Ochre Bio

MONDAY MUSING: WEIGHT LOST IS THE WRONG SCOREBOARD I think about the obesity drugs a lot — partly because what's good for your liver tends to be good for your whole-body health. It's been fascinating to watch the media wars over which weight loss jab wins on percentage of body weight lost, but that framing is one-dimensional. I get more excited about readouts like Boehringer Ingelheim's survodutide (Phase III results below). Survodutide is a glucagon/GLP-1 receptor dual agonist. The GLP-1 arm curbs appetite — familiar territory. The interesting part is the glucagon arm, which acts directly on the liver: burning hepatic fat and dampening inflammation. In the SYNCHRONIZE-MASLD Phase III trial, 60% of patients normalised their liver fat without exessive weight loss. The last bit is important, as it could mean better liver fibrosis protection without the side effects of weight loss (such as muscle wasting). It's not about who loses the most weight but who repairs the most metabolic damage. Read the Phase III results here: https://lnkd.in/e66VKFfc

Rather than getting hung up on what to call DEI in the workplace, leaders should take three specific actions to help their employees embrace and engage with it. Companies and the patients they serve will benefit. Quin Wills, CEO and founder of Ochre Bio, discusses the topic. #DEI #biopharma #biospace https://hubs.li/Q04kgCGv0

Most biotechs never get the deal their science deserves. Jack Castle joined Oscar Vallejo on the Beyond the Clinic Podcast to talk about how we think about this at Ochre, and what most biotech companies get wrong when they try to translate what they've built into a story for investors and partners. Listen here: Spotify: https://lnkd.in/e6qE-FJT Apple Podcasts: https://lnkd.in/e7Cqte9w

The ambition is clear: build a liver antifibrotic toolbox that works across aetiology, stage of disease, and the many stratifiers we still do not fully understand. That will not be simple. Even so, the recent progress in metabolic therapies is worth celebrating. Several agents have now shown that fibrosis can be reversed in a subset of MASH patients without worsening steatohepatitis.  That is real progress. It changes the baseline assumption for the field. But it also sharpens the next question. As programmes move into cirrhosis, we will learn whether fibrosis reversal alone is the right therapeutic goal. A better biopsy is useful. Lower morbidity and mortality matter more. Over the next decade, longer-term outcomes will tell us whether reducing scar tissue is enough, or whether we need therapies that also restore function, address residual biology, and improve survival. Read the full article on EMJ here: https://lnkd.in/eMC7UWiS

Reversing fibrosis matters but it is not the same thing as a cure. We now know fibrosis can regress through bariatric, long-term viral suppression and curative HCV therapy. But the harder question is this: if scar tissue improves, has the liver really returned to normal? We know cancer risk does not simply reset to whatever fibrosis stage a patient appears to regress to, which suggests fibrosis is only part of the story. Distorted tissue architecture, damaged microcirculation, persistent inflammatory signals, and residual oncogenic change may all outlast histological improvement. That matters for how we think about drug development in MASH and cirrhosis. The goal should not be “less fibrosis” in isolation. It should be restoration of liver function, reduction in clinical events, and extension of transplant-free survival. That is why regeneration matters. The next wave of liver therapies may need to do two things at once: reduce fibrosis and rebuild function. Read the full article on EMJ here: https://lnkd.in/eMC7UWiS

The future of liver antifibrotics is precision medicine — the right combination, in the right patient, at the right time. Different patients are expected to respond differently to the same antifibrotic. Some patients with F3 fibrosis progress to cirrhosis within years; others remain stable for over a decade. What is clear: few, if any, patients with advanced disease will benefit from monotherapy alone. Yet past trials offer little to guide future combination strategies — most notably the failed MASH Phase II combination of selonsertib, cilofexor, and fircostat. We are entering an era where patient stratification — not just drug potency — will define therapeutic success. Building the evidence base for rational combination strategies is one of the most important challenges our field faces. It's a challenge we're ready to take on. Read the full article on EMJ here: https://lnkd.in/eMC7UWiS

2024 marked a watershed moment for MASH therapeutics. For the first time, a therapy – resmetirom – received FDA accelerated approval for non-cirrhotic MASH, meeting both the FDA and EMA's histological surrogate endpoints in a Phase III trial. Semaglutide (GLP-1) and efruxifermin (FGF21) have since followed, creating a genuine metabolic toolbox for physicians to treat MASH and compensated cirrhosis. Importantly, there is no one-size-fits-all approach. Patients with “lean MASH” may benefit from therapies that don't promote weight loss, meanwhile, GLP-1 agents may be the frontline choice for patients with a higher BMI and cardiometabolic comorbidities. Intriguingly, semaglutide has also been linked to reduced alcohol intake, opening a potential new avenue in alcohol-associated liver disease. With response rates still low across the board, the future will likely see combined therapeutic approaches across different mechanisms, target populations, and side-effect profiles, including novel therapies targeting non-hepatocyte liver cells. The metabolic toolbox is being built and patients will soon have different options that target their condition with precision. We're proud to be part of that effort. Read the full article on EMJ here: https://lnkd.in/eMC7UWiS

Worldwide, 1 out of 25 deaths is due to liver disease. From MASH and alcohol-associated liver disease, to viral hepatitis, primary biliary cholangitis, to haemochromatosis, the burden is vast and growing. The MASH 'tsunami', driven by rising global obesity rates, is particularly alarming. At the heart of all these conditions lies a common, devastating outcome: fibrosis. Left unchecked, it progresses to cirrhosis. Reversing it has long been considered the therapeutic 'holy grail' of hepatology, and until recently, the search for those therapies has failed repeatedly. However, momentum is building in this field. New direct- and indirect-acting metabolic agents targeting MASH are offering real hope — and we believe we're at the beginning of a turning point for patients living with chronic liver disease. Read the full article on EMJ here: https://lnkd.in/eMC7UWiS

Reversing fibrosis matters but it is not the same thing as a cure. We now know fibrosis can regress through bariatric, long-term viral suppression and curative HCV therapy. But the harder question is this: if scar tissue improves, has the liver really returned to normal? We know cancer risk does not simply reset to whatever fibrosis stage a patient appears to regress to, which suggests fibrosis is only part of the story. Distorted tissue architecture, damaged microcirculation, persistent inflammatory signals, and residual oncogenic change may all outlast histological improvement. That matters for how we think about drug development in MASH and cirrhosis. The goal should not be “less fibrosis” in isolation. It should be restoration of liver function, reduction in clinical events, and extension of transplant-free survival. That is why regeneration matters. The next wave of liver therapies may need to do two things at once: reduce fibrosis and rebuild function. Read the full article on EMJ here: https://lnkd.in/eMC7UWiS

The future of liver antifibrotics is precision medicine — the right combination, in the right patient, at the right time. Different patients are expected to respond differently to the same antifibrotic. Some patients with F3 fibrosis progress to cirrhosis within years; others remain stable for over a decade. What is clear: few, if any, patients with advanced disease will benefit from monotherapy alone. Yet past trials offer little to guide future combination strategies — most notably the failed MASH Phase II combination of selonsertib, cilofexor, and fircostat. We are entering an era where patient stratification — not just drug potency — will define therapeutic success. Building the evidence base for rational combination strategies is one of the most important challenges our field faces. It's a challenge we're ready to take on. Read the full article on EMJ here: https://lnkd.in/eMC7UWiS