On October 23, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported the presentation of early clinical data from the ongoing Phase 1/2 CARE study in pediatric and young adult patients with advanced solid tumors harboring ALK, ROS1 or NTRK alterations (Press release, Turning Point Therapeutics, OCT 23, 2021, View Source [SID1234591834]). These data are being presented today at the virtual 53rd Congress of the International Society of Paediatric Oncology (SIOP) being held October 21-24.

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"These early data for repotrectinib demonstrate encouraging clinical activity in this pediatric patient population," said Mohammad Hirmand, M.D., chief medical officer. "Patient enrollment is continuing in the Phase 1/2 CARE study, and we look forward to further advancing the development of repotrectinib in this patient population."

Early Data from Phase 1/2 CARE Study
The primary objective of the Phase 1 dose escalation portion of the study is to evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of repotrectinib in pediatric patients less than 12 years old. The primary objective of the Phase 2 portion of the study is to determine the anti-tumor activity of repotrectinib in pediatric and young adult patients less than 25 years old. Repotrectinib is administrated in capsule or suspension formulation using weight-based dosing for patients less than 12 years old. Patients 12 to 25 years old can enroll directly into the Phase 2 portion of the study with a repotrectinib dose of 160 mg QD for the first 14 days and may increase to 160 mg BID thereafter.

The early Phase 1/2 CARE dataset utilizes an August 2, 2021 data cutoff date. Ten patients were treated across two dose levels. The safety analysis includes the ten treated patients, and the preliminary efficacy analysis includes eight evaluable patients. Patients included in the efficacy analysis had baseline measurable disease and at least one post-baseline evaluable scan. Response evaluation was by physician assessment and per RECIST v1.1 or RANO for CNS tumors. Responses were confirmed with a subsequent scan at least 28 days later.

The findings were reported in a pre-recorded presentation by Steven G. Dubois, M.D., associate professor of Pediatrics, Harvard Medical School available on October 23 at 9:12 a.m. ET on the meeting website.

Preliminary Safety Analysis (n=10) and Pharmacokinetic Analysis

Repotrectinib was generally well tolerated.

The most frequently reported treatment-emergent adverse events (TEAEs) were anemia (n=5) and fatigue (n=5). Among patients with anemia, three had baseline history of anemia.

Dizziness events (n=4) were grade 1 or 2 and none led to treatment discontinuation.

No patients discontinued treatment due to reasons other than disease progression and no patients had TEAEs that led to dose reduction.

No dose-limiting toxicities were reported.

Preliminary pharmacokinetics data indicated that the exposure of repotrectinib in different age groups was comparable to the adult exposure at steady-state.
Preliminary Efficacy Analysis (n=8)

Eight patients were evaluable for efficacy, including four TKI-naïve and four TKI-pretreated patients. TKI-naive patients included those with NTRK amplified anaplastic ependymoma (n=1), NTRK fusion glioblastoma multiforme (GBM)/high grade glioma (n=1), NTRK fusion sarcoma (n=1), and ROS1 fusion inflammatory myofibroblastic tumor (IMT) (n=1). TKI-pretreated patients included those with NTRK fusion GBM/high grade glioma (n=2), NTRK fusion mesoblastic nephroma (n=1), and NTRK fusion sarcoma (n=1).

Three TKI-naïve patients (2 NTRK fusion solid tumors; 1 ROS1 fusion IMT) achieved confirmed responses. One of the three responding patients had a NTRK fusion GBM/high grade glioma, was previously treated with tumor resection, whole brain radiotherapy, and multi-agent chemotherapy, and achieved a complete response (CR) and remained in a response for 3.8+ months as of the data cutoff date. The other two confirmed responders remained in response with duration of response of 7.3+ and 12.1+ months, respectively.

Of the four TKI-pretreated patients, one patient with NTRK fusion sarcoma had a best response of stable disease.
The Phase 1 dose finding portion of the study is ongoing in pediatric patients less than 12 years old to confirm the pediatric RP2D. The Phase 2 portion of the study is ongoing for patients 12 to 25 years old.

