Transthyretin Amyloid Cardiomyopathy

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

AstraZeneca’s rare disease portfolio generated $7.76bn in global sales in 2023, as per the company’s Q4 financials. Image Credit: EllaSt / Shutterstock. AstraZeneca has signed a definitive agreement to acquire Amolyt Pharma, which specialises in therapies for rare endocrine diseases, in a deal worth $1.05bn. As per the contract, AstraZeneca will pay $800m upfront along with potential regulatory milestone payments of $250m. The deal is expected to close in Q3 2024. Amolyt’s lead candidate, eneboparatide (AZP-3601), was a central part of the acquisition. Eneboparatide is a subcutaneous parathyroid hormone receptor 1 (PTHR1) agonist for the treatment of hypoparathyroidism. This condition is caused by a deficiency in the parathyroid hormone that results in decreased calcium and elevated phosphorus levels in the blood. Dysregulation of parathyroid hormone can lead to osteoporosis and chronic kidney disease. Amolyt launched a Phase III CALYPSO trial (NCT05778071) for eneboparatide in May 2023. Topline data from the trial is expected by the end of this year. Another candidate in Amolyt’s pipeline is AZP-3813. The therapy is a peptide growth hormone receptor antagonist, which is being developed as a potential add-on to somatostatin analogues for the treatment of acromegaly, a condition associated with abnormally high secretion of growth hormone. It can lead to a variety of complications including heart failure and impaired glucose tolerance. The company initiated a Phase I trial for AZP-3813 in June 2023. See Also: Almirall to license Eloxx’s ZKN-013 for rare skin conditions Risk adjusted net present value: What is the current valuation of AstraZeneca’s AZD-3427? AstraZeneca’s rare disease portfolio generated $7.76bn in global sales in 2023, as per the company’s Q4 financials. The UK pharma giant has been investing heavily in rare disease therapies starting with the $39bn acquisition of Alexion in 2021. Last year, the company paid $1bn to acquire an early-stage gene therapy portfolio for rare diseases from Pfizer. According to a GlobalData report, innovation in rare diseases is seen as a risky investment, with rare oncology indications dominating most of the rare disease pipeline. GlobalData is the parent company of Pharmaceutical Technology . Despite this, AstraZeneca has seen some success amongst rare diseases that are not cancer-related. In September 2023, the Phase III trial for a rare vasculitis therapy, Fasenra (benralizumab), met its primary endpoint. The study found that Fasenra was non-inferior to the current standard of care, Pfizer’s Nucala (mepolizumab). Earlier this year, AstraZeneca reported positive outcomes from its Japan Phase III clinical trial of acoramidis, an investigational treatment for a rare cardiomyopathy, transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).

