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Acknowledgements
We thank Dr. Lin Gan from the Institutional Mouse Transgenic Core Facility at the University of Rochester for generating the Sirt6 transgenic mice.
Published: 22 April 2024
Hepatic Sirt6 activation abrogates acute liver failure
Discussion
In this work, we revealed a crucial role of Sirt6 in protecting against both APAP-induced and BDL-induced ALF. Our investigation has begun from an interesting observation that hepatic Sirt6 expression significantly downregulated in the livers of human and mice with acute liver failure. The rescue and maintenance of Sirt6 expression in the Sirt6-Tg mice after APAP administration protected against the pathological changes during APAP-induced liver toxicity by limiting oxidative stress and inflammation. The protective effect of hepatic Sirt6 was further validated in Sirt6-HepTg mice and in the mice treated with the specific Sirt6 activator MDL-800. Hepatic-specific Sirt6 knockout in mice exacerbated, but hepatic overexpression of Sirt6 ameliorated, acute liver damages-induced by both APAP and BDL. Furthermore, the Sirt6 activator MDL-800 presented better therapeutic potential to alleviate liver injury in mice than NAC, which is the only proved antidote for APAP overdose up to now. Taken together, these results demonstrate that Sirt6 could be an important therapeutic target for the treatment of ALF.
..............
In conclusion, our results revealed a crucial role of hepatic Sirt6 in the protection of acute hepatotoxicity. Genetic overexpression of Sirt6 and the pharmacological activation of Sirt6 ameliorated oxidative stress, inflammation, and liver injury. The potential mechanisms whereby Sirt6 protects against hepatotoxicity include that Sirt6 inhibits JNK and caspase 3/9 activation, enhanced Nrf2/HO-1 pathway and attenuates PARP1 expression and activity. Therefore, Sirt6 orchestrates the safeguard against hepatotoxicity and may serve as a new therapeutic target for the ALF.
hTtps://www.nature.com/articles/s41419-024-06537-5
The liver is the only organ that can regrow and repair itself and Ochre Bio will seek to develop drugs that restore this ability in diseased livers.
The company’s work to date has involved analysing thousands of donated human livers to develop an understanding of the causes of disease, and studying whether making changes to RNA — a vital molecule for translating genetic information into proteins — can extend the lifespan of transplanted livers.
“What we’re trying to do is give the liver a little nudge in the right direction to support it to regenerate,” said Quin Wills, chief scientific officer and co-founder of Ochre Bio. “What happens in a cirrhotic liver is [cells] don’t have that decision-making process any more to start dividing and restoring capacity. By changing certain ‘switches’, using these RNA therapies, we help them make those decisions again.”
There have been a series of recent developments in the treatment of liver disease, which is the third-largest cause of early death in the UK and other high-income countries. It is also the largest killer of 35- to 49-year-olds in the UK, according to the UK Health Security Agency.
The US Food and Drug Administration recently approved the first-ever drug designed specifically for the most common liver disease, metabolic dysfunction-associated steatohepatitis or mash, developed by Madrigal Pharmaceuticals.
People with mash have a build-up of fat deposits in the liver and it is estimated to affect 115mn people worldwide. The approval of Madrigal’s drug should help other treatments to pass regulatory hurdles, according to analysts at investment bank William Blair.
The disease is often linked with weight gain and has become more common as obesity levels have risen.
Pharma groups are optimistic about the potential for new weight loss and diabetes drugs known as GLP-1s to treat liver diseases.
A weight-loss drug licensed by Boehringer Ingelheim from Danish biotech Zealand Pharma has had positive results in liver disease trials, while Novo Nordisk is looking at the effect of its weight-loss drug Wegovy on mash.
But while these drugs could be used to treat early-stage disease, the industry thinks they will be less helpful against more advanced mash, which can involve extensive scarring or cirrhosis of the liver. New ways of tackling late-stage liver disease could delay the need for transplants, currently the only effective treatment.
Jack O’Meara, chief executive of Ochre Bio, told the Financial Times: “There still remains a huge unmet need there and we hope this partnership with Boehringer will be able to develop medicines that solve or offer solutions for patients at a later stage.”
Søren Tullin, head of cardiometabolic disease research at Boehringer Ingelheim, said Ochre Bio’s genomics experience and technology “holds the potential to uncover novel regenerative pathways that will make a meaningful difference in the lives of those a
UK biotech signs $1bn deal to develop liver disease drugs
Ochre Bio partnering with Germany’s Boehringer Ingelheim on treatments that will harness the organ’s capacity to regenerate
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https://www.ft.com/content/3cd4fc3c-e52b-4042-9540-08ce2444b5bd
German pharma group Boehringer Ingelheim has struck an up to $1bn partnership with a UK biotech to develop treatments for chronic liver disease that aim to harness the organ’s capacity to regenerate.