Turning Point also announced the publication of preclinical data of repotrectinib in neuroblastoma, the most common pediatric extracranial solid tumor, in the American Association of Cancer Research’s peer reviewed journal, Molecular Cancer Therapeutics. Preclinical studies described in the publication titled "Translational Strategies for Repotrectinib in Neuroblastoma" show that repotrectinib inhibits tumor growth and prolongs survival in patient-derived neuroblastoma xenograft models. In addition, the studies indicated that combining repotrectinib with chemotherapy may be a promising treatment paradigm for neuroblastoma patients.

On October 23, 2021 NANOBIOTIX (Euronext: NANO – NASDAQ: NBTX – the ‘‘Company’’), a late-stage clinical biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported first ever survival data from its priority head and neck cancer development program at the 2021 Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Press release, Nanobiotix, OCT 23, 2021, View Source [SID1234591835]).

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As specified by the ASTRO Annual Meeting embargo policy, "information beyond what is included in the abstract, such as updated or additional results, is embargoed until the date and time of scientific presentation or presentation at an ASTRO news briefing, whichever occurs first." However, Nanobiotix has become aware that ASTRO made a late decision to release the posters at the same time as the abstracts and did not sufficiently update the embargo policy. As a result, the Company is releasing this data in advance of its intended embargo date.

New Data from Locally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC) Program

Data show a median Overall Survival (mOS) of 18.1 months and a median Progression Free survival of (mPFS) of 10.6 months in the evaluable population (n=41) from the dose expansion part of its phase I, multicenter, open-label, non-randomized dose escalation and dose expansion study evaluating NBTXR3 as a single-agent activated by radiotherapy in tough-to-treat elderly and frail LA-HNSCC patients ineligible for cisplatin and intolerant to cetuximab (Study 102 Expansion). In the full population (all evaluable and non-evaluable patients treated; n=54), data showed a 14.1-month mOS and a 9.4-month mPFS. The data suggest that lower mOS and mPFS observed in the full population versus the evaluable population in the study could be related to early death associated with high burden of comorbidity in the non-evaluable population.

Evaluability in Study 102 Expansion was determined based on the patient receiving at least 80% of the intended intratumoral dose of NBTXR3, at least 60 Gy of radiotherapy, and the required imaging to assess the target lesion at baseline and at least once post treatment.

Response rates remained consistent with previously reported results from the dose escalation and dose expansion study, showing a best observed target lesion objective response rate (ORR) of 85.4% and a best observed target lesion complete response rate (CRR) of 63.4%2.

"I have held the belief that NBTXR3 could have a real impact for patients with solid tumors since reviewing the proof-of-concept data from the phase II/III in soft tissue sarcoma and throughout my participation in Study 102 Expansion," said study principal investigator Professor Christophe Le Tourneau, senior medical oncologist and head of the Department of Drug Development and Innovation (D3i) at Institut Curie. "This first look at survival data has added to my confidence that NBTXR3 could provide a promising new therapeutic option for the practice. I look forward to leading the upcoming phase III global registration study, and to have the opportunity to evaluate the promise of this innovation in a larger patient population."

Of the 21 evaluable patients with a best observed overall response of complete response (CR) with a mean follow-up of 16.1 months, 6 patients died for non-oncologic reasons and only one died from disease progression.

NBTXR3 administration was feasible and well-tolerated overall. A total of 8 Grade 3-4 NBTXR3-related adverse events (AEs) were observed in 8 patients, representing 1.3% of all observed AEs. Of these AEs related to NBTXR3, 5 serious adverse events (SAEs) were observed including dysphagia, sepsis, soft tissue necrosis, stomatitis, and tumor hemorrhage. Of the SAEs, one death from sepsis assessed by the investigator as possibly related to NBTXR3, radiotherapy, and cancer was observed.

While the incidence of LA-HNSCC has continued to rise, patients in the elderly and frail LA-HNSCC population have significant unmet needs. Many are not eligible to receive concurrent chemoradiation due to frailty associated with comorbidities. The modified Charlson Comorbidity Index (mCCI) is a measure of comorbidity burden on a patient-by-patient basis, and high mCCI (i.e., mCCI ≥ 4) is correlated with higher risk of death relative to the broader population. In this study, 63% of all patients treated had high mCCI, which is two to three times the prevalence of comorbidity in the overall LA-HNSCC population3.