Bayer CEO Bill Anderson aims to rejuvenate the company's pharma pipeline, advance new strategies to address litigation, pay down debt and reduce bureaucracy. Bill Anderson, nine months into Bayer’s CEO role, has laid out his priorities for the troubled German conglomerate in the next few years—and it doesn’t involve an immediate business split-up as many investors had hoped for. Forgoing the hoity-toity podium on an elevated stage in exchange for a three-leg desk, Anderson during an investor day Tuesday presented four challenges at Bayer that he plans to address in the next two to three years: a weak pipeline at the pharma division, U.S. litigation, high debt levels and bureaucracy. As to separating pharma and consumer health from agriculture, “our answer is ‘not now’—and this shouldn’t be misunderstood as ‘never,’” Anderson said in a statement. Anderson is adopting the new strategy because of the limited options that Bayer has, and the goal, he said, is to boost Bayer’s performance to create “strategic flexibility” so that more ambitious moves could be possible. Anderson’s plan is both disappointing and reassuring for investors. They could be disappointed because despite years of outcries for a breakup, Bayer will remain in one piece for at least another two years. But Anderson articulated that separation remains an option that he’s willing to turn to once Bayer gains that “strategic flexibility.” “Virtually all our competitors are now pure-play, and it’s pretty clear why that happens—that is the simplest approach, and it’s got a lot of appeal,” Anderson said of a potential breakup. “That said, you also have to consider where your starting point is. Those four broken areas that I mentioned, they do limit our degrees of freedom.” Whatever form a separation may take, whether it’s an IPO or a spinoff, Bayer will have to put all hands on deck for at least two years to execute it. That means Bayer wouldn’t be able to simultaneously tackle the many other problems that the company is facing, Anderson said, citing his conversations with fellow CEOs who have done a business breakup. Bayer considered a potential sale of consumer health, Anderson said. But although such a deal would immediately give Bayer some cash to pay down debt, the tax losses would be significant, and Bayer would lose a business that’s reliably generating cash flow. Besides, consumer health businesses don’t boast the best valuations in recent years, he noted. But more importantly, a business separation wouldn’t address Bayer’s litigation problem around its Roundup weedkiller and polychlorinated biphenyls—both inherited from Monsanto—or the pharma patent cliff, Anderson said. Bayer’s two top-selling drugs, Johnson & Johnson-partnered blood thinner Xarelto and Regeneron-partnered eye med Eylea, are losing patent protection outside the U.S. up to around 2026. That’s why Bayer is launching a “full-scale effort” to rejuvenate its pharma pipeline, Anderson, a pharma veteran, wrote in a LinkedIn post. Bayer’s pharma pipeline has big upside potential, Anderson said, “but we got to make it happen.” To Anderson, Bayer has a strong early pipeline, with 13 new molecules that it’s moving into clinical studies over the last two years. “But we need more in phase 2 and phase 3,” Anderson said. Moving in that direction, Bayer on Monday unveiled a deal with BridgeBio, paying $310 million in upfront and near-term milestones for European rights to acoramidis, a potential rival to Pfizer’s blockbuster Vyndaqel heart disease franchise. A European Medicines Agency application for the drug in transthyretin amyloid cardiomyopathy was just filed in January. As for the litigation burden, Bayer is “updating its strategy and pursuing new approaches,” the company said Tuesday. It’s clear that “defense is not enough,” Andersons said Tuesday. “We’re going to look at litigation through every angle, both inside the courtroom and outside the courtroom. We have to thoroughly engage with more stakeholders on this because it’s not just a Bayer problem.” “You should expect to see considerably more action from us,” Anderson continued, “but we will only be talking about these things when and where it’s in our interests.” Bayer had already spent about 13 billion euros on litigation in the past five years and another 11.7 billion euros on dividends. As of the end of 2023, Bayer had 34.5 billion euros of net debt, which wasn’t so different from the 35.7 billion euros the company had as of the end of 2018, the year that the Monsanto acquisition closed. Bayer is already targeting its dividend to reduce its debt. A few days ago, the company said it would propose a dividend of 0.11 euro for 2023, compared with 2.4 euros for the prior year. Eventually, Bayer hopes to achieve an A credit rating.  To reduce bureaucracy, the company recently launched a restructuring that will cut managerial roles. The overhaul will take out 2 billion euros in annual organizational costs from 2026, according to Bayer. During Tuesday’s event, Anderson assured that the reorg wasn’t aimed at letting fewer people handle more tasks but at reducing the multiple hierarchy levels. “The problem at Bayer is not the culture—it’s the bureaucracy, it’s the layers, it’s the approvals,” Anderson said. “You can have all the positive culture you want, but if it takes five signatures to replace a pump in the plant, then the culture is not going to save you. This is the phenomenon we face at Bayer.” Anderson pointed to a 1,362-page rulebook that all employees are supposed to follow and a recent case in which a top-20 senior executive had to sign off on a 52,000-euro refund from a contractor, calling it “craziness.” “What I found is the people of Bayer are ready for change, they’re saying, bring it on,” Anderson said. With the new strategies kicking off, Bayer expects to generate sales of 47 billion to 49 billion euros in 2024 on a currency-adjusted basis, compared with 47.6 billion euros in 2023. Within the forecast, pharma is expected to drop 4% or stay flat, while consumer health is anticipated to grow 3% to 6%.