Under the drug discovery partnership, Ochre Bio will receive $35mn in upfront and near-term payments, rising to more than $1bn in payments and royalties if treatments are successfully brought through clinical trials. It is a similar milestone-based structure to many partnerships in the pharmaceutical industry.
https://www.ft.com/content/3cd4fc3c-e52b-4042-9540-08ce2444b5bd
Regeneron launches five-year $500m biotech fund
1 HOUR AGO
Biopharma giant commits $100m annually to Regeneron Ventures as it seeks to ‘fuel promising biotech innovation.’
Yesterday, as we revealed 2023 was another tough year for longevity investment, biotech heavyweight Regeneron quietly announced the formation of Regeneron Ventures, a new $500 million venture capital fund. As the fund’s exclusive limited partner, Regeneron has pledged $100 million annually over the next five years to invest in promising life sciences companies.
While the new fund’s investment mandate is broadly health focused, Regeneron Ventures says its interest is “skewed towards biotechnology, devices, tools, and enabling technologies.” The fund says that investment decisions will be guided by the quality of the science, people, and data, prioritizing “breakthrough innovation” despite the inherent risks and uncertainties. All of which should resonate well with founders in the longevity sector, offering a potential new source of funding for biotech startups targeting aging and age-related diseases.
htTps://longevity.technology/news/regeneron-launches-five-year-500m-biotech-fund/amp/
SIRT6 is an enzyme that plays an essential role in human health and contributes to epigenetic regulation of gene expression, mitochondrial health, and DNA repair. A review of literature suggests that SIRT6 could potentially help address diseases of aging, neurodegeneration, diabetes and obesity, in addition to depression. Arrivo is exploring the potential of SP-624 in multiple therapeutic areas beyond depression.
Arrivo Bio Initiates Large Phase 2b Clinical Trial in Major Depressive Disorder with Novel SIRT6 Activator
Epigenetic mechanism of action offers a promising new approach to tackling MDD
April 16, 2024 08:00 AM Eastern Daylight Time
MORRISVILLE, N.C.--(BUSINESS WIRE)-
-Arrivo Bio announced today a significant step forward in the fight against major depressive disorder (MDD) with the dosing of the first patient in the SP-624-202 clinical trial.
htTps://www.businesswire.com/news/home/20240416487796/en/Arrivo-Bio-Initiates-Large-Phase-2b-Clinical-Trial-in-Major-Depressive-Disorder-with-Novel-SIRT6-Activator
Key highlights of the Founders Longevity Forum:
Exclusive event – The Founders Longevity Forum will host a minimum of 120 approved guests, including high-caliber investors, family offices, longevity founders and VIPs.
Comprehensive program – guests will enjoy a half-day of content, a welcome reception, a full-day program and automatic registration for London Tech Week.
Global reach – following the London event, the Founders Longevity Forum will travel to Abu Dhabi and San Francisco.
Longevity takes center stage – The Longevity Village at London Tech Week will elevate this dynamic industry, showcasing the companies applying new technologies to extend human healthspan.
htTtps://longevity.technology/news/founders-forum-and-longevity-technology-join-forces-to-accelerate-longevity-investment/
10th - 11th June 2024 - Organised by Longeity Technology who hold 3%. Gla ;-)
New international event program launches to bring longevity entrepreneurs and investors together.
Founders Forum and Longevity.Technology today announced the launch of the Founders Longevity Forum, a premier event series designed to educate and connect investors with the vast potential within the longevity market.
The inaugural Founders Longevity Forum will take place at Olympia London during the renowned London Tech Week, focusing on a sector that is projected to exceed $600 billion by 2025. This partnership aims to foster meaningful connections between startups, venture capitalists (VCs), corporate venture capitalists (CVCs), family offices and CEOs leading the charge in longevity.
Brent Hoberman, Co-Founder and Executive Chair of Founders Forum Group, said: “Longevity is becoming a mega trend as science makes increased healthspans more realistic, converging with a wider shift towards preventative healthcare.
“We’ve noticed a need to connect top scientists and innovative startups with funds to help them turn their dreams into reality. By bringing together the best and brightest minds working on longevity today, we can galvanize progress in this area and transform the demographic landscape.”
Taking place on New international event program launches to bring longevity entrepreneurs and investors together.4, the Founders Longevity Forum will address the investment opportunities across the longevity space, from established longevity business models such as diagnostics, longevity clinics and supplements, through to cutting-edge longevity biotech companies poised to revolutionize the biotech industry and transform society.
