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Rambam Hospital Trials Gene Therapies For Non-genetic Diseases

To date, genetically modified therapies have been mainly intended for people suffering from rare genetic diseases. Gaining traction, however, is the idea that gene editing can also be used to treat diseases that are not necessarily hereditary or rare. Only recently, a gene therapy developed by US firm Intellia Therapeutics was first trialed at Rambam Health Care Campus to treat a non-hereditary genetic disease: Transthyretin cardiac amyloidosis (ATTR-CA). A therapy for non-genetic high cholesterol is being tested in locations around the world; its mechanism is similar to that of the ATTR-CA product being tested at Rambam.

Disease no longer a death sentence

Amyloidosis is an umbrella term for diseases characterized by the accumulation of proteins in excessive quantities or in the wrong places, explains Dr. Oren Caspi, Director of the Heart Failure Unit and Head of Rambam's Cardiovascular Research and Innovation Center, who led the clinical trial with Dr. Sirouch Petcherski and Dr. Aharon (Ronnie) Abbo. Genes are the program by which proteins are encoded. When there is a defect in the coding chain - from DNA to protein - proteins may form that do not fold well and therefore end up in the wrong place, or the system that is supposed to break them down fails, creating an unnecessary accumulation of proteins.

In ATTR-CA, the proteins do not fold well because of a genetic defect or, more commonly, due to old age. The accumulation of proteins causes heart failure, cardiac arrhythmias, and even death. It is estimated that about 5% of those diagnosed with heart failure have this type of amyloidosis.

"When I studied medicine, this disease was considered serious and even terminal," Caspi says. However, in recent years, there have been extremely rapid developments in its treatment. "In 2016, an article was published for the first time showing that the disease can be identified with a relatively simple test. The race to develop a drug began immediately, and there has been one on the market for over two years. But the existing drug doesn't stop the deterioration, it only slows it down."

An easier solution for patients

Two features of the disease make it well-suited to treatment with genetic editing. First, the body can function without large amounts of the protein, meaning its production can safely be halted. Second, the protein is produced in the liver, an organ that readily absorbs genetically edited therapies.

The drug, based on Nobel Prize-winning gene-editing technology CRISPR-Cas9, reaches the liver cells and splices out the defective gene so that it cannot manufacture the protein that causes the disease. Once treated, the change to the liver cells is irreversible.

This gene therapy is designed to halt the progression of the disease. It offers long-term benefit - potentially as a one-time treatment, though in some cases periodic maintenance may be needed over months or years as liver cells regenerate. When administered early, it can even prevent heart failure from developing. For older patients, the hospital notes, the prospect of infrequent treatment is especially valuable, as managing complex drug regimens can be particularly challenging for them

The existence of such a treatment increases the incentive to detect those whose heart failure is due to amyloidosis, even before the condition worsens, in a way that will save high costs of treatment. "This is really personalized medicine, which can bring about a complete change in the course of the disease, and we are interested in helping additional patients as part of the research that continues to take place at Rambam," says Dr. Abbo.

What does the treatment look like?

Caspi: "The patient receives the drug intravenously. Before that, they receive immunosuppressive therapy, because we know that the body can have an immune response, not to the drug itself, but to the envelope in which the drug is delivered. Immunosuppression is only for the course of treatment."

And we know there's no other changes aside from the gene you intended to edit?

"In pre-clinical trials, that is, in animals, it has been demonstrated many times that there are no such changes. We strongly believe in the safety levels of the product, but of course this is also part of what is tested in the trial."

A promising cholesterol trial

Genetically modified drugs are already being used today to treat hereditary diseases resulting from a defect in a single gene, such as beta thalassemia or sickle cell anemia. Until now, there have been no such drugs to treat the disease, which develops with age. The advantage in the case of amyloidosis is that the mechanism that produces protein in the body can be halted almost without any damage. There are other diseases with this potential, Caspi and Abbo say. One of the most interesting of them is hypercholesterolemia or high cholesterol.

Intellia, the company for which Caspi and his group conducted the current experiment, is one of the companies operating in this field, along with companies such as CRISPR Therapeutics, Beam Therapeutics, and Verve, which is expected to be acquired soon by Eli Lilly for $1-1.3 billion.

