The RTW Podcast

→ WHAT IT COVERS Rod Wong, founder and CIO of RTW Investments, traces biotech's evolution from the 2000 Human Genome Project through today's commercialization era. The discussion covers how the sector transformed from a $300 billion market dominated by four companies to a $1.5 trillion industry with broadening leadership and record numbers of new medicines reaching patients.

→ WHAT IT COVERS UroGen Pharma CEO Liz Barrett recounts navigating a split 4-5 FDA advisory committee vote for bladder cancer drug Jelmido, where only two of nine panelists were urologists. She details the ten-day period after the negative vote, strategic FDA negotiations, and ultimate approval despite stock dropping 50 percent. → KEY INSIGHTS - **FDA Advisory Panel Composition Risk:** UroGen faced an oncology advisory committee with only two urologists among nine voters for a urothelial cancer...

→ WHAT IT COVERS Michelle Krueger shares how her daughter Ellie received gene therapy for IRF2BPL-related disease just 14 months after diagnosis in February 2024, achieving one of the fastest rare disease therapy deployments ever. The family founded Ellie's Team, partnered with RTW Foundation, and self-managed drug development to accelerate treatment from research to patient administration.

→ WHAT IT COVERS Matthew Walker, UC Berkeley neuroscience professor and author of Why We Sleep, explains the science behind sleep stages, circadian rhythms, and sleep's impact on health. He covers jet lag protocols, teenage sleep biology, the creativity-dreaming connection, PTSD treatment breakthroughs, and immune function decline from sleep deprivation, plus his personalized sleep analytics service.

→ WHAT IT COVERS Akero CEO Andrew Cheng discusses the company's development of efroxiferman for MASH treatment, explaining how a failed 36-week trial result transformed into success at 96 weeks, making Akero the leading candidate for treating cirrhotic MASH patients with 50% five-year mortality rates. → KEY INSIGHTS - **Clinical trial design strategy:** Akero designed their SYMMETRY phase 2 trial with dual endpoints at 36 weeks and 2 years, providing a safety net when initial results failed...

→ WHAT IT COVERS GH Research CEO Vili Valcheva discusses GH001 (mebifotidine), a synthetic five-methoxy-DMT therapy for treatment-resistant depression that shows 57.5% remission rates at day eight versus SPRAVATO's 21% at day 28, with same-day symptom improvement and infrequent dosing averaging four treatments per six months. → KEY INSIGHTS - **Ultra-Rapid Treatment Response:** GH001 delivers measurable improvement in depressive symptoms within two hours of administration, with patients...

→ WHAT IT COVERS Connor Williams, Senior Research Analyst at RTW Investments, examines the evolution of psychedelic compounds from counterculture substances to legitimate psychiatric medicines. The discussion covers treatment-resistant depression affecting two million Americans, regulatory pathways for scheduled substances, and GH Research's breakthrough phase 2b results showing 15.5-point improvement on depression scales with five-methoxy-DMT.

→ WHAT IT COVERS Dr. Rekha B. Kumar, endocrinologist and Chief Medical Officer at Found, explains GLP-1 medications for weight management, covering efficacy rates (90% lose 5%+ body weight on newest drugs), side effects, patient selection criteria, telehealth delivery models, and long-term treatment expectations including weight regain patterns when medications stop. → KEY INSIGHTS - **Drug Efficacy Evolution:** First FDA-approved GLP-1 Saxenda showed 60% response rate for 5%+ body weight loss.

→ WHAT IT COVERS Rod Wong, founder and CIO of RTW Investments, explains how GLP-1 drugs for obesity represent the first healthcare innovation to create over $1 trillion in value. He covers current market dynamics, future drug development waves through 2030, cost effectiveness analysis, manufacturing constraints, and investment opportunities in both public and private companies.

→ WHAT IT COVERS Sarah Boyce, CEO of Avidity Biosciences, explains how the company solved RNA delivery to skeletal muscle and cardiac tissue using antibody-conjugated therapeutics. She details clinical development strategies for myotonic dystrophy and FSHD programs, FDA negotiations for accelerated approval pathways, and building a platform technology company targeting rare genetic diseases.