The event will also benefit from an advisory panel that has decades of longevity and geroscience expertise between them; the panel includes Eric Verdin, Andrea Maier, Jim Mellon and Aubrey de Grey, with further members to be announced.
“Multiple longevity events are happening and they’re all great, but few are specifically focused on bringing more investors into this rapidly accelerating field,” said Phil Newman, Founder and CEO, Longevity.Technology.
“We plan to stage events in London, Abu Dhabi and San Francisco initially to accelerate longevity investment globally, and catalyze a wave of innovation and collaboration that will redefine the future of human health.”
“We’re keen to educate investors on the vast opportunities in longevity whilst fostering meaningful connections for startups and scaleups in this niche,” said Carolyn Dawson, CEO, Founders Forum Group.
“Helping create these connections is central to our mission at Founders Forum Group as we seek to empower entrepreneurs at every stage of their journeys; with Longevity.Technology as our partner, we can forge formative alliances that propel longevity innovation.”
Major Shareholders
ERIC LEIRE 124,000,000 35.5%
PREMIER MITON 32,000,000 9.2%
ARIAN BEESTON 17,475,000 5.0%
JONATHAN MARK SWANN 16,874,000 4.8%
SAMANTHA BAUER 14,500,000 4.1%
LONGEVITY TECH FUND 10,499,998 3.0%
SARAH BEESTON 10,000,000 2.9%
Very impressive, this is going to bounce big very soon. Gl :-)
Eric's £50k share subscription declared along with another 1.8% for Jonathan Swan who declared his 3% back in March. The smart Money is accumulating. Gla :-)
It's going to big...On and UP!!! Gla :-)
Cheers Porter, an excellent and informative interview and very encouraging on prospects and potential going forward. Exciting times ahead. Gl :-)
Great find Northeast and exciting news for Genflow. Gl :-)
First in human proof-of-concept Phase I/ II Trial in NASH
NASH or Non-Alcoholic Steatohepatitis is a liver disease with a significant unmet medical need. Effecting an estimated 35 million people worldwide, it is the most chronic liver condition in the West and patient numbers are growing rapidly. It is the leading cause of liver transplants due to the lack of approved therapies with the market for NASH therapy expected to reach $27.2B by 2029.
Recent pre-clinical programs have highlighted the adipogenic, anti-fibrotic, and anti-tumoral effects of GF-1002 positioning it as a promising treatment candidate for NASH.
By targeting NASH, Genflow Biosciences stands to benefit from a clear regulatory pathway that could lead to accelerated development and the potential for conditional fast-track approval.
It's all good and now look forward to a flow if positive news. Gla ;-)
Genflow Biosciences (LON:GENF) (OTCQB:GENFF)
1,558 followers
7h
The first #NASH treatment is FDA approved! Despite its growing rates, the disease went largely understudied for decades - until now. Genflow Biosciences (LON:GENF) (OTCQB:GENFF) and its peers are developing life saving medicine to change the lives of millions.
Read more: htTps://loom.ly/fYAsZzA
Healthy Returns: The first drug for a common, deadly liver disease is here – and more are coming
PUBLISHED TUE, MAR 19 2024
In a landmark decision on Thursday, the Food and Drug Administration approved Madrigal Pharmaceuticals' drug "Rezdiffra," to be used along with diet and exercise. The company expects the medicine to be available next month with a hefty price tag of $47,400 per year before insurance and other rebates.
The agency's approval is also a big deal because it means Madrigal has succeeded in an area where several other drugmakers have failed – or are still trying to crack.
That gives Madrigal an edge in a market that could be huge: The MASH industry could be worth nearly $26 billion by 2032 across the U.S., France, Germany, Italy, Spain, the U.K. and Japan, according to an estimate from data analytics firm GlobalData.
Madrigal's drug is setting the bar for efficacy and safety for MASH treatment, while also opening the door for medicines still in development.
There's one important detail in the approval that could bode well for the entire MASH space: The FDA isn't requiring patients to get a liver biopsy to determine their eligibility for Madrigal's drug.
That refers to a procedure in which a doctor removes a small piece of liver tissue from a patient so they can examine it under a microscope for signs of damage or disease.
"The absence of liver biopsy requirement in Rezdiffra's label should buoy biotech stocks" of companies developing MASH treatments and "potentially accelerate and broaden patient access," William Blair analyst Andy Hsieh wrote in a note on Friday.
htTps://www.cnbc.com/2024/03/19/healthy-returns-first-nash-liver-disease-drug-is-here-more-coming.html
March 2024 Company Presentation
hTtps://genflowbio.com/wp-content/uploads/2024/03/GenflowBio_Presentation_3-6-24.pdf
That's my plan......On and UP!!! Gla ;-)