Amyloidosis

ST. LOUIS--( BUSINESS WIRE )--New research finds that C₂N Diagnostics, LLC’s proprietary algorithm used in its PrecivityAD2 blood test, which is used by healthcare providers to determine Alzheimer’s disease (AD) pathology in individuals with early cognitive impairment, can identify brain amyloid status with “sensitivity, specificity, positive and negative predictive values that approximate those of amyloid positron emission tomography (PET) imaging.” C₂N Diagnostics believes the findings in “ Alzheimer's & Dementia: The Journal of the Alzheimer's Association ” are significant as the healthcare sector needs a PET scan alternative that’s widely accessible, accurate and cost-effective that can aid in the differential diagnosis of AD and AD-related dementias. The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2 (APS2), was 0.94, yielding 88% agreement with brain amyloid status based on a single cut-off value. Diagnostic performance of the APS2 was similar by ethnicity, sex, age and apoE4 status. The APS2 result was the most robust method among the individual plasma amyloid and tau analytes measured to identify disease. The research findings also showed that the AUC-ROC for the %p-tau217 (0.94), one of the core components of the APS2 algorithm, was superior to that for the p-tau217 concentration (0.91) for identifying brain amyloidosis. The researchers define %p-tau217 as the percentage of p-tau217 relative to np-tau217. These data showing the superiority of %p-tau217 over p-tau217 alone reaffirm the findings of another ground-breaking study recently published involving C 2 N’s technology to identify amyloid pathology in pre-clinical AD with high accuracy comparable to amyloid PET. Data Give Healthcare Providers Assurance as Patients Want Answers In the published study, the PrecivityAD2 blood test was clinically validated in 583 individuals with cognitive impairment across two independent cohorts. The robustness of the findings was enhanced by the fact that one of the study cohorts, PARIS, included a prospective, difficult-to-diagnose, real-world population of U.S. Medicare beneficiaries presenting with memory concerns to clinics as part of a substudy of IDEAS 1 . The PrecivityAD2 blood test determines a patient’s likelihood (positive or negative) for the presence of amyloid plaques in the brain, one of the brain pathology findings of Alzheimer’s disease. In addition to helping healthcare providers determine Alzheimer’s disease pathology, the PrecivityAD2 test aids in medical management and treatment decisions. Dr. Joel Braunstein, C₂N’s CEO says, “This latest research adds to the growing body of data that affirms the PrecivityAD2 test’s outstanding diagnostic performance and builds further confidence in the healthcare sector. The PrecivityAD2 blood test provides a less costly, more accessible and vitally needed option for healthcare providers who must conduct diagnostic testing for their patients facing memory and dementia care issues. We’re excited that additional studies are underway throughout the world that are seeking to further demonstrate the robust clinical performance and generalizability of the APS2 model.” Dr. Braunstein and others note the PrecivityAD2 test’s appeal because of PET’s limitations for screening large number of patients as new disease-modifying drugs that can specifically treat the underlying causes of AD become available. These limitations include: PET’s cost for research use (currently estimated at around $6,500); that it exposes patients to radiation; and that it’s not easily accessible outside of large cities. The PrecivityAD2 blood test is intended for use in patients aged 55 and older with signs or symptoms of mild cognitive impairment or dementia who are undergoing evaluation of Alzheimer’s disease or dementia. Only a healthcare provider can order the PrecivityAD2 test. The test is available in 49 states, the District of Columbia and Puerto Rico; the exception is New York, which requires an individual state process for CLIA labs. C₂N is working toward obtaining the requisite certification that will permit the PrecivityAD2 test to be available in New York in the near future. Healthcare providers interested in ordering the PrecivityAD2 test can call 1.877.C2N.DIAG (226.3424) or visit https://precivityad.com . About C 2 N Diagnostics, LLC C ₂ N is a specialty diagnostics company with a vision to bring Clarity Through Innovation®. C ₂ N strives to provide exceptional clinical laboratory services and advanced diagnostic solutions in the field of brain health. C ₂ N’s high-resolution mass spectrometry-based biomarker services and products are used for: clinical decision-making to improve patient care, including diagnosis and treatment monitoring; maximizing the quality and efficiency of clinical trials that test novel treatments for neurodegeneration; and providing innovative tools to help healthcare researchers better understand novel mechanisms of disease, identify new treatment targets, and conduct important epidemiologic studies to improve global public health. C ₂ N assays have been used in over 150 Alzheimer’s disease and other research studies throughout the U.S. and the world. This includes landmark treatment and prevention trials involving disease-modifying therapies (DMTs) that are changing the trajectory of Alzheimer’s disease. C ₂ N has ongoing collaborations with multi-national pharmaceutical and biotech companies, leading academic institutions, National Institute on Aging, Alzheimer’s Association, and other non-profits and consortiums. Over 15,000 Precivity™-related biomarker measures have been reported through peer-reviewed publications, with many more manuscripts currently under review. The company acknowledges generous support from National Institute on Aging, GHR Foundation, Alzheimer’s Drug Discovery Foundation, BrightFocus Foundation and Alzheimer’s Association. For more information visit www.C2N.com . 1 www.ideas-study.org/Original-Study ; ClinicalTrials.gov Identifier: NCT02420756.

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

Dive Brief:AstraZeneca is bolstering its rare disease division with the purchase of Amolyt Pharma, an endocrine disease specialist backed by Novo Holdings.Under the deal announced Thursday, AstraZeneca will pay Amolyt shareholders $800 million in cash up front, with the potential for another $250 million for reaching a specific regulatory milestone. The companies expect the transaction to close in the third quarter.For AstraZeneca, the jewel of the acquisition is eneboparatide, a drug in Phase 3 testing to treat patients with hypoparathyroidism. The disease, which mostly affects women, is caused by a deficiency in parathyroid production that lowers calcium in the blood and can lead to debilitating symptoms including kidney disease. It affects about 115,000 people in the U.S.Dive Insight:The $39 billion acquisition of Alexion three years ago instantly transformedAstraZeneca into a major player in rare diseases. Since then, the U.K. drugmaker has been selectively picking up additional assets.In September 2021, the company exercised an option to buy the rest of rare disease drugmaker Caelum Biosciences for $150 million. A few months later, AstraZeneca struck two deals in transthyretin amyloidosis, paying $30 million to Switzerlands Neurimmunefor rights to an experimental therapy and inking a development pact with Ionis Pharmaceuticals for a drug that won approval in late 2023.AstraZeneca is also using its foothold in rare diseases to make forays into genetic medicine, acquiring gene-editing specialist LogicBio Therapeutics and scooping up Pfizers early gene therapy work for as much as $1 billion. And last year, the company announced plans to work with Quell Therapeutics to develop cell-based treatments for autoimmune diseases.Amolyt has moved from a startup with preclinical assets to a Phase 3 company in less than five years. Its largest investor is Novo Holdings, the controlling shareholder of both Novo Nordisk and Novozymes. Owned by the Novo Nordisk Foundation, Novo Holdings co-led the Series A financing for Amolyt in 2019 and added to its investment with Series B and Series C funding rounds.In addition to eneboparatide, Amolyt has an experimental drug called AZP-3813 designed as a potential treatment for acromegaly, which occurs when the body makes too much growth hormone. '