strong year-over-year growth in revenue and test report volume, reflecting solid execution by our Castle team," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "Further, we believe our success continues to lay the foundation for future growth in 2023 and beyond. We are pleased to provide our financial outlook for 2023, expecting between $170-180 million in total revenue.
"We expect continued progress on our growth initiatives in 2023, including expanded evidence development supporting our proprietary commercial and pipeline tests and the continued integrations of our acquired franchises–gastroenterology and mental health–which we expect to contribute to achieving our 2025 financial targets of total revenue between $255-330 million and net operating cash flow positivity."
Twelve Months Ended Dec. 31, 2022, Financial and Operational Highlights
•Revenues were $137.0 million, a 46% increase compared to $94.1 million during 2021. Included in revenues for the year were revenue adjustments related to tests delivered in prior periods. These prior period revenue adjustments for the twelve months ended Dec. 31, 2022, were $2.0 million of net negative revenue adjustments, compared to $3.3 million of net positive revenue adjustments for 2021.
•Adjusted revenues, which exclude the effects of revenue adjustments related to tests delivered in prior periods, were $139.0 million, a 53% increase, compared to $90.8 million for 2021.
•Total test reports delivered in 2022 were 44,419, a 58% increase compared to 28,145 in 2021:
◦DecisionDx-Melanoma test reports delivered in 2022 were 27,803, compared to 20,328 in 2021, an increase of 37%.
◦DecisionDx-SCC test reports delivered in 2022 were 5,967, compared to 3,510 in 2021, an increase of 70%.
◦MyPath Melanoma and DiffDx-Melanoma diagnostic gene expression profile (GEP) aggregate test reports delivered in 2022 were 3,561, compared to 2,662 in 2021, an increase of 34%.
◦DecisionDx-UM test reports delivered in 2022 were 1,711, compared to 1,618 in 2021, an increase of 6%.
◦TissueCypher Barrett’s Esophagus test reports delivered in 2022 were 2,128, compared to 27 in 2021.
◦IDgenetix test reports delivered in 2022 were 3,249. No test reports were delivered by Castle in 2021.
•Gross margin for 2022 was 71%, and adjusted gross margin for 2022 was 77%.
•Operating cash flow was $(41.7) million, compared to $(19.0) million for 2021, and adjusted operating cash flow was $(41.7) million, compared to $(12.5) million in 2021.
•Net loss for 2022, which includes non-cash stock-based compensation expense of $36.3 million, was $(67.1) million, compared to $(31.3) million for 2021.
•Adjusted EBITDA for 2022 was $(42.6) million, compared to $(14.9) million in 2021.

Cash, Cash Equivalents and Marketable Investment Securities

As of Dec. 31, 2022, the Company’s cash, cash equivalents and marketable investment securities totaled $258.6 million.

Fourth Quarter Ended Dec. 31, 2022, Financial and Operational Highlights
•Revenues were $38.3 million, a 53% increase compared to $25.0 million during the same period in 2021. Included in revenue for the period were revenue adjustments related to tests delivered in prior periods. These prior period revenue adjustments for the quarter ended Dec. 31, 2022, were $0.8 million of net positive revenue adjustments, compared to $0.8 million of net negative revenue adjustments for the same period in 2021.
•Adjusted revenues, which exclude the effects of revenue adjustments related to tests delivered in prior periods, were $37.5 million, a 45% increase compared to $25.8 million for the same period in 2021.
•Delivered 12,644 total test reports in the fourth quarter of 2022, an increase of 53% compared to 8,269 in the same period of 2021:
◦DecisionDx-Melanoma test reports delivered in the quarter were 7,301, compared to 5,635 in the fourth quarter of 2021, an increase of 30%.
◦DecisionDx-SCC test reports delivered in the quarter were 1,845, compared to 1,265 in the fourth quarter of 2021, an increase of 46%.
◦MyPath Melanoma and DiffDx-Melanoma diagnostic GEP aggregate test reports delivered in the quarter were 822, compared to 904 in the fourth quarter of 2021, a decrease of 9%.
◦DecisionDx-UM test reports delivered in the quarter were 432, compared to 438 in the fourth quarter of 2021, a decrease of 1%.
◦TissueCypher Barrett’s Esophagus test reports delivered in the quarter were 1,030, compared to 27 in the fourth quarter of 2021.
◦IDgenetix test reports delivered in the quarter were 1,214. No test reports were delivered by Castle in the fourth quarter of 2021.
•Gross margin for the quarter ended Dec. 31, 2022, was 69%, and adjusted gross margin was 75%.
•Operating cash flow was $(6.0) million, compared to $(2.8) million for the same period in 2021, and adjusted operating cash flow was $(6.0) million, compared to $0.2 million for the same period in 2021.
•Net loss for the fourth quarter was $(20.6) million, compared to $(6.4) million for the same period in 2021.
•Adjusted EBITDA for the fourth quarter was $(10.4) million, compared to $(6.9) million for the same period in 2021.

