EA - Alvea's Story, Wins, and Challenges [Unofficial] by kyle fish

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Alvea's Story, Wins, and Challenges [Unofficial], published by kyle fish on November 1, 2023 on The Effective Altruism Forum.IntroA few months ago, the other (former) Alvea executives and I made the difficult decision towind Alvea downand return our remaining funding to investors. In this post, I'll share an overview of Alvea's story and highlight a few of our wins and challenges from my perspective as an Alvea Co-Founder and former CTO, in hopes that our experiences might be useful to others who are working on (or considering) ambitious projects to solve the biggest problems in the world. I'm sharing everything below in a personal capacity and as a window into my current thinking - this is not the definitive or official word on Alvea and it doesn't necessarily represent the views of any other Alvea team members. I expect my reflections to continue evolving as I further process the journey and outcomes of this project, and hope to share more along the way.Alvea's StoryFirst vaccine sprint and decision to continue Alvea (December 2021 through April 2022)We launched Alvea in response to the Omicron wave of COVID-19 (the most transmissible and immune-evasive variant then to have arisen) as a short-term, high-risk project with the goal of developing an easily-deployable, room temperature-stable DNA vaccine against Omicron as quickly as humanly possible, without compromising on safety and quality. We ultimately carried this vaccine candidate into Phase I clinical trials in less than 6 months, becoming the fastest startup ever to take a new drug candidate from company launch to a human clinical trial. Our success in this initial sprint caused us to expand our ambitions for Alvea and explore ways of building on the track record and momentum we'd built up.One of our initial strategies was to deploy our first vaccine (which was optimized for the Omicron BA.2 variant), and then leverage our development platform to roll out updated versions in response to the emergence of new variants. However, a few key updates convinced us that this was not a promising path. First, the time between waves of new variants continued to drop, making it more difficult to keep up with viral evolution. Second, the FDA and other regulators began an expedited approval process for updated versions of the mRNA vaccines that had already been authorized, making it more difficult for new vaccines to break into the commercial market (a great pandemic regulatory move, though!). Additionally, early efficacy results for our vaccine were underwhelming and suggested that it was unlikely to provide sufficient protection to justify continued investment, particularly against the newest variants in low- and middle-income countries. In light of these updates we decided to stop development of our candidate and consider other paths forward.Product pursuits (May 2022 through July 2022)Despite discontinuing our first vaccine program, we believed we'd landed on a compelling model for general-purpose acceleration of promising drugs and vaccines into the clinic, so we set out to find other high-impact products we could accelerate with this approach. We specifically targeted products and technologies with early published preclinical data that were nearing readiness for clinical testing, with the idea that we could pick them up and dramatically speed up their development and deployment. We ran multiple "product pursuits" in parallel to explore possible technologies, with particular focus on nucleic acid vaccines that could be formulated as dry powders for inhaled administration and on therapeutic interfering particles, a class of RNA therapeutics/prophylactics that are expected to be highly resistant to viral evolution. Neither of these efforts uncovered product opportunities that were clearly good bets under this m...