Despite the prevalence of high mCCI in Study 102 Expansion, these preliminary data support further evaluation of NBTXR3 activated by radiotherapy as a therapeutic option that may translate to a survival benefit for elderly and frail LA-HNSCC patients. The data also suggest that the potential benefits of the therapy could improve in a population with a lower burden of comorbidity.

"Bringing innovation to the patients that need it most has always been the backbone of our development strategy for NBTXR3," said Laurent Levy, co-founder and chief executive officer of Nanobiotix. "We started with soft tissue sarcoma—a disease indication notoriously resistant to radiotherapy. After proving we could provide a therapeutic benefit versus radiotherapy alone for patients with locally advanced disease and achieving European market approval, we pivoted to patients with locally advanced head and neck cancer that have substantially limited treatment options. The new survival data we are seeing from Study 102 Expansion bolster our confidence in the promise of NBTXR3 as we near the launch of our pivotal phase III study in head and neck cancer. We have designed this study with the benefit of our learnings from the phase I and look forward to the opportunity to prove that our product candidate can expand treatment possibilities for patients with cancer around the world."

About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy; and the launch of a phase III global registrational study is planned. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the planned phase III study.

Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company sponsored phase I clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3 , Nanobiotix has engaged in a strategic collaboration strategy with world class partners to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations.

On October 23, 2021 Orion Biotechnology reported that The Bio-Europe Conference will be held virtually again this year, and Orion Biotechnology will be providing a pre-recorded presentation describing our exciting drug discovery technology for unlocking the therapeutic potential of G Protein-Coupled Receptors (GPCRs), a very large and important group of drug targets in the human body (Press release, Orion Biotechnology, OCT 23, 2021, View Source [SID1234591885]).

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On October 22, 2021 Humanigen, Inc. (Nasdaq: HGEN), a clinical-stage biopharmaceutical company, reported its research partners will present Phase 1 results from a study of ifabotuzumab in glioblastoma multiforme (GBM) at the Annual Congress of the European Association of Nuclear Medicine (EANM’21) and plan to initiate a follow-on Phase 1b study in non-CNS solid tumors in early 2022 (Press release, Humanigen, OCT 22, 2021, View Source [SID1234591790]). EANM is the largest organization dedicated to nuclear medicine in Europe and represents more than 9,000 specialists from 41 different countries.

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The abstract will be presented virtually by Principal Investigator Prof. Andrew Scott, Head, Tumor Targeting Laboratory, Olivia Newton-John Cancer Research Institute; Director of the Department of Molecular Imaging and Therapy, Austin Health; and Professor, School of Cancer Medicine, La Trobe University. The abstract (OP-0854) entitled: "Phase I safety and bioimaging trial of ifabotuzumab in patients with glioblastoma" has been published in the EANM‘21 abstract book and was chosen to be included in a TOP 3 trials session at EANM’21 that will take place from 3:05-4:35pm Central European Standard Time on October 22, 2021.1

"The biodistribution characteristics demonstrated in the Phase 1 GBM study indicate ifabotuzumab has ideal characteristics for a range of therapeutic options including the creation of an antibody-drug conjugate," said Prof. Scott. "Our preclinical studies with antibody-drug conjugate forms of ifabotuzumab have shown promising results. We hope to take this payload delivery approach into the clinic in the next 1-2 years."

The Olivia Newton-John Cancer Research Institute plans to conduct a Phase 1b dose-escalation and imaging study in non-CNS solid tumors that is scheduled to begin in early 2022. This will be led by Prof. Andrew Scott and Prof. Hui Gan, Clinical Research Lead, Olivia Newton-John Cancer Research Institute and Director, Cancer Clinical Trials Center, Austin Health.

"We are excited by the potential ifabotuzumab holds to create a novel cancer therapeutic that delivers cytotoxic agents to tumor cells while minimizing toxicity to normal tissue," said Cameron Durrant, Chairman and CEO of Humanigen. "We look forward to supporting our valued partners in Australia as they advance research of ifabotuzumab into solid tumors."

About Ifabotuzumab
Ifabotuzumab is a proprietary Humaneered monoclonal antibody that binds the EphA3 receptor, which plays an important role during fetal development but is not thought to be expressed nor play a significant role in healthy adults. EphA3 is a tyrosine kinase receptor, aberrantly expressed on the tumor vasculature and tumor stroma in many solid tumors including melanoma, breast cancer, lung cancer, colorectal cancer, GBM and prostate cancer, making it an attractive target for a range of cancers.