Although cholesterol itself is a fatty substance rather than a protein, the therapeutic goal is to target the genes that encode the proteins responsible for regulating cholesterol levels in the body. The treatment is designed to replicate a naturally occurring genetic mutation found in a subset of the population, which results in lower cholesterol production-without causing them any harmful health effects

In an initial trial by CRISPR Therapeutics, the results of which were published last May, there was a substantial reduction in the patients' levels of "bad" cholesterol and triglycerides. The trial subjects had particularly high cholesterol levels, due to genetic mutation, or else they simply had abnormally high cholesterol levels. In the future, the treatment may also be relevant to a wider population, those with moderate cholesterol levels regardless of origin -- usually a combination of hereditary and environmental factors. So far, no problematic side effects have been observed for the treatment.

Verve is expected to present results in the coming months from a larger trial, using a slightly different mechanism, of a gene-edited anti-cholesterol drug.

Existing cholesterol medications, such as statins, are effective and safe in most of the population, but cause side effects in some patients, and the regimen can be complex and burdensome. Long-term treatment may be an advantageous alternative.

The politics of approvals

In the meantime, any gene therapy will have to go through the US Food and Drug Administration's Center for Biologics Evaluation and Research. Recently, Dr. Vinayak "Vinay" Prasad was appointed head of this division. He is considered tough in terms of the requirements he sets for pharmaceutical companies. Two weeks ago, Prasad was fired from his position, due to doubts about the extent of his support for US President Donald Trump and following the halt in marketing Sarepta's gene therapy for Duchenne muscular dystrophy. At the end of last week, it was decided to reinstate him. If Prasad does remain in his position for a long time, his tough approach may affect the speed at which these treatments will reach the market, but it will mean we can assume that they were tested rigorously and thoroughly.

Published by Globes, Israel business news - en.Globes.Co.Il - on August 21, 2025.

© Copyright of Globes Publisher Itonut (1983) Ltd., 2025.


Lexeo Therapeutics Announces Strategic Partnership And Up To $40 Million In Financing For Advancement Of RNA-based Therapies In Cardiac Genetic Diseases

Lexeo Therapeutics partners for $40 million investment to develop RNA-based therapies for genetic cardiac diseases using non-viral delivery technology.

Quiver AI Summary

Lexeo Therapeutics, Inc. Announced a strategic partnership aimed at developing therapies for genetic cardiac diseases using a new non-viral RNA delivery platform, supported by up to $40 million in private equity financing from Perceptive Xontogeny Venture Funds and venBio Partners. This collaboration will leverage Lexeo's expertise and existing preclinical intellectual property to create an innovative entity focused on advancing RNA-based therapeutics, which address cardiovascular conditions that current adeno-associated virus (AAV) platforms cannot treat. Lexeo will retain a significant equity position in the new entity and expects to receive future milestone payments and royalties. Both investors emphasize the potential of RNA therapeutics in transforming cardiac treatment strategies as the genetic cardiology market continues to grow significantly in the coming years.

Potential Positives
  • Secured up to $40 million in private equity financing from reputable investors, enhancing financial backing for future initiatives.
  • Development of a new entity focused on advancing novel RNA-based therapeutics, indicating a commitment to innovative treatment approaches in cardiovascular medicine.
  • Positioned to take advantage of a growing market estimated to be worth up to $40 billion by 2033, indicating significant business potential.
  • Lexeo's contributions include expertise and intellectual property, resulting in equity ownership and potential future milestone payments, which may strengthen the company's financial position.
  • Potential Negatives
  • Announcement of a new entity to address cardiac genetic diseases may indicate that existing AAV platforms used by Lexeo are inadequate, raising concerns about the effectiveness of their current technologies.
  • The need to secure private equity financing suggests potential liquidity issues or challenges in attracting investment for internal projects, which may signal instability or lack of confidence from the market.
  • The forward-looking statements caution about risks and uncertainties may undermine investor confidence, indicating that actual outcomes may differ significantly from expectations.
  • FAQ What is Lexeo Therapeutics' latest funding announcement about?

    Lexeo Therapeutics announced up to $40 million in financing for a new entity focused on treating cardiac genetic diseases using non-viral RNA delivery.