2023 Outlook
•The Company anticipates generating between $170-180 million in total revenue in 2023.

Fourth Quarter and Recent Accomplishments and Highlights
Dermatology
•In November, the Company announced new data showing how its DecisionDx-SCC test can provide objective, independent and significant risk-stratification for cutaneous squamous cell carcinoma (SCC) tumors with uncertainty in differentiation status. The data were shared in an oral presentation given at the American Society of Dermatopathology (ASDP) 59th Annual Meeting by Sarah Estrada, M.D., dermatopathologist with Affiliated Dermatology in Scottsdale, Arizona. These data demonstrate how DecisionDx-SCC can significantly stratify the risk of metastasis in high-risk SCC patients with an ambiguous tumor differentiation status. Additionally, the study shows that incorporating the test’s results into clinical SCC risk assessments improves risk-stratification, which enhances current patient management decisions to improve patient outcomes. See the Company’s news release from November 15, 2022, for more information.

•In October, the Company announced the publication of real-world clinical utility data in Cancer Investigation showing that clinicians are ordering DecisionDx-SCC for the intended high-risk SCC patient population and that use of the test’s results can lead to risk-aligned changes in patient management strategies. The paper, titled "Real-World Evidence Shows Clinicians Appropriately Use the Prognostic 40-GEP Test for High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients," evaluated metrics from one year of clinical DecisionDx-SCC orders and the test’s impact on real-world risk assessments and treatment decisions. Overall, the study data support the clinical impact that DecisionDx-SCC’s personalized, risk-stratification results can have on patient management plans, including helping avoid the overtreatment of patients and guiding risk-appropriate disease management decisions, alongside traditional risk factor assessments. See the Company’s news release from October 31, 2022, for more information.
•In October, the Company announced new data from two studies demonstrating the potential of DecisionDx-Melanoma and DecisionDx-UM to accurately stratify risk of death from melanoma (cutaneous melanoma (CM) and uveal melanoma (UM), respectively) in a group of real-world, unselected and prospectively tested patients. The studies are part of the Company’s ongoing collaboration with the National Cancer Institute (NCI) to link DecisionDx-Melanoma and DecisionDx-UM clinical testing data with data from the Surveillance, Epidemiology and End Results (SEER) Program’s registries on CM and UM cases, respectively. The data were shared in poster presentations at the 19th International Congress of the Society for Melanoma Research (SMR) in Edinburgh, United Kingdom. See the Company’s news release from October 27, 2022, for more information.
•In October, the Company announced new data from UTILISE (Clinical Utility and Health Outcomes Study), a prospective, multi-center, clinical utility study of DecisionDx-SCC, designed to capture the real-world impact of DecisionDx-SCC test results on the management of patients with SCC and one or more risk factors. This first analysis showed that DecisionDx-SCC test results positively impacted patient management in over 80% of the patients enrolled in the study, consistent with previous clinical utility studies demonstrating that the test’s results can impact risk-appropriate changes in patient management plans, within established guidelines. This data from the UTILISE study was presented during the 2022 Fall Clinical Dermatology Conference through a poster titled, "A prospective clinical utility study demonstrates that physicians use the 40-gene expression profile (40-GEP) to guide clinical management decisions for Medicare-eligible patients with cutaneous squamous cell carcinoma (cSCC)." See the Company’s news release from October 24, 2022, for more information.