Humanigen has completed a Phase 1 study in multiple hematologic malignancies that suggest it is well tolerated with mild-to-moderate infusion reactions that can be managed by stopping infusion, or using medications to treat reactions (chills, fever, nausea, hypertension, and rapid heart rate).

In 2021, a Phase 1 safety and bioimaging study of ifabotuzumab, supported by Cure Brain Cancer Foundation, and Humanigen, showed specific and reproducible targeting of the tumor and its microenvironment, with no normal tissue uptake, in all patients. Future development plans, in conjunction with our research partners in Australia, are intended to confirm highly specific tumor uptake in non-CNS solid tumors with the intention of creating an antibody-drug conjugate by linking ifabotuzumab to a cytotoxic (cell-killing) agent.

On October 22, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), applying innovative diagnostics to transform disease management and improve patient outcomes, reported recent poster presentations on the Company’s suite of dermatologic cancer gene expression profile (GEP) tests, as well as a poster describing the study design for its inflammatory skin disease pipeline initiative at the 2021 Fall Clinical Dermatology Conference, held Oct. 21-24 (Press release, Castle Biosciences, OCT 22, 2021, View Source [SID1234591791]).

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DecisionDx-Melanoma:

DecisionDx-Melanoma is Castle’s prognostic gene expression profile test for cutaneous melanoma. The Company utilizes two proprietary algorithms, i31-ROR and i31-SLNB, to produce an integrated test result designed to provide a precise, personalized prediction of risk of recurrence and likelihood of sentinel lymph node (SLN) positivity, respectively, by integrating DecisionDx-Melanoma with traditional assessment of the clinicopathologic features of a patient’s tumor.

The company presented new data on the capabilities of these independently validated algorithms through a poster titled, "Integrating the 31-gene expression profile and clinicopathologic data to determine the risk of sentinel lymph node positivity and recurrence-free survival in cutaneous melanoma." The poster can be found here.

"The risks associated with a melanoma diagnosis can lead to several different clinical procedures, including sentinel lymph node biopsy (SLNB), and many patients experience regional recurrence, distant metastasis or even death," said Bob Cook, Ph.D., senior vice president of research and development of Castle Biosciences. "The study results demonstrated that integrating the DecisionDx-Melanoma result with assessment of clinical and pathologic features improved individualized risk prediction for SLNB positivity, regional recurrence and distant metastasis, which could help clinicians make more informed and personalized risk-stratification decisions."

Study methods and findings:

The purpose of the study was to demonstrate the combined ability of two independently validated algorithms that incorporate the DecisionDx-Melanoma result with clinicopathologic features to predict individual SLNB positivity risk and recurrence-free survival (RFS).
Using artificial intelligence techniques, two algorithms were developed:
The i31-GEP-SLNB (i31-SLNB) algorithm, developed from 1398 cases and validated in an independent cohort of 1674 cases, was developed to determine the individual likelihood of SLN positivity.
The i31-GEP-outcomes (i31-ROR) algorithm, developed from 1581 cases and validated in an independent cohort of 523 cases, was developed to provide personalized survival predictions for recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS).
The i31-SLNB algorithm identified 31.2% (135/433) of patients with a <5% likelihood of SLN positivity who could potentially forego the SLNB surgical procedure. These patients all received a low-risk i31-ROR result and had high survival rates (>98% RFS, DMFS and MSS), reinforcing the i31-ROR algorithm’s risk prediction precision.
In the SLN negative population, 20% of patients were identified as high risk by the i31-ROR algorithm and had five-year RFS rates that were like those for patients with a positive SLNB (e.g., Stage III disease) (47.7% vs. 48.7%, respectively).
Overall, using National Comprehensive Cancer Network (NCCN) treatment guidelines, the test identified 44.8% (194/433) of patients who may have been able to avoid SLNB or were re-stratified as low or high risk compared to SLN status alone.
The i31-ROR algorithm was able to stratify patients with Stage IIB-IIC melanoma according to risk of recurrence with an absolute recurrence difference of 20% at 12 months. This is of particular interest given the recent announcement of the absolute treatment effect of Pembrolizumab in patients with Stage IIB-IIC melanoma of 5.7% at 12 months.
The study data demonstrated that DecisionDx-Melanoma’s integrated test result, using both i31-ROR and i31-SLNB algorithms, identified patients who may potentially forego SLNB and provide a more precise prediction of high and low risk of recurrence for more personalized patient care decisions.
Comprehensive Diagnostic Offering:

