For the final episode of Season 1 of @DevAndResearch, I'm sitting down with Ambassador Mark Dybul—one of the architects of the President's Emergency Plan for AIDS Relief—who argues that America has forgotten the core insight of the Marshall Plan: supporting other countries' economic growth creates markets for American businesses, not competition for American workers. We talk about drug development, too: • why many drugs don't work in women and people of color • how buying HIV drugs for Africa led to improved treatments for Americans • whether the FDA was wrong to reject MDMA for PTSD • the changes that could cut drug development expenses by orders of magnitude while producing treatments that actually work for everyone, supporting American geopolitical dominance, and defusing geopolitical instabilities that will “make pandemics looks like child’s play” 01:40 Introduction 02:20 PEPFAR’s systemic legacy 06:48 Why we make drugs that don’t work 10:18 PEPFAR’s legacy in the private sector 12:38 Covid lessons we failed to learn 16:33 MDMA for PTSD: Was the FDA wrong? 23:35 The President: “I want it to be big.” 26:22 A Marshall Plan for the 21st Century 29:00 US companies don’t understand Africa 37:02 Global-first drug development 45:45 What has Covid changed? 50:22 Global-health investment is stuck in the past 52:23 Immunotherapy and the Future of Medicine 58:03 What’s holding back change? 01:01:47 The Way Forward

This week on @DevAndResearch I'm chatting with @JessicaSacher, who has spent more than a decade studying natural viruses that kill bacteria. Oh, and she personally prepared experimental treatments that cured a dozen patients' chronic bacterial infections after all known antibiotics failed. We get into: • how Stalin's support for bacteriophage therapy led to a decades-long bias against "commie science" • convincing doctors to try something new when their patients are out of options • getting approval to collect clinical data when every patient receives a different treatment (score another point for Australia!) • how a flaw of clinical trial design sunk the largest phage-therapy efficacy trial to date... • ...and everything else it'll take to bring a treatment discovered in 1917—and completely outside the modern pharma paradigm—to patients today. 01:36 Introduction 02:14 What are phages? 03:28 What is phage therapy? 04:34 Phages vs antibiotics: A history 07:31 The limits of antibiotics 12:25 Step 1: Test for effective phages 15:45 Step 2: Purify the phage sample 21:12 Step 3: Get per-patient approval 24:13 Step 4: Treat the patient 28:13 Founding Phage Directory 33:09 Toward broader adoption of phages 46:13 What will commercial development (have to) look like? 53:57 Where are phages used today? 57:30 What if you treat, then test? 01:01:11 Why (else) do phage therapy trials keep failing? 01:05:32 Future directions

This week on @DevAndResearch, I sat down with @incredutility to talk about: • are there profitable investments in global public health? (and are there hundreds of millions of dollars of them?) • what makes investing in public health is harder (and easier) than conventional biotech VC, • which clinical trials cost an order of magnitude less than you'd expect, • which applications FDA reviewers love to see cross their desks, • the 40% tax credit attracting early-stage clinical trials to Australia, • and the looming rise of a “less unipolar” biotech world. Timestamps: 01:03 Introduction 01:27 Why is infectious disease commercially difficult? 05:26 Where do our healthcare dollars go? 07:49 GHIC: the Global Health Investment Corporation 10:07 Alternative business model #1: Selling to pharmaceutical stockpiles 12:59 Alternative business model #2: Priority Review Vouchers 18:06 Alternative business model #3: Making your own investment opportunities 21:10 Portfolio composition: New tech vs known platforms 23:00 Evaluating (counterfactual) impact 26:26 Working with company management 28:55 “Most people are in this business to improve the world” 31:09 More expensive and slower: “We’re in it with everyone else” 38:44 “Burning tens of millions of dollars a year in overhead” 42:06 Can trials cost less? 48:02 Clinical trials outside the US 54:13 The rise of Chinese biopharma 57:41 Ex-US / ex-China drug development 01:01:09 Who should regulate drugs for the world? 01:05:30 The future of global public health

We're back with @DevAndResearch, where I spoke with @Finrow on: • why we should grow more drugs in algae, and fewer in Chinese Hamster Ovary cells, • why "monoclonal antibodies" are particularly safe and effective as drugs—but incredibly expensive to manufacture, • and whether the fundamental problem of the biotech industry is that everyone just has too much money. Timestamps: 01:17 What makes a molecule a drug? 04:48 What’s so great about antibody drugs? 05:59 The humble Chinese Hamster Ovary cell 11:27 Introducing: Lumen Biosciences 12:40 Why spirulina? 19:14 Why isn't everyone doing this? 23:53 Going after gut infections 33:44 “Cocktails” of protein drugs 50:25 Other diseases of outside-of-body lumens 01:04:36 How to run a different breed of biotech 01:17:44 “Everyone just has too much money” 01:21:07 Extinction events in the biotech industry…and “little mammals scurrying around” 01:24:28 Speculations about the future (for Lumen and the world of direct-to-consumer drugs)

For the first episode of Development & Research, I spoke with @meribeckwith on: • being a patient in an incompetently-run clinical trial, • how many drug trials fail b/c of bad paperwork, • who benefits when trials are expensive, • just how quickly biotech founders lose control to investors, • why no one is picking up the billion-dollar bills on the sidewalk. Timestamps: 00:01:51 - "Eroom's Law" 00:03:12 - The gap between new science and new medicine 00:04:51 - Clinical trials: the patient experience 00:08:19 - The lifecycle of a biotech startup 00:10:22 - Clinical Research Organizations 00:13:19 - 10% of trials fail b/c of clerical errors 00:17:27 - Lindus Health (Meri's Series-B startup) 00:19:03 - Recruiting more patients won't save badly-planned trials 00:23:36 - Meri's skepticism of international trials 00:27:04 - Biotech culture vs tech culture 00:32:54 - What'll it take to get biotechs to act like tech companies? 00:35:13 - *Adaptive* clinical trials 00:39:10 - "Sidebar on the FDA..." 00:43:06 - *Decentralized* trials 00:46:13 - *Who* makes clinical trials expensive? 00:48:43 - (Not) picking up the billion-dollar bills on the sidewalk 00:53:22 - What does "better" look like? 00:56:08 - "...a lot of alpha if you're willing to disregard all of this b——..." 00:58:42 - What's changing with AI? 01:00:57 - What's going on with China? 01:03:10 - What's ahead for Lindus?

The way we develop new drugs is broken. The process costs too much, takes too long, and far too often it simply doesn't work. I sat down with five leaders in the field—from industry, VC, academia, and government—to hear their takes on how, and why, and what we can do about it.