•In October, the Company announced new data from its prospective, multicenter DECIDE study in which DecisionDx-Melanoma test results influenced 85% of clinicians’ decisions regarding the sentinel lymph node biopsy (SLNB) surgical procedure, demonstrating the role of the test’s results in guiding risk-aligned patient management decisions. When DecisionDx-Melanoma test results influenced for SLNB, the procedure was performed in 92% of the cases in the study; similarly, when the test result influenced against SLNB, the decision was made to forego SLNB in 70% of cases. This data indicates that the test’s results in conjunction with current guidelines can guide risk-aligned clinical decision-making regarding the SLNB surgical procedure. See the Company’s news release from October 20, 2022, for more information.
Gastroenterology
•In November, the Company announced that the Accreditation Committee of the College of American Pathologists (CAP) had accredited its clinical laboratory facility in Pittsburgh. This achievement followed an on-site inspection as part of the CAP’s Laboratory Accreditation Program. Recognized by the U.S. federal government as being equal to or more stringent than its own inspection program, CAP accreditation is awarded to facilities that meet the highest standards of quality in laboratory services. Once achieved, on-site inspections occur every two years to assess ongoing compliance with the CAP accreditation program requirements. Castle acquired its laboratory in Pittsburgh through the acquisition of Cernostics, Inc. in December 2021, and subsequently initiated ongoing process improvements and laboratory expansion efforts. With this accreditation, all of Castle’s laboratories are now CAP

accredited, reflecting the Company’s commitment to high-quality standards and excellence in patient care. See the Company’s news release from November 21, 2022, for more information.
•In October, the Company announced new data showing that the use of TissueCypher Barrett’s Esophagus test results can significantly improve management decisions for Barrett’s esophagus (BE) patients with low-grade dysplasia (LGD) to improve health outcomes. Overall, the study results show that TissueCypher may be used to standardize the management of BE patients with LGD to improve health outcomes, by helping ensure that patients at a high risk of progression receive earlier interventions and by potentially reducing unnecessary use of endoscopic eradication therapy (EET) and endoscopies for lower risk patients. See the Company’s news release from October 25, 2022, for more information.
Uveal Melanoma
•In November, the Company announced the publication of a study completed in collaboration with the Melanoma Research Foundation (MRF) in which most patients diagnosed with uveal melanoma (UM) indicated their desire for prognostic testing at diagnosis, reported finding value in their test result and experienced lower decision regret, regardless of whether their test result indicated that their UM tumor was at a high or low risk of metastasis. The study, titled "Uveal melanoma patient attitudes towards prognostic testing using gene expression profiling," was published in Melanoma Management. See the Company’s news release from November 17, 2022, for more information.
Corporate
•In November, the Company was named a Houston Chronicle Top Workplace for the second year in a row. More than 70,000 employees from 4,966 companies in the Houston metro area participated in the nomination process, but only 200 companies were named as 2022 Top Workplaces, including Castle. The Top Workplaces program starts with capturing employee feedback on what matters most about a company’s culture through an anonymous survey. The survey measures fifteen drivers of company culture that are critical to an organization’s success, as well as other insights related to a company’s leadership and employee engagement. See the Company’s news release from November 14, 2022, for more information.

Conference Call and Webcast Details
Castle Biosciences will hold a conference call on Tuesday, Feb. 28, 2023, at 4:30 p.m. Eastern time to discuss its fourth quarter and full-year 2022 results and provide a corporate update.