Castle’s Comprehensive Diagnostic Offering (CDO) leverages the strengths of both myPath Melanoma and DecisionDx DiffDx-Melanoma, two GEP tests designed to provide a highly accurate, objective result to aid dermatopathologists and dermatologists in characterizing difficult-to-diagnose melanocytic lesions.

Castle presented data validating the company’s implementation of its CDO via a poster presentation entitled "A comprehensive diagnostic offering workflow increases the rate of actionable results of the 23- and 35-gene expression profile tests for use as ancillary diagnostic tools for difficult-to-diagnose melanocytic lesions." The poster can be viewed here.

"Since Castle’s acquisition of the myPath laboratory earlier this year, we have looked forward to demonstrating the value that these two diagnostic GEP tests can offer together," said Matthew S. Goldberg, M.D., first study author and medical director at Castle Biosciences. "We are pleased to have evidence that demonstrated the complementary power of these tests, which could enable physicians to make more confident diagnoses for patients with difficult-to-diagnose melanocytic lesions and to create individualized care plans by interpreting the patient’s gene expression profile in the context of the clinical, laboratory and histopathologic information."

Study methods and findings:

This study highlighted the results of all CDO clinical cases submitted to Castle Biosciences between June 30-Aug. 31, 2021. Using the Company’s CDO workflow, all adult cases not receiving an actionable result of benign or malignant from myPath Melanoma had the opportunity to be run using DecisionDx DiffDx-Melanoma.
myPath Melanoma returned nonactionable classifications 22.3% of the time (nonactionable classifications are comprised of the combined total of intermediate risk results [12.9%] and technical failures [9.4%]).
The nonactionable cases underwent additional testing using DecisionDx DiffDx-Melanoma, at which point an additional 20.9% of originally submitted cases received an actionable result. Only 1.1% of cases received an intermediate result from both tests; the technical failure rate of both tests combined was 0.2%.
Leveraging both tests as a comprehensive diagnostic workflow substantially improved the reporting of clinically actionable results from a historic rate of 77.8% for myPath Melanoma alone to 98.7% when used in conjunction with DecisionDx DiffDx-Melanoma.
Psoriasis, Atopic Dermatitis and Related Conditions:

Inflammatory skin diseases, like psoriasis and atopic dermatitis, severely impact a patient’s quality of life. While there are many effective treatment options available for those with moderate-to-severe disease, current clinical practice relies on a costly and time-consuming trial-and-error approach to determine an individual patient’s response to systemic therapies. To answer this unmet clinical need, Castle Biosciences is developing a GEP test designed to predict response to systemic therapies for patients with moderate to severe psoriasis, atopic dermatitis and other related diseases. Personalized guidance for therapy selection and anticipated efficacy has the potential to improve patient health outcomes by enabling clinicians to select the best medication for their patients’ specific skin disease.

Castle initiated an IRB-approved clinical study to develop and validate one or more gene expression signatures to guide treatment selection in patients with psoriasis, atopic dermatitis and related conditions. The study’s design was presented via a poster titled "A study to help guide management decisions in patients with psoriasis and atopic dermatitis." The poster can be viewed here.

"Patients with psoriasis and atopic dermatitis could benefit immensely from a more straightforward path to finding an effective therapeutic treatment option for their inflammatory skin disease," said Aaron S. Farberg, M.D., the study’s first author and dermatologist at Baylor University Medical Center in Dallas. "Based on a history of success, Castle Biosciences is well positioned to potentially identify a molecular signature that could aid in finding the appropriate drug selection for a patient, based on their unique disease biology, saving patient time, money and contributing to a more effective use of healthcare resources."