    How will the $40 million financing impact current Lexeo shareholders?

    The financing is non-dilutive to existing Lexeo shareholders, meaning their ownership stakes will not be reduced.

    What innovative platform will be utilized in this partnership?

    The partnership will employ a novel non-viral RNA delivery platform to advance therapies for genetically mediated cardiac conditions.

    What is the projected market size for genetic cardiology?

    The genetic and precision cardiology market is expected to grow from over $13 billion in 2025 to nearly $40 billion by 2033.

    What expertise does Lexeo contribute to the new entity?

    Lexeo will provide its expertise in cardiac genetic medicines, preclinical intellectual property, and technology for developing RNA-based therapeutics.

    Disclaimer: This is an AI-generated summary of a press release distributed by GlobeNewswire. The model used to summarize this release may make mistakes. See the full release here.

    $LXEO Insider Trading Activity

    $LXEO insiders have traded $LXEO stock on the open market 8 times in the past 6 months. Of those trades, 0 have been purchases and 8 have been sales.

    Here's a breakdown of recent trading of $LXEO stock by insiders over the last 6 months:

  • RICHARD NOLAN TOWNSEND (Chief Executive Officer) has made 0 purchases and 2 sales selling 5,400 shares for an estimated $22,069.
  • ERIC ADLER (Chief Medical Officer) has made 0 purchases and 2 sales selling 2,944 shares for an estimated $12,033.
  • JENNY ROBERTSON (Chief Legal Officer) has made 0 purchases and 2 sales selling 2,622 shares for an estimated $10,716.
  • TAI SANDI SEE (Chief Development Officer) has made 0 purchases and 2 sales selling 1,853 shares for an estimated $7,575.
  • To track insider transactions, check out Quiver Quantitative's insider trading dashboard.

    $LXEO Hedge Fund Activity

    We have seen 42 institutional investors add shares of $LXEO stock to their portfolio, and 48 decrease their positions in their most recent quarter.

    Here are some of the largest recent moves:

  • ADAGE CAPITAL PARTNERS GP, L.L.C. Removed 1,971,662 shares (-89.2%) from their portfolio in Q1 2025, for an estimated $6,841,667
  • AFFINITY ASSET ADVISORS, LLC added 1,480,881 shares (+inf%) to their portfolio in Q1 2025, for an estimated $5,138,657
  • EVENTIDE ASSET MANAGEMENT, LLC removed 1,234,834 shares (-100.0%) from their portfolio in Q1 2025, for an estimated $4,284,873
  • D1 CAPITAL PARTNERS L.P. Removed 1,225,248 shares (-55.6%) from their portfolio in Q1 2025, for an estimated $4,251,610
  • MILLENNIUM MANAGEMENT LLC added 929,538 shares (+654.8%) to their portfolio in Q1 2025, for an estimated $3,225,496
  • BRAIDWELL LP removed 728,777 shares (-100.0%) from their portfolio in Q4 2024, for an estimated $4,795,352
  • AVIDITY PARTNERS MANAGEMENT LP added 645,000 shares (+inf%) to their portfolio in Q1 2025, for an estimated $2,238,150
  • To track hedge funds' stock portfolios, check out Quiver Quantitative's institutional holdings dashboard.

    Full Release

    Up to $40 Million Private Equity Financing into a New Entity Addressing Cardiac Genetic Diseases that Existing AAV Platforms are Unable to Treat

    Lexeo Contributing Expertise and Know-How in Cardiac Genetic Medicines, Preclinical Intellectual Property, and Technology, in Combination with Novel Non-Viral RNA Delivery Platform

    Represents Pipeline Diversification and Advancement of Leading-Edge Cardiovascular Science

    NEW YORK, June 24, 2025 (GLOBE NEWSWIRE) --Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering novel treatments for cardiovascular diseases, today announced a strategic partnership to develop therapies for genetic cardiac diseases utilizing a novel non-viral RNA platform. Combined with investment of up to $40 million from leading life-sciences investors Perceptive Xontogeny Venture Funds ("PXV Funds") and venBio Partners ("venBio"), the partnership seeks to further revolutionize the treatment of cardiovascular diseases. The proceeds will be used to seed a new entity, the funding of which is non-dilutive to existing Lexeo shareholders.