A live webcast of the conference call can be accessed here: or via the webcast link on the Investor Relations page of the Company’s website, View Source 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 21, 2023.

To access the live conference call via phone, please dial 844 200 6205 from the United States, or +1 929 526 1599 internationally, at least 10 minutes prior to the start of the call, using the conference ID 223262.

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 Revenues, Adjusted Gross Margin, Adjusted Operating Cash Flow and Adjusted EBITDA, which are non-GAAP financial measures and are not calculated in accordance with generally accepted accounting principles in the United States (GAAP). Adjusted Revenues and Adjusted Gross Margin reflect adjustments to net revenues to exclude changes in variable consideration related to test reports delivered in previous periods but not recorded as revenues until a subsequent period. Adjusted Gross Margin further excludes acquisition-related intangible asset amortization. Adjusted Operating Cash Flow excludes the effects of repayments to Medicare of COVID-19 government relief advancements to healthcare providers. Adjusted EBITDA excludes from net loss interest income, interest expense, income tax expense

(benefit), depreciation and amortization expense, stock-based compensation expense, change in fair value of contingent consideration, and acquisition-related transaction costs.

We use Adjusted Revenues, Adjusted Gross Margin, Adjusted Operating Cash Flow and Adjusted EBITDA internally because we believe these metrics provide useful supplemental information in assessing our revenue and cash flow performance reported in accordance with GAAP, respectively. We believe that Adjusted Revenues, when used in conjunction with our test report volume information, facilitates investors’ analysis of our current-period revenue performance and average selling price performance by excluding the effects of revenue adjustments related to test reports delivered in prior periods, since these adjustments may not be indicative of the current or future performance of our business. We believe that providing Adjusted Revenues may also help facilitate comparisons to our historical periods. Adjusted Gross Margin is calculated using Adjusted Revenues and therefore excludes the impact of revenue adjustments related to test reports delivered in prior periods, which we believe is useful to investors as described above. We further exclude acquisition-related intangible asset amortization in the calculation of Adjusted Gross Margin. We believe that excluding acquisition-related intangible asset amortization may facilitate gross margin comparisons to historical periods and may be useful in assessing current-period performance without regard to the historical accounting valuations of intangible assets, which are applicable only to tests we acquired rather than internally developed. 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 payment activity, which we believe are not indicative of our ongoing operations. We believe Adjusted EBITDA may enhance an evaluation of our operating performance because it excludes the impact of prior decisions made about capital investment, financing, investing and certain expenses we believe are not indicative of our ongoing performance, such as acquisition-related transaction costs. 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 considered in isolation or used as substitutes for net revenues, gross margin, net cash (used in) provided by operating activities or net loss reported in accordance with GAAP; should be considered in conjunction with our financial information presented in accordance with GAAP; have no standardized meaning prescribed by GAAP; are unaudited; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future, there may be other items that we may exclude for purposes of these non-GAAP financial measures, and we may in the future cease to exclude items that we have historically excluded for purposes of these non-GAAP financial measures. Likewise, we may determine to modify the nature of adjustments to arrive at these non-GAAP financial measures. Because of the non-standardized definitions of non-GAAP financial measures, the non-GAAP financial measure as used by us in this press release and the accompanying reconciliation tables have limits in their usefulness to investors and may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. 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.

On February 28, 2023 Bristol Myers Squibb (NYSE: BMY) reported that the company will take part in a fireside chat at Cowen’s 43rd Annual Health Care Conference on Tuesday, March 7, 2023. Samit Hirawat, M.D., Executive Vice President, Chief Medical Officer, Head of Development, will answer questions about the company at 9:50 a.m. ET (Press release, Bristol-Myers Squibb, FEB 28, 2023, View Source [SID1234627817]).

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!

Investors and the general public are invited to listen to a live webcast of the session at View Source An archived edition of the session will be available later that day.