Cutaneous Mastocytosis

CAMBRIDGE, Mass., March 18, 2024 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today announced the first patient dosed in the global pivotal, Phase 3 MAGNITUDE trial of NTLA-2001. NTLA-2001 is an investigational in vivo CRISPR-based therapy designed as a single-dose treatment to inactivate the TTR gene and thereby prevent the production of TTR protein for the treatment of transthyretin (ATTR) amyloidosis. The MAGNITUDE trial is evaluating the efficacy and safety of NTLA-2001 in patients with ATTR amyloidosis with cardiomyopathy. “Dosing of the first patient in the MAGNITUDE trial of NTLA-2001 puts us one step closer to bringing a potential one-time gene editing treatment to people living with ATTR amyloidosis,” said Intellia President and Chief Executive Officer John Leonard, M.D. “With multiple sites now enrolling patients, including in the U.S., we are off to a great start to rapidly enroll this landmark study. MAGNITUDE was informed by the compelling interim Phase 1 results reported last year. These data showed that a single-dose treatment of NTLA-2001 resulted in deep and durable reductions of the TTR protein responsible for the clinical consequences of the disease. We look forward to evaluating the efficacy and safety of NTLA-2001 in patients with cardiomyopathy in the pivotal Phase 3 trial. Assuming a positive outcome, it will pave the way for future global marketing applications, ultimately supporting our goal to bring forth a groundbreaking therapy for the ATTR amyloidosis community.” “The diagnosis of ATTR amyloidosis, a life-threatening condition leading to heart failure and other complications, is rapidly increasing,” said Julian Gillmore, M.D., Ph.D., Professor of Medicine, National Amyloidosis Centre, UCL Division of Medicine, Royal Free Hospital, U.K., and the Phase 3 study’s national coordinating investigator. “We, along with our colleagues at Richmond Pharmacology, are thrilled to be the first to dose a patient in the pivotal trial of NTLA-2001, an in vivo CRISPR-based treatment that offers the potential to dramatically reset the standard of care for people living with this devastating disease. There is remarkable interest from the ATTR amyloidosis patient community for a potential single-dose treatment, and we look forward to contributing to the advancement of novel treatment approaches.” About the MAGNITUDE Study The pivotal Phase 3 MAGNITUDE clinical trial is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of NTLA-2001 in approximately 765 patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The primary endpoint of the study is a composite endpoint of cardiovascular (CV)-related mortality and CV-related events. Adult patients with hereditary or wild type ATTR-CM will be randomized 2:1 to receive a single 55 mg infusion of NTLA-2001 or placebo. For more information on MAGNITUDE (NCT06128629), please visit clinicaltrials.gov. About NTLA-2001Based on Nobel prize-winning CRISPR/Cas9 technology, NTLA-2001 has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis. NTLA-2001 is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein. NTLA-2001 is the first investigational CRISPR therapy to be administered systemically to edit genes inside the human body. Interim Phase 1 clinical data showed the administration of NTLA-2001 led to consistent, deep and long-lasting transthyretin (TTR) reduction. Intellia leads development and commercialization of NTLA-2001 as part of a multi-target discovery, development and commercialization collaboration with Regeneron. About Transthyretin (ATTR) Amyloidosis Transthyretin amyloidosis, or ATTR amyloidosis, is a progressive and fatal disease. Hereditary ATTR (ATTRv) amyloidosis occurs when a person is born with mutations in the TTR gene, which causes the liver to produce structurally abnormal transthyretin (TTR) protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system. ATTRv amyloidosis predominantly manifests as polyneuropathy (ATTRv-PN), which can lead to nerve damage, or cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some individuals without the genetic mutation produce non-mutated, or wild-type, TTR proteins that become unstable over time, misfolding and aggregating in disease-causing amyloid deposits. This condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily affects the heart. There are an estimated 50,000 people worldwide living with ATTRv amyloidosis and between 200,000 and 500,000 people with ATTRwt amyloidosis. There is no known cure for ATTR amyloidosis and currently available medications are limited to slowing accumulation of misfolded TTR protein. About Intellia Therapeutics Intellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. The company’s in vivo programs use CRISPR to enable precise editing of disease-causing genes directly inside the human body. Intellia’s ex vivo programs use CRISPR to engineer human cells outside the body for the treatment of cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its people, is helping set the standard for a new class of medicine. To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies. Learn more at intelliatx.com and follow us @intelliatx. Forward-Looking Statements This press release contains “forward-looking statements” of Intellia Therapeutics, Inc. (“Intellia” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellia’s beliefs and expectations regarding: the safety, efficacy, success and advancement of its clinical program for NTLA-2001 for transthyretin (“ATTR”) amyloidosis pursuant to its clinical trial applications and investigational new drug submission, including its ability to rapidly enroll and complete the Phase 3 Magnitude study; the success of its Phase 3 Magnitude study; its submission of global marketing applications; and its ability to bring forth NTLA-2001 as a groundbreaking therapy to the ATTR amyloidosis community and dramatically reset the standard of care. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellia’s ability to protect and maintain its intellectual property position; risks related to Intellia’s relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the authorization, initiation, enrollment and conduct of studies and other development requirements for its product candidates, including NTLA-2001; the risk that any one or more of Intellia’s product candidates, including NTLA-2001, will not be successfully developed and commercialized; and the risk that the results of preclinical studies or clinical studies, such as the Phase 1 clinical study of NTLA-2001, will not be predictive of future results in connection with future studies for the same product candidate or Intellia’s other product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellia’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Intellia’s most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law. Intellia Contacts: Investors:Ian KarpSenior Vice President, Investor Relations and Corporate Communicationsian.karp@intelliatx.com Lina LiSenior Director, Investor Relations and Corporate Communications lina.li@intelliatx.com Media:Matt CrensonTen Bridge Communicationsmedia@intelliatx.commcrenson@tenbridgecommunications.com

ROTTERDAM, The Netherlands and SAN DIEGO, March 8, 2024 /PRNewswire/ -- SkylineDx, an innovative molecular diagnostics company, announces the forthcoming presentation of an impactful poster by Dr. Yu, from University Hospital Cleveland Medical Center, at the upcoming AAD Annual Meeting in San Diego. The abstract concludes that the CP-GEP assay improved risk stratification for nodal metastasis and disease recurrence in patients with cutaneous melanoma [1]. Cutaneous melanoma patients diagnosed over a period of 10 years at University Hospital Cleveland Medical Center undergoing a surgical procedure to determine metastatic spread to their lymph nodes, were analyzed with the non-invasive CP-GEP assay marketed by SkylineDx as Merlin test. Merlin classified these patients as either at low risk or high risk for developing nodal metastasis and disease recurrence. Out of 176 patients, Merlin identified 66 patients as low risk. These patients could have forgone the surgical procedure due to their low risk for having metastasis in the sentinel lymph nodes, equaling reducing the surgery rate by 37.5%. Furthermore, the Merlin low-risk patients have a significant better long-term survival outcome compared to the Merlin high-risk group, 93.6% versus 79.4% for Recurrence Free Survival and 98% versus 91.4% for Melanoma Specific Survival, respectively. The analysis unveiled Merlin test's pivotal role in effectively stratifying CM patients based on their risk of disease recurrence. The poster will be presented on March 9, 8:50AM at AAD (San Diego Convention Center, Upper Level, Sails Pavilion, Poster Center 20). SkylineDx's Chief Scientific Officer, Jvalini Dwarkasing comments: "The study's results confirm that in this institute, the CP-GEP model has potential in optimizing patient management strategies. Recurrence events may be more effectively captured by this test as compared to current standard of care." About CP-GEP CP-GEP is a non-invasive prediction model for cutaneous melanoma patients that combines clinicopathologic (CP) variables with gene expression profiling (GEP). This model is able to identify cutaneous melanoma patients at low-risk for nodal metastasis who may forgo the sentinel lymph node biopsy (SLNB) procedure. The CP-GEP model was developed by Mayo Clinic and SkylineDx BV and it has been clinically validated in multiple studies More information (including references) may be obtained at . The test has been launched in the United States and Europe as Merlin test. SkylineDx collaborates with diagnostic service providers globally to bring this test to market and increase the access. In the United States, Tempus is commercializing Tempus Merlin test. Quest Diagnostics launched their own LDT version of the CP-GEP