About Castle Biosciences Inc.

Anytime someone is diagnosed with cancer, many decisions have to be made regarding development of an optimal personalized treatment plan. Development of an optimal treatment plan requires accurate information regarding the diagnosis, prognosis and predicted responsiveness of a specific tumor – in other words accurate staging of the tumor. This information comes from several sources such as a physician's judgment based upon the physical signs and symptoms of a patient, traditional laboratory testing, and newer molecular testing.

Accurate information is required because all treatment plans (such as surgery, radiation, drug-therapy, surveillance, and even watching and waiting) have benefits and risks that the physician and patient need to weigh. These considerations help to determine an optimal treatment plan for that patient with that tumor at that time. Some cancers exhibit very little variation from patient to patient in terms of prognosis and predictive responsiveness. This means that the diagnosis, prognosis and predictive responsiveness achieved by traditional laboratory tests may be entirely appropriate to design an optimal treatment plan for a specific patient. Many cancers, however, exhibit a large variation in prognosis and predictive responsiveness from patient to patient. Often accurate information cannot be obtained through traditional laboratory testing alone – these cancers require the use of newer molecular tests to enable development of an optimal personalized treatment plan. Many common cancers have such molecular testing options available.

Unfortunately, development of molecular testing for rare cancers lags behind the advances made in common cancers. Sometimes testing has been developed in a given cancer institution and may be available only to patients treated at that institution.

At Castle Biosciences, we focus on addressing this gap. We work with leading cancer institutions to in-license proprietary technologies and complete development and validation. The ultimate goal is to make these proven tests available to all individuals afflicted with a rare cancer.

Licensing Opportunities

We are constantly responding to inquiries from leading cancer institutions regarding their technologies that may be appropriate for the patient afflicted with a rare cancer.

We use the following template when evaluating license opportunities:

Development efforts for (DecisionDx-GBM)

The proprietary DecisionDx-GBM gene expression profile test was discovered at The University of Texas M. D. Anderson Cancer Center for the purpose of increasing the accuracy of the prognosis and predicted responsiveness of glioblastoma multiforme to first line radiation plus temozolomide. The DecisionDx-GBM test is able to distinguish GBM tumors with a proneural phenotype (tumor signature) from those with a mesenchymal / angiogenic phenotype. Patients with a proneural phenotype tumor who are treated with first line radiation plus temozolomide experience a significantly longer median survival (over 7 years) compared to those patients with a mesenchymal / angiogenic phenotype tumor (approximately 1 year).

The assay has been fully validated and has been available for clinical use since 2008. The RTOG-0825 study is a two-arm, multi-center cooperative group study evaluating the first line use of bevacizumab (Avastin®, Genentech / Roche) with radiation plus temozolomide compared to radiation plus temozolomide ( http://www.cancer.gov/clinicaltrials/search/view?cdrid=640428&version=healthprofessional ). The DecisionDx-GBM molecular signature is one of two stratification factors used in this study. A secondary endpoint of the study is to determine whether the tumor molecular profile conferring a mesenchymal/angiogenic phenotype is associated with a selective increase in benefit from the addition of bevacizumab to temozolomide and radiotherapy. The study was initiated in April, 2009 and enrollment is now closed.

The RTOG-0525 study is a two-arm, multi-center cooperative group study evaluating two different dosing regimens of first line temozolomide. Topline results were presented at the American Society for Clinical Oncology in June, 2011. The DecisionDx-GBM molecular signature is being analyzed.

The DecisionDx-GBM test is also being incorporated into a number of other prospective and retrospective studies.

Development efforts for (DecisionDx-UM)

The proprietary DecisionDx-UM test was discovered at Washington University in St Louis in the laboratory of Dr. J. William Harbour.

The assay has been fully validated in uveal melanoma and has been available for clinical use since 2009.

The DecisionDx-UM test is also the subject of an ongoing, NCI sponsored study.

The DecisionDx-UM test is also used as an entry criteria in two, ongoing adjuvant protocols.

Preliminary data suggests that this assay may have application in other melanoma cancers.

Development efforts for (DecisionDx-EC)

The proprietary DecisionDx-EC test was discovered at The University of Texas M. D. Anderson Cancer Center for the purpose of predicting pathologic response to preoperative chemoradiation therapy in esophageal cancer (EC). The objective of the DecisionDx-EC test is to predict which patients may have a complete pathologic response to preoperative chemoradiation and which patients may be resistant to this regimen. This helps in the design of an optimal personalized treatment regimen.

The DecisionDx-EC test has completed assay development and clinical development. The verification study (n=60) demonstrated high sensitivity and specificity for detection of both the complete pathologic response group and the non-responsive group. The final validation study (n=167) was the focus of an NIH-sponsored grant and was completed in late 2010. Some of this data was presented at the American Society of Clinical Oncology (ASCO) in June, 2011.

We are currently completing the final steps of validation and anticipate having the DecisionDx-EC test available for clinical use in the next three months.

Preliminary data suggests that this assay may have application in other non-esophageal cancers.

Development efforts for (DecisionDx-Thymoma)

The proprietary DecisionDx-Thymoma test was discovered at Indiana University and exclusively licensed to Castle Biosciences Inc through the Indiana University Research and Technology Corporation. Thymomas and thymic cancers are rare. Controversy exists in the accurate prediction of an individual patient's risk of metastasis or recurrence. While histological classification and some clinical features such as tumor size, completeness of surgical excision and the presence of myasthenic symptoms provide some general information on likelihood of metastasis, these factors are based on small studies and are not optimal for predicting an individual patient's risk of metastasis.

The objective of the DecisionDx-Thymoma test is to provide an objective, accurate assessment of an individual patient's risk of metastasis so that appropriate, patient specific surveillance and treatment plans can be formulated and implemented.

Some of the developmental data was presented at the American Society of Clinical Oncology (ASCO) in June, 2011. The company is completing assay development and clinical validation. These studies are anticipated to be completed in early 2012.

Development efforts for BAP1

Drs. Harbour and Bowcock recently discovered the role of BAP1 as a predictor of metastasis in uveal melanoma (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087380/?tool=pmcentrez). Castle Biosciences exclusively licensed this technology from Washington University in St. Louis and is currently developing the technology for use in predicting the risk of metastasis in both uveal melanoma and cutaneous melanoma. The company also plans to investigate the role of BAP1 in metastasis in other cancers.