    "Delivery of DNA by adeno-associated virus has defined the first wave of genetic medicine, with potential to treat cardiovascular diseases that other modalities cannot address today. Over the next decade, however, new modalities will emerge allowing genetic medicines to treat an even broader range of cardiac diseases, and RNA therapeutics mediated by non-viral delivery are representative of this future," said R. Nolan Townsend, Chief Executive Officer of Lexeo Therapeutics. "This partnership reflects an innovative approach to realize the therapeutic and economic value of promising preclinical science in a manner that benefits all stakeholders."

    Under the terms of the agreement, the new entity will be focused on advancing research for novel RNA-based therapeutics via non-viral delivery for the treatment of genetically mediated cardiac conditions. Lexeo will contribute its expertise in developing cardiac genetic medicines, certain existing preclinical intellectual property, and technology, which will be combined with a novel non-viral delivery platform.   As consideration for its contributions, at transaction close Lexeo has received a double-digit percentage equity position in the new entity and will be entitled to future milestone payments, royalties, and opt-in rights to certain program(s).

    "The genetic and precision cardiology market is estimated to be worth over $13 billion this year, and it is expected to grow to almost $40 billion by 2033," said Fred Callori, PXV Funds Managing Director. "We see this as one of the most promising areas in biotech, where there is both a significant need and clear opportunity for innovation through the development of RNA therapeutics for cardiac disease. This collaboration brings together the right expertise, science, and strategic areas of focus to pursue and advance these treatments."

    Corey Goodman, venBio Managing Partner, added: "Lexeo is a leader in cardiac genetic medicine and there is a significant unmet need for broadening precision approaches in this category. We look forward to working with Lexeo to launch this new entity and foster innovation that has the potential to fundamentally change the treatment paradigm for patients with devastating heart conditions."

    About Lexeo Therapeutics

    Lexeo Therapeutics is a New York City-based, clinical stage genetic medicine company dedicated to reshaping heart health by applying pioneering science to fundamentally change how cardiovascular diseases are treated. The Company is advancing a portfolio of therapeutic candidates that take aim at the underlying genetic causes of conditions, including LX2006 for the treatment of Friedreich ataxia (FA) cardiomyopathy, LX2020 for the treatment of plakophilin-2 (PKP2) arrhythmogenic cardiomyopathy, and others for devastating diseases with high unmet need.

    Cautionary Note Regarding Forward-Looking Statements

    Certain statements in this press release may constitute "forward-looking statements" within the meaning of the federal securities laws, including, but not limited to, Lexeo's expectations regarding the new entity, the new entity's ability to obtain future financing, the amount of financing that the new entity may raise, the emergence of genetic medicines to treat cardiac diseases, Lexeo's ability to receive future milestone payments, royalties and opt-in rights through the partnership, and the estimate of the genetic and precision cardiology market. Words such as "may," "might," "will," "objective," "intend," "should," "could," "can," "would," "expect," "believe," "design," "estimate," "predict," "potential," "develop," "plan" or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While Lexeo believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements. These forward-looking statements are based upon current information available to the company as well as certain estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in Lexeo's filings with the U.S. Securities and Exchange Commission (SEC)), many of which are beyond the company's control and subject to change. Actual results could be materially different from those indicated by such forward-looking statements as a result of many factors, including but not limited to: risks and uncertainties related to global macroeconomic conditions and related volatility; expectations regarding the initiation, progress, and expected results of Lexeo's preclinical studies, clinical trials and research and development programs; the unpredictable relationship between preclinical study results and clinical study results; delays in submission of regulatory filings or failure to receive regulatory approval; liquidity and capital resources; and other risks and uncertainties identified in Lexeo's Annual Report on Form 10-K for the annual period ended December 31, 2024, filed with the SEC on March 24, 2025, Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025, filed with the SEC on May 12, 2025, as amended, and subsequent future filings Lexeo may make with the SEC. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Lexeo claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. Lexeo expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law.

    Media Response:

    Media@lexeotx.Com

    Investor Response:

    Carlo Tanzi, Ph.D.

    ctanzi@kendallir.Com

    This article was originally published on Quiver News, read the full story.

    The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.






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