model in the United States, under the brand name MelaNodal Predict™. About SkylineDx SkylineDx is a biotechnology company focused on research & development of molecular diagnostics in oncology and inflammatory diseases. SkylineDx uses its expertise to bridge the gap between academically discovered gene expression signatures and commercially available diagnostic products with high clinical utility, assisting healthcare professionals in accurately determining the type or status of disease or predicting a patient's response to treatment. Based on test results, healthcare professionals can tailor the treatment approach to the individual patient. SkylineDx is headquartered in Rotterdam. the Netherlands, complemented by a U.S. base of operations and a CAP/CLIA certified laboratory in San Diego California, USA. To learn more about SkylineDx, please visit . Footnotes 1. Hill et al. Primary cutaneous melanoma patients stratified by the Merlin assay (CP-GEP): risk of nodal metastasis and long-term survival outcome in a U.S. cohort. Abstract selected for poster presentation at AAD Annual Meeting 2024. Abstract AAD2024 Hill and Yu.pdf (falconprogram.com) SOURCE SkylineDx

Castle’s presentations at AAD include the latest findings from the Company’s ongoing collaboration with the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program Registries, providing new data from a study of more than 5,000 patients confirming that testing with DecisionDx®-Melanoma is associated with improved survival in patients with cutaneous melanoma (CM) FRIENDSWOOD, Texas--(BUSINESS WIRE)-- Castle Biosciences Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced that it will share data across its dermatologic portfolio of gene expression profile (GEP) tests via oral and electronic poster presentations at the 2024 AAD Annual Meeting, taking place March 8-12 in San Diego. “Our presentations at the 2024 AAD Annual Meeting add to the growing body of evidence supporting the use of our tests in guiding improved, personalized care for patients with skin cancers,” said Robert Cook, Ph.D., senior vice president of research and development at Castle Biosciences. “In collaboration with leading dermatologists dedicated to advancing patient care, we are excited to share our latest findings which highlight how our tests are empowering both clinicians and patients with meaningful, clinically actionable information that can refine risk and inform important treatment decisions.” Castle will present the following abstracts at AAD. Abstract content will be available throughout the meeting in the online viewing portal and at the on-site viewing stations, and will also be published online in the Fall 2024 Journal of the American Academy of Dermatology (JAAD) supplement. DecisionDx®-Melanoma Oral Poster Presentation Title: 31-GEP testing is associated with improved melanoma-specific survival relative to untested patients: an analysis of patients <65 years old Presenter and Lead Author: Michael Tassavor, M.D., Skin Cancer Center, Cincinnati Abstract Number: 51667 Date: March 9, 2024 Time: 4:50-4:55 p.m. Pacific Time Location: San Diego Convention Center (Upper Level, Sails Pavilion, Poster Center 1) Summary: For patients with CM, the median age at diagnosis is 66 years old, suggesting that almost half of newly diagnosed patients are younger than 65. In this large study of unselected, clinically tested patients with CM who were under 65 (n=5,183), the DecisionDx-Melanoma (31-GEP) test identified patients at higher risk of melanoma-specific death who may benefit from more aggressive management, including imaging surveillance. In the study, use of the DecisionDx-Melanoma test was associated with improved melanoma-specific survival relative to untested patients. This is clinically significant, as identifying high-risk patients allows for earlier detection of recurrence, while the tumor burden is lower, which has been shown to lead to better response to therapy. DecisionDx®-SCC Oral Poster Presentation Title: Consistent utilization of the 40-gene expression profile (40-GEP) test in high-risk cutaneous squamous cell carcinoma (cSCC) by clinicians according to intended use indications Presenter and Lead Author: Jane Yoo, M.D., Icahn School of Medicine at Mount Sinai, New York Abstract Number: 54153 Date: March 9, 2024 Time: 10:30-10:35 a.m. Pacific Time Location: San Diego Convention Center (Upper Level, Sails Pavilion, Poster Center 2) Summary: This study provides summary metrics regarding DecisionDx-SCC (40-GEP) test results and patient risk factors for tumor samples clinically tested in the first three years of the test’s availability between September 2020 and August 2023 (n=16,930). The study data demonstrate that clinicians are utilizing the DecisionDx-SCC test appropriately for patients with high-risk cutaneous squamous cell carcinoma (SCC). These patients are at a higher risk of poor outcomes compared to the general SCC patient population, yet