Study design:

Up to 4,850 patients between two and 85 years of age diagnosed with psoriasis, atopic dermatitis or a related disorder will be prospectively enrolled in the study.
At enrollment, disease severity will be documented. Superficial layers of diseased and healthy skin will be collected from participants. Clinical data including systemic treatment type, dose, response and side effects will be logged at subsequent visits.
RNA from samples will be isolated, and an unbiased assessment of RNA expression levels using microarray will be performed.
Through this study protocol, Castle is aiming to develop a GEP test that may help guide therapeutic choice for patients with moderate-to-severe psoriasis and atopic dermatitis for whom clinical diagnosis or drug selection may be challenging, thereby potentially decreasing the amount of time and money spent on finding a successful treatment option for each patient.

DecisionDx-SCC:

DecisionDx-SCC is Castle’s prognostic 40-GEP test designed to use a patient’s tumor biology to predict individual risk of metastasis for patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC) having one or more risk factors.

Castle presented data on DecisionDx-SCC through a poster entitled "Real-world clinical usage data demonstrates appropriate utilization of the prognostic 40-gene expression profile test for cutaneous squamous cell carcinoma with one or more risk factors."

Study methods and findings:

The objective of the study was to demonstrate independent prognostic value of DecisionDx-SCC via analyses with existing risk assessment methods and report on the early clinical usage of DecisionDx-SCC.
Summary metrics were generated on the first 1000 samples received for DecisionDx-SCC testing that met clinical testing criteria. Metrics on early clinical usage include:
Technical reliability of DecisionDx-SCC was 96.3%.
69.0% of samples received DecisionDx-SCC Class 1 results, 26.0% received DecisionDx-SCC Class 2A results and 1.3% received DecisionDx-SCC Class 2B results.
52% of tested patients had three or more risk factors.
This study demonstrated that the intended use population (high-risk SCC patients with one or more risk factors) aligned with the cases that were submitted for clinical testing.
The study also found that DecisionDx-SCC results can be applied as an adjunct to enhance SCC risk stratification and contribute to risk-appropriate surveillance and treatment decisions.
About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

In addition to reporting Class results, the Company also reports results that predict risk of recurrence and likelihood of sentinel lymph node positivity. Castle utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an integrated DecisionDx-Melanoma test result.

Through June 30, 2021, DecisionDx-Melanoma has been ordered 78,277 times for use in patients with cutaneous melanoma. More information about the test and disease can be found at www.CastleTestInfo.com.

About Castle Biosciences’ Comprehensive Diagnostic Offering for Difficult-to-Diagnose Melanocytic Lesions

Castle Biosciences’ comprehensive diagnostic offering leverages the strengths of myPath Melanoma and DecisionDx DiffDx-Melanoma. These gene expression profile tests are designed to provide a highly accurate, objective result to aid dermatopathologists and dermatologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately 2 million suspicious pigmented lesions biopsied annually in the U.S., Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. For these cases, the treatment plan can also be uncertain. Obtaining highly accurate, objective ancillary testing can mean the difference between a path of overtreatment or the risk of undertreatment. Interpreted in the context of other clinical, laboratory and histopathologic information, myPath Melanoma and DecisionDx DiffDx-Melanoma are designed to reduce uncertainty and provide confidence for dermatopathologists and help dermatologists deliver more informed patient management plans.

More information about the test and disease can be found at www.CastleTestInfo.com.

About Psoriasis, Atopic Dermatitis and Related Conditions

Inflammatory skin disease accounts for a significant number of patient visits to both primary care and dermatology clinics across the U.S. every year. Psoriasis and atopic dermatitis are among the most common inflammatory skin conditions, and patient quality of life is severely impacted by these chronic diseases. Fortunately, systemic medications developed over the past 15 years have demonstrated a significant improvement in patients’ lives. In the U.S. alone, there are about 18 million patients diagnosed with psoriasis and atopic dermatitis, and approximately 450,000 patients annually are eligible for these systemic therapies. While there are now many effective treatments options available for those with moderate to severe disease, current clinical practice relies on a trial-and-error approach for therapy selection. To answer this unmet clinical need, Castle Biosciences is developing a gene expression profile test designed to predict response to systemic therapies for patients with moderate to severe psoriasis, atopic dermatitis and other related diseases. Personalized guidance for therapy selection and anticipated efficacy has the potential to improve patient health outcomes by enabling clinicians to select the best medication for their patients’ specific skin disease.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

More information about the test and disease can be found at www.CastleTestInfo.com.