In what for ten months was shaping up as a brutal year for biotech, it should come as no surprise that all five of RApport’s most popular pieces of the year speak to the market downturn. So whether you’re a biotech employee looking to de-risk your next career move, a CEO wondering how and when to shut down a company, or an investor thinking about next year, grab a mug of peppermint mocha and dig in.

It’s time to start thinking about New Year’s Resolutions. We asked ten experienced biotech board members what they consider useful, not useful, and downright irrelevant in terms of corporate goals. How do you know if goals are effective? And how important is it that they can actually be measured?

Let’s talk about something everyone produces but nobody really likes – trash. People produce billions of tons of waste annually. While there are many ways to reduce the amount of waste we produce, it is not possible to stop it entirely. Waste is, quite literally, inevitable. The disorder (entropy) in the universe increases with time, which just means that things will always break and there will always be some amount of waste. Once our things become our trash, we have two options: we can dispose of them or we can try to reclaim them as a resource. From a planetary health perspective, there are a lot of reasons to want to reclaim wastes as resources. Unfortunately, it is not easy to do so economically.

Our mission at RA Capital Management (RACM) is simple: to improve the health of each and every person in the world. Staying true to RACM’s mission, the Planetary Health team invests in profit-seeking companies that benefit people by improving the health of the planet.

In covering how Egypt managed to eradicate hepatitis C, the New York Times rewrites a key bit of history that betrays its misunderstanding of global drug pricing. Egypt’s access to the life-saving Harvoni was a gift from Gilead, not a result of a bare knuckle negotiation. It’s important to understand and explain the increasingly vulnerable system that underpins that gift before bad policy dismantles it.

European central planners should stop trying to talk the US out of incentivizing the development of better medicines that then also help Europeans and the rest of the world. It’s one thing to argue that any one country can’t afford to pay more for new drugs. It’s another thing entirely to put new drugs in jeopardy for everybody by exporting that thinking to the one country whose market-based system has underpinned the last several decades of pharmaceutical advances.

Medicare coverage of anti-obesity medicines would boost competition due to an expanded market, more investors in search of better drugs, and more competitors. This would result in a true weight-loss revolution that can save lives and dramatically drive down the cost of these drugs.

There’s a convention that public biotech companies should plan to raise money by the time they get down to one year of cash left on their balance sheets to avoid a dreaded “going concern” clause in their financial statements. But if you’ve got data on the way, it’s not always necessary to try to raise cash - particularly if the only terms you can get are draconian. Here’s a roadmap for deliberately navigating through that one-year threshold, owning the clause, and letting your data guide your financing strategy.

We asked three Gateway members who are or have been on Audit Committees – Kim Drapkin (CEO, Graphite Bio), Adam Mostafa (CFO, X4 Pharmaceuticals), and Sen Sundaram (CEO, Terns Pharmaceuticals) – to offer their best advice on Audit-related topics.

The technological renaissance in covalent inhibitor technology over the past decade is impressive. Relatively recent advances in structure-based drug design have unlocked the tantalizing opportunity to engineer covalency into small molecules. Now, RA Capital has incubated and seeded Hyku Biosciences to unlock histidines, tyrosines, and lysines for covalent modification to greatly expand the druggable proteome.

Silverback Therapeutics’s wind-down and reverse merger process can serve as a template for other companies when their clinical trials fail. The company’s response to its setback also teaches us about scenario planning, the importance of moving quickly when a key program doesn’t deliver hoped-for data, and why we should look ahead to a biotech ecosystem that anticipates the consequences of – and opportunities stemming from – its inevitable clinical setbacks.

Often, a drug’s initial approval only hints at its full therapeutic potential and the eventual number of patients who may benefit over time. Continued R&D investment can unlock much more utility before the drug ultimately goes generic, but those investments require adequate incentives.

Our January 2023 analysis Semper Maior: Time to Reboot Biotech argued that the development-stage biotech industry had found its footing, following one of the sector’s most sustained and painful drawdowns. Now, in our first update to that analysis, we’re happy to report that development-stage biotech remains on solid ground. In the first half of 2023, biotech investors harvested considerable gains from M&A and have already partially redeployed that capital back into what is now a smaller, slightly more highly valued set of promising development-stage companies.

Clinical trials can fail, regulators change their minds, manufacturing might run into an unsolvable glitch, and venture capital might dry up. Given all the risks small biotech companies face that are outside of their immediate control, might it be safer to just work for a more stable, revenue-generating company? Maybe! But before you rule out jumping into a small biotech, consider the pros and cons.

It may surprise you to find out just how badly we’re failing to take a comprehensive approach to quantifying societal value from new innovations in medicine. The IRA’s investment in our climate future should be lauded; its treatment of medical innovation is unfortunately hobbled by its goal of lowering Medicare spending today at the expense of tomorrow’s patients – that is to say, all of us.

It’s long been assumed that as long as NICE-like cost-effectiveness analyses stay on the other side of the ocean, our US biotech ecosystem will be fine. But in recent years, toxic math has begun to make its way to US soil. Peter Kolchinsky sat down with Jayson Dallas to get his take on NICE’s tactics, their increasingly global reach, and how biopharma can fight back.

The treatment of NDA-path drugs in the Inflation Reduction Act materially degrades the investment case for these treatments in age-related diseases and thus jeopardizes future biotechnology progress and the health of America’s seniors.

On February 22, CMS announced that they would not be reconsidering the National Coverage Determination (NCD) that effectively denies Medicare patients access to lecanemab, a drug with accelerated approval for Alzheimer’s disease. CMS’s rationale was that “there is not yet evidence meeting the criteria for reconsideration.” It’s worth pausing to consider the highly unusual CMS precedent that is playing out in Alzheimer’s.

The federal government must address the failure of Silicon Valley Bank (SVB) with speed and clarity before it metastasizes into a national crisis, so the ecosystem of institutions in which SVB has operated, including other banks and investors, can help bridge companies so that they can continue to operate while they wait for their deposits.

The run-on-the-bank panic around SVB would have been quelled if everyone was dissuaded from succumbing to mass hysteria. Understanding what happened can help prevent further bank runs.