over 70% of patients received a Decision-SCC Class 1 test result, indicating they are at a lower biological risk for metastasis. Each DecisionDx-SCC Class result was present in the various subgroupings of risk factors in the study (patients with 1-2, 3-4 and more than 5 risk factors), demonstrating that the test provides independent risk assessment from clinicopathological presentation. These data support incorporating the test’s results into clinical practice to improve the accuracy of risk predictions to guide more personalized treatment plans for patients. MyPath® Melanoma ePoster Title: Enabling access to prognostic gene expression profile (GEP) testing for invasive melanoma by leveraging RNA-based testing in the diagnostic workflow Abstract Number: 52819 Summary: Reaching a definitive diagnosis of melanoma can be challenging. Ancillary testing can provide clarity and a definitive diagnosis for problematic lesions. The MyPath Melanoma (23-GEP) diagnostic test returns accurate results quickly, with approximately 80% of cases tested receiving an actionable result in a median of four business days. Between March 1 and July 31, 2023, approximately 60% of ambiguous lesions tested with MyPath received a benign test result, potentially reducing overdiagnosis and overtreatment for diagnostically challenging lesions. Lesions that receive a malignant test result (approximately 20% of lesions tested with MyPath in the five-month study timeframe) can be tested with the DecisionDx-Melanoma risk stratification test, using the same extracted tumor material when available, to inform risk-aligned decisions about sentinel lymph node biopsy, surveillance imaging and patient follow-up schedules. Approximately 80% of clinically tested lesions with a malignant MyPath result have sufficient biopsy tumor content for DecisionDx-Melanoma testing. About DecisionDx-Melanoma DecisionDx-Melanoma is a gene expression pro stratification test. It is designed to inform two clinical questions in the management of cutaneous melanoma: a patient’s individual risk of sentinel lymph node (SLN) positivity and a patient's personal risk of melanoma recurrence and/or metastasis. By integrating tumor biology with clinical and pathologic factors using a validated proprietary algorithm, DecisionDx-Melanoma is designed to provide a comprehensive and clinically actionable result to guide risk-aligned patient care. DecisionDx-Melanoma has been shown to be associated with improved patient survival and has been studied in more than 10,000 patient samples. DecisionDx-Melanoma’s clinical value is supported by 50 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test’s results. Through Dec. 31, 2023, DecisionDx-Melanoma has been ordered more than 150,000 times for patients diagnosed with cutaneous melanoma. About DecisionDx-SCC DecisionDx-SCC is a 40-gene expression pro 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), Class 2A (higher) or Class 2B (highest) 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. About MyPath Melanoma MyPath Melanoma is Castle’s gene expression pro designed to provide an accurate, objective result to aid dermatopathologists and dermatologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately two 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 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 is designed to reduce uncertainty and provide confidence for dermatopathologists and help dermatologists deliver more informed patient management plans. About Castle Biosciences Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. The Company aims to transform disease management by keeping people first: patients, clinicians, employees and investors. Castle’s current portfolio consists of tests for skin cancers, Barrett’s esophagus, mental health conditions and uveal melanoma. Additionally, the Company has active research and development programs for tests in other diseases with high clinical need, including its test in development to help guide systemic therapy selection for patients with moderate-to-severe atopic dermatitis, psoriasis and related conditions. To learn more, please visit and connect with us on LinkedIn, Facebook, X and Instagram. DecisionDx-Melanoma, DecisionDx-CMSeq, DecisionDx-SCC, MyPath Melanoma, DiffDx-Melanoma, TissueCypher, IDgenetix, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning: the ability of our tests to (i) guide improved, personalized care for patients with skin cancers and (ii) provide meaningful, clinically actionable information that can refine risk and inform important treatment decisions. The words “believe,” “can” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results obtained in these studies, including with respect to the discussion of our tests in this press release; actual application of our tests may not provide the aforementioned benefits to patients; and the risks set forth under the heading “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law.