The strongest evidence for tadalafil as a longevity candidate is large scale observational. In a propensity matched cohort of 509,788 men with erectile dysfunction, tadalafil over 3 years was associated with 34% lower all cause mortality, 32% lower dementia, 27% lower MI, and 34% lower stroke. Supporting cohorts show the same direction, including a dose dependent gradient: in higher risk men the top PDE5 inhibitor exposure quartile reached a mortality risk reduction of 49%. For a drug discussed as “longevity medicine,” that is close to the ceiling of current human evidence. No drug, tadalafil included, has a completed RCT with lifespan or healthspan as the primary endpoint, so observational signal on hard endpoints is the best the field has, and tadalafil’s is unusually large and consistent. The mechanism is also coherent. PDE5 inhibition raises cGMP, improves endothelial function and NO signaling, and the cardiovascular event data line up with that pathway. That supports causal plausibility for the vascular benefit, though it does not establish a lifespan effect. Disease specific and healthy user bias cannot be ruled out. The disease specific part: ED is itself a sign of vascular disease or dysfunction, which tadalafil’s mechanism can help directly. The healthy user part: wanting to maintain a healthy sex life in older age is a marker of relatively good health. None of this is a recommendation to take tadalafil on your own. It should follow from your individual health and biomarker profile, and only under specialized physician advice and oversight.

8VC hired one of HHS Secretary Kennedy's sons to work for their VC firm & one of the firm's partners appears to be the only VC appointed to a new council advising the HHS Secretary & the CMS Administrator

almost exactly 3 years ago Dimension led a $40M Series A in @newlimit, inspired by the pioneering vision of @jacobkimmel @byersblake and @brian_armstrong. today, we announce a $435M Series C led by Founders Fund w Thrive and Greenoaks as new partners. lets go chart the future.

Reflections on “in-licensing” as the nucleating substrate for NewCo’s in VC-backed Biotech. It’s not new - it's been a tried-and-true component of venture creation for decades - finding great assets and starting companies around them. ~20% of our startups (out of ~50) in the 2002-2014 window (Funds VI-IX) were nucleated with in-licensed assets from Pharma at inception. None of the assets were from Chinese pharma - mostly US/EU/JPN. ~20% of our startups (~70) in the 2018-2026 window (Funds XI-XIV) were similarly nucleated with in-licensed assets at inception. A few of those began with assets from Chinese partners, but also others in US/EU/JPN Most of what we continue to do is de novo venture creation around great science with talented entrepreneurs and founders.  I suspect other early stage VCs are similar.

$abvx Cancer risk.

After decades of work and billions of dollars, this is what passes for a revolution in cancer research. This drug is being hyped to no end on social media. At the oncology conference, there is a standing ovation from a crowd of 40,000 doctors and industry people celebrating it as a major breakthrough and the defining achievements of cancer research over the last decade. The scientists behind it will win a Nobel Prize. What exactly is the achievement? A drug that extends life by six months in less than 10% of cancer patients. The cumulative R&D costs run into the billions of dollars. The drug is not a cure and pancreatic cancer mortality does not change. Resistance develops and more drugs need to be developed. When those drugs are hailed as breakthroughs, resistance develops again. Everyone in the industry knows this approach does not scale as a durable solution. It is not a cure for cancer. This work follows a narrow line of thinking based on oncogene theories that has consumed enormous amounts of federal funding and biotech R&D for four decades. At the same time, environmental factors, prevention, detection, the root causes of cancer, tumor evolution, diet, exercise, and many other areas of cancer research were neglected. Any criticism of this model is immediately met by a coalition of interests invested in preserving it. Academic researchers, pharmaceutical companies, investors, journals, science media, professional societies, consultants, patient advocacy groups who have been told there is no other way, and online activists all have incentives tied to the existing model. Critics are accused of attacking patients, opposing progress, or undermining science itself. Cancer patients become shields in a bigger issue that is really about the performance of the cancer research enterprise. After decades of effort and billions of dollars, this is what the cancer establishment is giving itself a standing ovation for.

Sounds about right. No wonder this guy works for NHS commissioning.

I celebrate medical progress! Pancreatic cancer is awful and every step forward should be praised That said it is sad to see how much ground we have ceded to the belief that p-values are a substitute for measures of clinically relevant effects